Alicia Fanning, MD

Early detection of breast cancer is vital to reducing the morbidity and mortality associated with this disease. After a brief overview of breast cancer epidemiology and risk assessment, this article describes screening and diagnostic imaging techniques as they are currently practiced to promote early breast cancer detection. We conclude with a review of image-guided needle biopsy techniques and a recommended approach to breast cancer screening in the general population.

EPIDEMIOLOGY OF BREAST CANCER: DAUNTING BUT SLOWLY IMPROVING

After nonmelanoma skin cancers, breast cancer is the most common form of cancer in women today, accounting for more than 1 in 4 cancers diagnosed in US women.¹ If the current incidence of breast cancer remains constant, US females born today have an average risk of 12.7% of being diagnosed with breast cancer during their lifetime (ie, 1-in-8 lifetime risk), based on National Cancer Institute statistics.^2,3 The American Cancer Society estimated that 178,480 new cases of invasive breast cancer and 62,030 new cases of in situ breast cancer would be diagnosed in the United States in 2007, and that 40,460 US women would die from breast cancer that year.¹ Only lung cancer accounts for more cancer deaths in women.

The role of race and ethnicity

Breast cancer risk varies by race and ethnicity in the United States. After age 40 years, white women have a higher incidence of breast cancer compared with African American women; conversely, before age 40, African American women have a higher incidence compared with white women. African American women are more likely than their white counterparts to die from their breast cancer at any age. Incidence and death rates from breast cancer are lower among Asian American, American Indian, and Hispanic women compared with both white and African American women.¹

Recent hopeful trends

Despite the daunting incidence numbers reviewed above, recent years have seen encouraging trends in US breast cancer epidemiology.

For invasive breast cancer, the growth in incidence rates slowed during the 1990s, and rates actually declined by 3.5% per year during the period 2001–2004.¹ These changes are likely attributable to multiple factors, including variations in rates of mammography screening and decreased use of hormone replacement therapy after the 2002 publication of results from the Women’s Health Initiative trial. Still, the trend is encouraging.

Incidence rates of in situ breast cancer rose rapidly during the 1980s and 1990s, largely due to increased diagnosis by mammography, but have plateaued since 2000 among women aged 50 years or older while continuing to rise modestly in younger women.¹

Meanwhile, the overall death rate from breast cancer in women declined by 2.2% annually from 1990 to 2004.¹

RISK FACTORS AND RISK MODELING

Risk factors for breast cancer have been well described and include the following:

• Age ( ≥ 65 years vs < 65 years, although risk increases across all ages up to 80 years)
• Family history of breast cancer
• Late age at first full-term pregnancy (> 30 years)
• Never having a full-term pregnancy
• Early menarche and/or late menopause
• Certain genetic mutations for breast cancer (eg, in the BRCA1, BRCA2, ATM, and CHEK2 genes)
• Certain breast disorders, such as atypical hyper­plasia or lobular carcinoma in situ
• High breast tissue density
• High bone density (postmenopausal)
• High-dose radiation to the chest.

The above risk factors are, in general, fixed. More elusive risk factors, in that they are variable and modifiable, include obesity, use of exogenous hormones (recent and long-term hormone replacement therapy; recent oral contraceptive use), alcohol use, tobacco use, diet, and a low level of physical activity. Breast implants are not a risk factor for breast cancer, though their presence does obscure breast tissue on imaging, limiting the detectability of a tumor when it does develop (see “Screening the Surgically Altered Breast” below).

Women with a genetic predisposition to breast can­cer merit special consideration. Hereditary breast cancers account for about 5% to 10% of breast cancer cases, and the BRCA1 and BRCA2 mutations are responsible for 80% to 90% of these cases, while other gene mutations (noted above) or genetic syndromes account for the rest. Clinical options for managing women with a genetic predisposition include surveillance, chemoprevention, and prophylactic surgery.⁴ Detailed discussion of the management of these women is beyond the scope of this article, but readers are referred to www.nccn.org/professionals/physician_gls/PDF/ genetics_screening.pdf for practice guidelines from the National Comprehensive Cancer Network.⁵

Tools for risk assessment

Several tools are available to predict a woman’s risk of developing breast cancer. Probably the most widely used is the Gail model,⁶ which was published in 1989 and forms the statistical basis for the National Cancer Institute’s Breast Cancer Risk Assessment Tool, which is available for downloading at www.cancer.gov/bcrisktool.⁷ The model uses a woman’s personal medical and reproductive histories and her family history of breast cancer to predict her 5-year and lifetime risk of developing invasive breast cancer. Factors included in the risk calculation are age, race, number of first-degree relatives with a history of breast cancer, age at first live birth (or nulliparity), age at menarche, number of breast biopsies, and presence or absence of a history of atypical hyperplasia. The relative risk for each of these factors is multiplied to generate a composite risk. The Gail model has been validated for white women but has been shown to underestimate breast cancer risk in African American women; it remains to be validated for Hispanic women, Asian women, and other subgroups of women.⁷

The commonly taught “triple test” for palpable breast lesions is another risk model that incorporates clinical findings. It consists of a physical examination, mammography, and fine-needle aspiration⁸ (in the “modified triple test,” ultrasonography replaces mammography⁹). When all three elements of the test are concordant (either all benign or all malignant), the triple test has been reported to have 100% diagnostic accuracy.^8,9

 

 

A WORD ABOUT BREAST EXAMINATION

Breast self-examination

The role of breast self-examination is controversial in the literature. There are currently no data to support the contention that it increases detection of breast cancer. As a result, the American Cancer Society no longer recommends that all women perform monthly breast self-exams, although it advises that all women be told about the potential benefits and limitations of breast self-examination (Table 1).¹⁰ Research suggests that structured breast self-examination is less important than self-awareness. Women who detect breast tumors themselves typically find them outside of a structured examination, such as when bathing or getting dressed.¹

Clinical breast examination

As noted in Table 1, regular clinical breast examinations are recommended by the American Cancer Society for asymptomatic women at average risk for breast cancer, with the recommended frequency depending on the woman’s age.¹⁰ The US Preventive Services Task Force takes the stance that there is insufficient evidence to recommend for or against breast cancer screening with clinical breast examination alone.¹¹ While it is unclear precisely what contribution clinical breast exams make to the detection of breast cancer, they certainly provide clinicians an opportunity to raise awareness about breast cancer and educate patients about breast symptoms, risk factors, and new detection technologies.¹⁰

SCREENING MAMMOGRAPHY

Screening mammography is the single most effective method of early breast cancer detection,¹ and the American Cancer Society recommends that women at average risk for breast cancer have annual screening mammograms beginning at age 40 years (Table 1).¹⁰

The evidence base

The primary evidence supporting the recommendation for screening mammography comes from eight randomized trials that studied the effectiveness of screening mammography for cancer detection in Sweden,^12,13 the United States,¹⁴ Canada,^15,16 and the United Kingdom.¹⁷ Overall, breast cancers detected by screening mammography are smaller and have a more favorable history and tumor biology than those detected clinically without the use of imaging. A pooled analysis of the most recent data from all randomized trials of screening mammography in women aged 39 to 74 years showed a 24% reduction in mortality (95% CI, 18% to 30%) in women undergoing screening mammography, although not all individual trials showed a statistically significant mortality reduction.¹⁰

The screening procedure at a glance

A screening mammogram, as distinguished from a diagnostic mammogram (Table 2), consists of two standard radiographic views of each breast (mediolateral oblique and craniocaudal).¹⁸ The woman being screened is advised to wear no powders or deodorants and should be asymptomatic. Women with symptoms (eg, breast lump, focal tenderness, nipple discharge) should be scheduled for a diagnostic mammogram (Table 2), not a screening mammogram.

The mammography technologist obtains the standard radiographs of each breast, and computer-assisted detection software can be applied to the mammogram films to aid in the identification of abnormalities as a computer-generated second opinion. Although computer-assisted detection is not currently standard of care, it is available at most institutions. The films are read later by a radiologist who will interpret them according to the American College of Radiology’s standard system of describing mammogram findings, called the Breast Imaging Reporting and Data System (BI-RADS). In this system, results are assigned a category rating on a scale from 0 to 6 (Table 3). This standardization allows physicians to use consistent language, ensures better follow-up of suspicious findings, and reduces interobserver variability.

Analog vs digital

Breast radiographs can be obtained by the traditional film-screen (analog) method or obtained digitally (Figure 1).

Digital mammograms are radiographs that are acquired digitally and allow digital enhancement to aid in interpretation. When receiving a digital mammogram, the woman being screened still undergoes compression and positioning as for a conventional film-screen mammogram, and the images are still produced with x-rays. However, digitization allows manipulation of the images as they are being interpreted, enabling the radiologist to focus on areas of interest or to “window” and “level” the image, similar to adjusting the tint and contrast on a television set.

Research trials comparing digital and film mammography, such as the Digital Mammographic Imaging Screening Trial (DMIST),¹⁹ have found digital mammography to be especially helpful in women with extremely dense breasts, who have an elevated risk for breast cancer. For women with fatty breasts the differences between the types of mammogram are less significant.

The type of mammogram a woman receives generally depends on the equipment available at the site she visits. Digital mammography units currently cost approximately 3 times as much as corresponding film-screen units, yet digital mammograms command reimbursement rates only about 1.6 times higher than those for film mammograms (Table 4). A hard copy of the digitized image can be printed, although the hope is that eventually fewer mammogram images will be printed and space-saving electronic storage will supplant storage of printed films.

For further detail on digital mammography, readers are referred to the recent review by D’Orsi and Newell.²⁰

SCREENING THE SURGICALLY ALTERED BREAST

Following surgical cancer treatment or reconstructive surgery, screening of remaining breast tissue for cancer is still performed and is just as essential to patient care as presurgery screening. The first line of defense for any patient with a surgically altered breast is mammography.

When a patient has had breast reconstruction following mastectomy, it is presumed that very little breast tissue remains. There is no standard of care for screening the nonbreast tissue introduced by the reconstructive procedure. Nonetheless, at our institution we perform a single mediolateral oblique projec­tion on any flap-reconstructed breast in light of rare anecdotal accounts of cancer found in and around the reconstructed breast. When problem-solving is needed to evaluate a new palpable abnormality, special angled views (tangential) and directed ultrasonography can be used. We do not routinely perform screening mammography on mastectomy patients who have had reconstruction with implants, but we can investigate areas of clinical concern (eg, due to palpable masses) with directed ultrasonography.²¹

The cosmetically altered breast presents its own issues in cancer detection. Both silicone-gel and saline implants obscure breast tissue that could contain cancer. For this reason, special implant-displaced views are performed that allow visualization of a larger portion of breast tissue beyond that allowed by standard mammograms. Therefore, an asymptomatic patient with implants who presents for screening mammography will have eight mammography views obtained instead of the routine four views.²²

Patients who have had breast reduction, excisional biopsy, or prior breast conservation surgery (lumpectomy and radiation) are screened in a routine manner with mammography.²³ Patients who have had prior surgical procedures often have architectural distortion at the surgical site, which is generally stable over time. Any prior surgical procedure can predispose the patient to the development of fat necrosis, which is a benign entity but can mimic cancer in its early phases through the development of calcifications and, occasionally, a new palpable lump. We most commonly confront this issue in the period 2 to 4 years after the operation.²⁴ Occasionally the findings are such that a biopsy is needed to determine whether fat necrosis is the cause. In this population, magnetic resonance imaging (MRI) can also be used as an adjunctive tool, and can sometimes clarify the presence of fat necrosis and other postoperative findings, such as seroma, hematoma, or inflammation. In other instances, only a biopsy can determine what a particular finding represents.

 

 

DIAGNOSTIC MAMMOGRAPHY

Any mammography performed for a problem-solving purpose is considered diagnostic mammography (Table 2); the exam is tailored to the patient’s individual issue.²⁵ Diagnostic mammography requires the presence of a qualified radiologist at the time of imaging. The goal is to come to a final conclusion about the mammographic or clinical finding at the time of the patient’s visit. Special views are usually performed that include, but are not limited to, spot-compression or spot-magnification views, depending on the finding.²⁶ The patient is then given a same-day written account of the results at the conclusion of the study.

Examples of problems that may prompt diagnostic mammography include patient-reported palpable findings, screening mammography findings that are recalled for further investigation, or physician-detected findings. Often, ultrasonography is also used at the same visit and its results are integrated with the mammography findings to arrive at the final impression.

BREAST ULTRASONOGRAPHY AND BREAST MRI

Ultrasonography and MRI are two very useful adjunctive tools for breast lesion detection and analysis. At this time, however, neither is a replacement for screening mammography as a primary screening modality; rather, each is used in a complementary fashion for lesion analysis and biopsy guidance.^10,27

Ultrasonography: Best for further study of areas of interest

Ultrasonography uses high-frequency sound waves to create a picture using a probe directed to an area of interest in the breast. The optimal probe for breast imaging is one typically operating in a frequency of 12 to 18 MHz and 4 cm in scanning width.

Because ultrasonography provides views of only a small area of breast tissue at a time, it is operator and patient dependent. It is best used when a known area of interest needs further evaluation, such as when a patient reports a palpable abnormality or when a mass is detected on mammography.

Ultrasonography uses no ionizing radiation, so it is especially helpful in young or pregnant women who present with a palpable abnormality. It is also useful for patients who have recently undergone a surgical procedure. As ultrasonography is currently used, no compression is needed and it can be performed easily in patients with limited mobility. Needle biopsies are most easily performed using ultrasonographic guidance.

MRI: An emerging adjunct under study in high-risk patients

Breast MRI is an emerging modality under active research that shows promise for adjunctive breast imaging. It is commonly being used as a tool for local staging in women with newly diagnosed breast cancer.^28,29 Current research is focused on its suitability as a screening modality, in conjunction with mammography, in high-risk populations based on family history and other factors addressed in the Gail model6 and similar risk models.

The limitations of breast MRI include its high cost, unsuitability for some patients (eg, the obese [due to table weight constraints], patients with pacemakers, patients with renal failure), the potential for unnecessary biopsies due to decreased specificity, lack of portability, and the length of time required for imaging.

Breast MRI is a four-dimensional study, with time as the fourth dimension (in addition to length, width, and depth). The patient receives an intravenous line and is given gadolinium for contrast enhancement. Imaging time depends on the protocol used and is specific to the imaging center, but it typically involves approximately 20 minutes of motionless scan time for the patient.³⁰ Lesions are detectable by their level of vascularity, and diagnostic images are dependent on adequate contrast enhancement (Figure 2). Several software packages are commercially available that perform post-processing of breast MRI data. Although cancer on MRI has a characteristic enhancement curve, there is much overlap with benign entities; as a result, morphologic characteristics of the lesion—such as size, shape, and borders—are paramount.³¹

When a lesion is initially detected with MRI, an attempt is usually made to identify it with ultrasonography as well, owing to the ease of ultrasonography-guided biopsy.³² It is important, however, for an imaging center that performs breast MRI to be able to perform biopsies using MRI guidance since not all lesions are identifiable by other modalities.³³ Breast MRI studies are not easily portable between imaging facilities since a typical study contains a thousand or more images that are best viewed on a site-specific workstation monitor.

HISTOLOGIC CONFIRMATION

Once an abnormality is detected on imaging, a confirmatory histologic diagnosis is needed before embarking on medical or surgical treatments. Image-guided biopsy plays a critical role in this regard. In our breast imaging section, we perform ultrasonography-guided core needle biopsy and aspiration, stereotactic needle biopsy, and MRI-guided needle biopsy, as well as wire localizations on the day of surgery. All procedures performed are considered minimally invasive and are suitable for a vast majority of patients for whom they are recommended.³⁴

Ultrasonography-guided procedures

Ultrasonography-guided core needle biopsy is the modality of choice for most patients when a suspicious abnormality is visible on ultrasonography.³⁵ Generally, the patient is placed in an angled supine position, with her arm elevated for optimal lesion accessibility. Following administration of a local anesthetic, a small nick is made in the skin and a specialized 14- or 18­gauge spring-loaded core biopsy needle is inserted during real-time imaging with the ultrasonographic probe (Figure 3). Several samples are obtained, and the pathologic diagnosis is generally available within a few working days. Breast core biopsy needles are also commercially available as handheld vacuum-assisted devices, which can sample larger amounts of tissue in a short time but are more expensive and often accompanied by a noisy vacuum device.

Ultrasonography-guided fine-needle aspiration is an additional option for patients when core biopsy cannot be performed because the lesion is located adjacent to sensitive structures, such as implants or the pectoralis muscle. Fine-needle aspiration is also used to evaluate complicated breast cysts and, occasionally, lymph nodes. Drawbacks of fine-needle aspiration (relative to larger core needle biopsy) are that it is limited to cytologic, not histologic, examination and that it yields a higher false-negative rate.

Stereotactically guided procedures

Stereotactic core biopsy is performed when lesions—usually calcifications, but sometimes masses—are visible only on mammography.^36,37 “Stereotactic” refers to the means by which the target is localized, ie, with a “stereo pair” of digital mammogram pictures with a small field of view. The patient is placed in a prone position with the breast of interest placed through a hole at the undersurface of the table in a light compression. The biopsy unit is attached to a dedicated computer that calculates coordinates. The needle is then brought to the coordinate position for sampling to take place.

The biopsy needle used for this procedure is vacuum-assisted, which means the needle is placed only one time, and samples in the vicinity of the target are vacuumed into a reservoir for retrieval. If the target is calcifications, a specimen radiograph is routinely performed to verify adequate sample acquisition before the patient leaves the biopsy table.³⁸ When the original target is no longer visible, a titanium marker clip is often placed. This facilitates localization of the biopsied area should surgery be needed.

Stereotactic biopsy has several limitations that ultrasonography-guided biopsy does not. The patient must be cooperative and mobile enough to get on the table and hold a prone position for the duration of the procedure (about 45 minutes). If the patient is taking warfarin or has a bleeding diathesis, preprocedure steps such as clinical evaluation to check the international normalized ratio and prothrombin time, or even stopping the warfarin temporarily, may be needed to minimize bleeding during the procedure, as a 9- or 12-gauge needle is used. Stereotactic biopsy is also limited by lesion position. A far posterior lesion may not be accessible if it does not reach through the hole in the table. Also, there is a limit to the compressed thinness of breast tissue that can be biopsied. Finally, most tables used for stereotactic biopsy have a functioning weight limit of 300 pounds.

Open surgical biopsy

A final option is open surgical biopsy, which is used when the more minimally invasive techniques are equivocal, discordant, or impossible due to the limitations noted above, or when atypical cells are found.

HOW SHOULD WE SCREEN OUR PATIENTS?

The various screening options for breast cancer are listed in Table 4, along with their market approval status and Medicare reimbursement levels.

For women at average risk for breast cancer, the American Cancer Society recommends an annual mammogram and clinical breast examination by a physician beginning at age 40 (Table 1).¹⁰

For women at high risk for developing breast cancer (> 20% to 25% lifetime risk, based on the Gail model6 or similar risk models), breast MRI should be considered as an adjunct to annual screening mammography (Table 5).³⁹ Evidence is currently insufficient, however, to support the adjunctive use of breast MRI for women with other risk factors (Table 5), although studies are ongoing.³⁹

In conclusion, the process of finding breast cancer includes regular screening with mammography and clinical breast examination (plus MRI in high-risk women) and the diagnostic modalities of ultrasonography, MRI, and diagnostic mammography. Our ultimate goal is to find cancer at the earliest time possible by all means necessary for the individual patient.

Early detection of breast cancer is vital to reducing the morbidity and mortality associated with this disease. After a brief overview of breast cancer epidemiology and risk assessment, this article describes screening and diagnostic imaging techniques as they are currently practiced to promote early breast cancer detection. We conclude with a review of image-guided needle biopsy techniques and a recommended approach to breast cancer screening in the general population.

EPIDEMIOLOGY OF BREAST CANCER: DAUNTING BUT SLOWLY IMPROVING

After nonmelanoma skin cancers, breast cancer is the most common form of cancer in women today, accounting for more than 1 in 4 cancers diagnosed in US women.¹ If the current incidence of breast cancer remains constant, US females born today have an average risk of 12.7% of being diagnosed with breast cancer during their lifetime (ie, 1-in-8 lifetime risk), based on National Cancer Institute statistics.^2,3 The American Cancer Society estimated that 178,480 new cases of invasive breast cancer and 62,030 new cases of in situ breast cancer would be diagnosed in the United States in 2007, and that 40,460 US women would die from breast cancer that year.¹ Only lung cancer accounts for more cancer deaths in women.

The role of race and ethnicity

Breast cancer risk varies by race and ethnicity in the United States. After age 40 years, white women have a higher incidence of breast cancer compared with African American women; conversely, before age 40, African American women have a higher incidence compared with white women. African American women are more likely than their white counterparts to die from their breast cancer at any age. Incidence and death rates from breast cancer are lower among Asian American, American Indian, and Hispanic women compared with both white and African American women.¹

Recent hopeful trends

Despite the daunting incidence numbers reviewed above, recent years have seen encouraging trends in US breast cancer epidemiology.

For invasive breast cancer, the growth in incidence rates slowed during the 1990s, and rates actually declined by 3.5% per year during the period 2001–2004.¹ These changes are likely attributable to multiple factors, including variations in rates of mammography screening and decreased use of hormone replacement therapy after the 2002 publication of results from the Women’s Health Initiative trial. Still, the trend is encouraging.

Incidence rates of in situ breast cancer rose rapidly during the 1980s and 1990s, largely due to increased diagnosis by mammography, but have plateaued since 2000 among women aged 50 years or older while continuing to rise modestly in younger women.¹

Meanwhile, the overall death rate from breast cancer in women declined by 2.2% annually from 1990 to 2004.¹

RISK FACTORS AND RISK MODELING

Risk factors for breast cancer have been well described and include the following:

• Age ( ≥ 65 years vs < 65 years, although risk increases across all ages up to 80 years)
• Family history of breast cancer
• Late age at first full-term pregnancy (> 30 years)
• Never having a full-term pregnancy
• Early menarche and/or late menopause
• Certain genetic mutations for breast cancer (eg, in the BRCA1, BRCA2, ATM, and CHEK2 genes)
• Certain breast disorders, such as atypical hyper­plasia or lobular carcinoma in situ
• High breast tissue density
• High bone density (postmenopausal)
• High-dose radiation to the chest.

The above risk factors are, in general, fixed. More elusive risk factors, in that they are variable and modifiable, include obesity, use of exogenous hormones (recent and long-term hormone replacement therapy; recent oral contraceptive use), alcohol use, tobacco use, diet, and a low level of physical activity. Breast implants are not a risk factor for breast cancer, though their presence does obscure breast tissue on imaging, limiting the detectability of a tumor when it does develop (see “Screening the Surgically Altered Breast” below).

Women with a genetic predisposition to breast can­cer merit special consideration. Hereditary breast cancers account for about 5% to 10% of breast cancer cases, and the BRCA1 and BRCA2 mutations are responsible for 80% to 90% of these cases, while other gene mutations (noted above) or genetic syndromes account for the rest. Clinical options for managing women with a genetic predisposition include surveillance, chemoprevention, and prophylactic surgery.⁴ Detailed discussion of the management of these women is beyond the scope of this article, but readers are referred to www.nccn.org/professionals/physician_gls/PDF/ genetics_screening.pdf for practice guidelines from the National Comprehensive Cancer Network.⁵

Tools for risk assessment

Several tools are available to predict a woman’s risk of developing breast cancer. Probably the most widely used is the Gail model,⁶ which was published in 1989 and forms the statistical basis for the National Cancer Institute’s Breast Cancer Risk Assessment Tool, which is available for downloading at www.cancer.gov/bcrisktool.⁷ The model uses a woman’s personal medical and reproductive histories and her family history of breast cancer to predict her 5-year and lifetime risk of developing invasive breast cancer. Factors included in the risk calculation are age, race, number of first-degree relatives with a history of breast cancer, age at first live birth (or nulliparity), age at menarche, number of breast biopsies, and presence or absence of a history of atypical hyperplasia. The relative risk for each of these factors is multiplied to generate a composite risk. The Gail model has been validated for white women but has been shown to underestimate breast cancer risk in African American women; it remains to be validated for Hispanic women, Asian women, and other subgroups of women.⁷

The commonly taught “triple test” for palpable breast lesions is another risk model that incorporates clinical findings. It consists of a physical examination, mammography, and fine-needle aspiration⁸ (in the “modified triple test,” ultrasonography replaces mammography⁹). When all three elements of the test are concordant (either all benign or all malignant), the triple test has been reported to have 100% diagnostic accuracy.^8,9

 

 

A WORD ABOUT BREAST EXAMINATION

Breast self-examination

The role of breast self-examination is controversial in the literature. There are currently no data to support the contention that it increases detection of breast cancer. As a result, the American Cancer Society no longer recommends that all women perform monthly breast self-exams, although it advises that all women be told about the potential benefits and limitations of breast self-examination (Table 1).¹⁰ Research suggests that structured breast self-examination is less important than self-awareness. Women who detect breast tumors themselves typically find them outside of a structured examination, such as when bathing or getting dressed.¹

Clinical breast examination

As noted in Table 1, regular clinical breast examinations are recommended by the American Cancer Society for asymptomatic women at average risk for breast cancer, with the recommended frequency depending on the woman’s age.¹⁰ The US Preventive Services Task Force takes the stance that there is insufficient evidence to recommend for or against breast cancer screening with clinical breast examination alone.¹¹ While it is unclear precisely what contribution clinical breast exams make to the detection of breast cancer, they certainly provide clinicians an opportunity to raise awareness about breast cancer and educate patients about breast symptoms, risk factors, and new detection technologies.¹⁰

SCREENING MAMMOGRAPHY

Screening mammography is the single most effective method of early breast cancer detection,¹ and the American Cancer Society recommends that women at average risk for breast cancer have annual screening mammograms beginning at age 40 years (Table 1).¹⁰

The evidence base

The primary evidence supporting the recommendation for screening mammography comes from eight randomized trials that studied the effectiveness of screening mammography for cancer detection in Sweden,^12,13 the United States,¹⁴ Canada,^15,16 and the United Kingdom.¹⁷ Overall, breast cancers detected by screening mammography are smaller and have a more favorable history and tumor biology than those detected clinically without the use of imaging. A pooled analysis of the most recent data from all randomized trials of screening mammography in women aged 39 to 74 years showed a 24% reduction in mortality (95% CI, 18% to 30%) in women undergoing screening mammography, although not all individual trials showed a statistically significant mortality reduction.¹⁰

The screening procedure at a glance

A screening mammogram, as distinguished from a diagnostic mammogram (Table 2), consists of two standard radiographic views of each breast (mediolateral oblique and craniocaudal).¹⁸ The woman being screened is advised to wear no powders or deodorants and should be asymptomatic. Women with symptoms (eg, breast lump, focal tenderness, nipple discharge) should be scheduled for a diagnostic mammogram (Table 2), not a screening mammogram.

The mammography technologist obtains the standard radiographs of each breast, and computer-assisted detection software can be applied to the mammogram films to aid in the identification of abnormalities as a computer-generated second opinion. Although computer-assisted detection is not currently standard of care, it is available at most institutions. The films are read later by a radiologist who will interpret them according to the American College of Radiology’s standard system of describing mammogram findings, called the Breast Imaging Reporting and Data System (BI-RADS). In this system, results are assigned a category rating on a scale from 0 to 6 (Table 3). This standardization allows physicians to use consistent language, ensures better follow-up of suspicious findings, and reduces interobserver variability.

Analog vs digital

Breast radiographs can be obtained by the traditional film-screen (analog) method or obtained digitally (Figure 1).

Digital mammograms are radiographs that are acquired digitally and allow digital enhancement to aid in interpretation. When receiving a digital mammogram, the woman being screened still undergoes compression and positioning as for a conventional film-screen mammogram, and the images are still produced with x-rays. However, digitization allows manipulation of the images as they are being interpreted, enabling the radiologist to focus on areas of interest or to “window” and “level” the image, similar to adjusting the tint and contrast on a television set.

Research trials comparing digital and film mammography, such as the Digital Mammographic Imaging Screening Trial (DMIST),¹⁹ have found digital mammography to be especially helpful in women with extremely dense breasts, who have an elevated risk for breast cancer. For women with fatty breasts the differences between the types of mammogram are less significant.

The type of mammogram a woman receives generally depends on the equipment available at the site she visits. Digital mammography units currently cost approximately 3 times as much as corresponding film-screen units, yet digital mammograms command reimbursement rates only about 1.6 times higher than those for film mammograms (Table 4). A hard copy of the digitized image can be printed, although the hope is that eventually fewer mammogram images will be printed and space-saving electronic storage will supplant storage of printed films.

For further detail on digital mammography, readers are referred to the recent review by D’Orsi and Newell.²⁰

SCREENING THE SURGICALLY ALTERED BREAST

Following surgical cancer treatment or reconstructive surgery, screening of remaining breast tissue for cancer is still performed and is just as essential to patient care as presurgery screening. The first line of defense for any patient with a surgically altered breast is mammography.

When a patient has had breast reconstruction following mastectomy, it is presumed that very little breast tissue remains. There is no standard of care for screening the nonbreast tissue introduced by the reconstructive procedure. Nonetheless, at our institution we perform a single mediolateral oblique projec­tion on any flap-reconstructed breast in light of rare anecdotal accounts of cancer found in and around the reconstructed breast. When problem-solving is needed to evaluate a new palpable abnormality, special angled views (tangential) and directed ultrasonography can be used. We do not routinely perform screening mammography on mastectomy patients who have had reconstruction with implants, but we can investigate areas of clinical concern (eg, due to palpable masses) with directed ultrasonography.²¹

The cosmetically altered breast presents its own issues in cancer detection. Both silicone-gel and saline implants obscure breast tissue that could contain cancer. For this reason, special implant-displaced views are performed that allow visualization of a larger portion of breast tissue beyond that allowed by standard mammograms. Therefore, an asymptomatic patient with implants who presents for screening mammography will have eight mammography views obtained instead of the routine four views.²²

Patients who have had breast reduction, excisional biopsy, or prior breast conservation surgery (lumpectomy and radiation) are screened in a routine manner with mammography.²³ Patients who have had prior surgical procedures often have architectural distortion at the surgical site, which is generally stable over time. Any prior surgical procedure can predispose the patient to the development of fat necrosis, which is a benign entity but can mimic cancer in its early phases through the development of calcifications and, occasionally, a new palpable lump. We most commonly confront this issue in the period 2 to 4 years after the operation.²⁴ Occasionally the findings are such that a biopsy is needed to determine whether fat necrosis is the cause. In this population, magnetic resonance imaging (MRI) can also be used as an adjunctive tool, and can sometimes clarify the presence of fat necrosis and other postoperative findings, such as seroma, hematoma, or inflammation. In other instances, only a biopsy can determine what a particular finding represents.

 

 

DIAGNOSTIC MAMMOGRAPHY

Any mammography performed for a problem-solving purpose is considered diagnostic mammography (Table 2); the exam is tailored to the patient’s individual issue.²⁵ Diagnostic mammography requires the presence of a qualified radiologist at the time of imaging. The goal is to come to a final conclusion about the mammographic or clinical finding at the time of the patient’s visit. Special views are usually performed that include, but are not limited to, spot-compression or spot-magnification views, depending on the finding.²⁶ The patient is then given a same-day written account of the results at the conclusion of the study.

Examples of problems that may prompt diagnostic mammography include patient-reported palpable findings, screening mammography findings that are recalled for further investigation, or physician-detected findings. Often, ultrasonography is also used at the same visit and its results are integrated with the mammography findings to arrive at the final impression.

BREAST ULTRASONOGRAPHY AND BREAST MRI

Ultrasonography and MRI are two very useful adjunctive tools for breast lesion detection and analysis. At this time, however, neither is a replacement for screening mammography as a primary screening modality; rather, each is used in a complementary fashion for lesion analysis and biopsy guidance.^10,27

Ultrasonography: Best for further study of areas of interest

Ultrasonography uses high-frequency sound waves to create a picture using a probe directed to an area of interest in the breast. The optimal probe for breast imaging is one typically operating in a frequency of 12 to 18 MHz and 4 cm in scanning width.

Because ultrasonography provides views of only a small area of breast tissue at a time, it is operator and patient dependent. It is best used when a known area of interest needs further evaluation, such as when a patient reports a palpable abnormality or when a mass is detected on mammography.

Ultrasonography uses no ionizing radiation, so it is especially helpful in young or pregnant women who present with a palpable abnormality. It is also useful for patients who have recently undergone a surgical procedure. As ultrasonography is currently used, no compression is needed and it can be performed easily in patients with limited mobility. Needle biopsies are most easily performed using ultrasonographic guidance.

MRI: An emerging adjunct under study in high-risk patients

Breast MRI is an emerging modality under active research that shows promise for adjunctive breast imaging. It is commonly being used as a tool for local staging in women with newly diagnosed breast cancer.^28,29 Current research is focused on its suitability as a screening modality, in conjunction with mammography, in high-risk populations based on family history and other factors addressed in the Gail model6 and similar risk models.

The limitations of breast MRI include its high cost, unsuitability for some patients (eg, the obese [due to table weight constraints], patients with pacemakers, patients with renal failure), the potential for unnecessary biopsies due to decreased specificity, lack of portability, and the length of time required for imaging.

Breast MRI is a four-dimensional study, with time as the fourth dimension (in addition to length, width, and depth). The patient receives an intravenous line and is given gadolinium for contrast enhancement. Imaging time depends on the protocol used and is specific to the imaging center, but it typically involves approximately 20 minutes of motionless scan time for the patient.³⁰ Lesions are detectable by their level of vascularity, and diagnostic images are dependent on adequate contrast enhancement (Figure 2). Several software packages are commercially available that perform post-processing of breast MRI data. Although cancer on MRI has a characteristic enhancement curve, there is much overlap with benign entities; as a result, morphologic characteristics of the lesion—such as size, shape, and borders—are paramount.³¹

When a lesion is initially detected with MRI, an attempt is usually made to identify it with ultrasonography as well, owing to the ease of ultrasonography-guided biopsy.³² It is important, however, for an imaging center that performs breast MRI to be able to perform biopsies using MRI guidance since not all lesions are identifiable by other modalities.³³ Breast MRI studies are not easily portable between imaging facilities since a typical study contains a thousand or more images that are best viewed on a site-specific workstation monitor.

HISTOLOGIC CONFIRMATION

Once an abnormality is detected on imaging, a confirmatory histologic diagnosis is needed before embarking on medical or surgical treatments. Image-guided biopsy plays a critical role in this regard. In our breast imaging section, we perform ultrasonography-guided core needle biopsy and aspiration, stereotactic needle biopsy, and MRI-guided needle biopsy, as well as wire localizations on the day of surgery. All procedures performed are considered minimally invasive and are suitable for a vast majority of patients for whom they are recommended.³⁴

Ultrasonography-guided procedures

Ultrasonography-guided core needle biopsy is the modality of choice for most patients when a suspicious abnormality is visible on ultrasonography.³⁵ Generally, the patient is placed in an angled supine position, with her arm elevated for optimal lesion accessibility. Following administration of a local anesthetic, a small nick is made in the skin and a specialized 14- or 18­gauge spring-loaded core biopsy needle is inserted during real-time imaging with the ultrasonographic probe (Figure 3). Several samples are obtained, and the pathologic diagnosis is generally available within a few working days. Breast core biopsy needles are also commercially available as handheld vacuum-assisted devices, which can sample larger amounts of tissue in a short time but are more expensive and often accompanied by a noisy vacuum device.

Ultrasonography-guided fine-needle aspiration is an additional option for patients when core biopsy cannot be performed because the lesion is located adjacent to sensitive structures, such as implants or the pectoralis muscle. Fine-needle aspiration is also used to evaluate complicated breast cysts and, occasionally, lymph nodes. Drawbacks of fine-needle aspiration (relative to larger core needle biopsy) are that it is limited to cytologic, not histologic, examination and that it yields a higher false-negative rate.

Stereotactically guided procedures

Stereotactic core biopsy is performed when lesions—usually calcifications, but sometimes masses—are visible only on mammography.^36,37 “Stereotactic” refers to the means by which the target is localized, ie, with a “stereo pair” of digital mammogram pictures with a small field of view. The patient is placed in a prone position with the breast of interest placed through a hole at the undersurface of the table in a light compression. The biopsy unit is attached to a dedicated computer that calculates coordinates. The needle is then brought to the coordinate position for sampling to take place.

The biopsy needle used for this procedure is vacuum-assisted, which means the needle is placed only one time, and samples in the vicinity of the target are vacuumed into a reservoir for retrieval. If the target is calcifications, a specimen radiograph is routinely performed to verify adequate sample acquisition before the patient leaves the biopsy table.³⁸ When the original target is no longer visible, a titanium marker clip is often placed. This facilitates localization of the biopsied area should surgery be needed.

Stereotactic biopsy has several limitations that ultrasonography-guided biopsy does not. The patient must be cooperative and mobile enough to get on the table and hold a prone position for the duration of the procedure (about 45 minutes). If the patient is taking warfarin or has a bleeding diathesis, preprocedure steps such as clinical evaluation to check the international normalized ratio and prothrombin time, or even stopping the warfarin temporarily, may be needed to minimize bleeding during the procedure, as a 9- or 12-gauge needle is used. Stereotactic biopsy is also limited by lesion position. A far posterior lesion may not be accessible if it does not reach through the hole in the table. Also, there is a limit to the compressed thinness of breast tissue that can be biopsied. Finally, most tables used for stereotactic biopsy have a functioning weight limit of 300 pounds.

Open surgical biopsy

A final option is open surgical biopsy, which is used when the more minimally invasive techniques are equivocal, discordant, or impossible due to the limitations noted above, or when atypical cells are found.

HOW SHOULD WE SCREEN OUR PATIENTS?

The various screening options for breast cancer are listed in Table 4, along with their market approval status and Medicare reimbursement levels.

For women at average risk for breast cancer, the American Cancer Society recommends an annual mammogram and clinical breast examination by a physician beginning at age 40 (Table 1).¹⁰

For women at high risk for developing breast cancer (> 20% to 25% lifetime risk, based on the Gail model6 or similar risk models), breast MRI should be considered as an adjunct to annual screening mammography (Table 5).³⁹ Evidence is currently insufficient, however, to support the adjunctive use of breast MRI for women with other risk factors (Table 5), although studies are ongoing.³⁹

In conclusion, the process of finding breast cancer includes regular screening with mammography and clinical breast examination (plus MRI in high-risk women) and the diagnostic modalities of ultrasonography, MRI, and diagnostic mammography. Our ultimate goal is to find cancer at the earliest time possible by all means necessary for the individual patient.

Early detection of breast cancer is vital to reducing the morbidity and mortality associated with this disease. After a brief overview of breast cancer epidemiology and risk assessment, this article describes screening and diagnostic imaging techniques as they are currently practiced to promote early breast cancer detection. We conclude with a review of image-guided needle biopsy techniques and a recommended approach to breast cancer screening in the general population.

EPIDEMIOLOGY OF BREAST CANCER: DAUNTING BUT SLOWLY IMPROVING

After nonmelanoma skin cancers, breast cancer is the most common form of cancer in women today, accounting for more than 1 in 4 cancers diagnosed in US women.¹ If the current incidence of breast cancer remains constant, US females born today have an average risk of 12.7% of being diagnosed with breast cancer during their lifetime (ie, 1-in-8 lifetime risk), based on National Cancer Institute statistics.^2,3 The American Cancer Society estimated that 178,480 new cases of invasive breast cancer and 62,030 new cases of in situ breast cancer would be diagnosed in the United States in 2007, and that 40,460 US women would die from breast cancer that year.¹ Only lung cancer accounts for more cancer deaths in women.

The role of race and ethnicity

Breast cancer risk varies by race and ethnicity in the United States. After age 40 years, white women have a higher incidence of breast cancer compared with African American women; conversely, before age 40, African American women have a higher incidence compared with white women. African American women are more likely than their white counterparts to die from their breast cancer at any age. Incidence and death rates from breast cancer are lower among Asian American, American Indian, and Hispanic women compared with both white and African American women.¹

Recent hopeful trends

Despite the daunting incidence numbers reviewed above, recent years have seen encouraging trends in US breast cancer epidemiology.

For invasive breast cancer, the growth in incidence rates slowed during the 1990s, and rates actually declined by 3.5% per year during the period 2001–2004.¹ These changes are likely attributable to multiple factors, including variations in rates of mammography screening and decreased use of hormone replacement therapy after the 2002 publication of results from the Women’s Health Initiative trial. Still, the trend is encouraging.

Incidence rates of in situ breast cancer rose rapidly during the 1980s and 1990s, largely due to increased diagnosis by mammography, but have plateaued since 2000 among women aged 50 years or older while continuing to rise modestly in younger women.¹

Meanwhile, the overall death rate from breast cancer in women declined by 2.2% annually from 1990 to 2004.¹

RISK FACTORS AND RISK MODELING

Risk factors for breast cancer have been well described and include the following:

• Age ( ≥ 65 years vs < 65 years, although risk increases across all ages up to 80 years)
• Family history of breast cancer
• Late age at first full-term pregnancy (> 30 years)
• Never having a full-term pregnancy
• Early menarche and/or late menopause
• Certain genetic mutations for breast cancer (eg, in the BRCA1, BRCA2, ATM, and CHEK2 genes)
• Certain breast disorders, such as atypical hyper­plasia or lobular carcinoma in situ
• High breast tissue density
• High bone density (postmenopausal)
• High-dose radiation to the chest.

The above risk factors are, in general, fixed. More elusive risk factors, in that they are variable and modifiable, include obesity, use of exogenous hormones (recent and long-term hormone replacement therapy; recent oral contraceptive use), alcohol use, tobacco use, diet, and a low level of physical activity. Breast implants are not a risk factor for breast cancer, though their presence does obscure breast tissue on imaging, limiting the detectability of a tumor when it does develop (see “Screening the Surgically Altered Breast” below).

Women with a genetic predisposition to breast can­cer merit special consideration. Hereditary breast cancers account for about 5% to 10% of breast cancer cases, and the BRCA1 and BRCA2 mutations are responsible for 80% to 90% of these cases, while other gene mutations (noted above) or genetic syndromes account for the rest. Clinical options for managing women with a genetic predisposition include surveillance, chemoprevention, and prophylactic surgery.⁴ Detailed discussion of the management of these women is beyond the scope of this article, but readers are referred to www.nccn.org/professionals/physician_gls/PDF/ genetics_screening.pdf for practice guidelines from the National Comprehensive Cancer Network.⁵

Tools for risk assessment

Several tools are available to predict a woman’s risk of developing breast cancer. Probably the most widely used is the Gail model,⁶ which was published in 1989 and forms the statistical basis for the National Cancer Institute’s Breast Cancer Risk Assessment Tool, which is available for downloading at www.cancer.gov/bcrisktool.⁷ The model uses a woman’s personal medical and reproductive histories and her family history of breast cancer to predict her 5-year and lifetime risk of developing invasive breast cancer. Factors included in the risk calculation are age, race, number of first-degree relatives with a history of breast cancer, age at first live birth (or nulliparity), age at menarche, number of breast biopsies, and presence or absence of a history of atypical hyperplasia. The relative risk for each of these factors is multiplied to generate a composite risk. The Gail model has been validated for white women but has been shown to underestimate breast cancer risk in African American women; it remains to be validated for Hispanic women, Asian women, and other subgroups of women.⁷

The commonly taught “triple test” for palpable breast lesions is another risk model that incorporates clinical findings. It consists of a physical examination, mammography, and fine-needle aspiration⁸ (in the “modified triple test,” ultrasonography replaces mammography⁹). When all three elements of the test are concordant (either all benign or all malignant), the triple test has been reported to have 100% diagnostic accuracy.^8,9

 

 

A WORD ABOUT BREAST EXAMINATION

Breast self-examination

The role of breast self-examination is controversial in the literature. There are currently no data to support the contention that it increases detection of breast cancer. As a result, the American Cancer Society no longer recommends that all women perform monthly breast self-exams, although it advises that all women be told about the potential benefits and limitations of breast self-examination (Table 1).¹⁰ Research suggests that structured breast self-examination is less important than self-awareness. Women who detect breast tumors themselves typically find them outside of a structured examination, such as when bathing or getting dressed.¹

Clinical breast examination

As noted in Table 1, regular clinical breast examinations are recommended by the American Cancer Society for asymptomatic women at average risk for breast cancer, with the recommended frequency depending on the woman’s age.¹⁰ The US Preventive Services Task Force takes the stance that there is insufficient evidence to recommend for or against breast cancer screening with clinical breast examination alone.¹¹ While it is unclear precisely what contribution clinical breast exams make to the detection of breast cancer, they certainly provide clinicians an opportunity to raise awareness about breast cancer and educate patients about breast symptoms, risk factors, and new detection technologies.¹⁰

SCREENING MAMMOGRAPHY

Screening mammography is the single most effective method of early breast cancer detection,¹ and the American Cancer Society recommends that women at average risk for breast cancer have annual screening mammograms beginning at age 40 years (Table 1).¹⁰

The evidence base

The primary evidence supporting the recommendation for screening mammography comes from eight randomized trials that studied the effectiveness of screening mammography for cancer detection in Sweden,^12,13 the United States,¹⁴ Canada,^15,16 and the United Kingdom.¹⁷ Overall, breast cancers detected by screening mammography are smaller and have a more favorable history and tumor biology than those detected clinically without the use of imaging. A pooled analysis of the most recent data from all randomized trials of screening mammography in women aged 39 to 74 years showed a 24% reduction in mortality (95% CI, 18% to 30%) in women undergoing screening mammography, although not all individual trials showed a statistically significant mortality reduction.¹⁰

The screening procedure at a glance

A screening mammogram, as distinguished from a diagnostic mammogram (Table 2), consists of two standard radiographic views of each breast (mediolateral oblique and craniocaudal).¹⁸ The woman being screened is advised to wear no powders or deodorants and should be asymptomatic. Women with symptoms (eg, breast lump, focal tenderness, nipple discharge) should be scheduled for a diagnostic mammogram (Table 2), not a screening mammogram.

The mammography technologist obtains the standard radiographs of each breast, and computer-assisted detection software can be applied to the mammogram films to aid in the identification of abnormalities as a computer-generated second opinion. Although computer-assisted detection is not currently standard of care, it is available at most institutions. The films are read later by a radiologist who will interpret them according to the American College of Radiology’s standard system of describing mammogram findings, called the Breast Imaging Reporting and Data System (BI-RADS). In this system, results are assigned a category rating on a scale from 0 to 6 (Table 3). This standardization allows physicians to use consistent language, ensures better follow-up of suspicious findings, and reduces interobserver variability.

Analog vs digital

Breast radiographs can be obtained by the traditional film-screen (analog) method or obtained digitally (Figure 1).

Digital mammograms are radiographs that are acquired digitally and allow digital enhancement to aid in interpretation. When receiving a digital mammogram, the woman being screened still undergoes compression and positioning as for a conventional film-screen mammogram, and the images are still produced with x-rays. However, digitization allows manipulation of the images as they are being interpreted, enabling the radiologist to focus on areas of interest or to “window” and “level” the image, similar to adjusting the tint and contrast on a television set.

Research trials comparing digital and film mammography, such as the Digital Mammographic Imaging Screening Trial (DMIST),¹⁹ have found digital mammography to be especially helpful in women with extremely dense breasts, who have an elevated risk for breast cancer. For women with fatty breasts the differences between the types of mammogram are less significant.

The type of mammogram a woman receives generally depends on the equipment available at the site she visits. Digital mammography units currently cost approximately 3 times as much as corresponding film-screen units, yet digital mammograms command reimbursement rates only about 1.6 times higher than those for film mammograms (Table 4). A hard copy of the digitized image can be printed, although the hope is that eventually fewer mammogram images will be printed and space-saving electronic storage will supplant storage of printed films.

For further detail on digital mammography, readers are referred to the recent review by D’Orsi and Newell.²⁰

SCREENING THE SURGICALLY ALTERED BREAST

Following surgical cancer treatment or reconstructive surgery, screening of remaining breast tissue for cancer is still performed and is just as essential to patient care as presurgery screening. The first line of defense for any patient with a surgically altered breast is mammography.

When a patient has had breast reconstruction following mastectomy, it is presumed that very little breast tissue remains. There is no standard of care for screening the nonbreast tissue introduced by the reconstructive procedure. Nonetheless, at our institution we perform a single mediolateral oblique projec­tion on any flap-reconstructed breast in light of rare anecdotal accounts of cancer found in and around the reconstructed breast. When problem-solving is needed to evaluate a new palpable abnormality, special angled views (tangential) and directed ultrasonography can be used. We do not routinely perform screening mammography on mastectomy patients who have had reconstruction with implants, but we can investigate areas of clinical concern (eg, due to palpable masses) with directed ultrasonography.²¹

The cosmetically altered breast presents its own issues in cancer detection. Both silicone-gel and saline implants obscure breast tissue that could contain cancer. For this reason, special implant-displaced views are performed that allow visualization of a larger portion of breast tissue beyond that allowed by standard mammograms. Therefore, an asymptomatic patient with implants who presents for screening mammography will have eight mammography views obtained instead of the routine four views.²²

Patients who have had breast reduction, excisional biopsy, or prior breast conservation surgery (lumpectomy and radiation) are screened in a routine manner with mammography.²³ Patients who have had prior surgical procedures often have architectural distortion at the surgical site, which is generally stable over time. Any prior surgical procedure can predispose the patient to the development of fat necrosis, which is a benign entity but can mimic cancer in its early phases through the development of calcifications and, occasionally, a new palpable lump. We most commonly confront this issue in the period 2 to 4 years after the operation.²⁴ Occasionally the findings are such that a biopsy is needed to determine whether fat necrosis is the cause. In this population, magnetic resonance imaging (MRI) can also be used as an adjunctive tool, and can sometimes clarify the presence of fat necrosis and other postoperative findings, such as seroma, hematoma, or inflammation. In other instances, only a biopsy can determine what a particular finding represents.

 

 

DIAGNOSTIC MAMMOGRAPHY

Any mammography performed for a problem-solving purpose is considered diagnostic mammography (Table 2); the exam is tailored to the patient’s individual issue.²⁵ Diagnostic mammography requires the presence of a qualified radiologist at the time of imaging. The goal is to come to a final conclusion about the mammographic or clinical finding at the time of the patient’s visit. Special views are usually performed that include, but are not limited to, spot-compression or spot-magnification views, depending on the finding.²⁶ The patient is then given a same-day written account of the results at the conclusion of the study.

Examples of problems that may prompt diagnostic mammography include patient-reported palpable findings, screening mammography findings that are recalled for further investigation, or physician-detected findings. Often, ultrasonography is also used at the same visit and its results are integrated with the mammography findings to arrive at the final impression.

BREAST ULTRASONOGRAPHY AND BREAST MRI

Ultrasonography and MRI are two very useful adjunctive tools for breast lesion detection and analysis. At this time, however, neither is a replacement for screening mammography as a primary screening modality; rather, each is used in a complementary fashion for lesion analysis and biopsy guidance.^10,27

Ultrasonography: Best for further study of areas of interest

Ultrasonography uses high-frequency sound waves to create a picture using a probe directed to an area of interest in the breast. The optimal probe for breast imaging is one typically operating in a frequency of 12 to 18 MHz and 4 cm in scanning width.

Because ultrasonography provides views of only a small area of breast tissue at a time, it is operator and patient dependent. It is best used when a known area of interest needs further evaluation, such as when a patient reports a palpable abnormality or when a mass is detected on mammography.

Ultrasonography uses no ionizing radiation, so it is especially helpful in young or pregnant women who present with a palpable abnormality. It is also useful for patients who have recently undergone a surgical procedure. As ultrasonography is currently used, no compression is needed and it can be performed easily in patients with limited mobility. Needle biopsies are most easily performed using ultrasonographic guidance.

MRI: An emerging adjunct under study in high-risk patients

Breast MRI is an emerging modality under active research that shows promise for adjunctive breast imaging. It is commonly being used as a tool for local staging in women with newly diagnosed breast cancer.^28,29 Current research is focused on its suitability as a screening modality, in conjunction with mammography, in high-risk populations based on family history and other factors addressed in the Gail model6 and similar risk models.

The limitations of breast MRI include its high cost, unsuitability for some patients (eg, the obese [due to table weight constraints], patients with pacemakers, patients with renal failure), the potential for unnecessary biopsies due to decreased specificity, lack of portability, and the length of time required for imaging.

Breast MRI is a four-dimensional study, with time as the fourth dimension (in addition to length, width, and depth). The patient receives an intravenous line and is given gadolinium for contrast enhancement. Imaging time depends on the protocol used and is specific to the imaging center, but it typically involves approximately 20 minutes of motionless scan time for the patient.³⁰ Lesions are detectable by their level of vascularity, and diagnostic images are dependent on adequate contrast enhancement (Figure 2). Several software packages are commercially available that perform post-processing of breast MRI data. Although cancer on MRI has a characteristic enhancement curve, there is much overlap with benign entities; as a result, morphologic characteristics of the lesion—such as size, shape, and borders—are paramount.³¹

When a lesion is initially detected with MRI, an attempt is usually made to identify it with ultrasonography as well, owing to the ease of ultrasonography-guided biopsy.³² It is important, however, for an imaging center that performs breast MRI to be able to perform biopsies using MRI guidance since not all lesions are identifiable by other modalities.³³ Breast MRI studies are not easily portable between imaging facilities since a typical study contains a thousand or more images that are best viewed on a site-specific workstation monitor.

HISTOLOGIC CONFIRMATION

Once an abnormality is detected on imaging, a confirmatory histologic diagnosis is needed before embarking on medical or surgical treatments. Image-guided biopsy plays a critical role in this regard. In our breast imaging section, we perform ultrasonography-guided core needle biopsy and aspiration, stereotactic needle biopsy, and MRI-guided needle biopsy, as well as wire localizations on the day of surgery. All procedures performed are considered minimally invasive and are suitable for a vast majority of patients for whom they are recommended.³⁴

Ultrasonography-guided procedures

Ultrasonography-guided core needle biopsy is the modality of choice for most patients when a suspicious abnormality is visible on ultrasonography.³⁵ Generally, the patient is placed in an angled supine position, with her arm elevated for optimal lesion accessibility. Following administration of a local anesthetic, a small nick is made in the skin and a specialized 14- or 18­gauge spring-loaded core biopsy needle is inserted during real-time imaging with the ultrasonographic probe (Figure 3). Several samples are obtained, and the pathologic diagnosis is generally available within a few working days. Breast core biopsy needles are also commercially available as handheld vacuum-assisted devices, which can sample larger amounts of tissue in a short time but are more expensive and often accompanied by a noisy vacuum device.

Ultrasonography-guided fine-needle aspiration is an additional option for patients when core biopsy cannot be performed because the lesion is located adjacent to sensitive structures, such as implants or the pectoralis muscle. Fine-needle aspiration is also used to evaluate complicated breast cysts and, occasionally, lymph nodes. Drawbacks of fine-needle aspiration (relative to larger core needle biopsy) are that it is limited to cytologic, not histologic, examination and that it yields a higher false-negative rate.

Stereotactically guided procedures

Stereotactic core biopsy is performed when lesions—usually calcifications, but sometimes masses—are visible only on mammography.^36,37 “Stereotactic” refers to the means by which the target is localized, ie, with a “stereo pair” of digital mammogram pictures with a small field of view. The patient is placed in a prone position with the breast of interest placed through a hole at the undersurface of the table in a light compression. The biopsy unit is attached to a dedicated computer that calculates coordinates. The needle is then brought to the coordinate position for sampling to take place.

The biopsy needle used for this procedure is vacuum-assisted, which means the needle is placed only one time, and samples in the vicinity of the target are vacuumed into a reservoir for retrieval. If the target is calcifications, a specimen radiograph is routinely performed to verify adequate sample acquisition before the patient leaves the biopsy table.³⁸ When the original target is no longer visible, a titanium marker clip is often placed. This facilitates localization of the biopsied area should surgery be needed.

Stereotactic biopsy has several limitations that ultrasonography-guided biopsy does not. The patient must be cooperative and mobile enough to get on the table and hold a prone position for the duration of the procedure (about 45 minutes). If the patient is taking warfarin or has a bleeding diathesis, preprocedure steps such as clinical evaluation to check the international normalized ratio and prothrombin time, or even stopping the warfarin temporarily, may be needed to minimize bleeding during the procedure, as a 9- or 12-gauge needle is used. Stereotactic biopsy is also limited by lesion position. A far posterior lesion may not be accessible if it does not reach through the hole in the table. Also, there is a limit to the compressed thinness of breast tissue that can be biopsied. Finally, most tables used for stereotactic biopsy have a functioning weight limit of 300 pounds.

Open surgical biopsy

A final option is open surgical biopsy, which is used when the more minimally invasive techniques are equivocal, discordant, or impossible due to the limitations noted above, or when atypical cells are found.

HOW SHOULD WE SCREEN OUR PATIENTS?

The various screening options for breast cancer are listed in Table 4, along with their market approval status and Medicare reimbursement levels.

For women at average risk for breast cancer, the American Cancer Society recommends an annual mammogram and clinical breast examination by a physician beginning at age 40 (Table 1).¹⁰

For women at high risk for developing breast cancer (> 20% to 25% lifetime risk, based on the Gail model6 or similar risk models), breast MRI should be considered as an adjunct to annual screening mammography (Table 5).³⁹ Evidence is currently insufficient, however, to support the adjunctive use of breast MRI for women with other risk factors (Table 5), although studies are ongoing.³⁹

In conclusion, the process of finding breast cancer includes regular screening with mammography and clinical breast examination (plus MRI in high-risk women) and the diagnostic modalities of ultrasonography, MRI, and diagnostic mammography. Our ultimate goal is to find cancer at the earliest time possible by all means necessary for the individual patient.

In the late 19th century, breast cancer was considered a fatal disease. That began to change in the 1880s when W.S. Halsted described the radical mastectomy as the way to treat patients with breast cancer.¹ This aggressive surgical treatment—in which the breast, axillary lymph nodes, and chest muscles are all removed—remained the standard of care throughout much of the 20th century; as late as the early 1970s, nearly half (48%) of breast cancer patients were treated with radical mastectomy. During the 1970s, however, the Halsted radical mastectomy was largely abandoned for a less-disfiguring muscle-sparing technique called the modified radical mastectomy; by 1981, only 3% of patients underwent the Halsted mastectomy.²

The 1980s heralded even more minimally invasive techniques with the advent of breast conservation therapy, in which an incision is made over the tumor and the tumor is completely removed with negative margins, leaving behind normal breast tissue. (This procedure has been referred to by many different names, including definitive excision, lumpectomy, quadrantectomy, and partial mastectomy; since they all mean the same thing, for clarity and consistency this article will use “breast conservation therapy” throughout.) During the 1990s, surgical invasiveness was further minimized with the emergence of sentinel lymph node excision.

An important contributor to this evolution in the standard of breast cancer therapy since the 1970s has been the National Surgical Adjuvant Breast and Bowel Project (NSABP), a National Cancer Institute–funded clinical trials cooperative group. NSABP studies have been the driving force to show that the extent of surgery could be reduced without compromising outcome.³ These studies, along with several other trials, have resulted in a marked reduction in surgical aggressiveness and a multitude of adjuvant therapies for women with breast cancer. This article will briefly explore where this evolution has brought us in terms of the surgical options available for treatment of breast cancer today. We also discuss other key components in the management of women with newly diagnosed breast cancer, including cancer staging, patient counseling, and assessment of axillary lymph nodes.

BREAST CANCER CLASSIFICATION AND STAGING

Pathologic classification

Breast cancer is an adenocarcinoma that occurs primarily in two forms: ductal or lobular carcinoma, in which malignancy develops in the breast ducts or lobules, respectively. The majority of breast cancers are ductal in origin. Another key pathologic distinction is between in situ versus invasive carcinoma, which depends on whether the cancer cell remains within the duct or lobule (stage 0, or in situ) or has spread on a microscopic level to the adjacent breast parenchyma (invasive or infiltrating) (Figure 1). Despite its nomenclature, lobular carcinoma in situ is not a cancer; it is merely a marker of increased risk for developing invasive cancer (either ductal or lobular) that may appear on either side (right or left breast), not just the side of the original biopsy.

Cancer staging

“What stage am I?” is a question every patient asks upon receiving a new diagnosis of breast cancer. Breast cancer staging is based on the TNM system, defined by the American Joint Committee on Cancer, which takes into account tumor (T) size, the extent of regional lymph node (N) involvement, and the presence or absence of metastasis (M) beyond the regional lymph nodes.⁴ Using this system, whose criteria and details are outlined in Table 1, breast cancer is staged from 0 to IV. Stage 0 implies in situ cancer, while stages I to IV indicate invasive cancer, with IV implying metastatic spread to distant organs.

A simpler method relies on the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) summary staging system.⁵ This system classifies tumors as “localized” (contained in the breast, either in situ or invasive), “regional” (identified in regional lymph nodes), or “metastatic” (spread to distant organ systems).

Of course, patients cannot be told their stage until after surgery, when a final pathologic report detailing tumor size and nodal status is available. Some patients will never be definitively staged—for instance, those who undergo neoadjuvant chemotherapy for locally advanced disease prior to lymph node dissection, or those who do not have a metastatic work-up. The metastatic work-up involves ordering of additional tests to assess for metastasis, but only when prompted by specific patient symptoms. Thus, if the patient has shortness of breath, a chest radiograph or a chest computed tomograph (CT) needs to be ordered; for elevated liver enzymes, CTs of the abdomen and pelvis are ordered; for central nervous system symptoms, brain magnetic resonance imaging (MRI) is ordered; and for back pain or bone pain, a bone scan is ordered to rule out metastatic disease to bone.

INITIAL PATIENT ASSESSMENT AND COUNSELING

Relationship-building is fundamental

Following an initial diagnosis of breast cancer, the patient must undergo an assessment for local and systemic disease. The surgeon, as a member of a multi-disciplinary breast cancer treatment team, often spearheads this initial assessment. This first visit must go beyond mere clinical evaluation, however, and include thorough discussion and relationship-building with the patient, as this early meeting establishes a relationship with the patient that will carry through her entire process of cancer care. For a true understanding between patient and surgeon to occur, it is critical for patients to be comfortable in sharing their fears, expectations, and lifestyle needs. Following a diagnosis of breast cancer, the initial reactions women go through include both fear and realization of one’s own mortality. Although these responses may no longer be justified by the reality of patient outcomes in most cases, they are normal and fully understandable reactions. For this reason, clinicians must be sensitive to these reactions while being supportive about the efficacy of the treatment options available.

 

 

History, breast exam, and review of imaging studies

In addition to the establishment of communication and understanding, the vital components of this first meeting include a detailed medical history, a clinical breast examination, a review of imaging studies, and a discussion of treatment options.

The history should include all aspects of the patient’s reproductive history, her family history of breast cancer, and any comorbidities and medications being taken.

The clinical breast examination should give special attention to the shape (asymmetry), appearance (eg, dimpling, erythema, nipple inversion), and overall feel of the breasts. A palpable mass must be recorded in terms of its location in relation to the skin, the nipple-areola complex, and the chest wall, as well as the quadrant of the breast in which it lies. The regional lymph node basins need to be examined closely, including the axilla and supraclavicular nodes.

Imaging studies also need to be reviewed closely. Patients today frequently present with multiple types of imaging studies, including mammography, ultrasonography, and MRI. Occasionally patients also may present with nuclear medicine exam results, CTs, thermographic images, positron emission tomography studies, and bone scans. All radiology studies need to be reviewed closely and examined in the context of what they were ordered for and what utility they potentially provide.

Treatment options: Surgery is first step in most cases

Once the above components are addressed, the patient should be engaged in a discussion of treatment options. Most women with breast cancer will undergo some type of surgery in conjunction with radiation therapy, chemotherapy, or both. Generally, surgery takes place as the first part of a multiple-component therapy plan. The main goal of surgery is to remove the cancer and accurately define the stage of the disease.

Consider plastic surgery consultation

When indicated and available, consultation with a plastic surgery team may be appropriate at this stage to provide support and comfort to the patient so that she better understands her options for breast reconstruction along with those for breast cancer surgery. Recent data show that most general surgeons do not discuss reconstruction with their breast cancer patients before surgical breast cancer therapy, but that when such discussions do occur, they significantly influence patients’ treatment choices.⁶ Giving patients the chance to learn about reconstructive options through discussion with a plastic surgeon represents a good opportunity to provide complete patient care in a multidisciplinary way.

OVERVIEW OF SURGICAL OPTIONS

Two general approaches, no difference in survival

The two mainstays of surgical treatment today are (1) breast conservation therapy, generally followed by total or partial breast irradiation, and (2) mastectomy.

The prospective randomized trial data obtained from the NSABP trials have demonstrated no survival differences between patients with early-stage breast cancer based on whether they were treated with breast conservation therapy or mastectomy.² Beyond this fundamental issue of survival, there are a number of nuances, many of them logistical, related to the success of either operation that the clinician must keep in mind when presenting these surgical choices to patients. These considerations are reviewed below.

Breast conservation therapy

For breast conservation therapy, the ratio of tumor size to breast size must be small enough to ensure complete tumor removal with an acceptable cosmetic outcome. In general, it is estimated that up to 25% of the breast can be removed while still ensuring a “good” cosmetic outcome. Advances in closure techniques allowing for more tissue to be removed with even better cosmetic outcomes are known as oncoplastic closure. These techniques are mostly performed by breast oncologic surgeons, often in consultation or conjunction with plastic surgeons. (Reconstructive options following breast conservation therapy are reviewed in a subsequent article in this supplement.) Additionally, the patient must agree and be deemed a candidate for postoperative radiation therapy. The patient must be able to be followed clinically to enable early detection of a potential local recurrence.

Figure 2 depicts needle localization and tumor excision in breast conservation therapy. The mainstay of breast conservation therapy is removal of the tumor with adequate normal breast tissue surrounding the cancer. Much debate surrounds “margin status,” or the width of normal breast tissue surrounding a gross tumor that has been removed. While it is understood that the goal of breast conservation therapy is to reduce tumor burden and obtain negative margins, a negative tumor margin does not guarantee complete absence of tumor. However, a negative margin is assurance that the tumor burden is reduced to microscopic levels that can be controlled by radiation therapy. Often the margin status is not known until the final pathologic specimen is serially sectioned and examined microscopically. A positive margin after initial breast conservation therapy generally requires a return to the operating room for further resection and clearance.

 

 

Mastectomy

A second surgical option for patients is mastectomy. Today “mastectomy” can refer to any of several subtypes of surgical procedures, which are outlined below and should be considered on a patient-by-patient basis. Mastectomy is appropriate when breast conservation therapy is not possible (due to a large or multicentric tumor) or would result in poor cosmetic outcome, or when the patient specifically chooses a mastectomy.

Modified radical mastectomy (Figure 3, left) involves complete removal of the breast with preservation of the pectoralis major and minor muscles (unlike radical mastectomy) and dissection of level I and II axillary lymph nodes. Level I lymph nodes are the lowest-lying nodes in the axilla, inferior to the lower edge of the pectoralis minor muscle; level II nodes lie underneath the pectoralis minor muscle. (Level III axillary lymph nodes, which are not dissected in this proce­dure, lie above the pectoralis minor muscle.)

Simple mastectomy involves removal of the breast only, without removal of lymph nodes. Either of the incisions depicted in the left and center panels of Figure 3 can be used. Both modified radical mastectomy and simple mastectomy involve removal of the nipple and areola (nipple-areola complex).

Skin-sparing mastectomy (Figure 3, center) is performed when a patient is undergoing immediate breast reconstruction (using either a silicone or saline implant or autologous tissue). The goal is to remove all breast tissue, along with the nipple-areola complex, while preserving as much viable skin as possible to optimize the cosmetic outcome.^7,8

Nipple-areola–sparing mastectomy. There is increasing experience with attempts to preserve the nipple-areola complex. These procedures attempt to preserve either the whole complex, termed nipple-areola–sparing mastectomy (sometimes called simply nipple-sparing mastectomy) (Figure 3, right), or just the areola, with removal of the nipple (areola-sparing mastectomy). These procedures are also performed in a skin-sparing fashion.

There is some controversy surrounding these techniques to spare the nipple and/or areola, including debate over which technique.nipple-areola–sparing mastectomy or areola-sparing mastectomy.may be more oncologically safe. Currently the literature shows that both are probably safe oncologic alternatives for remote tumors that do not have an extensive intraductal component. Generally, frozen sections are performed intraoperatively on the retroareola tissue to document that there is no evidence of tumor.⁹

The main driving force behind all of these types of skin-sparing techniques is aesthetic outcome; Figure 4 depicts the comparative outcomes in a patient who underwent skin-sparing mastectomy in the right breast and nipple-sparing mastectomy in the left. Ongoing randomized controlled studies are being conducted to further validate these procedures.

SURGICAL COMPLICATIONS

Breast procedures are fairly safe operations, but every operation has a risk of complications. Reported complications of breast surgery include the following:

• Bleeding
• Infection (including both cellulitis and abscess)
• Seroma
• Arm morbidity (including lymphedema)
• Phantom breast syndrome
• Injury to the motor nerves.

Seromas often occur in patients after mastectomy or lymph node surgery. Prolonged lymphatic drainage is usually exacerbated by extensive axillary node involvement and obesity.

Arm morbidity can present in different ways. Lymphedema is the most common manifestation, with reported incidences of approximately 15% to 20% when axillary lymph node dissection is performed versus 7% when sentinel lymph node biopsy is done.¹⁰ The risk of lymphedema can be reduced by avoiding blood pressure measurements, venipunctures, and intravenous insertions in the arm on the side of the operation, as well as by wearing a compression sleeve on the affected arm during airplane flights.

Phantom breast syndrome is rare but may manifest as pain that may also involve itching, nipple sensation, erotic sensations, or premenstrual-type soreness.

Many surgeons have historically removed the intercostobrachial nerves but are now trying to preserve these nerves, which when removed cause loss of sensation in the upper inner arm. Although rare, nerve injury during an axillary procedure has been reported. It may involve the long thoracic nerve (denervating the serratus anterior muscle and causing a winged scapula) or the thoracodorsal bundle (denervating the latissimus dorsi muscle and causing difficulty with arm/shoulder adduction).

LOCAL CANCER RECURRENCE

Among women undergoing mastectomy for breast cancer, 10% to 15% will have a recurrence of cancer in the chest wall or axillary lymph nodes within 10 years.¹¹ Similarly, among women undergoing breast conservation therapy plus radiation therapy, 10% to 15% will have in-breast cancer recurrence or recurrence in axillary lymph nodes within 10 years, although women who undergo breast conservation therapy without radiation have a much higher recurrence rate.¹¹Considerations for screening the surgically altered breast are discussed in the previous article in this supplement.

ASSESSMENT OF AXILLARY LYMPH NODES FOR METASTASIS

Even when patients have a known histologic diagnosis of breast cancer and have made a firm decision regarding the surgical option for removal of their cancer, the status of their axillary lymph nodes remains a great unanswered question until after the surgical procedure is completed. Lymph node status—ie, determining whether the cancer has spread to the axillary lymph nodes—still serves as the critical determinant for guiding adjuvant treatment, predicting survival, and assessing the risk of recurrence.

Axillary lymph node dissection

The standard approach for evaluating lymph node status has been a complete dissection of the axillary space, or axillary lymph node dissection. As briefly noted above, the axillary lymph nodes are anatomically classified into three levels as defined by their location relative to the pectoralis minor muscle. The extent of a nodal dissection can be defined by the number of nodes removed.

 

 

Sentinel node biopsy: A less-invasive alternative

Axillary lymph node dissection has been called into question over the last 15 years due to its invasiveness and the potential morbidity associated with it (including lymphedema and paresthesias). As a result, sen­tinel lymph node biopsy, a minimally invasive technique for identifying axillary metastasis, was developed to avoid the need for (and risk of complications from) axillary lymph node dissection in patients who have a low probability of axillary metastasis.

The concept of the sentinel node is based on two basic principles: (1) there is an orderly and predictable pattern of lymphatic drainage to a respective nodal basin, and (2) the first lymph node functions as an effective filter for tumor cells.¹² The technique of mapping the sentinel node in breast cancer patients was developed in the early 1990s and has since been studied, refined, and validated. The technique is performed intraoperatively with periareolar injection of vital blue dye, technetium-labeled sulfur colloid, or a combination of the two (Figure 5). The axillary lymph nodes are then inspected for staining and/or the radioactive tracer, and any node that has taken up the dye or tracer is designated as a sentinel lymph node and removed (Figure 6). Generally, the sentinel node is sent for intraoperative frozen section examination to determine the presence or absence of metastasis. If the sentinel lymph node biopsy is positive for metastasis, then axillary lymph node dissection is warranted; if it is negative, no additional axillary surgery is needed.

Reprinted from Contemporary Surgery (Pawlik TM, Gershenwald JE. Sentinel lymph node biopsy for melanoma. Contemp Surg 2005; 61:175–182.) with permission of Dowden Health Media.

If this mapping procedure fails to clearly identify a sentinel node, then a complete axillary lymph node dissection is performed. Reasons for failed mapping include technical issues as well as anatomic ones.¹³ Performing sentinel lymph node biopsies clearly involves a learning curve, and the sensitivity and specificity of these biopsies do vary among surgeons, correlating with the surgeons’ technical experience.¹⁴ Disruption of the breast lymphatics from prior breast surgery can reduce the sensitivity of a sentinel lymph node biopsy. Similarly, the presence of a hematoma or seroma from a prior biopsy can impede sentinel node detection. Tumor location can also be a factor in detecting a sentinel node, especially for tumors located in the inner quadrants of the breast, as they may drain to the internal mammary nodes.

Overall, however, it is now accepted that intraoperative lymph node mapping with sentinel lymphadenectomy is an effective and minimally invasive alternative to axillary lymph node dissection for identifying nodes containing metastases.

CONCLUSIONS

Decisions surrounding the choice of breast surgery procedure must be individualized to the patient and her desires and based on comprehensive patient evaluation and thorough patient counseling. Optimal results for the patient—oncologically, psychologically, and in terms of cosmetic outcomes—require consultation and collaboration among general surgeons, medical oncologists, genetic counselors, radiation oncologists, radiologists, and plastic surgeons to clarify the risks and benefits of various intervention options. Striving for this multidisciplinary collaboration will promote optimal patient management and the most favorable clinical outcomes.

In the late 19th century, breast cancer was considered a fatal disease. That began to change in the 1880s when W.S. Halsted described the radical mastectomy as the way to treat patients with breast cancer.¹ This aggressive surgical treatment—in which the breast, axillary lymph nodes, and chest muscles are all removed—remained the standard of care throughout much of the 20th century; as late as the early 1970s, nearly half (48%) of breast cancer patients were treated with radical mastectomy. During the 1970s, however, the Halsted radical mastectomy was largely abandoned for a less-disfiguring muscle-sparing technique called the modified radical mastectomy; by 1981, only 3% of patients underwent the Halsted mastectomy.²

The 1980s heralded even more minimally invasive techniques with the advent of breast conservation therapy, in which an incision is made over the tumor and the tumor is completely removed with negative margins, leaving behind normal breast tissue. (This procedure has been referred to by many different names, including definitive excision, lumpectomy, quadrantectomy, and partial mastectomy; since they all mean the same thing, for clarity and consistency this article will use “breast conservation therapy” throughout.) During the 1990s, surgical invasiveness was further minimized with the emergence of sentinel lymph node excision.

An important contributor to this evolution in the standard of breast cancer therapy since the 1970s has been the National Surgical Adjuvant Breast and Bowel Project (NSABP), a National Cancer Institute–funded clinical trials cooperative group. NSABP studies have been the driving force to show that the extent of surgery could be reduced without compromising outcome.³ These studies, along with several other trials, have resulted in a marked reduction in surgical aggressiveness and a multitude of adjuvant therapies for women with breast cancer. This article will briefly explore where this evolution has brought us in terms of the surgical options available for treatment of breast cancer today. We also discuss other key components in the management of women with newly diagnosed breast cancer, including cancer staging, patient counseling, and assessment of axillary lymph nodes.

BREAST CANCER CLASSIFICATION AND STAGING

Pathologic classification

Breast cancer is an adenocarcinoma that occurs primarily in two forms: ductal or lobular carcinoma, in which malignancy develops in the breast ducts or lobules, respectively. The majority of breast cancers are ductal in origin. Another key pathologic distinction is between in situ versus invasive carcinoma, which depends on whether the cancer cell remains within the duct or lobule (stage 0, or in situ) or has spread on a microscopic level to the adjacent breast parenchyma (invasive or infiltrating) (Figure 1). Despite its nomenclature, lobular carcinoma in situ is not a cancer; it is merely a marker of increased risk for developing invasive cancer (either ductal or lobular) that may appear on either side (right or left breast), not just the side of the original biopsy.

Cancer staging

“What stage am I?” is a question every patient asks upon receiving a new diagnosis of breast cancer. Breast cancer staging is based on the TNM system, defined by the American Joint Committee on Cancer, which takes into account tumor (T) size, the extent of regional lymph node (N) involvement, and the presence or absence of metastasis (M) beyond the regional lymph nodes.⁴ Using this system, whose criteria and details are outlined in Table 1, breast cancer is staged from 0 to IV. Stage 0 implies in situ cancer, while stages I to IV indicate invasive cancer, with IV implying metastatic spread to distant organs.

A simpler method relies on the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) summary staging system.⁵ This system classifies tumors as “localized” (contained in the breast, either in situ or invasive), “regional” (identified in regional lymph nodes), or “metastatic” (spread to distant organ systems).

Of course, patients cannot be told their stage until after surgery, when a final pathologic report detailing tumor size and nodal status is available. Some patients will never be definitively staged—for instance, those who undergo neoadjuvant chemotherapy for locally advanced disease prior to lymph node dissection, or those who do not have a metastatic work-up. The metastatic work-up involves ordering of additional tests to assess for metastasis, but only when prompted by specific patient symptoms. Thus, if the patient has shortness of breath, a chest radiograph or a chest computed tomograph (CT) needs to be ordered; for elevated liver enzymes, CTs of the abdomen and pelvis are ordered; for central nervous system symptoms, brain magnetic resonance imaging (MRI) is ordered; and for back pain or bone pain, a bone scan is ordered to rule out metastatic disease to bone.

INITIAL PATIENT ASSESSMENT AND COUNSELING

Relationship-building is fundamental

Following an initial diagnosis of breast cancer, the patient must undergo an assessment for local and systemic disease. The surgeon, as a member of a multi-disciplinary breast cancer treatment team, often spearheads this initial assessment. This first visit must go beyond mere clinical evaluation, however, and include thorough discussion and relationship-building with the patient, as this early meeting establishes a relationship with the patient that will carry through her entire process of cancer care. For a true understanding between patient and surgeon to occur, it is critical for patients to be comfortable in sharing their fears, expectations, and lifestyle needs. Following a diagnosis of breast cancer, the initial reactions women go through include both fear and realization of one’s own mortality. Although these responses may no longer be justified by the reality of patient outcomes in most cases, they are normal and fully understandable reactions. For this reason, clinicians must be sensitive to these reactions while being supportive about the efficacy of the treatment options available.

 

 

History, breast exam, and review of imaging studies

In addition to the establishment of communication and understanding, the vital components of this first meeting include a detailed medical history, a clinical breast examination, a review of imaging studies, and a discussion of treatment options.

The history should include all aspects of the patient’s reproductive history, her family history of breast cancer, and any comorbidities and medications being taken.

The clinical breast examination should give special attention to the shape (asymmetry), appearance (eg, dimpling, erythema, nipple inversion), and overall feel of the breasts. A palpable mass must be recorded in terms of its location in relation to the skin, the nipple-areola complex, and the chest wall, as well as the quadrant of the breast in which it lies. The regional lymph node basins need to be examined closely, including the axilla and supraclavicular nodes.

Imaging studies also need to be reviewed closely. Patients today frequently present with multiple types of imaging studies, including mammography, ultrasonography, and MRI. Occasionally patients also may present with nuclear medicine exam results, CTs, thermographic images, positron emission tomography studies, and bone scans. All radiology studies need to be reviewed closely and examined in the context of what they were ordered for and what utility they potentially provide.

Treatment options: Surgery is first step in most cases

Once the above components are addressed, the patient should be engaged in a discussion of treatment options. Most women with breast cancer will undergo some type of surgery in conjunction with radiation therapy, chemotherapy, or both. Generally, surgery takes place as the first part of a multiple-component therapy plan. The main goal of surgery is to remove the cancer and accurately define the stage of the disease.

Consider plastic surgery consultation

When indicated and available, consultation with a plastic surgery team may be appropriate at this stage to provide support and comfort to the patient so that she better understands her options for breast reconstruction along with those for breast cancer surgery. Recent data show that most general surgeons do not discuss reconstruction with their breast cancer patients before surgical breast cancer therapy, but that when such discussions do occur, they significantly influence patients’ treatment choices.⁶ Giving patients the chance to learn about reconstructive options through discussion with a plastic surgeon represents a good opportunity to provide complete patient care in a multidisciplinary way.

OVERVIEW OF SURGICAL OPTIONS

Two general approaches, no difference in survival

The two mainstays of surgical treatment today are (1) breast conservation therapy, generally followed by total or partial breast irradiation, and (2) mastectomy.

The prospective randomized trial data obtained from the NSABP trials have demonstrated no survival differences between patients with early-stage breast cancer based on whether they were treated with breast conservation therapy or mastectomy.² Beyond this fundamental issue of survival, there are a number of nuances, many of them logistical, related to the success of either operation that the clinician must keep in mind when presenting these surgical choices to patients. These considerations are reviewed below.

Breast conservation therapy

For breast conservation therapy, the ratio of tumor size to breast size must be small enough to ensure complete tumor removal with an acceptable cosmetic outcome. In general, it is estimated that up to 25% of the breast can be removed while still ensuring a “good” cosmetic outcome. Advances in closure techniques allowing for more tissue to be removed with even better cosmetic outcomes are known as oncoplastic closure. These techniques are mostly performed by breast oncologic surgeons, often in consultation or conjunction with plastic surgeons. (Reconstructive options following breast conservation therapy are reviewed in a subsequent article in this supplement.) Additionally, the patient must agree and be deemed a candidate for postoperative radiation therapy. The patient must be able to be followed clinically to enable early detection of a potential local recurrence.

Figure 2 depicts needle localization and tumor excision in breast conservation therapy. The mainstay of breast conservation therapy is removal of the tumor with adequate normal breast tissue surrounding the cancer. Much debate surrounds “margin status,” or the width of normal breast tissue surrounding a gross tumor that has been removed. While it is understood that the goal of breast conservation therapy is to reduce tumor burden and obtain negative margins, a negative tumor margin does not guarantee complete absence of tumor. However, a negative margin is assurance that the tumor burden is reduced to microscopic levels that can be controlled by radiation therapy. Often the margin status is not known until the final pathologic specimen is serially sectioned and examined microscopically. A positive margin after initial breast conservation therapy generally requires a return to the operating room for further resection and clearance.

 

 

Mastectomy

A second surgical option for patients is mastectomy. Today “mastectomy” can refer to any of several subtypes of surgical procedures, which are outlined below and should be considered on a patient-by-patient basis. Mastectomy is appropriate when breast conservation therapy is not possible (due to a large or multicentric tumor) or would result in poor cosmetic outcome, or when the patient specifically chooses a mastectomy.

Modified radical mastectomy (Figure 3, left) involves complete removal of the breast with preservation of the pectoralis major and minor muscles (unlike radical mastectomy) and dissection of level I and II axillary lymph nodes. Level I lymph nodes are the lowest-lying nodes in the axilla, inferior to the lower edge of the pectoralis minor muscle; level II nodes lie underneath the pectoralis minor muscle. (Level III axillary lymph nodes, which are not dissected in this proce­dure, lie above the pectoralis minor muscle.)

Simple mastectomy involves removal of the breast only, without removal of lymph nodes. Either of the incisions depicted in the left and center panels of Figure 3 can be used. Both modified radical mastectomy and simple mastectomy involve removal of the nipple and areola (nipple-areola complex).

Skin-sparing mastectomy (Figure 3, center) is performed when a patient is undergoing immediate breast reconstruction (using either a silicone or saline implant or autologous tissue). The goal is to remove all breast tissue, along with the nipple-areola complex, while preserving as much viable skin as possible to optimize the cosmetic outcome.^7,8

Nipple-areola–sparing mastectomy. There is increasing experience with attempts to preserve the nipple-areola complex. These procedures attempt to preserve either the whole complex, termed nipple-areola–sparing mastectomy (sometimes called simply nipple-sparing mastectomy) (Figure 3, right), or just the areola, with removal of the nipple (areola-sparing mastectomy). These procedures are also performed in a skin-sparing fashion.

There is some controversy surrounding these techniques to spare the nipple and/or areola, including debate over which technique.nipple-areola–sparing mastectomy or areola-sparing mastectomy.may be more oncologically safe. Currently the literature shows that both are probably safe oncologic alternatives for remote tumors that do not have an extensive intraductal component. Generally, frozen sections are performed intraoperatively on the retroareola tissue to document that there is no evidence of tumor.⁹

The main driving force behind all of these types of skin-sparing techniques is aesthetic outcome; Figure 4 depicts the comparative outcomes in a patient who underwent skin-sparing mastectomy in the right breast and nipple-sparing mastectomy in the left. Ongoing randomized controlled studies are being conducted to further validate these procedures.

SURGICAL COMPLICATIONS

Breast procedures are fairly safe operations, but every operation has a risk of complications. Reported complications of breast surgery include the following:

• Bleeding
• Infection (including both cellulitis and abscess)
• Seroma
• Arm morbidity (including lymphedema)
• Phantom breast syndrome
• Injury to the motor nerves.

Seromas often occur in patients after mastectomy or lymph node surgery. Prolonged lymphatic drainage is usually exacerbated by extensive axillary node involvement and obesity.

Arm morbidity can present in different ways. Lymphedema is the most common manifestation, with reported incidences of approximately 15% to 20% when axillary lymph node dissection is performed versus 7% when sentinel lymph node biopsy is done.¹⁰ The risk of lymphedema can be reduced by avoiding blood pressure measurements, venipunctures, and intravenous insertions in the arm on the side of the operation, as well as by wearing a compression sleeve on the affected arm during airplane flights.

Phantom breast syndrome is rare but may manifest as pain that may also involve itching, nipple sensation, erotic sensations, or premenstrual-type soreness.

Many surgeons have historically removed the intercostobrachial nerves but are now trying to preserve these nerves, which when removed cause loss of sensation in the upper inner arm. Although rare, nerve injury during an axillary procedure has been reported. It may involve the long thoracic nerve (denervating the serratus anterior muscle and causing a winged scapula) or the thoracodorsal bundle (denervating the latissimus dorsi muscle and causing difficulty with arm/shoulder adduction).

LOCAL CANCER RECURRENCE

Among women undergoing mastectomy for breast cancer, 10% to 15% will have a recurrence of cancer in the chest wall or axillary lymph nodes within 10 years.¹¹ Similarly, among women undergoing breast conservation therapy plus radiation therapy, 10% to 15% will have in-breast cancer recurrence or recurrence in axillary lymph nodes within 10 years, although women who undergo breast conservation therapy without radiation have a much higher recurrence rate.¹¹Considerations for screening the surgically altered breast are discussed in the previous article in this supplement.

ASSESSMENT OF AXILLARY LYMPH NODES FOR METASTASIS

Even when patients have a known histologic diagnosis of breast cancer and have made a firm decision regarding the surgical option for removal of their cancer, the status of their axillary lymph nodes remains a great unanswered question until after the surgical procedure is completed. Lymph node status—ie, determining whether the cancer has spread to the axillary lymph nodes—still serves as the critical determinant for guiding adjuvant treatment, predicting survival, and assessing the risk of recurrence.

Axillary lymph node dissection

The standard approach for evaluating lymph node status has been a complete dissection of the axillary space, or axillary lymph node dissection. As briefly noted above, the axillary lymph nodes are anatomically classified into three levels as defined by their location relative to the pectoralis minor muscle. The extent of a nodal dissection can be defined by the number of nodes removed.

 

 

Sentinel node biopsy: A less-invasive alternative

Axillary lymph node dissection has been called into question over the last 15 years due to its invasiveness and the potential morbidity associated with it (including lymphedema and paresthesias). As a result, sen­tinel lymph node biopsy, a minimally invasive technique for identifying axillary metastasis, was developed to avoid the need for (and risk of complications from) axillary lymph node dissection in patients who have a low probability of axillary metastasis.

The concept of the sentinel node is based on two basic principles: (1) there is an orderly and predictable pattern of lymphatic drainage to a respective nodal basin, and (2) the first lymph node functions as an effective filter for tumor cells.¹² The technique of mapping the sentinel node in breast cancer patients was developed in the early 1990s and has since been studied, refined, and validated. The technique is performed intraoperatively with periareolar injection of vital blue dye, technetium-labeled sulfur colloid, or a combination of the two (Figure 5). The axillary lymph nodes are then inspected for staining and/or the radioactive tracer, and any node that has taken up the dye or tracer is designated as a sentinel lymph node and removed (Figure 6). Generally, the sentinel node is sent for intraoperative frozen section examination to determine the presence or absence of metastasis. If the sentinel lymph node biopsy is positive for metastasis, then axillary lymph node dissection is warranted; if it is negative, no additional axillary surgery is needed.

Reprinted from Contemporary Surgery (Pawlik TM, Gershenwald JE. Sentinel lymph node biopsy for melanoma. Contemp Surg 2005; 61:175–182.) with permission of Dowden Health Media.

If this mapping procedure fails to clearly identify a sentinel node, then a complete axillary lymph node dissection is performed. Reasons for failed mapping include technical issues as well as anatomic ones.¹³ Performing sentinel lymph node biopsies clearly involves a learning curve, and the sensitivity and specificity of these biopsies do vary among surgeons, correlating with the surgeons’ technical experience.¹⁴ Disruption of the breast lymphatics from prior breast surgery can reduce the sensitivity of a sentinel lymph node biopsy. Similarly, the presence of a hematoma or seroma from a prior biopsy can impede sentinel node detection. Tumor location can also be a factor in detecting a sentinel node, especially for tumors located in the inner quadrants of the breast, as they may drain to the internal mammary nodes.

Overall, however, it is now accepted that intraoperative lymph node mapping with sentinel lymphadenectomy is an effective and minimally invasive alternative to axillary lymph node dissection for identifying nodes containing metastases.

CONCLUSIONS

Decisions surrounding the choice of breast surgery procedure must be individualized to the patient and her desires and based on comprehensive patient evaluation and thorough patient counseling. Optimal results for the patient—oncologically, psychologically, and in terms of cosmetic outcomes—require consultation and collaboration among general surgeons, medical oncologists, genetic counselors, radiation oncologists, radiologists, and plastic surgeons to clarify the risks and benefits of various intervention options. Striving for this multidisciplinary collaboration will promote optimal patient management and the most favorable clinical outcomes.

In the late 19th century, breast cancer was considered a fatal disease. That began to change in the 1880s when W.S. Halsted described the radical mastectomy as the way to treat patients with breast cancer.¹ This aggressive surgical treatment—in which the breast, axillary lymph nodes, and chest muscles are all removed—remained the standard of care throughout much of the 20th century; as late as the early 1970s, nearly half (48%) of breast cancer patients were treated with radical mastectomy. During the 1970s, however, the Halsted radical mastectomy was largely abandoned for a less-disfiguring muscle-sparing technique called the modified radical mastectomy; by 1981, only 3% of patients underwent the Halsted mastectomy.²

The 1980s heralded even more minimally invasive techniques with the advent of breast conservation therapy, in which an incision is made over the tumor and the tumor is completely removed with negative margins, leaving behind normal breast tissue. (This procedure has been referred to by many different names, including definitive excision, lumpectomy, quadrantectomy, and partial mastectomy; since they all mean the same thing, for clarity and consistency this article will use “breast conservation therapy” throughout.) During the 1990s, surgical invasiveness was further minimized with the emergence of sentinel lymph node excision.

An important contributor to this evolution in the standard of breast cancer therapy since the 1970s has been the National Surgical Adjuvant Breast and Bowel Project (NSABP), a National Cancer Institute–funded clinical trials cooperative group. NSABP studies have been the driving force to show that the extent of surgery could be reduced without compromising outcome.³ These studies, along with several other trials, have resulted in a marked reduction in surgical aggressiveness and a multitude of adjuvant therapies for women with breast cancer. This article will briefly explore where this evolution has brought us in terms of the surgical options available for treatment of breast cancer today. We also discuss other key components in the management of women with newly diagnosed breast cancer, including cancer staging, patient counseling, and assessment of axillary lymph nodes.

BREAST CANCER CLASSIFICATION AND STAGING

Pathologic classification

Breast cancer is an adenocarcinoma that occurs primarily in two forms: ductal or lobular carcinoma, in which malignancy develops in the breast ducts or lobules, respectively. The majority of breast cancers are ductal in origin. Another key pathologic distinction is between in situ versus invasive carcinoma, which depends on whether the cancer cell remains within the duct or lobule (stage 0, or in situ) or has spread on a microscopic level to the adjacent breast parenchyma (invasive or infiltrating) (Figure 1). Despite its nomenclature, lobular carcinoma in situ is not a cancer; it is merely a marker of increased risk for developing invasive cancer (either ductal or lobular) that may appear on either side (right or left breast), not just the side of the original biopsy.

Cancer staging

“What stage am I?” is a question every patient asks upon receiving a new diagnosis of breast cancer. Breast cancer staging is based on the TNM system, defined by the American Joint Committee on Cancer, which takes into account tumor (T) size, the extent of regional lymph node (N) involvement, and the presence or absence of metastasis (M) beyond the regional lymph nodes.⁴ Using this system, whose criteria and details are outlined in Table 1, breast cancer is staged from 0 to IV. Stage 0 implies in situ cancer, while stages I to IV indicate invasive cancer, with IV implying metastatic spread to distant organs.

A simpler method relies on the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) summary staging system.⁵ This system classifies tumors as “localized” (contained in the breast, either in situ or invasive), “regional” (identified in regional lymph nodes), or “metastatic” (spread to distant organ systems).

Of course, patients cannot be told their stage until after surgery, when a final pathologic report detailing tumor size and nodal status is available. Some patients will never be definitively staged—for instance, those who undergo neoadjuvant chemotherapy for locally advanced disease prior to lymph node dissection, or those who do not have a metastatic work-up. The metastatic work-up involves ordering of additional tests to assess for metastasis, but only when prompted by specific patient symptoms. Thus, if the patient has shortness of breath, a chest radiograph or a chest computed tomograph (CT) needs to be ordered; for elevated liver enzymes, CTs of the abdomen and pelvis are ordered; for central nervous system symptoms, brain magnetic resonance imaging (MRI) is ordered; and for back pain or bone pain, a bone scan is ordered to rule out metastatic disease to bone.

INITIAL PATIENT ASSESSMENT AND COUNSELING

Relationship-building is fundamental

Following an initial diagnosis of breast cancer, the patient must undergo an assessment for local and systemic disease. The surgeon, as a member of a multi-disciplinary breast cancer treatment team, often spearheads this initial assessment. This first visit must go beyond mere clinical evaluation, however, and include thorough discussion and relationship-building with the patient, as this early meeting establishes a relationship with the patient that will carry through her entire process of cancer care. For a true understanding between patient and surgeon to occur, it is critical for patients to be comfortable in sharing their fears, expectations, and lifestyle needs. Following a diagnosis of breast cancer, the initial reactions women go through include both fear and realization of one’s own mortality. Although these responses may no longer be justified by the reality of patient outcomes in most cases, they are normal and fully understandable reactions. For this reason, clinicians must be sensitive to these reactions while being supportive about the efficacy of the treatment options available.

 

 

History, breast exam, and review of imaging studies

In addition to the establishment of communication and understanding, the vital components of this first meeting include a detailed medical history, a clinical breast examination, a review of imaging studies, and a discussion of treatment options.

The history should include all aspects of the patient’s reproductive history, her family history of breast cancer, and any comorbidities and medications being taken.

The clinical breast examination should give special attention to the shape (asymmetry), appearance (eg, dimpling, erythema, nipple inversion), and overall feel of the breasts. A palpable mass must be recorded in terms of its location in relation to the skin, the nipple-areola complex, and the chest wall, as well as the quadrant of the breast in which it lies. The regional lymph node basins need to be examined closely, including the axilla and supraclavicular nodes.

Imaging studies also need to be reviewed closely. Patients today frequently present with multiple types of imaging studies, including mammography, ultrasonography, and MRI. Occasionally patients also may present with nuclear medicine exam results, CTs, thermographic images, positron emission tomography studies, and bone scans. All radiology studies need to be reviewed closely and examined in the context of what they were ordered for and what utility they potentially provide.

Treatment options: Surgery is first step in most cases

Once the above components are addressed, the patient should be engaged in a discussion of treatment options. Most women with breast cancer will undergo some type of surgery in conjunction with radiation therapy, chemotherapy, or both. Generally, surgery takes place as the first part of a multiple-component therapy plan. The main goal of surgery is to remove the cancer and accurately define the stage of the disease.

Consider plastic surgery consultation

When indicated and available, consultation with a plastic surgery team may be appropriate at this stage to provide support and comfort to the patient so that she better understands her options for breast reconstruction along with those for breast cancer surgery. Recent data show that most general surgeons do not discuss reconstruction with their breast cancer patients before surgical breast cancer therapy, but that when such discussions do occur, they significantly influence patients’ treatment choices.⁶ Giving patients the chance to learn about reconstructive options through discussion with a plastic surgeon represents a good opportunity to provide complete patient care in a multidisciplinary way.

OVERVIEW OF SURGICAL OPTIONS

Two general approaches, no difference in survival

The two mainstays of surgical treatment today are (1) breast conservation therapy, generally followed by total or partial breast irradiation, and (2) mastectomy.

The prospective randomized trial data obtained from the NSABP trials have demonstrated no survival differences between patients with early-stage breast cancer based on whether they were treated with breast conservation therapy or mastectomy.² Beyond this fundamental issue of survival, there are a number of nuances, many of them logistical, related to the success of either operation that the clinician must keep in mind when presenting these surgical choices to patients. These considerations are reviewed below.

Breast conservation therapy

For breast conservation therapy, the ratio of tumor size to breast size must be small enough to ensure complete tumor removal with an acceptable cosmetic outcome. In general, it is estimated that up to 25% of the breast can be removed while still ensuring a “good” cosmetic outcome. Advances in closure techniques allowing for more tissue to be removed with even better cosmetic outcomes are known as oncoplastic closure. These techniques are mostly performed by breast oncologic surgeons, often in consultation or conjunction with plastic surgeons. (Reconstructive options following breast conservation therapy are reviewed in a subsequent article in this supplement.) Additionally, the patient must agree and be deemed a candidate for postoperative radiation therapy. The patient must be able to be followed clinically to enable early detection of a potential local recurrence.

Figure 2 depicts needle localization and tumor excision in breast conservation therapy. The mainstay of breast conservation therapy is removal of the tumor with adequate normal breast tissue surrounding the cancer. Much debate surrounds “margin status,” or the width of normal breast tissue surrounding a gross tumor that has been removed. While it is understood that the goal of breast conservation therapy is to reduce tumor burden and obtain negative margins, a negative tumor margin does not guarantee complete absence of tumor. However, a negative margin is assurance that the tumor burden is reduced to microscopic levels that can be controlled by radiation therapy. Often the margin status is not known until the final pathologic specimen is serially sectioned and examined microscopically. A positive margin after initial breast conservation therapy generally requires a return to the operating room for further resection and clearance.

 

 

Mastectomy

A second surgical option for patients is mastectomy. Today “mastectomy” can refer to any of several subtypes of surgical procedures, which are outlined below and should be considered on a patient-by-patient basis. Mastectomy is appropriate when breast conservation therapy is not possible (due to a large or multicentric tumor) or would result in poor cosmetic outcome, or when the patient specifically chooses a mastectomy.

Modified radical mastectomy (Figure 3, left) involves complete removal of the breast with preservation of the pectoralis major and minor muscles (unlike radical mastectomy) and dissection of level I and II axillary lymph nodes. Level I lymph nodes are the lowest-lying nodes in the axilla, inferior to the lower edge of the pectoralis minor muscle; level II nodes lie underneath the pectoralis minor muscle. (Level III axillary lymph nodes, which are not dissected in this proce­dure, lie above the pectoralis minor muscle.)

Simple mastectomy involves removal of the breast only, without removal of lymph nodes. Either of the incisions depicted in the left and center panels of Figure 3 can be used. Both modified radical mastectomy and simple mastectomy involve removal of the nipple and areola (nipple-areola complex).

Skin-sparing mastectomy (Figure 3, center) is performed when a patient is undergoing immediate breast reconstruction (using either a silicone or saline implant or autologous tissue). The goal is to remove all breast tissue, along with the nipple-areola complex, while preserving as much viable skin as possible to optimize the cosmetic outcome.^7,8

Nipple-areola–sparing mastectomy. There is increasing experience with attempts to preserve the nipple-areola complex. These procedures attempt to preserve either the whole complex, termed nipple-areola–sparing mastectomy (sometimes called simply nipple-sparing mastectomy) (Figure 3, right), or just the areola, with removal of the nipple (areola-sparing mastectomy). These procedures are also performed in a skin-sparing fashion.

There is some controversy surrounding these techniques to spare the nipple and/or areola, including debate over which technique.nipple-areola–sparing mastectomy or areola-sparing mastectomy.may be more oncologically safe. Currently the literature shows that both are probably safe oncologic alternatives for remote tumors that do not have an extensive intraductal component. Generally, frozen sections are performed intraoperatively on the retroareola tissue to document that there is no evidence of tumor.⁹

The main driving force behind all of these types of skin-sparing techniques is aesthetic outcome; Figure 4 depicts the comparative outcomes in a patient who underwent skin-sparing mastectomy in the right breast and nipple-sparing mastectomy in the left. Ongoing randomized controlled studies are being conducted to further validate these procedures.

SURGICAL COMPLICATIONS

Breast procedures are fairly safe operations, but every operation has a risk of complications. Reported complications of breast surgery include the following:

• Bleeding
• Infection (including both cellulitis and abscess)
• Seroma
• Arm morbidity (including lymphedema)
• Phantom breast syndrome
• Injury to the motor nerves.

Seromas often occur in patients after mastectomy or lymph node surgery. Prolonged lymphatic drainage is usually exacerbated by extensive axillary node involvement and obesity.

Arm morbidity can present in different ways. Lymphedema is the most common manifestation, with reported incidences of approximately 15% to 20% when axillary lymph node dissection is performed versus 7% when sentinel lymph node biopsy is done.¹⁰ The risk of lymphedema can be reduced by avoiding blood pressure measurements, venipunctures, and intravenous insertions in the arm on the side of the operation, as well as by wearing a compression sleeve on the affected arm during airplane flights.

Phantom breast syndrome is rare but may manifest as pain that may also involve itching, nipple sensation, erotic sensations, or premenstrual-type soreness.

Many surgeons have historically removed the intercostobrachial nerves but are now trying to preserve these nerves, which when removed cause loss of sensation in the upper inner arm. Although rare, nerve injury during an axillary procedure has been reported. It may involve the long thoracic nerve (denervating the serratus anterior muscle and causing a winged scapula) or the thoracodorsal bundle (denervating the latissimus dorsi muscle and causing difficulty with arm/shoulder adduction).

LOCAL CANCER RECURRENCE

Among women undergoing mastectomy for breast cancer, 10% to 15% will have a recurrence of cancer in the chest wall or axillary lymph nodes within 10 years.¹¹ Similarly, among women undergoing breast conservation therapy plus radiation therapy, 10% to 15% will have in-breast cancer recurrence or recurrence in axillary lymph nodes within 10 years, although women who undergo breast conservation therapy without radiation have a much higher recurrence rate.¹¹Considerations for screening the surgically altered breast are discussed in the previous article in this supplement.

ASSESSMENT OF AXILLARY LYMPH NODES FOR METASTASIS

Even when patients have a known histologic diagnosis of breast cancer and have made a firm decision regarding the surgical option for removal of their cancer, the status of their axillary lymph nodes remains a great unanswered question until after the surgical procedure is completed. Lymph node status—ie, determining whether the cancer has spread to the axillary lymph nodes—still serves as the critical determinant for guiding adjuvant treatment, predicting survival, and assessing the risk of recurrence.

Axillary lymph node dissection

The standard approach for evaluating lymph node status has been a complete dissection of the axillary space, or axillary lymph node dissection. As briefly noted above, the axillary lymph nodes are anatomically classified into three levels as defined by their location relative to the pectoralis minor muscle. The extent of a nodal dissection can be defined by the number of nodes removed.

 

 

Sentinel node biopsy: A less-invasive alternative

Axillary lymph node dissection has been called into question over the last 15 years due to its invasiveness and the potential morbidity associated with it (including lymphedema and paresthesias). As a result, sen­tinel lymph node biopsy, a minimally invasive technique for identifying axillary metastasis, was developed to avoid the need for (and risk of complications from) axillary lymph node dissection in patients who have a low probability of axillary metastasis.

The concept of the sentinel node is based on two basic principles: (1) there is an orderly and predictable pattern of lymphatic drainage to a respective nodal basin, and (2) the first lymph node functions as an effective filter for tumor cells.¹² The technique of mapping the sentinel node in breast cancer patients was developed in the early 1990s and has since been studied, refined, and validated. The technique is performed intraoperatively with periareolar injection of vital blue dye, technetium-labeled sulfur colloid, or a combination of the two (Figure 5). The axillary lymph nodes are then inspected for staining and/or the radioactive tracer, and any node that has taken up the dye or tracer is designated as a sentinel lymph node and removed (Figure 6). Generally, the sentinel node is sent for intraoperative frozen section examination to determine the presence or absence of metastasis. If the sentinel lymph node biopsy is positive for metastasis, then axillary lymph node dissection is warranted; if it is negative, no additional axillary surgery is needed.

Reprinted from Contemporary Surgery (Pawlik TM, Gershenwald JE. Sentinel lymph node biopsy for melanoma. Contemp Surg 2005; 61:175–182.) with permission of Dowden Health Media.

If this mapping procedure fails to clearly identify a sentinel node, then a complete axillary lymph node dissection is performed. Reasons for failed mapping include technical issues as well as anatomic ones.¹³ Performing sentinel lymph node biopsies clearly involves a learning curve, and the sensitivity and specificity of these biopsies do vary among surgeons, correlating with the surgeons’ technical experience.¹⁴ Disruption of the breast lymphatics from prior breast surgery can reduce the sensitivity of a sentinel lymph node biopsy. Similarly, the presence of a hematoma or seroma from a prior biopsy can impede sentinel node detection. Tumor location can also be a factor in detecting a sentinel node, especially for tumors located in the inner quadrants of the breast, as they may drain to the internal mammary nodes.

Overall, however, it is now accepted that intraoperative lymph node mapping with sentinel lymphadenectomy is an effective and minimally invasive alternative to axillary lymph node dissection for identifying nodes containing metastases.

CONCLUSIONS

Decisions surrounding the choice of breast surgery procedure must be individualized to the patient and her desires and based on comprehensive patient evaluation and thorough patient counseling. Optimal results for the patient—oncologically, psychologically, and in terms of cosmetic outcomes—require consultation and collaboration among general surgeons, medical oncologists, genetic counselors, radiation oncologists, radiologists, and plastic surgeons to clarify the risks and benefits of various intervention options. Striving for this multidisciplinary collaboration will promote optimal patient management and the most favorable clinical outcomes.