Women with advanced ‘triple-negative’ breast cancer and BRCA gene mutations respond better to the chemotherapy drug carboplatin than standard treatment, according to the findings of a major clinical trial published last night.
The results from the trial could change international clinical practice guidelines, researchers say. This would be because women with triple-negative breast cancer could be considered for BRCA testing so that treatment can be improved.
Researchers found that women with advanced ‘triple-negative’ breast cancer who had inherited a BRCA mutation were twice as likely to benefit from carboplatin as docetaxel.
The study, published in Nature Medicine, was largely funded by Breast Cancer Now and Cancer Research UK and led by a team at The Institute of Cancer Research, London, and King’s College London.
Researchers designed the trial to compare the effectiveness of docetaxel with carboplatin because the two treatments affect cancer cells in different ways.
The team found that when they analysed the response in the 376 women with advanced triple-negative breast cancer, the two drugs worked similarly well, regardless of BRCA gene status.
However, of the 43 women who also had BRCA gene mutations, those who received carboplatin were twice as likely to respond to therapy as those given docetaxel. Tumours reduced in 68% of cases, compared with 33%.
Women taking carboplatin reported fewer side effects and for those with BRAC mutation gene, there was delayed tumour progression for longer – stalling tumour growth for about seven months, compared with four months for docetaxel.
The research team believe carboplatin is more effective for this patient group because it damages tumour DNA.
BRCA mutations impair the ability of cancer cells to repair the type of DNA damage created by this kind of ‘platinum’ drug.
Study leader Andrew Tutt, professor of breast oncology at The Institute of Cancer Research, London, said: “Our study has found that women with triple-negative breast cancer who have BRCA1 or 2 mutations are twice as likely to respond to carboplatin as they are to standard treatment.
“It strongly suggests that many women with triple-negative breast cancer should be considered for testing for faults in the BRCA genes so those who test positive can benefit from carboplatin. Using this simple test enables us to guide treatment for women within this type of breast cancer. I am keen for these findings to be brought into the clinic as soon as possible.
“This is a great example of using personalised genetics to repurpose a chemotherapy drug into a targeted treatment, by understanding that its DNA-damaging effects might be particularly effective against cancer cells with deficiencies in DNA repair in appropriately selected patients.”
Professor Judith Bliss, director of the clinical trials and statistics unit at The Institute of Cancer Research, London, who led the management of the study, added: “Women with triple-negative breast cancer often only survive for one to two years after the cancer has relapsed and spread to other parts of the body so there is an urgent need to find alternative treatments for this group of patients.
“Our study has shown that this doesn’t have to mean developing new drugs. We can use existing – and often cheaper, generic – drugs more effectively by targeting treatment based on weaknesses in individual patients’ tumours.”
Professor Charles Swanton, Cancer Research UK’s chief clinician, described the results of the study as “exciting”, adding that it has brought medical science a step closer to delivering precise care to patients with breast cancer.
Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nature Medicine 30 April 2018;
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