A liquid biopsy test has detected changes in the BRCA1 or BRCA2 genes associated with breast and ovarian cancer that signal when the disease stops responding to treatment through platinum chemotherapy or poly ADP-ribose polymerase (PARP) inhibitors.
U.K. and U.S.-based researchers said that the test, detailed in a study, could someday help physicians monitor how patients are responding to cancer therapies, so that those who show resistance to treatment can be switched to alternative therapies as soon as possible, before the cancer starts to progress.
“With this new liquid biopsy, we picked up changes in tumor DNA that could give us early warning if a woman’s cancer is likely to stop responding to treatment,” Prof. Nicholas Turner, Ph.D., professor of molecular oncology at The Institute of Cancer Research (ICR), said in a statement.
Researchers at the Breast Cancer Now Toby Robins Research Centre at ICR, partnered with U.S. investigators to study blood samples from women who were treated at The Royal Marsden NHS Foundation Trust or at Memorial Sloan Kettering Cancer Center.
Using the liquid biopsy, the researchers analyzed blood samples from 24 women who had an inherited fault in one of the cancer risk genes BRCA1 or BRCA2—including 19 patients with platinum-resistant/refractory ovarian cancer and five patients with platinum and/or PARP inhibitor pretreated metastatic breast cancer. The women had previously been treated with platinum chemotherapy or PARP inhibitors, until the treatments no longer worked for them.
Researchers found DNA changes enabling tumors to resist treatment in the blood of 4 of 19 women (21%) with ovarian cancer, and in 2 out of 5 (40%) with breast cancer. In 4 out of 6 of the women who developed resistance mutations, the tumor DNA contained more than one change – suggesting that cancer finds multiple different ways to resist targeted drugs.
“The DNA changes identified with this new liquid biopsy test could help us understand how cancer evolves to become resistant to treatment,” Prof. Paul Workman, Ph.D. Chief Executive of the ICR. “Precision medicine is now delivering real benefits for many women with breast and ovarian cancer – but drug resistance is still an important challenge.”
Significantly, the DNA changes detected in the blood samples through the test appear to have arisen during treatment, since they were not found in tumor tissue taken when the women were first diagnosed.
“Putative BRCA1/2 reversion mutations can be detected by [cell-free DNA] cfDNA sequencing analysis in patients with ovarian and breast cancer,” the researchers concluded in Diverse BRCA1 and BRCA2 Reversion Mutations in Circulating Cell-Free DNA of Therapy-Resistant Breast or Ovarian Cancer, published in the journal Clinical Cancer Research. “Our findings warrant further investigation of cfDNA sequencing to identify putative BRCA1/2 reversion mutations and to aid the selection of patients for PARP inhibition therapy.”
Researchers added that they will further evaluate the blood test as part of a large clinical trial.
“Our study also opens up further research into how to stop cancer evolving to become resistant to targeted drugs,” added Dr. Turner, who is also consultant medical oncologist at The Royal Marsden NHS Foundation Trust. “In the future, this liquid biopsy could help us pick out those women with breast or ovarian cancer who are most likely to benefit from targeted therapy, and offer alternative treatment to women as soon as they develop drug resistance.”
The study was largely funded by Breast Cancer Now, the UK's largest breast cancer charity.