27 Feb Cancers That Survive Chemotherapy Acquire Resistance Genes in Different Ways

MedicalResearch.com Interview with:

Dr. Pusztai

Lajos Pusztai, M.D, D.Phil.
Professor of Medicine
Director, Breast Cancer Translational Research
Co-Director, Yale Cancer Center Genetics and Genomics Program
Yale Cancer Center
Yale School of Medicine
New Haven, CT 05620 

MedicalResearch.com: What is the background for this study?

Response: We analyzed breast cancer tissues obtained before any therapy and the same cancers after 20 weeks of chemotherapy. This setting is ideal to find out what genomic changes have occurred in cancers that survived therapy. Due to the paucity of such specimens few other studies exist in this space.

MedicalResearch.com: What are the main findings?

Response: All patients received very similar chemotherapy but we found no evidence that a single gene or mutation mediate response to therapy.

Each cancer that survived chemo harbored  a different combination of mutations. However, mutations were significantly more common in genes that regulated cell proliferation. We also found that at baseline those cancers that showed genomic signs of DNA repair deficiency had high sensitivity to chemotherapy and these cancers rarely survived the chemo (we call this pathologic complete response).

MedicalResearch.com: What should readers take away from your report?

Response: Breast cancers with genomic scars are more sensitive to chemotherapy. Cancers that have survived chemotherapy tend to have more dysregulated proliferation after treatment due to acquired mutations in many different genes compared to pretreatment cancer.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Studying drug resistance is very challenging because each cancer develops resistance through its own way.

Any disclosures? This study was funded by the Breast Cancer Research Foundation, the Susan Komen Foundation and the HOPE foundation.

Citation:

Analysis of pre- and post-treatment tissues from the SWOG S0800 trial reveals an effect of neoadjuvant chemotherapy on the breast cancer genome

Ryan L. Powles, Vikram B. Wali, Xiaotong Li, William E. Barlow, Zeina Nahleh, Alastair M Thompson, Andrew K. Godwin, Christos Hatzis and Lajos Pusztai
Clin Cancer Res January 9 2020 DOI: 10.1158/1078-0432.CCR-19-2405

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Last Updated on February 27, 2020 by Marie Benz MD FAAD