Is hormone therapy in non-metastatic breast cancer limited to adjuvant therapy or can it also be given as neoadjuvant therapy?

Hormone Therapy in Non-Metastatic Breast Cancer: Neoadjuvant vs. Adjuvant Use

The statement is FALSE—hormone therapy can be given as both neoadjuvant and adjuvant therapy in non-metastatic breast cancer, though neoadjuvant hormone therapy is specifically indicated for select populations, particularly elderly postmenopausal women with hormone receptor-positive tumors where surgery is not immediately feasible. 1, 2

Neoadjuvant Hormone Therapy: Established Option

Neoadjuvant treatment with antiestrogens can be used in elderly women with slowly evolving hormone-sensitive tumors (option, level of evidence: B1), followed when possible by optimal locoregional treatment. 1

Specific Indications for Neoadjuvant Hormone Therapy:

• Postmenopausal women with hormone receptor-positive tumors where breast-conserving surgery is not initially possible 1
• Elderly patients where chemotherapy toxicity is a concern 3
• Patients with slowly evolving hormone-sensitive tumors 1

Important Caveat:

• At present, antiestrogens cannot be considered as standard neoadjuvant treatment for initially operable tumors 1
• Neoadjuvant hormone therapy is not standard for all operable breast cancers, but remains a viable option in appropriately selected patients 1, 4

Adjuvant Hormone Therapy: The Standard Approach

Treatment with adjuvant tamoxifen is beneficial, despite its side effects, irrespective of the patients' age, if the tumor expresses estrogen receptors (standard, level of evidence: A). 1

Standard Adjuvant Regimens:

• Tamoxifen 20 mg daily for 5 years is the standard duration 1, 2, 5
• For postmenopausal women, aromatase inhibitors are superior to tamoxifen in first-line therapy 2
• For premenopausal women, tamoxifen with ovarian ablation is the standard approach 2

Evidence Supporting Neoadjuvant Hormone Therapy

Neoadjuvant hormonal therapy is associated with comparable outcomes to neoadjuvant chemotherapy in post-menopausal women with estrogen receptor-positive breast cancer, with no differences in 4-year locoregional relapse-free survival, distant metastasis-free survival, or overall survival. 4

Key Findings:

• NAHT is a viable and potentially less toxic option than neoadjuvant chemotherapy in appropriately selected patients 4
• Neoadjuvant endocrine therapy is highly effective and appropriate for nearly all women with hormone receptor-positive tumors 6
• The approach allows for defining patients who might not require chemotherapy by using their response to neoadjuvant endocrine therapy 3

Clinical Algorithm for Decision-Making

When to Consider Neoadjuvant Hormone Therapy:

1. Patient is postmenopausal 1, 3, 4
2. Tumor is hormone receptor-positive (ER+) 1, 4
3. HER2-negative disease 3, 4
4. One or more of the following applies:
   • Elderly patient with safety concerns regarding chemotherapy 1, 3
   • Slowly evolving tumor 1
   • Breast-conserving surgery not initially possible 1
   • Patient preference for less toxic therapy 4

When Neoadjuvant Hormone Therapy Should NOT Be Used:

• Hormone receptor-negative tumors 1, 2
• Immediately life-threatening disease requiring rapid response 2
• Initially operable tumors where surgery can proceed without delay (not standard in this setting) 1

Common Pitfalls to Avoid

Do not prescribe hormone therapy to women with tumors that do not express estrogen receptors. 1, 2

• Neoadjuvant chemotherapy has limited effect in hormone receptor-positive disease in terms of pathologic complete response rate, making neoadjuvant hormone therapy a reasonable alternative 3
• Regular gynecological examinations are required for patients on tamoxifen due to increased endometrial cancer risk 1, 2, 7, 5
• After neoadjuvant hormone therapy, locoregional treatment should be performed in the same manner as first-line locoregional treatment 1