About the Investigator:

Dr. Shlomit Strulov Shachar is a medical oncologist specializing in breast cancer. She received her MD from the Ruth and Bruce Rappaport Faculty of Medicine, Technion, Israel (2009) and completed her medical oncology Residency at Rambam Health Care Campus in Haifa, Israel. Dr. Shachar is ECFMG certified (2015) and completed a fellowship in breast cancer and geriatric oncology at Lineberger Comprehensive Cancer Center at the University of North Carolina (2016). She was a senior medical oncologist in the breast cancer service at Rambam Health Care Campus in Haifa, Israel, between 2017-2020 and since 2020 she has been a senior medical oncologist and researcher in Sourasky Tel Aviv Medical Center. Dr. Shachar has over 50 publications in peer-review journals, has written two chapters in books, and has presented at numerous international professional meetings. Her research interests have spanned a broad range of topics in breast cancer, including body composition and treatment outcomes, geriatric oncology, treatment toxicity, and translational research. Dr. Shachar is a recipient of several research grants for body composition and breast cancer research and performs peer review for oncology, breast cancer, and body composition journals.

About the Research:

Breast cancer (BC) is the most common cancer diagnosis and the leading cause of cancer death among females worldwide. The most common BC the is hormone receptor-positive (HR+) type, and there has been major progress in the treatment of HR+ metastatic breast cancer (MBC). The first line of treatment has been enhanced thanks to the combination of CDK4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) which improved time without disease progression and survival. However, drug resistance, which develops in nearly all patients, remains a critical unmet medical need, and the optimal sequence of treatment after its occurrence is unknown. For HR+MBC (40% have a specific change in the tumor named PIK3CA-mutation) after the disease progress on the first combination therapy, Alpelisib and everolimus are 2 biological drugs that, together with ET, can significantly improve outcome in terms of time without disease progression and higher response rates (such as shrinkage of the tumor). Both drugs work on the same pathway. The optimal sequence of delivering them in order to take full advantage of each, and whether there is any benefit in taking a second drug after progressing on one of them are unknown.

The goal of Dr. Shachar’s research to initiate a concerted effort involving tumor cultures taken from biopsies from patients with HR+MBC in order to test the responses to both drugs and to correlate molecular changes with those responses. In the second part of the study, her team will recruit patients that have progressed on the first drug and determine whether they have any response to the second drug. This will enable the team to characterize changes in the genetic material of the tumor that are associated with responses to the drugs by means of a simple blood test. The results of this proposal will help identify patients that can benefit from the treatment as well as those that will not: the latter is no less important in order to avoid an unnecessary toxicity burden.