Gene test might benefit women with hard-to-treat breast cancer

Cancer Research UK

Aggressive breast cancers carrying a faulty BRCA gene responded better to a certain type of chemotherapy than standard treatment, according to a clinical trial.

The study, funded by Cancer Research UK and Breast Cancer Now, showed that triple negative breast cancers carrying the gene fault were twice as likely to respond to the drug carboplatin (Paraplatin) than docetaxel (Taxotere).

Testing for a faulty BRCA gene is not routine for women with this type of breast cancer.

Professor Andrew Tutt, from The Institute of Cancer Research, London (ICR) who led the research, said the study strongly suggests that women with triple negative breast cancer should be tested for faults in the BRCA genes as those who test positive may benefit from carboplatin.

Triple negative breast cancer affects around 7,500 women in the UK each year. Hormone therapies used to treat the more common types of breast cancer don’t work on these tumour types.

Professor Judith Bliss, also from The ICR, said: “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.”

What did the study look at?

The study, published in Nature Medicine, followed 376 women with advanced triple negative breast cancer. Half were treated with carboplatin and half received standard treatment, docetaxel.

Both drugs worked equally as well, but those who took carboplatin had fewer side effects.

After treatment, the women were tested for faults in the BRCA1 and BRCA2 genes. 45 women had a faulty BRCA gene.

  • Tumours with the faulty gene treated with carboplatin shrunk on average by 68%.
  • Tumours with the faulty gene treated with docetaxel shrunk on average by 33%.

Why did the drug work better in these patients?

The team think carboplatin was more effective in women with a faulty BRCA gene because of how the drug works.

The molecules made by the BRCA genes are part of the machinery that repairs cells’ DNA if it becomes damaged. When BRCA is faulty, cancer-causing mistakes in the genetic code are more likely.

Carboplatin works by interfering with this DNA repair machinery.

The researchers believe that combining the drug’s effects with faulty BRCA causes a double hit to the cell’s DNA repair efforts. This may overload the cancer cell’s DNA repair system, causing it to die.

Docetaxel causes cells to die in a different way, interfering with the machinery that helps cells divide.

A move towards personalised medicine

Tutt said the results show how genetics can turn an existing chemotherapy drug into a targeted treatment.

“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,” he said.

Professor Charles Swanton, Cancer Research UK’s chief clinician called the study “exciting”, and said it brings precise care for these patients closer.

“Rather than offering all women the same standard of care, these results show that, for patients with inherited BRCA mutations, the drug carboplatin is not only a more effective treatment option, but also comes with fewer side effects, sparing patients possible health problems, physical discomfort and emotional distress.

This study also showed that both drugs worked equally well in women without the genetic fault, and side effects were more manageable for those who took carboplatin. This suggests carboplatin could be an additional treatment option for women whose disease doesn’t respond to standard treatment. 

References

Tutt, A, et al. (2018) A randomised phase III trial of carboplatin compared with docetaxel in BRCA1/2 mutated and pre-specified triple negative breast cancer “BRCAness” subgroups: the TNT Trial. Nature Medicine. DOI:10.1038/s41591-018-0009-7