What is the risk of breast cancer in transgender women on hormone replacement therapy (HRT)?

Breast Cancer Risk in Transgender Women on Hormone Replacement Therapy

Transgender women on hormone replacement therapy (HRT) for 5 or more years have a significantly increased risk of breast cancer compared to cisgender men, but their risk remains lower than cisgender women. Transgender women who have been on feminizing hormone therapy for 5 or more years should undergo screening mammography starting at age 50, with annual or biennial screening depending on additional risk factors 1.

Risk Assessment

The risk profile for transgender women on HRT shows:

• Breast cancer incidence in transgender women on hormone therapy is approximately 31.4 per 100,000 person-years, which is higher than cisgender men (1.2 per 100,000 person-years) but lower than cisgender women (170 per 100,000 person-years) 2
• A Dutch cohort study of 3,489 transgender patients showed transgender women receiving gender-affirming hormone therapy had a 46.7 times higher risk of breast cancer compared to cisgender men (SIR: 46.7,95% CI: 27.2-75.4) 2
• Risk increases with duration of hormone exposure, with significant increases noted after a median of 18 years (range 7-37 years) 2

Screening Recommendations

For Average-Risk Transgender Women:

• Begin screening at age 50 if on HRT for ≥5 years
• Annual or biennial mammography using digital mammography or digital breast tomosynthesis (DBT)
• No routine screening needed for transgender women with <5 years of hormone therapy 1

For Higher-Risk Transgender Women:

• Begin screening earlier if additional risk factors are present:
  • Personal history of breast cancer
  • Chest irradiation between ages 10-30
  • Genetic predisposition (BRCA mutations)
  • Family history of breast or ovarian cancer 2, 1
• The American College of Radiology recommends screening 10 years earlier than the age at diagnosis of an affected relative (but not before age 30) 2

Screening Modalities

1. Digital mammography or digital breast tomosynthesis (DBT): First-line screening modality 2, 1
2. MRI with contrast: Limited use, primarily for patients who have undergone direct injection of particles for breast augmentation 2
3. Ultrasound: Insufficient evidence to support routine screening 1

Clinical Considerations

• Mammary development in transgender women includes formation of ducts, lobules, and acini, histologically identical to cisgender females 2
• Transgender women can develop the same breast pathologies as cisgender women, including benign conditions (fibroadenomas, cysts) and malignancies (ductal and lobular carcinomas) 2, 3
• Transgender women may experience nipple discharge related to hormone-induced hyperprolactinemia 2

Common Pitfalls to Avoid

• Assuming transgender women have the same breast cancer risk as cisgender women 1
• Failing to account for duration of hormone therapy when determining screening needs 1
• Overlooking additional risk factors that may necessitate earlier or more frequent screening 1
• Not recognizing that breast tissue in transgender women should not be referred to as gynecomastia, as it is histologically identical to cisgender female breast tissue 2

The evidence regarding breast cancer risk in transgender women continues to evolve, with current recommendations based on limited data. However, the increased risk associated with long-term hormone therapy warrants appropriate screening to reduce morbidity and mortality from breast cancer in this population.