What is the recommended hormone therapy for breast cancer patients with hormone receptor-positive tumors?

From the Guidelines

The recommended hormone therapy for breast cancer patients with hormone receptor-positive tumors is aromatase inhibitors (AIs) as first-line treatment for postmenopausal women, and ovarian suppression or ablation in combination with hormonal therapy for premenopausal women, as stated in the 2021 ASCO guideline update 1.

Key Recommendations

• Postmenopausal women with metastatic, HR-positive breast cancer should be offered AIs as first-line endocrine therapy (ET) 1.
• Premenopausal women with metastatic HR-positive breast cancer should be offered ovarian suppression or ablation in combination with hormonal therapy, with ovarian suppression using GnRH agonists or ablation with oophorectomy achieving similar results 1.
• The choice of hormone therapy should take into account the biology of the tumor and the menopausal status of the patient, with careful attention paid to ovarian production of estrogen 1.

Treatment Options

• AIs such as anastrozole, letrozole, or exemestane are recommended for postmenopausal women, with a dose of 1mg daily for anastrozole, 2.5mg daily for letrozole, or 25mg daily for exemestane 1.
• Tamoxifen at 20mg daily for 5-10 years may be considered for premenopausal women, sometimes combined with ovarian suppression using GnRH agonists or ablation with oophorectomy 1.
• Fulvestrant should be administered using the 500 mg dose and with a loading schedule, and may be offered in combination with a nonsteroidal AI for patients with metastatic breast cancer without prior exposure to adjuvant ET 1.

Monitoring and Adherence

• Regular monitoring for side effects and adherence to the prescribed duration is crucial for treatment success, as premature discontinuation can significantly increase recurrence risk 1.
• Treatment should be given until there is unequivocal evidence of disease progression, as documented by imaging, clinical examination, or disease-related symptoms 1.

From the FDA Drug Label

LETROZOLE tablets, for oral use Initial U. S. Approval: 1997 INDICATIONS AND USAGE Letrozole Tablets, USP are aromatase inhibitor indicated for: Adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer ( 1.1) Extended adjuvant treatment of postmenopausal women with early breast cancer who have received prior standard adjuvant tamoxifen therapy ( 1. 2) First and second-line treatment of postmenopausal women with hormone receptor positive or unknown advanced breast cancer ( 1.3)

The recommended hormone therapy for breast cancer patients with hormone receptor-positive tumors is letrozole.

• Indications for letrozole include:
  • Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
  • Extended adjuvant treatment of postmenopausal women with early breast cancer who have received prior standard adjuvant tamoxifen therapy
  • First and second-line treatment of postmenopausal women with hormone receptor-positive or unknown advanced breast cancer
• The recommended dose of letrozole is 2.5 mg once daily 2 2.

From the Research

Hormone Therapy for Breast Cancer Patients

Hormone therapy is a crucial treatment for breast cancer patients with hormone receptor-positive tumors. The goal of hormone therapy is to reduce the production of hormones that fuel the growth of cancer cells or to prevent these hormones from binding to cancer cells.

Recommended Hormone Therapies

• Tamoxifen is the only active adjuvant hormonal therapy in pre- and postmenopause, and its treatment duration influences disease-free survival, the risk of a contralateral breast cancer apparition, and overall survival 3.
• Aromatase inhibitors, such as Anastrozol, Letrozol, and Exemestan, are used in postmenopause and have been shown to be effective in reducing the risk of breast cancer recurrence 4.
• Fulvestrant is used in recurrent disease after or during treatment with Tamoxifen 3.
• LHRH analogues are used in premenopausal patients in adjuvantcy and sometimes in case of recurrences 3, 5.

Treatment Sequencing and Resistance

• There is no optimal treatment sequence for hormone-receptor-positive, HER2-negative advanced breast cancer, but a reasonable approach may be starting with tamoxifen, aromatase inhibitors, or fulvestrant in absence of visceral crisis 6.
• Resistance to hormone therapy is a significant challenge, and multiple modalities are being addressed to overcome such resistance, including the use of CKD4/6 inhibitors, mTOR inhibitors, and PI3K inhibitors 6.
• CDK4/6 inhibitors work best when used in frontline setting, and treatment of breast cancer remains a growing field, with more studies awaited 6.

Side Effects and Management

• Aromatase inhibitors can lead to non-compliance or discontinuation of treatment due to side effects such as vasomotor symptoms, vaginal dryness, dyspareunia, bone loss, arthralgias, and myalgias 7.
• Management of these side effects can lead to improved adherence and persistence with therapy, and it is essential to monitor patients for changes in bone mineral density and cardiovascular disease risk factors and outcomes 4, 7.