Male breast cancer remains underdiagnosed and, due to delays in diagnosis, is often also undertreated. The investigation and management of male breast cancer are based on studies on female patients. At present there is a need for further research into male breast cancer. The symptoms, diagnosis and treatment for male breast cancer are all similar to female breast cancer.
It is estimated that more than 90% of male breast cancers are oestrogen receptor-positive (ER+) and an even greater percentage are progesterone receptor-positive.Male breast cancer tissue may also be positive for androgen receptors.
- There are about 350 men diagnosed each year in the UK, compared with around 50,000 cases of breast cancer in women.
- Male breast cancer is diagnosed in 1% of cases of male breast enlargement. The incidence of male breast cancer has increased over a period of 25 years.
- The peak age for presentation of male breast cancer is >60 years.
- Increasing age.
- Up to one fifth of men with breast cancer have a first-degree relative similarly affected.
- Significantly more male breast cancers than female breast cancers arise with an underlying germline cancer predisposition and they display a vastly different penetrance compared with females.
- The genophenotypical association with BRCA1 present in female breast cancer is not observed in male breast cancer.
- Male breast cancer is more commonly associated with BRCA2 mutations.Most population-based studies show that 10-15% of men with breast cancer carry a mutation in BRCA2.
- Exogenous oestrogen.
- Klinefelter's syndrome (47XXY) - low testosterone and increased gonadotrophins. Breast cancer is up to 50 times more frequent in this group.
- Chronic liver conditions.
- Pituitary adenomas leading to hyperprolactinaemia (associated with bilateral breast cancer).
- Gynaecomastia does not lead to an increased risk.
- Alcohol consumption.
- Chest irradiation.
Male breast cancer tends to present at a later stage and at a higher stage; it is more often ER+ and progesterone receptor-positive and it is less often HER2 receptor-positive.
- Painless lump.
- Pain (rarely).
- Nipple inversion or discharge,
- Skin changes - eg, ulceration.
- Gynaecomastia - very rarely (see box, below).
- Skin change.
- Palpable mass.
- Palpable lymph nodes.
Red flags which increase suspicion of breast cancer in men who present with gynaecomastia
- Unilateral enlargement.
- Hard or irregular breast tissue.
- Rapidly enlarging.
- Recent onset.
- Fixed mass.
- Nipple or skin abnormalities.
- Painful breast.
- Axillary lymphadenopathy.
Refer to a local one-stop breast clinic if there is any doubt or any suspicion of breast cancer.
- Imaging: mammography or ultrasonography.
- Tissue: fine-needle aspiration cytology (FNAC) or either core or open biopsy. Biopsy is preferred, as malignant cells on FNAC may be a ductal carcinoma in situ rather than more invasive disease.
Infiltrating ductal cancer is the most common tumour type. Inflammatory carcinoma and Paget's disease of the breast have also been seen in men. Lymph node involvement and the pattern of metastatic spread are similar to those found in female breast cancer.
The tumour, nodes, metastases (TNM) staging system for male breast cancer is identical to the staging system for female breast cancer:
- Stage 0: around 10% of male breast cancer is ductal carcinoma in situ.
- Stage I: tumour up to 2 cms in diameter and no lymph node involvement or metastasis.
- Stage II: tumour between 2 and 5 cms in diameter or there is spread to the axillary lymph nodes on the same side and the nodes are not adherent.
- Stage IIIA: tumour is over 5 cms in diameter or the nodes are adherent.
- Stage IIIB: invasive breast cancer in which a tumour of any size has spread to the breast skin, chest wall or internal mammary lymph nodes and includes inflammatory breast cancer with peau d'orange.
- Stage IV: spread beyond the breast, axilla and internal mammary nodes. It may have spread to supraclavicular nodes, bone, liver, lung or brain.
NB: there are limited data regarding optimal treatment and follow-up strategies for those men with breast cancer.Currently, most follow-up guidelines are drawn from the vast literature on female breast cancer, despite the fact that male breast cancer has unique biological characteristics.
- Most men are currently treated with modified radical mastectomy or simple mastectomy. This may be associated with axillary lymph node sampling and clearance. Sentinel node biopsy is being used in clinically node-negative disease. The patient may need skin flap or nipple reconstruction.
- There is evidence that breast-conserving therapy for early-stage male breast cancer results in comparable survival compared with more invasive surgery.
- Radical mastectomy has now been replaced by less invasive procedures such as modified radical or simple mastectomy. Axillary node dissection may be performed but may cause complications such as lymphoedema and paraesthesia.
Adjuvant hormone therapy
- Treatment guidelines for male breast cancer are derived from studies on the treatment of female breast cancer and are based on molecular and clinical characteristics, such as hormone receptor positivity. For ER+ breast cancers, the standard of care usually includes selective oestrogen receptor modulators, aromatase inhibitors, and pure anti-oestrogens. However, in contrast to female ER+ breast cancers, there is less known about the optimal treatment for male ER+ breast cancer.
- Tamoxifen is usually the standard hormonal agent used in men.
- Although endocrine therapy is an important treatment modality, men often encounter challenges with toxicity and adherence.
- Adjuvant local radiotherapy or post-mastectomy. Regional lymph nodes may also be treated with radiotherapy.
- Regimens using cyclophosphamide, methotrexate, doxorubicin, 5-fluorouracil and taxanes (paclitaxel, docetaxel) have been used with improved survival rates.
- For metastatic or more advanced disease, hormonal therapies are the main treatments used. Chemotherapy has been used as a second line (and for palliative purposes also).
- Other therapies that have been used include:
- Gonadal ablation in metastatic male breast cancer.
- Adjuvant aromatase inhibitors - eg, anastrozole.
- Men with breast cancer have a poorer disease-free survival and overall survival when compared with women.
- Men also have a higher risk of contralateral tumours and second primaries compared to women.
- Five-year survival depends on the stage of the disease.
- The risk of carcinoma in the other breast is also increased.
- Man with breast cancer have an increased risk of certain non-breast second malignancies (including prostate, lung, colorectal and oesophageal cancers).
Further reading and references
Yu XF, Yang HJ, Yu Y, et al; A Prognostic Analysis of Male Breast Cancer (MBC) Compared with Post-Menopausal Female Breast Cancer (FBC). PLoS One. 2015 Aug 2710(8):e0136670. doi: 10.1371/journal.pone.0136670. eCollection 2015.
Breast cancer incidence in males; Cancer Research UK
Deb S, Lakhani SR, Ottini L, et al; The cancer genetics and pathology of male breast cancer. Histopathology. 2016 Jan68(1):110-8. doi: 10.1111/his.12862.
Ferzoco RM, Ruddy KJ; The Epidemiology of Male Breast Cancer. Curr Oncol Rep. 2016 Jan18(1):1. doi: 10.1007/s11912-015-0487-4.
Ferzoco RM, Ruddy KJ; Optimal delivery of male breast cancer follow-up care: improving outcomes. Breast Cancer (Dove Med Press). 2015 Nov 237:371-9. doi: 10.2147/BCTT.S75630. eCollection 2015.
Grundy A, Harris SA, Demers PA, et al; Occupational exposure to magnetic fields and breast cancer among Canadian men. Cancer Med. 2016 Jan 21. doi: 10.1002/cam4.581.
Humphries MP, Jordan VC, Speirs V; Obesity and male breast cancer: provocative parallels? BMC Med. 2015 Jun 413:134. doi: 10.1186/s12916-015-0380-x.
Gies I, Unuane D, Velkeniers B, et al; Management of Klinefelter syndrome during transition. Eur J Endocrinol. 2014 Aug171(2):R67-77. doi: 10.1530/EJE-14-0213. Epub 2014 May 6.
Zaenger D, Rabatic BM, Dasher B, et al; Is Breast Conserving Therapy a Safe Modality for Early-Stage Male Breast Cancer? Clin Breast Cancer. 2015 Nov 17. pii: S1526-8209(15)00278-5. doi: 10.1016/j.clbc.2015.11.005.
Zhu J, Davis CT, Silberman S, et al; A role for the androgen receptor in the treatment of male breast cancer. Crit Rev Oncol Hematol. 2016 Feb98:358-63. doi: 10.1016/j.critrevonc.2015.11.013. Epub 2015 Nov 26.
Bradley KL, Tyldesley S, Speers CH, et al; Contemporary systemic therapy for male breast cancer. Clin Breast Cancer. 2014 Feb14(1):31-9. doi: 10.1016/j.clbc.2013.09.001. Epub 2013 Oct 1.
Motofei IG, Rowland DL, Popa F, et al; A Pilot Study on Tamoxifen Sexual Side Effects and Hand Preference in Male Breast Cancer. Arch Sex Behav. 2015 Aug44(6):1589-94. doi: 10.1007/s10508-015-0530-4. Epub 2015 Jun 25.
Iorfida M, Bagnardi V, Rotmensz N, et al; Outcome of male breast cancer: a matched single-institution series. Clin Breast Cancer. 2014 Oct14(5):371-7. doi: 10.1016/j.clbc.2014.02.008. Epub 2014 Mar 1.
Cutuli B, Le-Nir CC, Serin D, et al; Male breast cancer. Evolution of treatment and prognostic factors. Analysis of 489 cases. Crit Rev Oncol Hematol. 2010 Mar73(3):246-54. doi: 10.1016/j.critrevonc.2009.04.002. Epub 2009 May 12.