Role of hormonal therapy in male breast cancer

1. Male breast cancer
• Accounts for less than 1% of all breast cancers.
• Median age of diagnosis is 65 years with 15%
of patients diagnosed at the age <50 years.
• Current clinical knowledge is mainly derived
from small retrospective studies, case reports
and small single center studies.

2. Risk factors
• Age
• BRCA 2 mutation
• Klinefelter syndrome (20-50%) increased risk
• Hormonal imbalance ( Increased estrogen
level d/t obesity, liver cirrhosis, testicular
dysfunction (inguinal hernia and undescended
testes)
• Gynecomastia

3. • Invasive ductal carcinoma is most common histological
type.
• Male breast lacks terminal lobules therefore invasive
lobular carcinoma is <1%. (15% in female breast cancer)
• Precursor lesion: 10% in male, 30% in female.
– ER positive: 99.3%
– PR positive: 96.9%
– Her2 Neu: 8%
• ER alpha receptors ( endometrium and ovary) ER Beta
receptors (Brain, bones, prostate and kidneys)
• Female breast cancer ER has Alpha receptor and male
breast cancer ER receptor has beta receptors.

4. • Less than 10% of male breast cancer patients
undergoes BCS. (central location of disease)
• SLNB, Axillary node dissection, Neoadjuvant
and adjuvant chemotherapy and radiotherapy
guidelines are similar to female breast cancer
treatment guidelines.

5. Tamoxifen in male breast cancer
• Several retrospective studies have shown
improved OS with adjuvant tamoxifen
specially in node positive disease.
• Compliance: ( hot flashes, sexual dysfunction,
decreased libido, mood lability and venous TE)
• 1 year: 65%
• 2 year: 46%
• 3 year:29%
• 4 year: 18%

6. AIs in Male
• 5 years OS in female vs male on AIS: 85%:73%.
• In male 80% of estrogen is produced by
peripheral conversion of androgen via aromatase
and 20% is directly secreted by testes.
• AIs alone are not effective due to increased
secretion of estradiol from testes d/t negative
feedback increase in FSH and LH.
• Several guidelines including NCCN and ASCO have
recommended the combined use of AIs and
GnRH analogs in male breast cancer.

7. MALE trial
• 3 arms:
1. Tamoxifen alone
2. Tamoxifen with GnRH
3. AI with GNRH
• Result: consistent decrease in estradiol level in both
combination arms. No survival data was reported.
significant sexual dysfunctions in combination arms.
• Conclusion: in both prospective and retrospective
studies, there is consistent reduction of estradiol levels
in combinations arms, but weather GnRH plus AI is
superior to AI alone still needs to be evaluated in
prospective studies.