Applied Evidence

Breast cancer prevention and Tx: An evidence-based guide

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

When to begin screening mammography may be the latest controversy, but it’s not the only uncertainty regarding breast health and cancer care. We’ve culled the latest evidence to help you do what’s best.

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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.

PRACTICE RECOMMENDATIONS

• Offer screening magnetic resonance imaging (MRI) to patients with a known BRCA 1 or 2 mutation, a strong family history of breast cancer, or a lifetime risk of breast cancer >20% to 25%. B

• For early-stage breast cancer, lumpectomy and sentinel node mapping with excision is the preferred method for staging. A

• Monitor patients receiving tamoxifen for signs and symptoms of venous thromboembolism, cataracts, and uterine malignancy, and patients on aromatase inhibitors for the development of osteoporosis. A

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

Late last year, the US Preventive Services Task Force (USPSTF) sparked a nationwide controversy when it announced that it was recommending against routine screening mammography for women younger than age 50.¹ Indeed, that’s a recommendation that many other organizations, including the American Cancer Society (ACS),² the American College of Obstetricians and Gynecologists (ACOG),³ and the National Comprehensive Cancer Network (NCCN),⁴ disagree with. But the age at which women should begin routine mammography isn’t the only controversial question. Experts disagree on the benefits of breast self-examination, the optimal frequency of clinical breast exams, and the use of digital mammography—among other issues. This evidence-based review can help you cut through the confusion.

CASE Carrie, a 39-year-old woman who has never been pregnant, comes in for an annual Pap smear and gynecologic exam. She has a negative past medical history, but a positive family history for breast cancer—both her mother and 1 of her sisters had the disease. How would you assess Carrie’s risk of breast cancer, and what preventive measures would you recommend?

Use this predictive model to pinpoint your patient’s risk

When making decisions regarding primary prevention of and screening for breast cancer, an accurate assessment of risk is critical. Many predictive models have been developed with that in mind. The most widely studied, the Gail model, incorporates a number of important risk factors (TABLE 1), including age; race; family history; reproductive factors such as age of menarche, menopause, and first childbirth; and previous history of breast biopsy and atypical findings, to calculate a woman’s 5-year risk.⁵

A risk calculator (the Breast Cancer Risk Assessment Tool) based on the Gail model is available on the National Cancer Institute’s Web site, at http://www.cancer.gov/bcrisktool. Generally, a score ≥1.66%,⁵ which indicates that a patient has at least a 1.66% chance of developing breast cancer over the next 5 years, is considered high risk.^6,7

CASE Carrie’s 2 first-degree relatives affected by breast cancer and her nulliparous status place her at increased risk. Further questioning reveals a particularly strong family history, as both relatives were diagnosed before the age of 50 (her mom at 45 years of age and her sister, at 39). Carrie’s 5-year risk is 1.8%.

TABLE 1
Risk factors for breast cancer^5,29

Age (>50 years) Sex Ethnicity* Family history (≥1 first-degree relative diagnosed with breast cancer, particularly if diagnosed at <50 years of age) Early menarche (<12 years) Late menopause (>55 years) Late age at first full-term pregnancy (>30 years) Nulliparity Breast density History of breast biopsies Atypical hyperplasia or LCIS on prior biopsy History of radiation to chest wall Lack of breastfeeding Physical inactivity Obesity Alcohol use^† Exogenous hormones (HRT)
*African American and Caucasian women are at higher risk compared with Asian, Hispanic, and Native American women.
^†1 drink/day results in minimal increase in risk; 2-5 drinks/day result in 1.5 increased risk compared with nondrinkers.
HRT, hormone replacement therapy; LCIS, lobular carcinoma in situ.

All women can benefit from these preventive measures

As primary care physicians, we have a responsibility to stress lifestyle modification as the mainstay of breast cancer prevention. Whether or not a woman is at high risk, advise her that maintaining a normal weight, exercising vigorously, limiting alcohol consumption, and breastfeeding are evidence-based methods of primary prevention. Diets low in fat and high in fiber may be associated with a lower risk of invasive breast cancer, but there is no conclusive evidence to support specific dietary interventions to reduce the risk.^8-11 Nor has a link between active or passive smoking, antioxidants, or fruit and vegetable intake been firmly established.¹²

There is a clear association between prolonged estrogen exposure and breast cancer, however. Many reproductive factors, such as early menarche, late menopause, later age at time of first full-term pregnancy, and nulliparity, increase a woman’s exposure to endogenous estrogen—and her risk of developing breast cancer.^12,13

Exposure to exogenous estrogen is also linked to the development of breast cancer. In 2002, the Women’s Health Initiative (WHI) was stopped early after a report was released stating that the risks of hormone replacement therapy (HRT)—a higher incidence of cardiovascular events, stroke, and venous thromboembolism, as well as breast cancer—outweighed the benefits.¹⁴ Subsequent analyses have found a relationship between the declining incidence of breast cancer and the marked decrease in HRT use prompted by the WHI report. While causality has not been firmly established, multiple studies strongly suggest it.^15,16