This understudied male breast cancer accounts for around one percent of all breast cancers worldwide.
Breast cancer is the most common cancer in women, but men can get it, too. Male breast cancer is uncommon and accounts for approximately one percent of all breast cancer diagnosis. The low incidence of breast cancer in males is due to the relatively small amount of breast tissue in males, hence it is often understudied.
Most of the published literature studies small cohort of patients from different institutions and treatment recommendations usually follow the guidelines of postmenopausal female breast cancer. Most clinical trials on breast cancer also do not include male breast cancer patients due to the small number. Recently, there have been some reports on male breast cancer pertaining to its biology, treatment and prognosis.
Epidemiology and risk factors for breast cancer in men
In Singapore, specifically the National Cancer Centre Singapore, there were only 32 cases of male breast cancer for the period of 2010 to 2017. This is very low as compared to an average of 1,540 cases of female breast cancers diagnosed annually during the same period.
According to the Singapore Cancer Registry, for the period of 2011 to 2015, breast cancer was the most frequent cancer in females and the five year incidence of female breast cancer was around 9,634 cases during that period.1 Increase in male breast cancer incidence was shown in the United States as exemplified from the data from SEER. Age-adjusted rate of male breast cancer has increased from 0.85 cases per 100,000 cases in 1975 to 1.45 cases per 100,000 in 2011.2 The lifetime risk of male breast cancer is very low approximately at 1:1000, as compared to 1:8 for females in U.S. and 1:14 for females in Singapore.
The risk factors include old age, family history of breast cancer, and presence of BRCA 1 and BRCA 2 mutations (usually the latter). Men who carry BRCA 2 mutation have an approximate 6.5 percent cumulative risk for breast cancer by age 70, but this risk reduces to 1.2 percent in those with BRCA 1. The risk of male breast cancer in mutation carriers is still substantially lower as compared to females with mutations.3
The recommendations from the National Comprehensive Cancer Network (NCCN) guidelines for men with BRCA 1/2 mutations are breast self-examination training and education starting at age 35, monthly and yearly clinical breast examination starting from the age of 35, with prostate cancer screening at the age of 45. The guidelines did not recommend any screening investigations like mammography for the breast in male mutation carriers.4
Radiation and oestrogen exposure and oestrogen/testosterone imbalance are other risk factors. The presence of gynecomastia increases the risk of breast cancer if it is associated with oestrogen excess. Otherwise, gynecomastia does not increase the risk of breast cancer.
Majority of the male breast cancer patients present with painless and progressive enlarging breast lump in the retroareolar region (75 percent). Other presentations include nipple retraction, nipple discharge, ulceration, bleeding or pain. Physical examination usually reveals a hard lump in the retroareolar region and may be fixed to overlying skin or underlying muscle. Some patients may present with enlarged axillary nodes. Differential diagnosis includes gynecomastia, abscess, secondary metastasis, lipoma or sarcoma.3
The assessment of symptomatic men is similar to women. The triple assessment includes history taking and physical examination, radiological investigations (using mammogram and ultrasound) and biopsy for histological correlation. The characteristic feature on mammogram is retroareolar mass with irregular or spiculated edges. Ultrasound may also show irregular retroareolar mass with increased vascularity. Histological diagnosis can be achieved by core biopsy. When the diagnosis of cancer is confirmed, the disease can be further staged with computed tomography of the chest, abdomen, and a bone scan.
Histology of most of the symptomatic cancers is invasive ductal carcinoma. Lobular cancers accounts for two percent of the male breast cancers while ductal carcinoma in situ (DCIS) constitutes 10 percent of cancers. More than 90 percent of the invasive cancers are oestrogen and progesterone receptors positive compared to 60 to 70 percent in female cancers. They are usually negative for human epidermal growth factor receptor. The international male breast cancer program reported HER2 positivity in only nine percent of cases. The same study also evaluated subtypes of breast cancer with immunohistochemistry, 42 percent were luminal A like, 49 percent were luminal B like and HER2 negative, nine percent HER2 positive and less than one percent was triple negative.5
The management of male breast cancer involves a multidisciplinary team of breast care specialists working together towards a common goal of improving breast cancer treatment outcome and survival similar to female breast cancer.
In early stage breast cancers, the treatment is surgery followed by adjuvant therapy. The surgical management for male breast cancer is simple mastectomy with sentinel lymph node biopsy and axillary clearance if sentinel nodes are positive for malignancy. For majority of the patients, breast conserving surgery is not possible due to the small breast volume.
The adjuvant treatment recommendations are similar to female breast cancer. Genomic tests like the 21 Gene Recurrence Score can be used in male breast cancer patients to assess the prognosis and the likelihood that chemotherapy will be beneficial.6
Since the cancer is usually hormone receptor positive, which means it needs estrogen and/or progesterone to grow, endocrine therapy is the usual treatment. Tamoxifen is the main drug of choice, it works by attaching to the hormone receptor in the cancer cell, blocking estrogen from attaching to the receptor. This slows or stops the growth of the tumour by preventing the cancer cells from accessing the hormones they need to grow. Tamoxifen is often taken for 5 to 10 years, but the treatment duration would depend on the risk of recurrence and side effects. In males, aromatase inhibitors are not as effective as Tamoxifen due to the lack of complete oestradiol suppression.
The management of metastatic male breast cancer is also generally same as that in women. The efficacy of hormonal treatment in this group has not been studied in detail but there are studies in the use of Tamoxifen and fluvestrant with aromatase inhibitors and the latter has showed improvement in response.
The use of mTOR inhibitors and CDK inhibitors as a combination treatment with endocrine therapy can be considered in metastatic disease and the indications are similar to that in female breast cancer.3
Both male and female breast cancers are staged according to the AJCC staging system. Size and grade of the tumour, involvement of the lymph nodes and presence of metastasis are the most important prognostic factors.
The follow up recommendations for male breast cancer patients are the same as females. That means a recommended six-monthly clinical examination and yearly ultrasound of the opposite breast. Mammogram for screening of the opposite breast is not recommended routinely, since the incidence of second primary tumour is low. Bone mineral density should be monitored every two years in patients who are on GnRH analogues.
Male breast cancer is very rare, but it should be excluded in patients presenting with unilateral breast lumps. Suspicion should be increased if the masses are painless and non-tender. Genetic tests should be considered for all male breast cancer patients and family members should be screened appropriately.
- Singapore Cancer Registry, Annual Registry Report 2015, National Registry of Diseases Office.
- Surveillance, Epidemiology and End Results Program. SEER cancer statistics review (CSR)
- 1975-2014, April 2,2018 (https:\\seer.cancer.gov/csr/1975_2014/)
- Giordano SH. Breast cancer in men. N Eng J Med. 2018;378:2311-20
- NCCN Clinical Practice Guidelines in Oncology, Breast Cancer Screening and Diagnosis Version 3.2018.
- Massarweh SA, Sledge GW, Miller DP, McCullough D, Petkov VI, Shak S. Molecular characterisation and mortality from breast cancer in men. J Clin Oncol. 2018;36:1396-404.
- Turashvili G, Gonzalez-Loperena M, Brogi E, Dickler M, Norton L,Morrow M, Wen HY. The 21 Gene Recurrence Score in Male Breast Cancer. Ann Surg Oncol. 2018 Jun:25(6):1530-35
Dr. Preetha Madhukumar is a senior consultant surgical oncologist at the National Cancer Centre Singapore and the SingHealth Duke-NUS Breast Centre. She is also assistant professor at the Duke-NUS Medical School, Singapore.