Abstract MS1-3: Treatment of ER+/HER2+ breast cancer

Abstract Co-expression of hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) occurs in 10% of all breast cancers, and due to cross-talk mechanisms that influence cell signalling the co-expression of these receptors modulates response of these cancers to both HER2-directed and endocrine therapies. Prior to the advent of HER2 targeted therapies, patients with HR+/HER2+ breast cancer had a significantly worse prognosis compared with HR+/HER2- breast tumours, primarily related to HER2 signalling driving endocrine resistance. Likewise, prior clinical studies in the neoadjuvant setting showed that patients with HR+/HER2+ primary breast cancer had a lower pathological complete response rate to HER2-targeted therapy plus chemotherapy that those with HR-/HER2+ tumours, suggesting a different biology. As such, strategies that combine receptor blockade against HER2 and HR have been developed in metastatic breast cancer (MBC), confirming that combined blockade is better than endocrine therapy (ET) alone, and then that dual HER2 blockade + ET was superior to single HER2 therapy + ET. More recently combinations of a CDK 4/6 inhibitor with ET and HER2 therapy has shown significant clinical efficacy and survival benefit in heavily pre-treated patients, confirming the efficacy for non-chemotherapy targeted combinations in HR+/HER2+ MBC. In the early breast cancer (EBC) setting, most HER2 directed therapy is given in combination with chemotherapy in the neoadjuvant setting, while studies of combined ET and HER2 targeted strategies without chemotherapy work slower with lower pCR rates. As such, the real benefit for combined targeted therapy may be in the adjuvant setting where ET and HER2 therapy are routinely given together following completion of chemotherapy. Furthermore, extended adjuvant ET/HER2 therapy beyond completion of antibody based treatment may also provide extra benefit, and in higher risk patients longer treatment may prove an important consideration. Citation Format: Stephen Johnston. Treatment of ER+/HER2+ breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr MS1-3.