NEW YORK (Reuters Health) - The mutational landscape of drug-resistant estrogen receptor (ER)-positive metastatic breast cancer differs significantly from that of primary ER+ breast cancer, according to research presented today at the 2016 San Antonio Breast Cancer Symposium.
"The bottom line is that tumors do evolve and the metastatic setting is different than the primary setting," said Dr. Ofir Cohen of the Broad Institute and Dana-Farber Cancer Institute in Boston, during a press briefing.
"We were able to identify multiple clinically relevant genomic and molecular alterations in the metastatic biopsies with implications for choice of next therapy, clinical trial eligibility, and novel drug targets," he added in a conference statement.
Despite major advances in the treatment of ER+ breast cancer, patients often develop resistance to these therapies. "Knowledge of the molecular and genomic landscape of ER+ metastatic breast cancer is under-explored. Our current research is part of a growing effort by many researchers to start closing that gap," Dr. Cohen told reporters.
The research team studied 149 biopsies from ER+ metastatic breast cancer and 44 matched biopsies of the primary tumors.
Whole exome sequencing showed metastatic breast cancer samples to have more frequent alterations in several key genes, including ESR1, ERBB2, PIK3CA, PTEN, RB1, AKT1, among others, Dr. Cohen reported.
Transcriptome sequencing identified several types of resistance mutations that are likely to be clinically relevant and to help guide next choice of treatment, he said.
"With increasing numbers of patients from whom we were able to obtain and sequence the original primary tumor, we have been able to distinguish between pre-existing events (found in both the primary and the metastatic samples) and evolutionary, acquired events (found only in the metastatic sample)," Dr. Cohen explained in the statement.
"Pre-existing events may highlight events that predispose to metastasis, supporting the idea that comprehensive characterization of primary tumors might help predict metastatic potential, while acquired events may suggest novel therapeutic approaches to overcome or prevent resistance, and highlight the idea of periodic monitoring with technologies such as cell-free DNA from blood (liquid biopsies)," he added.
The researchers say the ultimate goal is to integrate the functional and clinical findings into a unified "Resistance Atlas" for ER+ metastatic breast cancer, which could help guide treatment decisions for individual patients as well as contribute to the development of new combination treatment strategies for ER+ metastatic breast cancer.
This is "wonderful work" and was "one of the highest ranked abstracts" submitted to the conference, said briefing moderator Dr. Virginia Kaklamani, co-director of the San Antonio Breast Cancer Symposium and professor of medicine at the UT Health Science Center San Antonio.
"It's hard to get paired samples (and) what was so interesting to me was that for every mutation identified as a key mutation in the metastatic compared to the primary tumor we have drug targets for it," she said.
The study had no commercial funding.
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