Optimal Choice of Neoadjuvant Chemotherapy for HER2-Negative Breast Cancer: Clinical Insights

Abstract

The neoadjuvant setting provides immense opportunities for translational research and drug development. The acceptance of pathological complete response (pCR) as a surrogate endpoint for clinical benefit has led to the widespread use of neoadjuvant treatment. Optimal neoadjuvant therapies are determined based on their ability to achieve the highest rates of pCR. Predicted rates of pCR for triple negative breast cancer (TNBC) treated with sequential taxane/anthracycline regimens range from 35% to 48%. With the addition of a platinum agent pCR rates of 55% are predicted. Further increases have been observed with the addition of immune checkpoint inhibitors to this standard chemotherapy backbone. In the pivotal KEYNOTE-522 clinical trial pCR rates of 65% and 69% were reported for chemotherapy plus pembrolizumab in the overall and PD-L1-positive subgroup respectively. The role of the neoadjuvant chemotherapy is less clear in hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative breast cancer. In general, HR–positive cancers have the least chance of achieving a pCR after neoadjuvant chemotherapy, especially if they are low-grade. If neoadjuvant chemotherapy is given for high-risk HR-positive, HER2-negative breast cancer, standard adjuvant anthracycline/taxane regimens are appropriate. Optimum endocrine therapy is the standard-of-care in the adjuvant setting regardless of pCR. There are several genomic signatures available to guide decisions regarding adjuvant chemotherapy use however these assays are not routinely used in the neoadjuvant setting. For high-risk patients meeting the criteria for the monarchE trial adjuvant abemaciclib in addition to endocrine therapy is associated with an improvement in disease free survival (DFS) at 3 years. Based on the OlympiA trial patients with germline BRCA mutations should be considered for adjuvant olaparib therapy. In this article we review neoadjuvant clinical trials that guide optimum treatment options for TNBC and HR-positive, HER2-negative breast cancer.

Analyzing Neoadjuvant Chemotherapy Effects in HER2-Low Breast Cancer: Real World Data

“…Though it is accepted that pCR is a relevant surrogate outcome in BC literature after NAC, the relation between pCR and hard outcomes is not completely clear. Interestingly, the KEYNOTE-522 trial (triple negative NAC eligible population) suggested a high pCR rate (around 60%) in patients receiving pembrolizumab [ 18 ]. This information might reinforce the association of HER2-expressing cells with poorer outcomes, likewise reported in other HER2-positive studies in women with BC that received trastuzumab as NAC (38% pCR rate) [ 19 , 20 ].…”

ZNF703 mRNA-Targeting Antisense Oligonucleotide Blocks Cell Proliferation and Induces Apoptosis in Breast Cancer Cell Lines

“…For high-risk, ER+, HER2− BC, standard adjuvant anthracycline-taxane regimens are appropriate when neoadjuvant chemotherapy is chosen. However, optimal hormone therapy is the standard of care in the adjuvant setting, whether or not a pathological complete response is obtained [ 78 ]. Tamoxifen is commonly used in the treatment of luminal BC.…”

Factors Affecting Pathological Complete Response in Locally Advanced Breast Cancer Cases Receiving Neoadjuvant Therapy: A Comprehensive Literature Review

“…With the addition of a platinum agent, pCR rates of 55% are predicted. Further increases have been observed with the addition of immune checkpoint inhibitors to this standard chemotherapy backbone (44). In the pivotal KEYNOTE-522 clinical trial, pCR rates of 65% and 69% were reported for chemotherapy plus pembrolizumab in the overall and PD-L1-positive subgroups, respectively (45).…”