Targeting Chemotherapy With Genetic Testing in Advanced Triple-Negative Breast Cancer

Key Points

  • Among the 43 women in the study who also had BRCA gene faults, those who received carboplatin were twice as likely to respond to therapy as those given docetaxel.
  • Carboplatin also had fewer side effects and delayed tumor progression for longer in women with BRCA gene faults—stalling tumor growth for around 7 months compared with 4 months for docetaxel.

Researchers have found that women with advanced triple-negative breast cancer with a BRCA mutation were twice as likely to benefit from carboplatin as docetaxel—the current standard of care for these patients. These findings were published by Tutt et al in Nature Medicine.

The trial is set to change international clinical practice guidelines by ensuring that women with triple-negative breast cancer who are young or with a family history are considered for BRCA testing, so the best available treatment can be selected for them. The study was led by Andrew Tutt, PhD, of the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research (ICR) and the charity’s Research Unit at King’s College London, and Judith Bliss, MD, in the Cancer Research UK-funded Clinical Trials and Statistics Unit at the ICR. It also involved hospitals around the UK.

Triple-negative breast cancer has limited treatment options because it doesn’t respond to standard hormone therapies or targeted drugs like trastuzumab (Herceptin). Advanced triple-negative breast cancer is usually treated with chemotherapy, but response rates remain low.

Researchers designed the trial to compare the effectiveness of docetaxel with carboplatin, as these two treatments affect cancer cells in different ways. Carboplatin creates a specific form of damage to a tumor’s DNA, exploiting a weakness in some triple-negative breast cancers’ DNA repair machinery.

Study Findings

When analyzing the response in the 376 women with advanced triple-negative breast cancer across the trial, regardless of BRCA gene status, the researchers found the 2 drugs worked similarly well. But among the 43 women in the study who also had BRCA gene faults, those who received carboplatin were twice as likely to respond to therapy as those given docetaxel.

In these women, there was a response in 68% of the patients treated with carboplatin, but only in 33% of the women on docetaxel.

Carboplatin also had fewer side effects and delayed tumor progression for longer in women with BRCA gene faults—stalling tumor growth for around 7 months compared with 4 months for docetaxel.

The researchers believe carboplatin is more effective for this patient group because it works by damaging tumor DNA, and BRCA mutations impair the ability of cancer cells to repair the type of DNA damage created by this kind of platinum drug.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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