UCLA at SABCS 2024: Advancing Breast Cancer Research in Survival, Genomics, and Disparities

UCLA investigators present the latest breast cancer research at the annual San Antonio Breast Cancer Symposium Dec. 10 to 13

Investigators from the UCLA Health Jonsson Comprehensive Cancer Center discussed the latest clinical breakthroughs and research at the San Antonio Breast Cancer Symposium 2024 (SABCS), which was hosted by UT Health San Antonio and the American Association for Cancer Research from Dec. 10 to 13.

The premier breast cancer meeting will feature UCLA-led studies in key areas of clinical and translational research, including experimental biology, etiology, prevention, diagnosis and treatment of breast cancer.

“The San Antonio Breast Cancer Symposium provides an invaluable platform to share and discuss major advancements that are reshaping breast cancer care.

This year’s presentations reflect the academic commitment to innovative research that aims to improve survival and quality of life for patients worldwide,” said Dr. Aditya Bardia, director of the Breast Oncology Program and Translational Research Integration at the UCLA Health Jonsson Comprehensive Cancer Center.

The UCLA team presented original research related to novel therapeutics, functional imaging, immunotherapy-related complications, socioeconomic disparities, and genomic interception strategies for patients with high risk for breast cancer recurrence.

In addition, Dr. Marla Lipsyc-Sharf, a breast medical oncologist and researcher at the UCLA Health Jonsson Comprehensive Cancer Center, discussed how to approach treatment of estrogen-receptor positive breast cancer during the Educational Session: Case Based Clinical Approach to ER Positive Metastatic Breast Cancer.

Dr. Mina Sedrak, Associate Professor of Medicine at the David Geffen School of Medicine at UCLA and Director of the Cancer and Aging Program at the UCLA Health Jonsson Comprehensive Cancer Center, moderated an educational session on breast cancer in older adults on Thursday, Dec. 12, and Bardia moderated an educational session on antibody-drug conjugates (ADCs) on Friday, Dec. 13.

Highlights of noteworthy presentations at the SABCS that are led by UCLA researchers include:

Improved survival for advanced breast cancer

LB1-04 – Abstract SESS-3676: Efficacy and safety of trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) by pace of disease progression on prior endocrine-based therapy: additional analysis from DESTINY-Breast06

A team of international researchers led by Bardia, who is also a professor of medicine in hematology/oncology at the David Geffen School of Medicine at UCLA, found trastuzumab deruxtecan (T-DXd), an ADC, significantly improves progression-free survival compared to standard chemotherapy for patients with advanced breast cancer who have already undergone hormone-based therapies.

The study included 866 patients diagnosed with hormone receptor-positive (HR+), HER2-low or HER2-ultralow metastatic breast cancer who had disease progression after at least one endocrine therapy and no prior chemotherapy for the cancer. Participants were randomized to receive either T-DXd or treatment of physician’s choice of chemotherapy.

The researchers previously reported that the drug extended progression-free survival to 13.2 months, compared to 8.1 months for patients on the chemotherapy arm.

At SABCS, additional results highlight activity of T-DXd in all subgroups, including patients with rapid progression (<6 months) on first-line endocrine-based therapy. T-DXd builds on trastuzumab backbone linking the HER2 antibody with a powerful chemotherapy agent, allowing it to deliver cancer-killing drugs preferentially to the tumor cells compared to normal cells.

While the drug was previously approved for use in later-line setting for patients with HER2-low tumors, this study shows T-DXd could be used earlier instead of chemotherapy in a broader patient population with advanced breast cancer, leading to potential change in clinical practice.

Bardia presented the additional findings during the Late-Breaking Oral Presentations. The initial findings were also published in the New England Journal of Medicine.

Using genomics to identify patients with high risk of recurrence

PS9-01 – Abstract SESS-1614: Actionable Genomic Alterations in Localized Hormone Receptor Positive (HR+) Breast Cancer and Impact on Clinical Outcomes: Results from Comprehensive Whole Exome Sequencing (WES) and Tumor-Informed circulating tumor DNA (ctDNA) analysis.

New research led by Lipsyc-Sharf provides valuable insight into how tumor genomic testing and circulating tumor DNA (ctDNA) monitoring could guide future treatment strategies, particularly for patients at high risk of recurrence.

The researchers analyzed data from over 1,600 U.S. patients with stage I-III HR+/HER2- breast cancer using a tumor-informed ctDNA test called Signatera that is personalized to each patient based on whole-exome sequencing of their tumor. The goal was to identify actionable genetic mutations and evaluate their impact on disease recurrence and survival.

They found that 17.5% of patients had detectable ctDNA after surgery, indicating minimal residual disease, and 44% of these patients had at least one actionable mutation, such as PIK3CA, AKT, or ESR1. Patients with detectable ctDNA and tumor PIK3CA mutations had significantly reduced distant recurrence-free survival compared to those patients whose tumors tested positive for ctDNA, but did not have a tumor PIK3CA mutation.

The findings suggest ctDNA monitoring and tumor genomic testing can identify high-risk patients and guide trials studying targeted treatment strategies for early-stage breast cancer, with the goal of reducing breast cancer recurrences in this population.

Lipsyc-Sharf presented the findings during Spotlight Session 9: ctDNA uses for Minimal Residual Disease testing, tumor evolution, and novel technologies.

How race/ethnicity influence the risk of heart failure in early-stage breast cancer

PS10-03 – Abstract SESS-1970: Socioeconomic disparities in long-term heart failure risk of trastuzumab with or without anthracyclines in early-stage breast cancer: A SEER-Medicare Database Analysis

To better understand how socioeconomic factors and race/ethnicity influence the risk of heart failure in early-stage breast cancer patients treated with the chemotherapy drugs trastuzumab and anthracyclines, UCLA researchers analyzed data from over 200,000 patients diagnosed with stage I-III breast cancer between 2005 and 2016. These patients had no prior history of congestive heart failure and were included in the SEER-Medicare database.

The team linked patients’ data to their zip codes and census information to examine the influence of socioeconomic variables such as income, education, poverty and language spoken at home.

They found that patients receiving both trastuzumab and anthracyclines had the highest risk of developing heart failure, followed by those treated with just anthracyclines, and then those treated with just trastuzumab.

Black patients had a 23% higher risk of heart failure compared to White patients, even after accounting for other factors. Patients in areas with lower income also had an 18% higher risk. Patients of Black, Hispanic, and American Indian/Alaskan Native backgrounds were also more likely to have larger, higher-grade tumors, and tumor severity was linked to lower income and education levels.

The findings emphasize that both cancer treatments and social factors influence heart failure risk. The researchers stress the need for strategies to address these disparities, focusing on reducing social inequities and managing heart-related risks during cancer care.

The study was led by Dr. Karissa Britten, a hematology/oncology fellow at UCLA Health, and Dr. Nicholas McAndrew, an assistant clinical professor of medicine at UCLA. Britten presented the findings during Spotlight Session 10: Addressing Racial Disparities in Breast Cancer Outcomes.

The full online program.

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