BCRF was well represented last week at the San Antonio Breast Cancer Symposium (SABCS), the largest annual meeting dedicated to breast cancer research, with our investigators receiving awards and presenting throughout the four-day conference.
Meetings like SABCS facilitate a collaborative environment and fuel ideas and innovation to propel the field forward. This year’s conference was no different, with researchers sharing potentially practice-changing clinical trial results, novel treatments being studied, updates on BRCA2 variants, and more.
Below, BCRF shares highlights and news from SABCS 2024.
There are several known mutations in the BRCA2 gene that are related to breast cancer. But research has shown there are other mutations whose functional effects on BRCA2 gene activity are unknown. These mutations are called variants of unknown significance (VUS).
Dr. Fergus Couch presented very exciting results regarding VUS and breast cancer risk prediction. In his BCRF-supported project, Dr. Couch and his team used cutting-edge CRISPR/cas9 targeting to evaluate more than 7,000 VUS in the key functional parts of BRCA2 gene at the same time. This project was an impressive undertaking—a true tour de force.
The 7,000 VUS were specifically located in the DNA-binding domain of BRCA2, which makes up one third of the entire gene. Of those, the team classified 785 variants as pathogenic or likely pathogenic whereas 5,569 variants were classified as benign or likely benign. These results may ultimately inform breast cancer care for anyone found to carry one of the 785 variants. And since most previous studies on gene mutations have been conducted in white women, these findings improve our understanding of VUS in all women, and particularly non-white women who tend to have many more of these variants.
BCRF Scientific Director Dr. Judy Garber provided updates on the OlympiA trial (NCT02032823), which examines adding one year of the oral PARP inhibitor olaparib (Lynparza®) after standard treatment for higher-risk breast cancer in individuals with pathogenic germline BRCA variants. These patients are more likely to be younger and have a strong family history of the disease. Follow-up for over six years demonstrated long-term survival benefits for the study’s patient population.
In the area of screening, BCRF investigator Dr. Constance Lehman discussed various mammographic strategies being tested. Regarding the use of contrast-enhanced mammography (CEM) for early detection of breast cancer, she showed that CEM can replace high-cost MRI for more precise risk assessment, regardless of breast density. This could be particularly impactful for younger women who tend to have dense breasts.
Dr. Matteo Lambertini of the University of Genova presented results from the BRCA BCY Collaboration (NCT03673306), an international, multicenter trial. The team investigated the association between risk-reducing mastectomy (RRM) and/or risk-reducing salpingo-oophorectomy (RRSO) with survival outcomes in the largest global cohort of young BRCA carriers with breast cancer: 5,290 patients who harbored germline BRCA1 and/or BRCA2 mutations and were diagnosed with stage 1-3 invasive breast cancer at a median age of 35. In this unique group, RRM and RRSO were both associated with a significant improvement in overall survival and disease-free survival. These findings support the critical importance of counseling young BRCA carriers with breast cancer on strategies for managing their disease.
In a poster session presentation, investigators shared the first report from BCRF’s Health Equity Initiative (HEI) made possible by The Estée Lauder Companies Charitable Foundation (ELCCF). This five-year study focuses on how social drivers of health intersect with Black women’s biology to impact their breast cancer outcomes. The key findings concern two of the factors studied:
Dr. Melissa Davis, a member of BCRF’s HEI steering committee, gave a plenary lecture about her work in disparities: “The Grand Challenge of Unraveling Social vs. Biological Drivers of Racial Disparities in Cancer Outcomes.” Earlier this year, Dr. Davis received a Cancer Grand Challenge Award, the first such award in disparities and the first granted to a historically Black medical school.
The BCRF-supported COMET trial (Comparing an Operation to Monitoring with or without Endocrine Therapy, NCT02926911)—the first-of-its-kind conducted in the U.S.—tested active monitoring as an alternative to surgery and radiation for patients with low-risk ductal carcinoma in situ (DCIS).
BCRF investigators and co-leads on this study, Drs. Shelley Hwang and Ann Partridge, reported that 5.9 percent of patients who underwent surgery developed invasive breast cancer within two years, while 4.2 percent of the patients who received active monitoring did. BCRF support will ensure necessary long-term follow-up, but these findings are potentially game-changing for patients with low-risk DCIS. Read more here.
Dr. Komal Jhaveri of Dana-Farber Cancer Institute presented the results of EMBER3 (NCT04975308) a study conducted with imlunestrant, a next-generation oral serum estrogen receptor degrader (SERD; a type of anti-estrogen hormone therapy).
EMBER3 compared outcomes with imlunestrant monotherapy or in combination with abemaciclib in estrogen receptor–positive/HER2-negative advanced breast cancer. Dr. Jhaveri reported that patients with estrogen receptor 1 (ESR1) mutations showed a 38 percent decrease in the risk of disease progression and death with imlunestrant alone. Adding abemaciclib resulted in improved progression-free survival of more than 9.4 months in all patients, regardless of ESR1 status.
These promising results move this treatment closer to FDA approval, and, if approved, would offer patients the option to take a SERD as a more-convenient pill (fulvestrant, the only currently approved SERD, requires an injection). Imlunestrant was also shown to cross the blood-brain barrier.
BCRF investigator Dr. Mafalda Oliveira presented updates from the phase 2 SOLTI VALENTINE (NCT05569811) trial that tested a first-in-class anti-HER3 antibody-drug conjugate (HER3-durextecan) as a single agent or in combination with letrozole in high-risk HR-positive/HER2-negative early breast cancer. Dr. Oliveira reported that pathological complete response and overall response rate was similar to that with chemotherapy. However, HER3-DXd compared to chemotherapy demonstrated lower incidence rates of grade 3 adverse events with fewer dose reductions, interruptions in treatment, and treatment discontinuation.
As in past conferences in recent years, antibody-drug conjugates (ADCs) were a major focus. There are currently eight FDA-approved ADCs, which have expanded the armamentarium of HER2-targeted therapies. But several studies highlighted at SABCS this year showed the utility of adding CDK4/6 inhibitors to ADCs, demonstrating that they still have a role, 15 years following their development. Further studies are focused on improving the efficacy of ADCs by refining each of its components: payload, linker, and antibody. Researchers are steadily homing in on understanding ADCs’ potential toxicities and resistance mechanisms.
Three BCRF investigators were honored with prestigious awards at this year’s meeting in recognition of their groundbreaking contributions to breast cancer research.
Dr. Laura J. van ’t Veer, a BCRF investigator since 2014, was honored with the William L. McGuire Memorial Lecture Award—the meeting’s top honor—for advancing breast cancer risk stratification and subtyping and for improving early breast cancer treatment. She invented MammaPrint, a test that predicts breast cancer recurrence by analyzing activity levels of 70 genes. Her tireless efforts in the I-SPY trials led to the creation of a biomarker bank and response-predictive subtypes, empowering clinicians to tailor treatments to individual patients.
BCRF investigator since 2011 Dr. Christina Curtis received the annual AACR–Breast Cancer Research Foundation Outstanding Investigator Award for Breast Cancer Research for her contributions to the field’s understanding of the molecular determinants of breast cancer. Her work has defined new disease subgroups, improved prediction of distant relapses, and developed biomarkers to improve patient stratification. Dr. Curtis acknowledged how BCRF support has given her invaluable freedom to pursue her ideas.
Dr. Steffi Oesterreich, a BCRF investigator since 2011, was honored with the AACR Distinguished Lectureship in Breast Cancer Research for her work in translational breast cancer research to advance our understanding of invasive lobular carcinoma (ILC). This work has redefined ILC as a distinct biological entity with unique disease drivers, distinguishing it from the more-studied form of breast cancer, invasive ductal carcinoma (IDC). Dr. Oesterreich thanked BCRF, acknowledging that her work in ILC would not have been possible without the Foundation’s initial and continued support.
In an off-site ceremony, three BCRF investigators also received the Susan G. Komen Brinker Awards: Dr. Curtis received the Brinker Award for Scientific Distinction in Basic Science, Dr. Fabrice André for Scientific Distinction in Clinical Research, and Dr. Graham Colditz for Scientific Distinction in Population Science (the inaugural award for this category).
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