What is the best treatment for a patient with breast cancer (Ca mammae) that is Human Epidermal growth factor Receptor 2 (HER2) negative, Estrogen Receptor (ER) positive, and Progesterone Receptor (PR) positive?

From the Guidelines

For HER2-negative, ER-positive, PR-positive breast cancer, the recommended treatment typically involves endocrine (hormone) therapy as the cornerstone approach, with the standard regimen including tamoxifen (20 mg daily for 5-10 years) for premenopausal women or an aromatase inhibitor such as anastrozole (1 mg daily), letrozole (2.5 mg daily), or exemestane (25 mg daily) for 5-10 years in postmenopausal women, as supported by the most recent guidelines 1.

Treatment Approach

The treatment approach for HER2-negative, ER-positive, PR-positive breast cancer involves:

• Endocrine therapy as the primary treatment
• Tamoxifen or aromatase inhibitors as the standard regimen
• Ovarian suppression with goserelin or leuprolide plus an aromatase inhibitor for some premenopausal patients
• Chemotherapy may be added before hormone therapy for higher-risk disease, with common regimens including AC-T or TC
• Genomic assays like Oncotype DX to determine the benefit of chemotherapy
• Surgery, such as lumpectomy with radiation or mastectomy, typically performed before systemic therapy unless neoadjuvant treatment is indicated

Key Considerations

• The magnitude of risk reduction from adjuvant endocrine therapy depends on the level of ER expression and the risk score of gene expression assay test results, as noted in the guidelines 1
• The St Gallen International Consensus Conference recommends extended therapy, implying 10 years of treatment, though some studies indicate that 10 years may not offer benefit beyond that seen with 7.5-8 years of endocrine therapy 1
• New targeted therapies, such as abemaciclib, are emerging for ER-positive, HER2-negative cancers, with the panelists strongly endorsing the addition of abemaciclib for a duration of 2 years 1

Evidence-Based Recommendations

The recommendations are based on the most recent and highest-quality studies, including the St Gallen International Consensus Conference for the primary therapy of individuals with early breast cancer 2023 1 and the NCCN Clinical Practice Guidelines in Oncology for breast cancer, version 3.2024 1. These guidelines emphasize the importance of endocrine therapy as the cornerstone approach for HER2-negative, ER-positive, PR-positive breast cancer, with a focus on individualized treatment based on risk factors and genomic assays.

From the FDA Drug Label

Among 29,441 patients with ER positive or unknown breast cancer, 58% were entered into trials comparing tamoxifen to no adjuvant therapy and 42% were entered into trials comparing tamoxifen in combination with chemotherapy vs. the same chemotherapy alone. Available evidence indicates that patients whose tumors are estrogen receptor positive are more likely to benefit from tamoxifen therapy. The estrogen and progesterone receptor values may help to predict whether adjuvant tamoxifen therapy is likely to be beneficial.

The best treatment for a patient with ER positive and PR positive breast cancer that is HER2 negative is tamoxifen 2, 2, 2.

• Tamoxifen is effective in the treatment of metastatic breast cancer in women and men.
• Tamoxifen is indicated for the treatment of node-positive breast cancer in women following total mastectomy or segmental mastectomy, axillary dissection, and breast irradiation.
• The decision regarding therapy with tamoxifen for the reduction in breast cancer incidence should be based upon an individual assessment of the benefits and risks of tamoxifen therapy.
• Current data from clinical trials support 5 years of adjuvant tamoxifen therapy for patients with breast cancer.

From the Research

Treatment Options for ER Positive, PR Positive, and HER2 Negative Breast Cancer

• The treatment for ER positive, PR positive, and HER2 negative breast cancer typically involves endocrine therapy, which may include tamoxifen or aromatase inhibitors 3, 4, 5, 6.
• Studies have shown that aromatase inhibitors can provide superior recurrence benefits compared to tamoxifen in the adjuvant setting for postmenopausal women with hormone receptor-positive breast cancer 5, 6.
• The addition of ovarian function suppression (OFS) to tamoxifen has been shown to improve disease-free survival and overall survival in premenopausal patients with breast cancer 3.
• The duration of adjuvant endocrine therapy is also an important consideration, with some studies suggesting that 10 years of tamoxifen may provide further benefit compared to 5 years 3.

Aromatase Inhibitors as a Treatment Option

• Aromatase inhibitors, such as anastrozole, letrozole, and exemestane, have become a standard treatment for postmenopausal women with ER-positive breast cancer 4, 5, 6.
• These inhibitors work by blocking the enzyme aromatase, which is involved in the conversion of androgens to estrogens, resulting in low estradiol levels 4.
• Aromatase inhibitors have been shown to have a more favorable tolerability profile compared to tamoxifen, with a reduced risk of serious adverse events such as endometrial cancer and thromboembolic events 6.

Individualized Treatment Approach

• The treatment approach for ER positive, PR positive, and HER2 negative breast cancer should be individualized based on the patient's menopausal status, tumor characteristics, and other factors 3, 4, 5.
• Multigene expression assays may also be used to help guide treatment decisions and predict the likelihood of recurrence 3.
• Regular monitoring and follow-up are essential to ensure that the treatment plan is effective and to make any necessary adjustments 7.