Navigating the Horizon: Anticipating Breakthroughs at SABCS 2023

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As the anticipation builds for the San Antonio Breast Cancer Symposium (SABCS) 2023, the global breast cancer community eagerly awaits the unveiling of cutting-edge research, groundbreaking therapies, and pivotal advancements in the field. As a breast medical oncologist, the symposium provides a unique opportunity to explore the latest developments, exchange insights, and chart the course for the future of breast cancer care.

In this article, we embark on a journey to distill the wealth of information that SABCS 2023 promises to deliver. From innovative treatment modalities to emerging biomarkers, we will navigate the landscape of breast cancer research, shedding light on the key presentations that are poised to shape the next frontier in breast oncology.

1. Advancements in Targeted Therapies

Tucatinib, a tyrosine kinase inhibitor selectively targeting human epidermal growth factor receptor 2 (HER2), has indisputably transformed the landscape since its FDA approval based on the HER2CLIMB-01 trial. This pivotal study demonstrated the effectiveness of combining tucatinib, trastuzumab, and capecitabine in metastatic HER2+ breast cancer. At SABCS23, we eagerly anticipate the inaugural results of the HER2CLIMB-02 — a randomized, double-blind phase 3 trial investigating tucatinib and trastuzumab emtansine for previously treated HER2-positive metastatic breast cancer.

The paradigm shift ushered in by CDK4/6 inhibitors in the treatment of hormone receptor (HR)-positive, HER2-negative metastatic breast cancer is unmistakable. The monarchE trial established the role of abemaciclib, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), in early-stage HR+ HER2-negative disease. At ASCO23, the NATALEE results unveiled the potential of another CDK4/6i — ribociclib — in managing early-stage HR+ breast cancer. At SABCS23, we await the presentation of the final invasive disease–free survival (iDFS) analysis from the NATALEE trial.

Capivasertib, an AKT inhibitor, recently gained FDA approval for use in combination with fulvestrant in HR+ HER2-negative metastatic breast cancer with PTEN/PI3K/AKT pathway alterations. At SABCS23, updated results from the phase 1b analysis of CAPItello-292, exploring capivasertib in combination with CDK4/6i and fulvestrant in HR+ HER2-negative metastatic breast cancer, will be unveiled.

2. Immunotherapy Breakthroughs

The integration of immunotherapy (IO) with chemotherapy stands as a game-changer in managing patients with early-stage and metastatic triple-negative breast cancer. However, the application of IO in HR+ HER2-negative metastatic breast cancer has faced disappointments. A glimmer of hope emerged at ESMO23 with the presentation of KEYNOTE-756: a Phase 3 study showcasing improved pathological complete response (pCR) with the addition of IO to chemotherapy for early-stage high-risk HR+/HER2-negative breast cancer. SABCS23 promises an update on this consequential study.

3. The Era of Antibody-Drug Conjugates

Antibody-drug conjugates (ADCs) have undeniably revolutionized oncology, defining this era of precision medicine with their remarkable efficacy across various cancers. Despite this excitement, questions linger, particularly regarding the viability of sequential ADC use. Three studies investigating the sequencing of ADCs in metastatic breast cancer will be presented in the "Poster Spotlight Sessions Block #3" on Wednesday, December 6, shedding light on this crucial query.

At SABCS23, the spotlight will also be on the TROPION-Breast01 trial — a randomized phase 3 study comparing datopotamab deruxtecan to chemotherapy for patients with inoperable or metastatic HR+ HER2-negative breast cancer.

4. Spotlight on Invasive Lobular Carcinoma

Invasive lobular carcinoma (ILC), an understudied emerging subtype of breast cancer, has garnered increased attention due to its unique behavior, characteristics, and responses to current therapies. This year, for the first time at SABCS, ILC will receive its dedicated educational session where researchers will illuminate the nuances and advancements in understanding and managing this distinct subtype.

Dr. Mouabbi reports consulting fees for BostonGene, GE Health Care, Novartis, AstraZeneca, Gilead, Genentech, and Cardinal Health, and honoraria from Novartis, Gilead, Cardinal Health, and Fresenius Kabi.

Illustration by Jennifer Bogartz

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