BRCA1: Immunotherapy shows promise in the fight against aggressive treatment-resistant breast cancer

The combination of two immunotherapy drugs has shown promising results in the treatment of triple-negative breast cancers that arise in women with BRCA1 mutations. The drug regimen appears to control tumour growth and to improve survival.

In a triple-negative breast cancer, the tumour does not have receptors for the hormones oestrogen or progesterone, or for the HER2 protein. It means that the growth of the cancer is not supported by these hormones nor by HER2. About 10 to 20% of breast cancers are found to be triple-negative and among the women affected, some have a faulty BRCA1 gene.

Triple-negative breast cancers are particularly hard to treat. Hormonal therapies do not work and the cancer often develops resistance to chemotherapy. Women often relapse and survival rates are low.

"There is a number of issues with current treatments. Some of these treatments, including chemotherapy, work for a number of patients but not for all. And even in those patients were the drugs work, the side effects can impair the quality of life and the disease can come back relatively quickly," Chris Lord, leader of the Gene Function Team at the Institute of Cancer Research, told IBTimes UK.

"A realistic aim for scientists at the moment is to develop kinder treatments that also extend that period where somebody is free of the disease."

In a study published in the journal Science Translational Medicine, scientists have now shown that a specific immunotherapy drug combination given with a common chemotherapy drug could help them reach this goal.

The benefits of immunotherapy

Immunotherapy works by boosting the body's immune cells to attack tumours. It has previously shown real promise in the treatment of melanoma and lung cancers - but results for breast cancer had so far been quite modest.

Working with rodent models of breast cancer, the scientists tested the effect of a combination of two therapies - the anti-PD1 and anti-CTLA4 immunotherapies. These work by releasing the brakes on critical immune cells which can then go on to attack the tumour.

The study shows that using the two immunotherapies with the widely-used chemotherapy cisplatin promoted tumour regression and increased survival rates.

"BRCA1-related triple-negative breast cancers have some of the most 'chaotic' genomes, and we see many immune cells accumulate in and around the tumour," study author Daniel Gray, from the Walter and Eliza Hall Institute of Medical Research in Melbourne said.

"This suggests that the immune cells can readily detect that something is awry, but they aren't able to respond properly, because they have been disabled by tumour cells. We showed that a combination of anti-PD1 and anti-CTLA4 therapies restored their ability to attack and kill triple-negative breast tumour cells, and very effectively control tumour growth."

Gray and his colleagues also noted that the tumours did not become resistant to the drug combination regimen over time. This kind of treatment still needs to be tested in humans. It does not amount to a cure, but it could leave patients with a lot more treatment options and a better quality of life as they fight the disease. The results are thought to be robust enough to move on to clinical trials.

"This is the first detailed study assessing in an animal model of cancer whether immunotherapy could be used in combination with commonly used chemotherapy in tumours that have mutations in BRCA1 tumour suppressive gene," Lord said.

"A lot of scientists have been working on this issue in recent years, and we now have confirmation that combination therapy using these immunotherapies could deliver a more sustained therapeutic response in this group of patients with BRCA1 mutations. It could delay relapse of the disease and potentially might allow one to use lower doses of chemotherapy - improving patients' quality of life."

These findings are published just as the annual meeting of the American Society of Clinical Oncology comes to an end. Other significant advances in the treatment of triple-negative breast cancer in women with BRCA1 mutations have also been reported over the past few days, including results from a phase III clinical trials showing that another immunotherapy drug, Pembrolizumab, was effective in shrinking tumours.