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Breast Cancer in Men

The incidence of breast cancer in men has been increasing.

Breast cancer predominately affects women, however, approximately 1% of the breast cancers diagnosed in the United States and the United Kingdom are in men.1,2 The incidence of breast cancer in men has been increasing, and between 2008 and 2012, the rate was 1.3 cases per 100,000 men.3 To put that in perspective, the incidence of breast cancer in women is 122.2 per 100,000 women, prostate cancer occurs in 105.3 per 100,000 men, and lung cancer occurs in 71.6 per 100,000 men and women.4 ,5

Breast cancer in men is treated and managed similarly to breast cancer in postmenopausal women,6 based on data from studies of women. Studies of breast cancer in men are limited. Men are diagnosed at a later age than women, with a median age at diagnosis of 68 years vs. 61 years for women.1,3 Many risk factors for breast cancer in men are comparable to those in postmenopausal women (see table).

Clinical Presentation
Signs and symptoms of breast cancer in men are similar to that in women, including lumps or swelling; skin dimpling or puckering; nipple retraction; redness or scaling of the nipple or breast skin; and nipple discharge.1 However, men usually present with a painless, firm, subareolar mass that involves the nipple; axillary adenopathy occurs in up to 50% of cases.7-9

Unfortunately, men tend to be diagnosed at a later, more advanced stage of disease. This may be because men and/or their healthcare providers are not aware that men can develop breast cancer; thus they ignore the symptoms or assume it is a nonmalignant condition.1,9 The differential diagnoses for palpable breast masses in men include gynecomastia, pseudogynecosmastia, infections/abscesses, lipomas, pseudoangiomatous stromal hyperplasia, granular cell tumors, fibromatosis or metastasis from another type of cancer.10

Diagnostic Evaluation and Staging
Men who present with breast masses or symptoms should be evaluated in the same manner as women, with mammogram and biopsy. Mammogram findings are abnormal in 80% to 90% of breast cancers in men, with sensitivity at 92% and specificity at 90%.11 Ultrasound can be a useful adjunct to evaluate axillary nodal status.

Breast cancer usually occurs as a spiculated mass and may be associated with microcalcifications on mammogram. However, microcalcifications are less common in men.12 Fine-needle aspiration may be used to diagnose the presence of malignancy, but core needle biopsy is preferred because it provides adequate tissue for determining the type of disease (invasive vs. noninvasive) and hormone receptor status.13

The most common type of breast cancer affecting men and women is invasive ductal carcinoma (80% to 95% of breast cancers in men), followed by ductal carcinoma in situ (DCIS; 5% to 10% of male cases).3,8,9 Invasive lobular carcinoma, medullary carcinoma and papilloma are much rarer.8

The majority of breast cancers in men are estrogen receptor positive, and few are progesterone receptor-positive.9,12,16 Breast cancers in men are less likely to overexpress HER 2, a proto-oncogene that promotes breast cancer cells.16

The staging system for men is the same as in women and is based on the TNM staging system developed by the American Joint Committee on Cancer and the Union for International Cancer Control: T = Tumor Size, N = Number of nodes involved with disease and M = Evidence of metastatic disease. The extent of disease can be determined by abdominal CT, chest x-ray, bone scan and laboratory studies, if clinically appropriate.9,16

Breast Cancer in MenTreatment
Because of the low incidence of breast cancer in men, few randomized clinical studies are available to guide treatment.9 Breast cancer in men is managed similarly to breast cancer in postmenopausal women,9 based on data from studies of women. Treatment for breast cancer in men may include surgery, chemotherapy, radiation and hormone therapy, if appropriate. The most common surgical procedure in men (70%) is modified radical mastectomy (entire breast removal including skin, areola, nipple and axillary nodes).17 Breast-conserving surgery (lumpectomy) is performed less often in men (1% to 13%).17 Sentinel lymph node (the first few nodes into which a tumor drains) biopsies are commonly performed, with progression to full axillary node dissection if the sentinel node(s) are positive for metastases.

Limited data exist about the effectiveness of chemotherapy in men, however, strong data support use in women and most healthcare providers follow similar guidelines for men and women.16 Chemotherapy may not be as beneficial in men. The majority of tumors are estrogen receptor positive, patients tend to be older, and multiple age-related comorbidities tend to be present.8 Chemotherapy benefits are more apparent in hormone receptor negative breast cancer, high-risk groups, and in younger men.8 As in women, men who have advanced or inflammatory disease are treated with chemotherapy followed by surgery due to higher rates of clinical response.8

In both men and women, the primary role of post-mastectomy radiation is to maximize local control. Few studies of post-mastectomy radiation in men have been performed; general recommendations are to provide the same treatment as for women with axillary node involvement.18

Hormone therapy is the first-line therapy for estrogen or progesterone receptor-positive breast cancer in women. The ATLAS Trial in women recommended the use of tamoxifen for 10 years, based on tumor characteristics. If a patient is at low risk for recurrence, the decision to continue treatment with tamoxifen for greater than 5 years should be based on individual concerns about side effects.19 Tamoxifen is the standard therapy in men with hormone receptor-positive breast cancers, for up to 10 years. This reduces recurrence risk by 50%.2 Side effects include hot flashes, decreased libido, impotence, and deep vein thrombosis.16

In postmenopausal women, aromatase inhibitors are now the drug of choice, due to the lower risk of recurrence compared to tamoxifen.20 Although breast cancer in men is considered most like that of postmenopausal women with hormone receptor-positive disease, the hormonal environment in men differs from that in women, and hormone usage may not be the same in men. Preclinical data suggest that the aromatase inhibitors may be less effective in men.21 Other studies show that long-term efficacy and safety of aromatase inhibitors are not established in men; therefore, use is not recommended.22

SEE ALSO: Breast Cancer Awareness Month

Prognosis
Five-year survival rates for men with breast cancer range from 20% to 100%, depending on stage at diagnosis.1 In general, men are often diagnosed with more advanced breast cancer than women. This may be due to women being routinely screened or decreased awareness and detection in men.8 Prognostic factors are similar to women: age, tumor size, stage and lymph node involvement.23

Black men have a worse prognosis and are significantly more likely to be diagnosed with advanced stage cancer and larger tumors; they have a threefold increased risk of dying compared to white men.24 The prognosis for men is similar to that of women with similar stage disease.23

Survivorship/Surveillance
Survivorship care and surveillance are fairly standardized for women. The best strategy for follow-up in men is unclear. Yearly mammograms are standard procedure in women after breast cancer treatment, but there is no reported benefit to screening of the contralateral breast in men. Consideration for mammographic surveillance should be given to those with risks associated with younger age, BRCA carriers, Kleinfelter or testicular disease, or strong family history of disease. National guidelines support clinical breast examination on a yearly basis, for both men and women.6

More Research Needed
The International Programme of Male Breast Cancer International Program in Men is working to develop treatments and improve outcomes for men with breast cancer.25 It is crucial to determine the role of genomics in male breast cancer, and guidelines specific to breast cancer in men are needed.

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References
1. American Cancer Society. Breast cancer in men. http://www.cancer.org/cancer/breastcancerinmen/detailedguide/index

2. White J, et al. Male breast carcinoma: increased awareness needed. Breast Cancer Res. 2011;13(5):219.

3. Breast Cancer Facts and Figures 2015-2016. http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-046381.pdf

4. Centers for Disease Control and Prevention. Division of Cancer Prevention and Control. Cancer Among Men. http://www.cdc.gov/cancer/dcpc/data/men.html

5. Centers for Disease Control and Prevention. Cancer Among Women. http://www.cdc.gov/cancer/dcpc/data/women.htm

6. Kiluk JV, et al. Male breast cancer: management and follow-up recommendations. Breast J. 2011;17(5):503-509.

7. Giordano SH, et al. Breast cancer in men. Ann Intern Med. 2002;137(8):678-687.

8. Korde LA, et al. Multidisciplinary meeting on male breast cancer: summary and research recommendations. J Clin Oncol. 2010;28(12):2114-2122.

9. Rudlowski C. Male breast cancer. Breast Care. 2008;3(3):183-189.

10. Lattin GE Jr, et al. From the radiologic pathology archives: diseases of the male breast: radiologic-pathologic correlation. Radiographics. 2013;33(2):461-489.

11. Evans GF, et al. The diagnostic accuracy of mammography in the evaluation of male breast disease. Am J Surg. 2001;181(2):96-100.

12. Chen L, et al. Imaging characteristics of malignant lesions of the male breast. Radiographics. 1999;19:559-568.

13. Moschetta M, et al. Comparison between fine needle aspiration cytology (FTAC) and core needle biopsy (CNB) in the diagnosis of breast lesions. G Chir. 2014; 35(7-8):171-176.

14. Clark JL, et al. Prognostic variable in male breast cancer. Am Surg. 2000;66(5):502-511.

15. Cutuli B, et al. Ductal carcinoma in situ of the male breast. Analysis of 31 cases. Eur J Cancer. 1997;33(1):35-38.

16. Giordano S. A review of the diagnosis and management of male breast cancer. Oncologist. 2005;10(7):471-479.

17. Cutuli B. Strategies in treating male breast cancer. Expert Opin Pharmacother. 2007;8(2):193-202.

18. Chakavarathy A, Kim CR. Post mastectomy radiation in male breast cancer. Radiother Oncol. 2002;65(2):99-103.

19. Davies C, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomized trial. Lancet. 2013;381(9869):805-816.

20. Early Breast Cancer Trialist Collaborative Group (EBCTG). Aromatase inhibitors vs. tamoxifen in early breast cancer: patient level meta-analysis of the randomized trials. Lancet. 2015;386(1001):1341-1352.

21. Giordano SH, Hortobagyi GN. Leuprolide acetate plus aromatase inhibitor for male breast cancer. J Clin Oncol. 2006;24(21):e42-e43.

22. de Ronde W, de Jong FH. Aromatase inhibitors in men: effects and therapeutic options. Reprod Biol Endocrinol. 2011;9:93.

23. Giordano SH, et al. Breast carcinoma in men: A population based study. Cancer. 2004;101(1):51-57.

24. Crew KD, et al. Racial disparities in treatment and survival in men with breast cancer. J Clin Oncol. 2007;25(9):1089-1098.

25. EORTC.The Future of Cancer Therapy. http://www.eortc.org/news/eortc-big-and-nabcg-follow-international-retrospective-male-breast-cancer-program -with-prospective-study

Betty Harris is an advanced practice nurse in the Department of Health Services Research at MD Anderson Cancer Center in Houston. Faith Strunk is an advanced practice nurse at MD Anderson Cancer Center and an assistant professor at the UTHealth School of Nursing.


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