Abstract SP092: Special topics in metastatic ER+ breast cancer

About 70% of all diagnosed breast cancers express hormone receptors (estrogen [ER+], progesterone [PR+] or both [HR+]). Despite an overall good prognosis, the clinicopathological and molecular heterogeneity of these tumors account for a diverse natural history of disease, with several patients still developing distant metastatic recurrence at virtually any point during the disease trajectory, regardless of endocrine therapy. Improved risk stratification and treatment individualization accounts for longer disease-free and overall survival, but distant metastatic recurrences still occur and about half of these occur beyond 6 years from the original diagnosis. A better understanding of breast cancer biology and mechanisms of endocrine therapy resistance has resulted in the approval of novel therapeutic strategies for patients with HR+ metastatic breast cancer (MBC), which now often include addition of targeted treatment, such as CDK4/6 or PI3K pathway inhibitors, to first, second or third line endocrine therapy. Improvement in progression-free survival and sometimes even overall survival, as well as a delay in chemotherapy use in the metastatic setting and maintenance of a good quality of life have been important achievements with these targeted therapies. However, more refined clinical and molecular biomarkers are lacking to determine which patients truly need (or not) the (early or at all) addition of these targeted treatments to conventional endocrine therapy, the timing and order of targeted therapy addition and even the timing to introduce chemotherapy. Currently, the amount of ER/PR expression in the tumor, presence of tumor actionable genomic alterations (such as PIK3CA, ESR1, BRCA mutations to name a few), the patient’s disease-free interval between original (early) and metastatic breast cancer diagnosis, metastatic burden and sites of metastasis, absence or presence of symptoms or visceral crisis, previous treatments, among others, are some of the main variables that clinicians take into account to customize HR+ MBC treatment. Several research efforts are under way, focusing on important questions addressing the optimal sequence and administration of drugs to circumvent current endocrine therapy with or without CDK4/6 inhibition strategies, such as (a) timing and order of CDK4/6 inhibitor addition to endocrine therapy, (b) if CDK4/6 inhibitors should be continued with a different endocrine therapy partners beyond progression of disease on endocrine therapy and CDK4/6 inhibitors, (c) novel combination of endocrine therapy with or without CDK4/6 inhibitors with targeted treatments or immunotherapy, (d) new endocrine therapy agents such as novel selective ER downregulators (SERDs) and selective ER covalent agonists (SERCAs), (e) serial collection of tumor tissue and blood for profiling at different timepoints during the metastatic setting treatment in an effort to identify new mechanisms of resistance, and (f) novel chemotherapy combinations with targeted treatment or immunotherapy. In conclusion: many therapeutic and diagnostic advances have contributed to better outcomes in HR+ MBC, but recognition of differences between clinicopathological and molecular characteristics of patients and their tumors is key in promoting optimization of treatment choices that would maximize survival, palliation of symptoms and quality of life for patients with HR+ MBC in the years to come. Citation Format: I Mayer. Special topics in metastatic ER+ breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP092.