Applied Evidence

Breast cancer prevention and Tx: An evidence-based guide

J Fam Pract. 2010 October;59(10):575-581a

References

1. US Preventive Services Task Force Screening for breast cancer. Available at: http://www.uspreventiveservicestaskforce.org/uspstf/uspsbrca.htm. Accessed September 2, 2010.

2. American Cancer Society. American Cancer Society guidelines for the early detection of cancer. Available at: http://www.cancer.org/Healthy/FindCancerEarly/CancerScreeningGuidelines/american-cancer-society-guidelines-for-the-early-detection-of-cancer. Accessed September 2, 2010.

3. American College of Obstetricians and Gynecologists. Response of the American College of Obstetricians and Gynecologists to the new breast cancer screening recommendations from the US Preventive Services Task Force. Available at: http://www.acog.org/from_home/misc/uspstfresponse.cfm. Accessed September 2, 2010.

4. National Comprehensive Cancer Network. Breast cancer screening and diagnosis. Clinical Practice Guidelines in Oncology-V.1.2010. Fort Washington, Pa: National Comprehensive Cancer Network: November 3, 2009. Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed September 17 , 2010.

5. National Cancer Institute. Breast cancer risk assessment tool. Available at: http://www.cancer.gov/bcrisktool/. Accessed September 2, 2010

6. Robson M, Offit K. Clinical practice. Management of an inherited predisposition to breast cancer. N Engl J Med. 2007;357:154-162.

7. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90:1371-1388.

8. Cummings SR, Tice JA, Bauer S, et al. Prevention of breast cancer in postmenopausal women: approaches to estimating and reducing risk. J Natl Cancer Inst. 2009;18:101,-384-398.

9. Prentice RL, Caan B, Chlebowski RT, et al. Low-fat dietary pattern and risk of invasive breast cancer: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006;295:629-642.

10. Pierce JP, Natarajan L, Caan BJ, et al. Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the Women’s Healthy Eating and Living (WHEL) randomized trial. JAMA. 2007;298:289-298.

11. Chlebowski RT, Blackburn GL, Thomson CA, et al. Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women’s Intervention Nutrition Study (WINS). J Natl Cancer Inst. 2006;98:1767-1776.

12. PDQ Cancer Information Summary. Breast Cancer Prevention (PRQ) – Health Professional. Date last modified April 30, 2009. Available at: http://www.cancer.gov/cancertopics/pdq/prevention/breast/healthprofessional. Accessed May 12, 2009.

13. Hulka BS, Moorman PG. Breast cancer: hormones and other risk factors. Maturitas. 2001;38:103-113.

14. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288:321-333.

15. Ravdin PM, Cronin KA, Howlader N, et al. The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med. 2007;356:1670-1674.

16. Chlebowski RT, Kuller LH, Prentice RL, et al. WHI Investigators. Breast cancer after use of estrogen plus progestin in postmenopausal women. N Engl J Med. 2009;360:573-587.

17. Kosters JP, Gotzsche PC. Regular self-examination or clinical examination for early detection of breast cancer. Cochrane Database Syst Rev. 2003;(2):CD003373.-

18. Canadian Task Force on the Periodic Health Examination Ottawa, Canada: Health Canada; 1994:788-795 (reaffirmed by the Canadian Task Force on the Periodic Health Examination 1999, 2001).Available at: http://www.ctfphc.org/index/html. Accessed August 12, 2009.

19. Green BB, Taplin SH. Breast cancer screening controversies. J Am Board Fam Pract. 2003;16:233-241.

20. Berry DA, Cronin KA, Plevritis SK, et al. Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med. 2005;353:1784-1792.

21. Tice JA, Kerlikowske K. Screening and prevention of breast cancer in primary care. Prim Care. 2009;36:533-558.

22. US Preventive Services Task Force. Screening for breast cancer. Systematic evidence review update for the US Preventive Services Task Force. Available at: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=es74. Accessed September 2, 2010.

23. Pisano ED, Gatsonis C, Hendrick E, et al. Digital Mammographic Imaging Screening Trial (DMIST) Investigators Group. Diagnostic performance of digital versus film mammography for breast-cancer screening. N Engl J Med. 2005;353:1773-1783.

24. Saslow D, Boetes C, Burke W, et al. American Cancer Society Breast Cancer Advisory Group. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57:75-89.

25. Berg W, Blume J, Cormack J, et al. Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer. JAMA. 2008;299:2151-2163.

26. King M, Wieand S, Hale K, et al. Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA. 2001;286:2251-2256.

27. Vogel VG, Costantino JP, Wickerham DL, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA. 2006;295:2727-2741.

28. Berg AO. US Preventive Services Task Force. Chemoprevention of breast cancer: recommendations and rationale. Am J Nurs. 2003;103:107-113.

29. National Comprehensive Cancer Network. Breast cancer risk reduction. Clinical Practice Guidelines in Oncology-V.2.2010. Fort Washington, Pa: National Comprehensive Cancer Network; August 7, 2010. Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed September 17, 2010.

30. Sickles EA, Filly RA, Cllen PW. Benign breast lesions: ultrasound detection and diagnosis. Radiology. 1984;151:467.-

31. Beavers TB, Anderson BO, Bonaccio E, et al. NCCN clinical practice guidelines in oncology: breast cancer screening and diagnosis. J Natl Compr Canc Netw. 2009;7:1060-1096.

32. Mansel RE, Fallowfield L, Kissin M, et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC trial. J Natl Canc Inst. 2006;98:599-609

33. Lyman GH, Guiliano AE, Somerfield MR, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early- stage breast cancer. J Clin Oncol. 2005;23:7703-7720.

34. Turner N, Jones A. Management of breast cancer-Part II. BMJ. 2008;337:a540.-

35. Harris L, Fritsche H, Mennel R, et al:. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer J Clin Oncol. 2007;25:5287-5312.

36. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Herceptin adjuvant (HERA) Trial Study Team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659-1672.

37. PDQ Cancer Information Summary Breast cancer treatment– health professional. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/breast/HealthProfessional. Accessed May 12, 2009.

38. Anderson BL, Yang HC, Farrar WB, et al. Psychologic intervention improves survival for breast cancer patients: a randomized clinical trial. Cancer. 2008;113:3450-3458.

39. Jin Y, Desta Z, Stearns V, et al. CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst. 2005;97:30-39.

Evidence is insufficient for or against MRI screening for women with a personal history of breast cancer, atypical hyperplasia, or lobular carcinoma in situ, however, and neither breast ultrasound (which is generally used diagnostically, not for screening purposes) nor MRI has been shown to be helpful as a screening tool in women with <15% lifetime risk of developing breast cancer.^24,25

TABLE 2
Guidelines for breast cancer screening for women with average risk

Organization	Age (years)	Breast self-exam	Clinical breast exam	Mammography
American Cancer Society²	20-40	Optional	Every 3 y	NA
American Cancer Society²	>40	Encourages	Annually	Annually
American College of Obstetricians and Gynecologists³	40-49	Encourages	Annually	1-2 y
American College of Obstetricians and Gynecologists³	50-69	Encourages	Annually	Annually
Canadian Task force on Preventive Health Care¹⁸	40-49	Recommends against teaching	Insufficient evidence	Insufficient evidence
Canadian Task force on Preventive Health Care¹⁸	50-69	Recommends against teaching	1-2 y	1-2 y
National Comprehensive Cancer Network⁴	20-40	Encourages	1-3 y	NA
National Comprehensive Cancer Network⁴	>40	Encourages	Annually	Annually
US Preventive Services Task Force¹	40-49	Recommends against teaching	Insufficient evidence	Not routinely recommended
US Preventive Services Task Force¹	50-74	Recommends against teaching	Insufficient evidence	Every 2 y
NA, not addressed.

When to consider chemoprevention

For women like Carrie, who are at high risk of developing breast cancer, selective estrogen receptor modulator (SERM) therapy and surgical interventions may be options to consider. The Breast Cancer Prevention Trial demonstrated the efficacy of tamoxifen as a preventive agent. This landmark trial showed that for high-risk women older than 35, 5 years of tamoxifen therapy can reduce the incidence of invasive breast cancer by nearly 50%.²⁶

Women with the BRCA 1 or 2 mutation—all of whom should be offered genetic counseling—were included in the study. Tamoxifen reduced the incidence of breast cancer in BRCA 2 carriers by 62%, the researchers found, but did not reduce risk in carriers of the BRCA 1 gene. This is likely due to the high prevalence of estrogen receptor-negative breast cancers among BRCA 1 carriers.²⁶

More recently, the Study of Tamoxifen and Raloxifene (STAR) trial compared the efficacy of tamoxifen and raloxifene, a second-generation SERM, in high-risk postmenopausal women ages 35 and older. The drugs were found to be equally effective in reducing the risk of invasive breast cancer, but raloxifene had a better side effect profile, with a lower incidence of thromboembolism and cataracts. ²⁷

What the guidelines call for. In 2003, the USPSTF recommended that clinicians discuss chemoprevention with women at high risk for breast cancer and low risk for adverse effects of SERMs.²⁸

The most recent update to the NCCN breast cancer risk reduction guidelines recommends that clinicians offer tamoxifen to premenopausal women with a 5-year projected breast cancer risk ≥1.7% and offer tamoxifen or raloxifene to high-risk postmenopausal women.²⁹ It is worth noting, however, that SERMs can have significant adverse effects, including venous thromboembolism, stroke, cataracts, uterine malignancy, and hot flashes, while lifestyle modifications and the avoidance of HRT have few, if any, negative effects.

CASE After consultation with a genetic counselor, Carrie underwent testing for both the BRCA 1 and BRCA 2 mutations. She tested negative for both. She declined chemoprevention and prophylactic surgery, opting for enhanced screening with yearly mammography and MRI and lifestyle modification instead.

When a mass is found

For women ages 30 or older with palpable masses or solid masses ≥2 cm found on imaging, core needle biopsy is recommended.^30,31 Biopsy is indicated for women younger than 30 as well, if the mass is >2 cm or imaging is suspicious. In general, a needle biopsy read as benign is considered adequate for diagnostic purposes only if the lesion appeared benign on imaging.

For lesions shown to be cystic on imaging, recommendations for follow-up or additional testing are based on the characteristics of the cyst. For simple cysts, 2- to 4-month follow up for stability, followed by routine screening, is adequate.²¹ Additional evaluation of complex cysts is indicated, including aspiration for complicated cysts and biopsy for complex cysts. After aspiration, surgical excision of bloody aspirates or persistent masses is recommended.^30,31

Staging using the TNM system
The TNM (tumor, node, metastases) classification system is used for the staging of breast cancer:

T refers to the tumor type, size, and extent of local involvement
N describes regional lymph node involvement
M refers to distant metastases.

The TNM classifications are also grouped by stage (I through IV).,

Lumpectomy and sentinel node mapping with excision is the preferred method for staging of early-stage breast cancer without palpable lymphadenopathy—provided that the surgical team has documented experience with sentinel node biopsy.³² Sentinel node biopsy is preferred because of its safety, low (<10%) false negative rate, and decreased morbidity compared with full axillary dissection, although dissection is recommended for patients with more advanced cancer or a positive sentinel node.³² The comparative effects of sentinel node biopsy vs axillary node dissection on tumor recurrence and patient survival are not known.³³

FAST TRACK

Lumpectomy and sentinel node mapping with excision is the preferred method for staging of early-stage breast cancer without palpable lymph-adenopathy.