By Dorys Lopez
From December 7th -10th the San Antonio Breast Cancer Symposium gathered breast cancer experts from all over the world to share the latest medical and scientific advances in the breast cancer field.
Our team attended the meeting to present our research on breast cancer. Here are some of the key take home messages from the conference.
KEYNOTE studies. Updated studies from KEYNOTE-522 and KEYNOTE-355 were presented at the conference by Dr. Peter Schmid and Dr. Javier Cortés. These results showed the clinical improvement of pembrolizumab in both early-stage and metastatic triple negative breast cancer (TNBC). However, there are concerning immune-related events in the combination treatment of chemotherapy and pembrolizumab, which decrease when the checkpoint inhibitor is given as monotherapy. There is still confusion around the real benefit of pembrolizumab vs chemotherapy for patients. In the KEYNOTE-355 study, for example, only 38% of patients benefited from pembrolizumab. Questions remain, among them: what group of patients is the most suitable for immune checkpoint inhibitors? Can we characterize this population of patients?
Immunotherapy biomarkers. There is need for better biomarkers of immunotherapy. As Dr. Hope Rugo mentioned during her discussion of the first half of General Session 1, PD-L1 is not an ideal biomarker, but it is the best one currently available. She also highlighted the discrepancies of PD-L1 as a biomarker for early-stage disease vs. metastatic disease, showing a higher impact on the latter. She emphasized the need for better tumor characterization and tied it nicely with Dr. Giampaolo Bianchini’s presentation. Dr. Bianchini talked about spatial characterization of immune cells in TNBC patients in the NeoTrip trial. These included the interactions between the epithelial and the tumor microenvironment and of note, further characterization was done according TNBC subtypes: basal-like-1, basal-like 2, luminal androgen receptor, mesenchymal, and mesenchymal stem-like. PD-L1 cell phenotypes seem to favor basal-like tumors, while T cell signature seems to benefit mesenchymal stem-like TNBCs.
TNBC subtypes. During the TNBC educational session all speakers Dr. Zhi-Ming Shao, Dr. Elizabeth Mittendorf and Dr. Alexandra Thomas highlighted TNBC heterogeneity. Dr. Mittendorf emphasized that a better understanding of the intrinsic and extrinsic factors that contribute to TNBC heterogeneity can improve the opportunity to target this disease. Dr. Shao’s described four TNBC molecular subtypes each one with different sensitivity to therapy. He further talked about precision treatment based on molecular subtyping and proposed a treatment strategy for each subtype. Dr. Thomas talked about the rare TNBCs which make up around 7% of TNBCs. She underscored the need to go beyond randomized trials to better understand and characterize these subtypes. During her talk she summarized TNBC heterogeneity by saying that TNBC subtypes only have in common their lack of receptor expression.
Single-cell spatial analysis. There is growing interest in understanding how the spatial distribution of cells in the tumor and the surrounding tissue, and their interactions affect response to therapy. As mentioned before, Dr. Bianchini presented results on the NeoTripaPDL1 trial. During the anti-cancer immune response session, Dr. Marleen Kok also talked about single-cell analysis and further spatial profiling of the cells. Besides touching on the NeoTrip results, she touched on the BioKey and TONIC trial results. Overall, single-cell data indicated that PD1+CD8+Tex, GRZMB+CD8+, CXCL13+CD8+ and PD-L1+DCs are key for immunotherapy response. Spatially, an inflamed TNBC seems to respond better, in particular when the inflammation comes from CD8+ cells and PD-L1+DCs.
Racial disparities in breast cancer. In a session called “Trust in healthcare”, Dr. Charles Perou talked about some of the biological differences between tumors from black and white women. Black women have a higher incidence of basal-like breast cancer (TNBC), while white women have a higher incidence of what he called “good type, if there’s such thing” luminal-A like breast cancer. Dr. Perou underscored that black women present delays in treatment initiation, lower treatment adherence, and are less likely to receive the proper medication compared to white women, according to Medicare data that he presented during his talk. Perhaps one of the most important messages was made by Dr. Perou, further supported by medical student Beverly Kyalwazi, BS, both showed data that indicated no difference in pCR rate when both racial groups receive equal treatment. As Dr. Olufunmilayo Olopade, winner of the William L. McGuire award, mentioned in her talk, it is tumor biology that truly impacts patient outcome.
No good news from MA.32A trial. Dr. Pamela Goodwin summarized results of the MA.32A trial where no benefit of metformin was observed in early breast cancer. In the Phase III, MA.32A trial impact of metformin vs. placebo on recurrence and survival in early breast cancer following standard of care found that metformin does not improve outcomes in most patients. Despite of the negative results, an exploratory analysis of HER2+ patients identified a subgroup that seem to benefit from this therapy, patients had a C allele of the rs11212617 variant.
CDK4/6i resistance. Two studies with conflicting results on CDK4/6i in HR+ early breast cancer were presented at the conference: PALLAS and MonarchE. While MonarchE showed positive results using abemaciclib, PALLAS showed no difference between Palbociclib and placebo. Although metadata is needed to better understand the results. There is also emphasis on improving treatment strategies after development of CDK4/6i resistance which inevitably occurs. CDK7 inhibitor in combination with fulvestrant showed positive results in a small, single-arm study for treatment of HR+ breast cancer patients that had been previously treated with CDK4/6i.
Antibody conjugates. Trastazumab antibody conjugates T-DXd and T-DM1 efficacy were compared in the DESTINY-Breast03 trial for patients HER2+ metastatic breast cancer patients that had been previously treated with trastuzumab and chemotherapy. The subgroup analyses presented by Dr. Sara Hurvitz showed that patients with brain metastases showed significant improvement with T-DXd compared to T-DM1 treatment, where 27.8% of T-DXd treated patients achieved a complete response compared to 2.8% in T-DM1 treated patients.
Social media. If you didn’t know already, one of the best ways to get in touch with doctors is via Twitter. And if you couldn’t attend the conference, you could have still followed twitter and feel like you were there. All thanks to the live tweeting from doctors and scientists who took over the social media platform to share the key messages of every session and their take on it