What hormone replacement therapy (HRT) options are available for patients with breast cancer?

Hormone Replacement Therapy Options for Breast Cancer Patients

For patients with breast cancer, endocrine therapy is the recommended treatment for hormone receptor-positive disease, while traditional hormone replacement therapy is generally contraindicated due to concerns about stimulating cancer recurrence.

Endocrine Therapy for Hormone Receptor-Positive Breast Cancer

First-Line Therapy Options

• For postmenopausal women with HR-positive metastatic breast cancer, aromatase inhibitors (AIs) are the preferred first-line endocrine therapy, with or without CDK4/6 inhibitors 1
• For premenopausal women with HR-positive metastatic breast cancer, ovarian suppression/ablation combined with endocrine therapy is recommended 1
• Tamoxifen with ovarian ablation is recommended for premenopausal patients with no prior adjuvant tamoxifen or if discontinued for >12 months 1

Sequential Therapy Approach

• Sequential hormone therapy should be offered to patients with endocrine-responsive disease 1
• A specific hormonal agent may be used again if recurrence occurs 12 months after last treatment 1
• Treatment recommendations should be based on type of adjuvant treatment, disease-free interval, and extent of disease at recurrence 1

Second-Line and Later Options

• Fulvestrant should be administered at 500 mg with a loading schedule and may be given with palbociclib for second-line therapy 1
• Exemestane with everolimus may be offered to postmenopausal women progressing on nonsteroidal AIs 1
• Second-line hormone therapy options include anastrozole, letrozole, exemestane, fulvestrant, megestrol acetate, and androgens 1

Special Considerations

Hormone Receptor Status

• Hormonal therapy should be offered to patients whose tumors express any level of estrogen and/or progesterone receptors 1
• Testing for receptors should be performed routinely on metastatic tumor tissue to confirm HR expression due to potential discordance between early and late-stage disease 1

Chemotherapy vs. Hormone Therapy

• Endocrine therapy should be recommended as initial treatment for HR-positive metastatic breast cancer, except for patients with immediately life-threatening disease 1
• Chemotherapy should be considered for patients with rapid recurrence of visceral dominant disease within 1-2 years of starting adjuvant hormone therapy 1
• Concomitant chemohormonal therapy is not recommended 1

Hormone Replacement Therapy After Breast Cancer

Current Guidelines and Evidence

• Traditional hormone replacement therapy (HRT) is generally avoided for women with a history of breast cancer due to concerns about stimulating recurrence 2, 3
• Recent systematic review and meta-analysis found that for HR-negative tumors, HRT might be considered with caution (category 2B and 2C), while for HR-positive tumors, it falls into categories 3B/3C (risks generally outweigh benefits) or 4A (should not be used) 4
• Some observational studies have not shown increased risk of tumor recurrence with HRT use in selected breast cancer survivors, but prospective studies show controversial results 5

Alternative Approaches for Menopausal Symptoms

• Non-hormonal pharmaceutical approaches can be used as second-line therapy for control of hot flashes, vulvo-vaginal atrophy, arthralgia, mood swings, sleep disturbance, and depression 2
• Alternatives to HRT for menopausal symptoms include vitamin E, clonidine, and selective serotonin reuptake inhibitors 3
• For osteoporosis prevention, bisphosphonates, diet, and exercise are alternatives; for cardiovascular disease prevention, diet, exercise, and statins can be considered 3

Treatment Duration

• The optimal duration of treatment with hormonal therapy for metastatic disease is not definitively established 1
• Treatment should focus on patient outcomes and symptoms rather than solely on tumor markers or imaging 1
• Assessment of progression may be challenging due to difficulty interpreting imaging and the indolent nature of HR-positive disease 1

Pitfalls and Caveats

• Tumor flare reactions can occur, particularly with tamoxifen and estradiol, and can be confused with disease progression 1
• Recurrence after short exposure to adjuvant hormone therapy suggests relative hormone resistance 1
• Recurrence on or within 12 months of last exposure to a specific hormonal agent indicates resistance to that agent; an alternate hormone therapy should be considered 1
• Treatment-related toxicity may necessitate changing therapy 1