Existing drug could treat ‘aggressive’ triple-negative breast cancer – study

An already approved cancer drug could be used to treat more aggressive forms of breast cancer, new research has found.

Researchers funded by Breast Cancer Now have identified a specific defect in some triple-negative breast cancers and a pre-existing drug that could help treat the disease.

The new research, led by Dr Rachael Natrajan at The Institute of Cancer Research, discovered a way to identify triple-negative breast tumours that could be more likely to respond to a class of drugs called CDK4/6 inhibitors, including palbociclib.

Palbociclib is currently used to treat other breast cancers that have spread to a different part of the body. However, the research found there is the potential to use the drug to treat around a fifth of people living with triple-negative breast cancer.

Dr Natrajan said: “Our study shows what drives the growth of some triple-negative breast cancers and suggests the exciting possibility that an already-approved breast cancer drug could be used to help women with this type of disease.”

It will take several years to carry out clinical trials to prove effectiveness but if these are successful, CDK4/6 inhibitors could be given to people within five years.

Triple-negative breast cancer refers to a group of cancers that lack the three molecules which are normally used to classify the disease — the oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) protein.

This type of cancer, which disproportionately affects younger women and black women, is often resistant to traditional chemotherapy and is more likely to spread sooner, becoming incurable. Instead, triple-negative breast cancer is treated with a combination of surgery, chemotherapy and radiotherapy.

Dr Simon Vincent, director of research, support and influencing at Breast Cancer Now, said the discovery was “hugely exciting”.

“Each year, around 8,000 UK women are diagnosed with this aggressive form of breast cancer and we desperately need new, effective ways to treat them and stop them dying from this devastating disease,” he said.

“We hope that if clinical trials confirm that palbociclib is beneficial for some of these women, it will be advanced through the approval process and made available for those who need it as quickly as possible.”

The team screened 200 of the most frequently altered genes in breast cancer to investigate how changes in these genes affect cancer’s ability to grow.

Researchers then used ‘mini-tumours’ grown in the lab and found that some triple-negative breast cancer cells cause a decrease in levels of the CREBBP protein.

Low levels of this protein are linked to poorer survival rates in patients with triple-negative breast cancer because the cells can grow faster and more aggressively.

But when the levels of this protein are low, tumour cells multiply relying on CDK4 and CDK6 proteins. These proteins can then be blocked with CDK4/6 inhibitors, such as palbociclib, which stops the cancer cells from growing.

The researchers tested the effectiveness of the drug on cancer cells with CREBBP alterations in the lab and in mice. The drug was effective even when tested on standard chemotherapy-resistant triple-negative breast cancer cells, that lacked CREBBP, donated by a patient.