Does a patient with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative breast cancer, with a Ki-67 index of 25%, and classified as T2N0M0, require adjuvant chemotherapy?

From the Guidelines

Adjuvant chemotherapy is recommended for this patient with HR-positive, HER2-negative breast cancer with T2N0M0 staging and Ki67 of 25%. The decision to recommend chemotherapy is based on several factors: the tumor size (T2 indicates >2 cm but ≤5 cm), the elevated Ki67 proliferation index of 25% (indicating more aggressive biology), and the hormone receptor positive status. While this patient has node-negative disease (N0), which is favorable, the combination of T2 staging with the elevated Ki67 suggests intermediate to high risk of recurrence. According to the NCCN guidelines 1, patients 50 years of age or younger with RS 16 to 25 had lower rates of distance recurrence with the addition of adjuvant chemotherapy to endocrine therapy. The preferred regimen would be an anthracycline and taxane-based combination such as dose-dense AC-T (doxorubicin/cyclophosphamide followed by paclitaxel) or TC (docetaxel/cyclophosphamide). For the AC-T regimen, this would typically involve 4 cycles of AC (doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m²) every 2 weeks followed by 4 cycles of paclitaxel 175 mg/m² every 2 weeks. Alternatively, TC would consist of 4-6 cycles of docetaxel 75 mg/m² with cyclophosphamide 600 mg/m² every 3 weeks. Following chemotherapy, the patient should receive appropriate endocrine therapy based on menopausal status, typically for 5-10 years, as suggested by the St Gallen International Consensus Conference for the primary therapy of individuals with early breast cancer 2023 1. It's also important to consider the risk stratification, where 'less favorable biology' includes higher-risk genomic signature, lower ER expression, intermediate to high grade, and/or higher baseline Ki67, as outlined in the St Gallen guidelines 1. The use of multigene tests to predict recurrence and guide the use of adjuvant chemotherapy is also recommended by the European Commission initiative on breast cancer 1. However, the most recent and highest quality study, the NCCN guidelines 1, should be prioritized when making a definitive recommendation. Some studies, such as the SWOG-8814 trial, have shown a clear benefit from adjuvant chemotherapy in patients with node-positive, HR-positive, HER2-negative tumors if they have a high RS ($31) 1. But for this patient with node-negative disease, the decision to recommend chemotherapy should be based on the tumor size, Ki67 proliferation index, and hormone receptor positive status. In summary, adjuvant chemotherapy is recommended for this patient, and the preferred regimen would be an anthracycline and taxane-based combination, followed by appropriate endocrine therapy. Key points to consider include:

• Tumor size and Ki67 proliferation index
• Hormone receptor positive status
• Node-negative disease
• Risk stratification and genomic signature
• Use of multigene tests to predict recurrence
• Prioritization of the most recent and highest quality study, the NCCN guidelines 1.

From the Research

Adjuvant Chemotherapy for HR-Positive, HER2-Negative Breast Cancer

• The decision to use adjuvant chemotherapy in patients with hormone receptor (HR)-positive, HER2-negative breast cancer is based on individualized risk assessment, taking into account factors such as clinical tumor features, biomarkers, and genomic risk 2.
• For patients with high-risk features, such as highly proliferative tumors, large tumor size, and significant nodal involvement, the risk of recurrence remains clinically significant despite appropriate adjuvant treatment with current standards of care 2.
• The use of adjuvant endocrine therapy and chemotherapy should be driven by a patient's risk for recurrence, preferences, and risk for side effects 2.

Role of Ki-67 in Treatment Decisions

• Ki-67 is a biomarker that can help predict the risk of recurrence in patients with HR-positive, HER2-negative breast cancer 3.
• A study found that high Ki-67 expression (≥20%) was associated with a higher risk of recurrence, and that Ki-67 testing was not widely used in patients with HR-positive, HER2-negative early breast cancer 3.
• However, another study suggested that Ki-67 expression is just one of many factors that should be considered when making treatment decisions, and that other clinical and pathological factors should also be taken into account 4.

Treatment Patterns and Outcomes

• A study found that most patients with HR-positive, HER2-negative early breast cancer were treated with adjuvant endocrine therapy, with or without chemotherapy 3.
• The use of cyclin-dependent kinase 4 and 6 inhibitors has been shown to improve outcomes in patients with high-risk, HR-positive, HER2-negative breast cancer 2, 5.
• A network meta-analysis found that CDK 4/6 inhibitors combined with aromatase inhibitors or fulvestrant resulted in a significantly longer progression-free survival compared to aromatase inhibitor monotherapy 5.

Individualized Treatment Decisions

• Treatment decisions for patients with HR-positive, HER2-negative breast cancer should be individualized, taking into account a patient's unique risk factors, preferences, and tumor characteristics 2, 6.
• Genomic assays and other biomarkers can help inform treatment decisions and provide a more personalized approach to care 6.
• Emerging data and new treatments, such as CDK 4/6 inhibitors, offer new strategies for improving outcomes in patients with HR-positive, HER2-negative breast cancer 2, 5, 6.