Miguel Bronchud, Co-Founder at Regenerative Medicine Solutions, shared on LinkedIn:
“Male breast cancer (MBC) is rare but, for reasons unclear, increasing globally, with limited data on trends in Spain. The study examines MBC trends, incidence, and mortality over a 25 year period (1999–2023) to guide public health strategies.
By Aurelio Cayuela et al (2026)- ‘Trends in male breast cancer in Spain, 1999–2023: a nationwide analysis of incidence and mortality‘ – Clinical and Translational Oncology (2026)
Breast cancer in men and women shares similar cellular origins, but they differ significantly in frequency, average age of diagnosis, underlying tissue composition, and hormonal risk factors.
It is the most common cancer in women worldwide. In Men: Very rare; accounting for less than 1% of all breast cancer cases (about 1 in 833 to 1 in 1,000 men).
Women: Have abundant glandular tissue, milk ducts, and active lobules that change and develop during puberty and pregnancy.
Men: Have mostly fatty and fibrous stroma tissue with very few ducts and virtually no functional lobules. Most male breast cancers start in the small number of milk ducts present.
Women: Higher natural estrogen and progesterone exposure over a lifetime (influenced by factors like early menstruation, late menopause, or never giving birth) strongly increases risk.
Men: Lower overall estrogen levels. Higher estrogen levels in men (due to conditions like gynecomastia, genetic disorders, or obesity) can elevate their risk. Both sexes share genetic risk factors like BRCA1and BRCA2 gene mutations, though BRCA2 mutations carry a higher relative risk for men than BRCA1.
Hormone Receptors: Male breast cancer (MBC) has an overwhelmingly high rate of estrogen receptor (ER) and progesterone receptor (PR) positivity (often over 90% ER-positive), and a higher dependence on sex hormone signaling.
Androgen receptor (AR) expression is also highly prevalent in MBC, marking an important pathway for targeted study.
Subtypes: Luminal A is the dominant molecular subtype in both sexes, but HER2-positive and triple-negative/basal subtypes appear at different or lower relative frequencies in men. (link)
Studies reveal that MBC exhibits higher or distinct mutation frequencies in genes like GATA3, BRCA2, MDM2, and CDK4 compared to matched female cases within the same luminal subtype. Female breast cancer (FBC) frequently shows higher mutation rates in TP53 and PIK3CA relative to specific male cohorts, along with a generally higher overall tumor mutation burden (TMB).
Germline mutations in high-risk susceptibility genes – particularly BRCA2 – play a much more prominent role in male breast cancer predisposition than in female cases. Mutations in CHEK2 and PALB2 are also notable in MBC. (link)”
Then added in the comments:
“Diagnosis and Awareness
Women: Benefit from routine screening mammograms and high public awareness, leading to earlier detection on average.
Men: Often experience delayed diagnoses because awareness is low, and men frequently mistake initial lumps for cysts or muscle injuries, leading to more advanced stages at detection.
A recent Chinese study suggests that mutation prevalence of PIK3CA was significantly different between MBC and female breast cancer (FBC).
CDK12 and ERBB2 had the highest prevalence of CNV in FBC, contrasting with their absence in MBC. Both in MBC and FBC, MYC had the highest prevalence in CNV. Furthermore, FBC demonstrated a higher tumor mutational burden (TMB) than MBC.
MBC private genes were involved in a variety of disease-related signaling pathways, with the ErbB and PI3K-Akt pathways being significantly enriched.”
“The Spanish study recorded 7594 MBC cases and 1,931 deaths.
ASMR declined from 0.65 to 0.39 per 100,000 (AAPC − 1.8%), with significant declines from 1999–2006 (APC − 5.1%) and 2013–2023 (APC − 3.6%). ASIR remained largely stable (AAPC 0.1%), increasing slightly from 1999–2006 (APC + 1.7%) and declining thereafter (APC − 0.5%).
The Mortality-to-Incidence Ratio decreased from 0.41 to 0.26. APC analysis demonstrated significant net declines in mortality (− 1.33%/year) and incidence (− 0.83%/year), primarily driven by period effects and lower risk among later birth cohorts.
Mortality reductions were most pronounced among men aged 55–64 years.
MBC mortality in Spain has declined steadily, reflecting improvements in clinical management, while stable incidence indicates minimal change in disease occurrence. Continued focus on early detection, male-specific awareness, and adherence to guideline-based therapy is essential to further reduce the MBC burden.”
Title: Trends in male breast cancer in Spain, 1999–2023: a nationwide analysis of incidence and mortality
Authors: Lucía Cayuela, Victoria Achaval, Gema Flox-Benítez, Julián Librero, Aurelio Cayuela
You can also read:
Yazan Masannat: A Global Push for Male Breast Cancer and Gynecomastia Awareness
