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Subtype of triple negative breast cancer responds better to chemotherapy

Date:
December 13, 2016
Source:
Yale Cancer Center
Summary:
Researchers have identified a new subtype of triple negative breast cancer that shows significantly improved response to chemotherapy. Patients with the newly defined subtype — BRCA-deficient triple negative breast cancer — had significantly higher survival rates with chemotherapy.
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Researchers at Yale Cancer Center have identified a new subtype of triple negative breast cancer that shows significantly improved response to chemotherapy. Patients with the newly defined "BRCA deficient" subtype experienced better survival with chemotherapy. The study was published on Dec. 13 in PLOS Medicine.

Triple negative breast cancer (TNBC) disproportionately affects younger women and women of African ancestry, contributing to health disparities. In the era of personalized cancer therapy, patients with TNBC remain at considerably higher risk of relapse and death than patients with other breast cancer subtypes, due to the aggressive nature of TNBC and the lack of newer targeted therapies for the disease.

The Yale-led study performed whole exome sequencing ¬ -- a technique for sequencing all the expressed genes in a genome ¬ -- on TNBC tumors to identify mutations in specific genes or pathways that may indicate response or resistance to the standard of care, which is anthracycline/taxane (ACT) chemotherapy. Researchers found that tumors carrying mutations in the AR and FOXA1 pathways had a significantly higher response rate, 94.1% compared to 16.6% in tumors without the mutations.

Analysis of genomic, epigenetic, and RNA sequencing data revealed that the combinations of mutations that lowered the levels of functioning BRCA1 and BRCA2 RNA -- genes that produce the breast cancer tumor suppressor proteins -- were associated with significantly better survival outcomes.

"Low levels of functional BRCA are associated with a greater number of clonal mutations and enhanced immune recruitment, which may explain the greater chemosensitivity of these tumors and better outcomes for patients," explained Christos Hatzis, assistant professor of medicine and director of Breast Bioinformatics, Yale Cancer Center and senior author on the paper.

"The strong connection of ACT chemosensitivity and immune activity in the newly defined BRCA-deficient phenotype of TNBC could help inform future therapeutic strategies for our patients," said Lajos Pusztai, M.D., professor of medicine (medical oncology), Yale Cancer Center, and disease aligned research team leader for the Breast Center at Smilow Cancer Hospital.


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Materials provided by Yale Cancer Center. Note: Content may be edited for style and length.


Journal Reference:

  1. Tingting Jiang, Weiwei Shi, Vikram B. Wali, Lőrinc S. Pongor, Charles Li, Rosanna Lau, Balázs Győrffy, Richard P. Lifton, William F. Symmans, Lajos Pusztai, Christos Hatzis. Predictors of Chemosensitivity in Triple Negative Breast Cancer: An Integrated Genomic Analysis. PLOS Medicine, 2016; 13 (12): e1002193 DOI: 10.1371/journal.pmed.1002193

Cite This Page:

Yale Cancer Center. "Subtype of triple negative breast cancer responds better to chemotherapy." ScienceDaily. ScienceDaily, 13 December 2016. <www.sciencedaily.com/releases/2016/12/161213175224.htm>.
Yale Cancer Center. (2016, December 13). Subtype of triple negative breast cancer responds better to chemotherapy. ScienceDaily. Retrieved May 25, 2017 from www.sciencedaily.com/releases/2016/12/161213175224.htm
Yale Cancer Center. "Subtype of triple negative breast cancer responds better to chemotherapy." ScienceDaily. www.sciencedaily.com/releases/2016/12/161213175224.htm (accessed May 25, 2017).

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