Male breast cancer
Men get breast cancer too, usually a hormone-sensitive kind found as a lump near the nipple. It is treated much as in women, with surgery, radiotherapy and tamoxifen, and inherited BRCA2 mutations are found often enough that every man diagnosed is offered genetic testing. The main fix under way is including men in trials so their care stops being borrowed from women.
Overview
Male breast cancer is almost always invasive ductal carcinoma, oestrogen-receptor positive (in the large majority) and HER2-negative; lobular carcinoma is rare because men lack terminal lobules, and triple-negative disease is uncommon. Germline BRCA2 mutations are the strongest hereditary factor (BRCA1 less so), and testing is recommended for every man with breast cancer regardless of age or family history; other risks are Klinefelter syndrome, oestrogen exposure, radiation, obesity and liver disease. Men present later and with higher stage than women because there is no screening and awareness is low, and the tumour sits close to the skin and nipple.
Treatment follows the female algorithm with adjustments. Mastectomy is usual because of tumour position, though breast-conserving surgery is feasible in some; sentinel node biopsy, radiotherapy and chemotherapy indications mirror women's. Endocrine therapy differs: tamoxifen is the preferred adjuvant agent, because aromatase inhibitors used alone in men raise testosterone and oestradiol through feedback and appear less effective, so if used they should be combined with a GnRH agonist. CDK4/6 inhibitors, HER2-directed therapy and PARP inhibitors for germline BRCA carriers are used in men on the basis of extrapolation and small cohorts. The EORTC 10085 / International Male Breast Cancer Program (Ann Oncol 2018) was the largest characterisation effort, and the FDA's 2020 guidance 'Male Breast Cancer: Developing Drugs for Treatment' instructs sponsors to include men in breast cancer trials rather than excluding them by default.
Open problems are adjuvant endocrine adherence and side effects in men, the biology of male-specific ER-positive disease, and the paucity of prospective data.
State of the art today
- Guidelines (ASCO 2020, NCCN) now state explicitly how to treat men rather than leaving it to inference from women's trials.
- Universal germline testing in men with breast cancer finds BRCA2 mutations often and opens PARP inhibitor therapy and family cascade testing.
- The FDA's 2020 guidance pushes sponsors to include men in breast cancer trials; labels for CDK4/6 inhibitors and other agents increasingly cover men.
- The International Male Breast Cancer Program built the first large prospective registry, showing high ER positivity, low HER2 rates and under-treatment with adjuvant endocrine therapy.
Where it starts and where it drains
Most cancers start in the ducts and drain first to the axillary nodes, which is why the armpit is checked and a sentinel node is sampled.
- Ducts (most cancers start here)Invasive ductal carcinoma, ER-positive / HER2-negative (most) · HER2-positive (minority) · Ductal carcinoma in situ (often papillary)
- Lobules (lobular carcinoma)
- Upper outer quadrant (commonest site)
- Nipple-areola
- axillary level I
- axillary level II-III
- internal mammary
- supraclavicular
Same organ: Triple-negative breast cancer (TNBC), HR-positive / HER2-negative breast cancer, HER2-positive breast cancer, Ductal carcinoma in situ (DCIS)
About one in a hundred breast cancers occurs in a man; the lifetime risk is roughly one in a thousand men, higher with a BRCA2 mutation, Klinefelter syndrome or a strong family history (SEER; NCI).
- Mammography & tomosynthesisStandard of care
- AI in radiologyEstablished
- cfDNA fragmentomicsEstablished
- Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)Standard of care
- DNA methylation profilingEstablished
- HCC surveillance in cirrhosis (ultrasound + AFP)Standard of care
- A 28-day national pathway for people with a positive multi-cancer blood test
- A breath test to rule out cancer in people with vague symptoms
- A cancer blood test for older people arriving at A&E with unexplained symptoms
- A legislated, publicly reported 28-day standard from urgent referral to diagnosis
- A live national dashboard of stage at diagnosis as the scorecard for early detection
- A single 'cancer check at 60' appointment bundling all screening tests
Background: Alpha-fetoprotein (AFP), Barrett's oesophagus, CA 19-9, Early detection, Faecal immunochemical test (FIT). Also on OnCo: Symptoms and red flags · Early detection roadmap.
Where the cases are
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
Mastectomy (or breast conservation where feasible) with sentinel node biopsy; adjuvant radiotherapy by the same criteria as women; chemotherapy and HER2-directed therapy as indicated.
Tamoxifen for five to ten years; aromatase inhibitor only with GnRH agonist suppression if tamoxifen is contraindicated.
Endocrine therapy (tamoxifen, or aromatase inhibitor or fulvestrant with GnRH agonist) with a CDK4/6 inhibitor by extrapolation; chemotherapy for visceral crisis.
PARP inhibitor (olaparib adjuvant per OlympiA; olaparib or talazoparib for metastatic disease) and cascade testing of relatives.
Subtypes & biomarkers
top- Invasive ductal carcinoma, ER-positive / HER2-negative (most)
- HER2-positive (minority)
- Triple-negative (rare)
- Ductal carcinoma in situ (often papillary)
- Hereditary (BRCA2, BRCA1, PALB2, CHEK2)
- ER, PR, HER2 (as in women)
- Germline BRCA1/2 and multigene panel (recommended for all men with breast cancer)
- Ki-67 and genomic assays (Oncotype DX validated mainly in women)
- Nodal status
- Testosterone and oestradiol if aromatase inhibitors are considered
Target prevalence in this cancer
- 1927First large series of male breast cancer
Wainwright's review of published cases.
- 1976Tamoxifen shown active in men
Early case series establish tamoxifen as the endocrine backbone.
- 1995BRCA2 linked to male breast cancer
Wooster and colleagues identify BRCA2; male breast cancer is one of its hallmark phenotypes.
- 2018International Male Breast Cancer Program (EORTC 10085)
Cardoso and colleagues (Ann Oncol 2018) characterise 1,483 men treated 1990 to 2010.
- 2020ASCO guideline and FDA guidance
First ASCO guideline on male breast cancer; FDA guidance on including men in breast cancer drug development.
- 2021OlympiA: adjuvant olaparib for germline BRCA carriers
Trial included men.
Open problems, and what is being done about each
Men are still under-enrolled in breast cancer trials; regulatory guidance and label harmonisation are the response.
Aromatase inhibitor efficacy and the need for GnRH co-treatment rest on small studies; registries are collecting outcomes.
Later diagnosis from low awareness; education campaigns and rapid referral pathways are the levers.
Adjuvant endocrine adherence and side effects in men are poorly studied.
and how the field plans to fix it →What is being done about thisSide effects and quality of lifeAvailable now- Sentinel lymph node biopsyStandard of care
- Cardio-oncologyEstablished
- Exercise & lifestyle oncologyEstablished
- Geriatric assessmentEstablished
- IMRT / IGRT (modern external beam)Standard of care
- Oncology nutrition assessment and medical nutrition therapyEstablished
In trialsIdeas and roadmaps- A cheap old tablet to restore appetite
- A coordinated FLASH radiotherapy evidence programme with shared dose-rate standards
- A dedicated programme for cachexia and treatment toxicity research
- A dietitian in every gastrointestinal and head and neck tumour board
- A funded programme of organ-preservation trials to avoid radical surgery
- A lifelong late-effects registry linked to every treatment for adult survivors
Background: CTCAE toxicity grading (grade 3-4 adverse events), De-escalation, escalation and response-adapted therapy, Immune-related adverse events (irAEs), Quality of life, Toxicity grade. Also on OnCo: Side effects, symptom first · Immune-related side effects · Toxicity compare · Survivorship planner.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Landmark trials in OnCo
Expert centres
topCentres linked to this cancer in OnCo
- via Trastuzumab deruxtecan
- via Olaparib
- via Sentinel lymph node biopsy
- via Trastuzumab deruxtecan
- Breast Cancer TrialsNewcastle, NSW, AUvia Olaparib, OlympiA, Trastuzumab
- Breast International Group (BIG)Brussels, BEvia Olaparib, OlympiA, Trastuzumab
- via Talazoparib, Germline (hereditary) testing, BRCA1 / BRCA2 (HRD)
- SOLTI Cancer Research GroupBarcelona, ESvia Palbociclib, Ribociclib, Trastuzumab
- via Olaparib, OlympiA
- Hadassah Medical CenterJerusalem, ILvia Germline (hereditary) testing, BRCA1 / BRCA2 (HRD)
- Hospital de Clínicas de Porto AlegrePorto Alegre, BRvia Germline (hereditary) testing, BRCA1 / BRCA2 (HRD)
- Instituto Alexander FlemingBuenos Aires, ARvia Palbociclib, Trastuzumab
- via Germline (hereditary) testing, BRCA1 / BRCA2 (HRD)
- Lagos University Teaching HospitalLagos, NGvia Germline (hereditary) testing, BRCA1 / BRCA2 (HRD)
- NRG OncologyPhiladelphia, PA, USvia Olaparib, OlympiA
- NSABP FoundationPittsburgh, PA, USvia Sentinel lymph node biopsy, Trastuzumab
- QIMR Berghofer Medical Research InstituteBrisbane, AUvia Germline (hereditary) testing, BRCA1 / BRCA2 (HRD)
- Shaare Zedek Medical CenterJerusalem, ILvia Germline (hereditary) testing, BRCA1 / BRCA2 (HRD)
- Sheba Medical CenterRamat Gan, ILvia Olaparib, BRCA1 / BRCA2 (HRD)
- via Palbociclib, Trastuzumab
- University of Malaya Medical CentreKuala Lumpur, MYvia Germline (hereditary) testing, BRCA1 / BRCA2 (HRD)
- A.C. Camargo Cancer CenterSão Paulo, BRvia Germline (hereditary) testing
- via BRCA1 / BRCA2 (HRD)
- Alliance for Clinical Trials in OncologyChicago, IL, USvia Sentinel lymph node biopsy
- ARCAGY-GINECOParis, FRvia Olaparib
- via Palbociclib
- Catalan Institute of Oncology (ICO)L'Hospitalet de Llobregat, ESvia Germline (hereditary) testing
- Central Drugs Standard Control OrganizationNew Delhi, INvia Trastuzumab
- Centre hospitalier de l'Université de Montréal (CHUM)Montréal, QC, CAvia Olaparib
- Children's Hospital of PhiladelphiaPhiladelphia, PA, USvia Germline (hereditary) testing
- via Palbociclib
- Edinburgh Cancer Centre / CRUK Scotland CentreEdinburgh, GBvia Germline (hereditary) testing
- European Society of Surgical OncologyBrussels, BEvia Sentinel lymph node biopsy
- via Germline (hereditary) testing
- GEICAM Spanish Breast Cancer GroupMadrid, ESvia Palbociclib
- via Trastuzumab
- via Germline (hereditary) testing
- Groote Schuur Hospital / University of Cape TownCape Town, ZAvia Germline (hereditary) testing
- via Germline (hereditary) testing
- via Trastuzumab
- Hospital Universitari i Politècnic La FeValencia, ESvia Germline (hereditary) testing
- via Germline (hereditary) testing
- Institut Jules BordetBrussels, BEvia Trastuzumab
- IRCCS Ospedale San RaffaeleMilan, ITvia Trastuzumab
- Istituto di Candiolo IRCCS – FPOCandiolo, ITvia Trastuzumab
- Istituto Oncologico Veneto IRCCSPadua, ITvia Trastuzumab
- Keio University HospitalTokyo, JPvia Sentinel lymph node biopsy
- via Germline (hereditary) testing
- King Hussein Cancer CenterAmman, JOvia Germline (hereditary) testing
- Korle Bu Teaching HospitalAccra, GHvia Germline (hereditary) testing
- MovemberMelbourne, AUvia Germline (hereditary) testing
- National Cancer Center Hospital EastKashiwa, Chiba, JPvia Trastuzumab deruxtecan
- Newcastle Cancer Centre / Northern Centre for Cancer CareNewcastle upon Tyne, GBvia BRCA1 / BRCA2 (HRD)
- Peking Union Medical College HospitalBeijing, CNvia Germline (hereditary) testing
- via Trastuzumab deruxtecan
- Ramathibodi Hospital, Mahidol UniversityBangkok, THvia Germline (hereditary) testing
- Shizuoka Cancer CenterNagaizumi, Shizuoka, JPvia Germline (hereditary) testing
- via Germline (hereditary) testing
- Society of Surgical OncologyRosemont, IL, USvia Sentinel lymph node biopsy
- via Olaparib
- The Hospital for Sick Children (SickKids)Toronto, ON, CAvia Germline (hereditary) testing
- The Institute of Cancer ResearchLondon, GBvia Olaparib
- Tohoku University HospitalSendai, JPvia Germline (hereditary) testing
- via Tamoxifen
Questions to ask
topQuestions to ask your oncologist about Male breast cancer
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example ER, PR, HER2, Germline BRCA1/2 and multigene panel, Ki-67 and genomic assays, Nodal status, Testosterone and oestradiol if aromatase inhibitors are considered), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Invasive ductal carcinoma, ER-positive / HER2-negative, HER2-positive, Triple-negative.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Early stage
- For my situation (early stage), which of the standard options do you recommend and why?Why: Guideline options include: Mastectomy (or breast conservation where feasible) with sentinel node biopsy; adjuvant radiotherapy by the same criteria as women; chemotherapy and HER2-directed therapy as indicated.
- Am I a candidate for Trastuzumab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Adjuvant endocrine, ER-positive
- For my situation (adjuvant endocrine, er-positive), which of the standard options do you recommend and why?Why: Guideline options include: Tamoxifen for five to ten years; aromatase inhibitor only with GnRH agonist suppression if tamoxifen is contraindicated.
- Am I a candidate for Tamoxifen, Goserelin / leuprolide (ovarian function suppression), Letrozole (and other aromatase inhibitors), and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Advanced, ER-positive
- For my situation (advanced, er-positive), which of the standard options do you recommend and why?Why: Guideline options include: Endocrine therapy (tamoxifen, or aromatase inhibitor or fulvestrant with GnRH agonist) with a CDK4/6 inhibitor by extrapolation; chemotherapy for visceral crisis.
- Am I a candidate for Tamoxifen, Fulvestrant, Palbociclib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Germline BRCA carriers
- For my situation (germline brca carriers), which of the standard options do you recommend and why?Why: Guideline options include: PARP inhibitor (olaparib adjuvant per OlympiA; olaparib or talazoparib for metastatic disease) and cascade testing of relatives.
- Am I a candidate for Olaparib, Talazoparib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of OlympiA apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of Olaparib, Palbociclib, Ribociclib, Trastuzumab deruxtecan?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Men are still under-enrolled in breast cancer trials; regulatory guidance and label harmonisation are the response”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Aromatase inhibitor efficacy and the need for GnRH co-treatment rest on small studies; registries are collecting outcomes”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
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