Abstract ES5-1: Neoadjuvant therapy for hormone receptor-positive breast cancer: challenges and advances

Neoadjuvant therapy in breast cancer has evolved from a modality able to facilitate surgery into a sophisticated treatment approach, where patterns of response influence the extent of surgery (i.e. breast and axilla) and inform treatment decisions in the adjuvant setting. This is particularly true for patients diagnosed with HER2-positive or triple-negative breast cancer (TNBC). In the subset of estrogen receptor-positive (ER+) disease, the neoadjuvant treatment model has proven to be a successful clinical research tool. Studies investigating pharmacodynamic markers (i.e., Ki67) demonstrated the differences in the relative effectiveness of tamoxifen versus aromatase inhibitor and, more recently, neoadjuvant studies with endocrine therapy plus CDK4/6 inhibitors demonstrated the efficacy of CDK4/6 inhibitors in potentiating the effects of endocrine therapy through a profound suppression of Ki67. However, in clinical practice neoadjuvant endocrine therapy remains underutilized. Routinely, ER+ candidates for neoadjuvant therapy are treated with chemotherapy with minimal attention to disease biology. By contrast, disease biology plays a major role in the adjuvant setting, and the “old notion” of disease burden predicting chemotherapy benefit is fading away. The disconnect between the choices of systemic therapy in the neoadjuvant versus adjuvant setting in ER+ breast cancer has multiple roots: 1) Physicians and patients may expect higher response rates to neoadjuvant chemotherapy; 2) genomic biomarkers to guide chemotherapy treatment decisions were developed using material from surgical specimens; 3) there are limited data with neoadjuvant endocrine therapy in premenopausal women; and 4) the objectives with neoadjuvant endocrine therapy are not always clear. While additional clinical studies are warranted, the available clinical data suggest neoadjuvant endocrine therapy is an appropriate treatment approach for patients with ER+ disease. When selecting patients by ER+ status only, response rates to neoadjuvant endocrine therapy are similar or higher than chemotherapy. Clinical studies have successfully used diagnostic biopsies for genomic profiling, and if anything, the quality of FFPE material should be superior due to pre-analytical variables (e.g., reduced ischemic time). Additionally, neoadjuvant endocrine therapy for ER+ breast cancer and favorable disease biology fulfills the promise of a tailored treatment approach and avoids unnecessary use of cytotoxic therapy. When selecting neoadjuvant endocrine therapy for patients, it is important to understand some key points regarding this treatment approach. The maximum treatment response is not expected before four to six months of therapy, and the interpretation of pathologic response should not be confounded by data from HER2+ and TNBC. Residual disease after neoadjuvant endocrine therapy is not a predictor of survival outcomes. And, lastly, if the patient was not deemed as an ideal candidate for neoadjuvant chemotherapy at baseline, the extent of residual disease should not be used a predictor of chemotherapy benefit. There are, however, caveats and extensive disease at the time of surgery (e.g., four or more positive nodes) might justify a course of adjuvant chemotherapy. In summary, neoadjuvant endocrine therapy should not be a treatment of exception for elderly patients when trying to avoid the toxicities of chemotherapy. Neoadjuvant endocrine therapy is an effective treatment modality with proven clinical utility for postmenopausal patients with ER+ breast cancer. Citation Format: O Metzger. Neoadjuvant therapy for hormone receptor-positive breast cancer: challenges and advances [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES5-1.