Why do breast cancer patients avoid hormone replacement therapy (HRT)?

Breast Cancer Patients Avoid Hormone Replacement Therapy Due to Increased Recurrence Risk

Hormone replacement therapy (HRT) is strongly discouraged in breast cancer patients because it increases the risk of cancer recurrence, particularly in hormone receptor-positive disease. 1

Evidence Against HRT in Breast Cancer Survivors

• HRT use in breast cancer survivors is associated with a 46% increased risk of breast cancer recurrence compared to placebo (HR 1.46,95% CI 1.12-1.91) 2
• The risk is significantly higher in patients with hormone receptor-positive disease (HR 1.8,95% CI 1.15-2.82) 2
• The European Society for Medical Oncology (ESMO) guidelines explicitly state that HRT increases the risk of recurrence and should be discouraged 1
• The Second Consensus on Medical Treatment of Metastatic Breast Cancer strongly discourages HRT use in metastatic breast cancer, as it may stimulate growth of receptor-positive cancers 1

Mechanism of Risk

• For the approximately 70% of breast cancer patients with hormone receptor-positive tumors, a mainstay of treatment is to block estrogen effects or reduce its production 1
• HRT may counteract the beneficial effects of endocrine therapies such as:
  • Tamoxifen (blocks estrogen receptors) 1
  • Aromatase inhibitors (reduce estrogen production) 1
• Even topical vaginal estrogens should be used with caution as they may impair aromatase inhibitor treatment 1

Alternative Management Approaches

• Non-hormonal approaches for managing menopausal symptoms should be considered first-line: 1
  • For vasomotor symptoms (hot flashes): selective serotonin reuptake inhibitors, gabapentin, or clonidine 1
  • For vaginal dryness: non-hormonal lubricants and moisturizers 1
• For bone health concerns (particularly with aromatase inhibitors):
  • Regular bone density evaluation is recommended 1
  • Bisphosphonates may be used to prevent osteoporosis 3

Special Considerations

• The risk of recurrence with HRT appears to be lower in hormone receptor-negative disease (HR 1.19,95% CI 0.80-1.77), though HRT is still not routinely recommended 2
• After stopping HRT, the increased risk of breast cancer dissipates within 2 years, suggesting that hormone-dependent cancers may regress when hormonal stimulation is removed 4
• Patients on tamoxifen should have annual gynecological examinations by an experienced gynecologist 1
• Patients on aromatase inhibitors should have regular bone density evaluations 1

Clinical Decision-Making

• The decision to use any form of HRT in breast cancer survivors should involve:
  • Assessment of hormone receptor status of the original tumor 2
  • Consideration of the severity of menopausal symptoms and impact on quality of life 5
  • Exhaustion of non-hormonal treatment options 6
  • Thorough discussion of the potential increased risk of recurrence 1

In conclusion, while HRT effectively manages menopausal symptoms, its use in breast cancer survivors carries a significant risk of cancer recurrence, particularly for those with hormone receptor-positive disease. Alternative non-hormonal approaches should be prioritized for symptom management.