Abstract ED11-2: HER2 positive breast cancer

Abstract

Abstract Neoadjuvant therapy of HER2+ breast cancer has been groundbreaking. It showed the superior results in terms of pathologic complete response (pCR) and event free survival (EFS) of adding trastuzumab to chemotherapy in women with locally advanced breast cancer (NOAH trial) that led to the first regulatory approval of a neoadjuvant approach in the field of breast cancer. In addition, neoadjuvant studies (NeoSphere, neoALLTO) clearly showed the improved antitumor activity of dual blockade of the HER2 receptor, paved the way to the Aphinity adjuvant study and justified the current worldwide use of dual black of HER2 in high/moderate risk HER2+ early breast cancer. In the above scenario the design and results of the Katherine study were a landmark achievement. By proving the clinical value of shifting treatment from trastuzumab to trastuzumab-DM1 in women with residual disease after neoadjuvant therapy the study provided firm clinical evidence that residual disease can be used as a surrogate of relative resistance that per se justifies the adoption of alternative non cross resistant regimens/therapies at the individual level. The clinical success of neoadjuvant trials in HER2+ early breast cancer went hand-to-hand with translational studies that that are identifying markers predicting for pCR and EFS that are and will be used to fine tuning a more individually tailored approach to treatment, and eventually effective and safe de-escalation strategies. The rich collection of neoadjuvant studies that shaped the modern approach to treatment of women with early HER2+ breast cancer will be enriched of studies with new drugs, trastuzumab deruxtecan and tucatinib to name some of the front runners. All current and future treatments will greatly depend on the neoadjuvant approach as a tool for a quick assessment of the clinical value of new therapies. Such approach has so far been used as basis or supporting evidence for regulatory approvals worldwide, based on the concept that pCR can be viewed as surrogate of long-term benefit. Individual trials and meta-analyses are challenging the dependability of pCR to predict EFS at trial level. However, the benefits of tumor eradication (pCR) at individual level continue to support the simple clinical concept that more pCR is better and that regimens leading to it deserve full credit. Acknowledgment: The work of Luca Gianni is supported by grants of the BCRF Citation Format: Luca Gianni, Giampaolo Bianchini. HER2 positive 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 ED11-2.