Current Perspectives on Non-Metastatic Male Breast Cancer: Genetics, Biology, and Treatment Advances: A Systematic Review
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
3. Results
3.1. Genetic Alterations Shaping Male Breast Cancer Risk
3.1.1. High-Penetrance Genes
3.1.2. Moderate-Penetrance Genes
3.1.3. Low-Penetrance Alleles and Susceptibility Loci
3.1.4. Somatic Alterations
3.1.5. Multigene Panels and Extended Spectrum
3.1.6. Epigenetic Alterations
3.2. Molecular Pathways and Clinicopathological Correlates in Male Breast Cancer
3.2.1. Histology and Hormone Receptor Status
3.2.2. Androgen Receptor (AR) Expression
3.2.3. HER2 Overexpression
3.2.4. Molecular Subtypes
3.2.5. Tumor Microenvironment and Lipid Metabolism
3.2.6. Emerging Biomarkers
3.2.7. Clinical Presentation and Prognostic Factors
3.3. Treatment Advances in Non-Metastatic Male Breast Cancer
3.3.1. Is Breast-Conserving Surgery a Safe and Feasible Alternative to Mastectomy?
3.3.2. Axillary Staging: Sentinel Lymph Node Biopsy (SLNB) Performance for Male Breast Cancer
3.3.3. Adjuvant Radiotherapy in Male Breast Cancer
3.3.4. Adjuvant Endocrine Treatment: Survival Impact and Compliance Challenges in Male Breast Cancer
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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OR [IC95%] | ||||||
---|---|---|---|---|---|---|
Gene | Chromosome | Inheritance | Pathogenic Variants | Clinical Syndrome | Pritzlaff et al. [12] | Janatova et al. [13] |
High penetrance | ||||||
BRCA2 | 13q12-13 | AD | LOF mutations | HBOC | 13,9 (5–22) | 44,0 (2–92) |
BRCA1 | 17q21 | AD | LOF mutations | HBOC | 1,8 (0,3–6,8) | 5,8 (0–14) |
TP53 * | 17p13 | AD | Missense/LOF mutation | Li-fraumeni | - | - |
PTEN * | 10q23 | AD | LOF mutations | Cowden | - | - |
STK11 * | 19 | AD | LOF mutations | Peutz Jeghers | - | - |
Moderate or Low penetrance | ||||||
CHEK2 | 22q11 | AD | 1100delC | Li-fraumeni variant | 2,4 (1,3,4,9) | 5,0 (1,3,8–12) |
ATM | 11q22-23 | AR/AD | Truncating/missense variants | HC: breast cancer risk; BA: Ataxia–Telangiectasia | 1,4 (0,1,3–5) | 1,3 (0–7) |
PALB2 | 16p22 | AD AR | Truncating variants | HBOC Syndrome Fanconi | 6,6 (1,7–21) | 8,3 (2–27) |
Study (Reference) | Kornegoor et al. [30] | Vermeulen et al. [33] | Moelans et al. [18] | Piscuoglio et al. [20] | |
---|---|---|---|---|---|
Histological type (%) - | Ductal Lobular Others | 95 2 3 | >90 <10 | 90 10 | NR |
Grade (%) | 1 2 3 | 19 43 38 | 19 42 39 | NR | NR |
ER−/ER+ | (%) | 1/99 | 1/99 | 4/96 | 0/100 |
PR−/PR+ | (%) | 18/82 | 18/82 | 34/66 | NR |
HER2−/HER2+ | (%) | 95/5 | 95/5 | 98/2 | 97/3 |
LN−/LN+ | (%) | 54/46 | 54/46 | NR | NR |
Ki-67 | (Low/High) | 79/21 | NR | NR | NR |
Subtypes (%) | Luminal A like Luminal B like Basal like HER2 | 75 21 4 0 | 81 13 6 0 | 50 46 4 0 | 29 71 |
First Autor (Reference) | Survival Data | ||
---|---|---|---|
BCS | Mastectomy | ||
5-Year DSS | Cloyd et al. [58] | 87% | 88% |
Zaenger et al. [50] | 100% | 97.3% | |
5-Year OS | Den et al. [49] | 84% | 86% |
Zaenger et al. [50] | 97% | 95% | |
Bateni et al. [59] | 41% | 40% | |
Cloyd et al. [58] | 66% | 70% | |
Fogh et al. [56] | 7 of 8 | 34 of 34 | |
10-Year-OS | Bateni et al. [59] | 6% | 5% |
Cloyd et al. [58] | 47% | 46% | |
Fogh et al. [56] | 6 of 8 | 23 of 34 |
First Authors, Year, Source | Study Design | N (SLNB) | Identification Rate (IR) | False-Negative Rate (FNR) |
---|---|---|---|---|
Parpex, 2024 [60] | Meta-analysis, no heterogeneity | 164 (IR)/50 (FNR) | 99.0% | 0% |
Koukouras, 2012 [62] | Retrospective study | 11 | 100% | 0% |
Gentilini, 2007 [63] | Retrospective study | 32 | 100% | 0% |
Maràz, 2016 [64] | Retrospective study | 16 | 100% | 3/12 |
Lin, 2011 [48] | Meta-analysis | 213 | 97.4% | 7.4% |
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Melan, K.; Loap, P.; Kirova, Y. Current Perspectives on Non-Metastatic Male Breast Cancer: Genetics, Biology, and Treatment Advances: A Systematic Review. Cancers 2025, 17, 3270. https://doi.org/10.3390/cancers17193270
Melan K, Loap P, Kirova Y. Current Perspectives on Non-Metastatic Male Breast Cancer: Genetics, Biology, and Treatment Advances: A Systematic Review. Cancers. 2025; 17(19):3270. https://doi.org/10.3390/cancers17193270
Chicago/Turabian StyleMelan, Kathleen, Pierre Loap, and Youlia Kirova. 2025. "Current Perspectives on Non-Metastatic Male Breast Cancer: Genetics, Biology, and Treatment Advances: A Systematic Review" Cancers 17, no. 19: 3270. https://doi.org/10.3390/cancers17193270
APA StyleMelan, K., Loap, P., & Kirova, Y. (2025). Current Perspectives on Non-Metastatic Male Breast Cancer: Genetics, Biology, and Treatment Advances: A Systematic Review. Cancers, 17(19), 3270. https://doi.org/10.3390/cancers17193270