What are the differences in incidence, risk factors, clinical presentation, diagnostic work‑up, treatment, and prognosis between male and female breast cancer?

Male vs Female Breast Cancer: Key Differences

Male breast cancer is fundamentally distinct from female breast cancer in incidence, age at diagnosis, biology, and treatment patterns, requiring sex-specific management considerations despite similar staging and surgical approaches.

Incidence and Epidemiology

Male breast cancer is exceedingly rare, accounting for less than 1% of all breast cancers, compared to the female incidence of 94.2 per 100,000 in Europe 1, 2.

• Men are diagnosed approximately 5 years later than women, with an average age of 67 years versus 62 years in women 3, 4
• The incidence of male breast cancer is rising worldwide, attributed to increased longevity, obesity, and improved detection 2
• Unlike women, men show no peak incidence at age 40; instead, rates rise steadily with age 3

Risk Factors: Critical Sex-Specific Differences

Male breast cancer has distinctly different risk factors centered on hormonal imbalances and genetic predisposition:

Hormonal and Medical Conditions

• Hyperestrogenism-related conditions including Klinefelter's syndrome, gynecomastia, and cirrhosis are major male-specific risk factors 1, 3
• Testicular diseases and tumors increase risk 2
• Obesity and increased longevity contribute to rising incidence 2

Genetic Predisposition: A Dominant Factor

• BRCA2 mutations occur in 4-16% of male breast cancer cases (versus much lower rates in women), conferring an 80-fold increased risk 4, 2
• BRCA1 mutations are rare in men (0-4% of cases) 4
• Other mutations (CHEK2, PALB2, PTEN) collectively account for approximately 20% of male cases 4
• All men with breast cancer should be offered genetic counseling and germline testing, given the high prevalence of hereditary mutations 3, 4

Female-Specific Risk Factors (Absent in Men)

• Endogenous and exogenous estrogen exposure, low parity, and atypical hyperplasia are primary female risk factors 1
• Western-style diet, obesity, and alcohol consumption contribute to female incidence 1

Clinical Presentation and Detection

Men typically present with more advanced disease due to lack of screening and delayed recognition:

• Most common presentation in men is a firm subareolar lump 5
• Men are more likely to present at advanced stages despite similar prognosis at equal stages 5
• No established screening programs exist for average-risk men, unlike the population-based mammography screening for women aged 50-69 years 1
• Men with genetic predisposing mutations may be offered contralateral annual mammography 3

Tumor Biology and Pathology

Male breast cancer demonstrates distinct histologic patterns and receptor profiles:

Histologic Differences

• Invasive ductal carcinoma of no special type predominates (approximately 89-90% of cases), typically grade 2 2, 5
• In situ and invasive papillary carcinomas are more common in men than women 2
• Infiltrating lobular carcinoma is extremely rare in men due to limited lobular development in male breast tissue 3

Receptor Status: A Critical Distinction

• Male breast cancer is predominantly hormone receptor-positive (92% estrogen receptor-positive, 100% progesterone receptor-positive in one series) 5, 6
• This high prevalence of hormone receptor positivity makes endocrine therapy highly effective 3, 4
• HER2-negative tumors are more common in men 2

Treatment Differences: Sex-Specific Considerations

Despite similar staging systems, treatment patterns differ significantly between sexes:

Surgical Management

• Men are more likely to undergo mastectomy (modified radical 65% vs 55.1%, radical 2.5% vs 0.9%, simple 7.6% vs 3.4% in women) 7
• Men treated with lumpectomy receive radiation therapy less frequently (54% vs 68% in women) 7
• Men receive post-mastectomy radiation more frequently (29% vs 11% in women) 7
• Ipsilateral annual mammography should be offered to men treated with lumpectomy 3

Systemic Therapy: Critical Sex-Based Modifications

Endocrine Therapy (The Cornerstone)

• Tamoxifen is the standard adjuvant therapy for hormone receptor-positive male breast cancer, given for an initial 5 years 3
• Men with high recurrence risk may receive an additional 5 years of tamoxifen after completing initial therapy 3
• Aromatase inhibitors alone are less effective in men and must be combined with GnRH agonist/antagonist if tamoxifen is contraindicated 3
• Testosterone/androgen supplementation is contraindicated in men with breast cancer 3

Chemotherapy

• Men receive chemotherapy less frequently than women (26.7% vs 40.6%) despite similar staging 7
• For advanced/metastatic hormone receptor-positive, HER2-negative disease, endocrine therapy is first-line except in visceral crisis 3
• Cyclin-dependent kinase 4/6 inhibitors can be used in men as in women 3

Common Pitfall

The critical error is treating men with aromatase inhibitors alone without GnRH suppression, as men continue to produce testosterone that can be aromatized to estrogen, rendering aromatase inhibitors ineffective 3.

Prognosis

When matched for stage, age, ethnicity, and income, male and female breast cancer have similar survival outcomes:

• 5-year overall survival of 86% and disease-free survival of 75% in men 5
• However, men often present at more advanced stages, resulting in worse population-level outcomes 5
• The similar stage-specific prognosis underscores that delayed diagnosis, not inherent tumor biology, drives worse outcomes in men 5

Surveillance and Follow-Up

Post-treatment surveillance differs based on surgical approach and genetic status:

• Ipsilateral annual mammography for men treated with lumpectomy 3
• Contralateral annual mammography may be offered to men with genetic predisposing mutations 3
• Breast MRI is not routinely recommended 3