Biologic Determinants of Response to Paclitaxel &amp; Radiation
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Since systemic therapy reduces the risk of dying of breast cancer, most breast cancer patients are prescribed adjuvant chemotherapy (after surgical removal of the tumor). Unfortunately, most patients derive no benefit from adjuvant chemotherapy. In fact, of 10 women treated by conventional adjuvant chemotherapy only one will benefit. The remaining nine derive no benefit, either because they would have fared as well in the absence of systemic treatment or because they will recur in spite of it. Patients and doctors share the frustration of not knowing how to identify that one patient before treatment.
 
 
 
 
 
 
 
 We are proposing a clinical paradigm that allows us to monitor the effect of therapy on the original cancer, instead of removing the breast cancer first, and then giving therapy. Moreover, advances in molecular biology make it possible to study the original tumor cell characteristics (from pre-treatment biopsies), to correlate them with tumor response to a specific treatment.
 
 
 
 
 
 
 
 We were successful in obtaining the support of the Breast Cancer Research Program for a pilot study that fostered collaboration among three institutions, the University of Southern California, Mayo Clinic-Jacksonville and New York University. Together we have generated preliminary data that demonstrates feasibility and safety of single agent paclitaxel in breast cancers measuring more than 2 cm in diameter (T2-T3). The pilot also generated biological information that justified the design of a second study that combines paclitaxel with radiation for women who present with locally advanced breast cancers.
 
 
 
 
 
 
 
 Both studies are designed to enable us to measure the extent of residual cancer after treatment. As predicted, a large range of tumor response exists: in some patients the cancer cells completely disappear, while in others the cancer persists. Original biological features are studied from pre-treatment tumor biopsies and are correlated with the response found in the surgical specimen obtained after therapy. This method identifies specific markers in the original tumor that can predict for pathological response to paclitaxel (clinical study #1) or to paclitaxel and radiation (clinical study #2).
 
 
 
 
 
 
 
 By joining the efforts of three separate institutions we plan to accrue over 36 months a total of 80 women for each study. Clinical study #1 will enables us to: a) measure chemosensitivity directly in the breast cancer, b) understand which molecular characteristics of the tumor may predict for response and, c) generate biological information on paclitaxel alone to better understand its impact when combined with radiation. Clinical study #2 is as important because it will generate data to: a) understand how to best combine paclitaxel and radiation, b) impact the treatment of breast cancer as well as tumors at other sites that are treated with this combination and, c) improve treatment for locally advanced tumors, a more common breast cancer presentation among underserved minority women.
 
 
 
 
 
 
 
 We expect a more rational, patient-specific use of the available treatment modalities to increase survival from breast cancer.