What is the adjuvant management for a 40-year-old premenopausal woman with T3 N0 Estrogen Receptor (ER) positive Human Epidermal growth factor Receptor 2 (HER2) negative breast cancer post-mastectomy?

From the Guidelines

The adjuvant management for a 40-year-old premenopausal woman with T3 N0 ER-positive HER2-negative breast cancer post-mastectomy should include chemotherapy, endocrine therapy, and consideration of radiation therapy. Chemotherapy should be administered first, typically with a regimen such as dose-dense AC-T (doxorubicin/cyclophosphamide followed by paclitaxel) or TC (docetaxel/cyclophosphamide) for 4-6 cycles, as recommended by the St Gallen International Consensus Conference for the primary therapy of individuals with early breast cancer 2023 1. After completing chemotherapy, endocrine therapy should be initiated with tamoxifen 20 mg daily for 5-10 years, or ovarian suppression (with goserelin 3.6 mg subcutaneously monthly or leuprolide 7.5 mg intramuscularly monthly) plus an aromatase inhibitor such as anastrozole 1 mg daily, letrozole 2.5 mg daily, or exemestane 25 mg daily for 5-10 years, as supported by the American Society of Clinical Oncology clinical practice guideline update on ovarian suppression 1. Post-mastectomy radiation therapy should be considered given the T3 status, even with negative nodes, typically delivered as 45-50 Gy in 25 fractions to the chest wall and regional lymph nodes. This multimodal approach is recommended because the patient has high-risk features including young age, premenopausal status, and a large tumor (T3), which increase recurrence risk despite node-negative disease, as noted in the NCCN Clinical Practice Guidelines in Oncology for breast cancer, version 3.2024 1. Chemotherapy provides direct cytotoxic effects, while endocrine therapy targets estrogen-dependent tumor growth, and radiation therapy helps eliminate any microscopic disease in the chest wall or regional nodes. The use of adjuvant bisphosphonates and targeted therapies such as abemaciclib may also be considered in certain cases, as discussed in the St Gallen International Consensus Conference for the primary therapy of individuals with early breast cancer 2023 1. The decision to extend the duration of endocrine therapy beyond 5 years should be based on individual patient factors, including the risk of recurrence and the presence of comorbidities, as recommended by the NCCN Clinical Practice Guidelines in Oncology for breast cancer, version 3.2024 1. Genomic assays may also be used to guide the decision to add chemotherapy to endocrine therapy, as supported by the TAILORx, RxPonder, and MIND-ACT trials, and discussed in the St Gallen International Consensus Conference for the primary therapy of individuals with early breast cancer 2023 1. Ultimately, the choice of adjuvant therapy should be individualized based on the patient's specific clinical and pathological features, as well as their personal preferences and values.

From the FDA Drug Label

Tamoxifen citrate tablets are indicated for the treatment of node-positive breast cancer in women following total mastectomy or segmental mastectomy, axillary dissection, and breast irradiation The estrogen and progesterone receptor values may help to predict whether adjuvant tamoxifen therapy is likely to be beneficial. Current data from clinical trials support 5 years of adjuvant tamoxifen therapy for patients with breast cancer

For a 40-year-old premenopausal woman with T3 N0 ER positive HER2 negative breast cancer post-mastectomy, the adjuvant management is tamoxifen therapy.

• The patient's ER positive status suggests that she may benefit from tamoxifen therapy.
• The patient's node-negative status (N0) also supports the use of tamoxifen as adjuvant therapy.
• The recommended duration of tamoxifen therapy is 5 years 2, 2.

From the Research

Adjuvant Management for ER Positive HER2 Negative Breast Cancer

The adjuvant management for a 40-year-old premenopausal woman with T3 N0 ER positive HER2 negative breast cancer post-mastectomy involves several considerations, including:

• The use of adjuvant hormonal therapy, which is mandatory for all patients with hormone receptor-positive breast neoplasms 3
• The selection of adjuvant chemotherapy, which may be beneficial for patients with an intermediate recurrence score (RS) of 16-25, particularly those under the age of 50 years 4
• The role of endocrine therapy, which is a crucial component of adjuvant management for HR-positive, HER2-negative breast cancer 5

Adjuvant Chemotherapy

The use of adjuvant chemotherapy in premenopausal patients with HR-positive, HER2-negative breast cancer is supported by studies such as the TAILORx trial and a retrospective analysis using the National Cancer Database 4. These studies suggest that adjuvant chemotherapy may improve progression-free survival and overall survival in patients with an intermediate RS.

Adjuvant Hormonal Therapy

Adjuvant hormonal therapy is a critical component of management for HR-positive breast cancer. Tamoxifen is the only active adjuvant hormonal therapy in pre- and postmenopause, while aromatase inhibitors are only used in postmenopause 3. The duration of adjuvant hormonal therapy influences disease-free survival, the risk of contralateral breast cancer, and overall survival.

Treatment Options

Treatment options for this patient may include:

• Adjuvant chemotherapy with a regimen such as doxorubicin-cyclophosphamide followed by weekly paclitaxel 6, 7
• Adjuvant hormonal therapy with tamoxifen or an aromatase inhibitor, depending on menopausal status 3
• Consideration of genomic assays and other biomarkers to guide treatment decisions 5