What are the recommendations for Hormone Replacement Therapy (HRT) in women with a high risk of breast cancer?

Hormone Replacement Therapy in Women with High Risk of Breast Cancer

HRT is not recommended for women at high risk of breast cancer due to the increased risk of breast cancer development, particularly with combined estrogen-progestin therapy. 1, 2

Risks of HRT in High-Risk Women

• Combined estrogen-progestin therapy significantly increases breast cancer risk, with a relative risk of 1.24 and absolute risk of 41 versus 33 cases per 10,000 women-years compared to placebo 2
• The risk is particularly elevated (relative risk 1.86) among women with prior hormone therapy use 2
• Long-term use of HRT (≥20 years) of estrogen alone is associated with increased breast cancer risk (relative risk 1.42) 1
• The U.S. Preventive Services Task Force (USPSTF) has concluded that there is fair to good evidence that HRT increases breast cancer incidence, with strongest evidence for combined estrogen-progestin therapy 1
• The increased risk of breast cancer appears to return to baseline approximately 5 years after stopping treatment 2, 3

Alternative Approaches for High-Risk Women

• For women at high risk of breast cancer, selective estrogen receptor modulators (SERMs) like tamoxifen or raloxifene could be considered as preventive strategies, depending on the woman's underlying risk for stroke and thromboembolic events 1
• Other effective interventions for preventing osteoporosis (a common reason for considering HRT) include:
  • Weight-bearing exercise 1
  • Bisphosphonates 1
  • Calcitonin 1
• For management of menopausal symptoms in high-risk women, non-hormonal alternatives should be considered:
  • Vitamin E, clonidine, and selective serotonin reuptake inhibitors for vasomotor symptoms 4
  • Lifestyle modifications including regular physical activity, which has been associated with decreased breast cancer risk 1
  • Limiting alcohol consumption to less than one drink per day, as moderate alcohol intake (1-2 drinks/day) is associated with 30-50% increase in breast cancer incidence 1

Special Considerations

• The FDA has placed a black box warning on estrogen products indicating they should be prescribed at the lowest effective dose and for the shortest duration consistent with treatment goals 1, 5
• The absolute increase in risk from HRT is modest but significant - per 10,000 women taking estrogen and progestin for 1 year, there might be 8 more invasive breast cancers, along with 7 additional CHD events, 8 more strokes, and 8 more pulmonary emboli 1, 6
• No randomized trials have prospectively evaluated the effect of timing of HRT initiation relative to menopause onset on breast cancer risk, though post hoc analyses suggest increased harm with longer duration of use 1
• Invasive breast cancers in women taking combined HRT tend to be larger, more likely node-positive, and diagnosed at more advanced stages compared to placebo groups 2

Monitoring Recommendations

• All women, especially those with high breast cancer risk, should receive yearly breast examinations by a healthcare provider 2
• Monthly breast self-examinations are recommended 2
• Mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results 2

For women at high risk of breast cancer who have severe menopausal symptoms refractory to non-hormonal treatments, any consideration of HRT should involve a thorough individualized risk-benefit discussion, with clear understanding that current guidelines recommend against this approach 5, 7.