PUBLISHED ON: 7 July 2021

Thanks to research, we now know more about triple negative breast cancer and are finding kinder and smarter ways to treat it.

Researcher in the lab

Triple negative breast cancer (TNBC) is the name given to breast cancer that is oestrogen receptor negative (ER-), progesterone receptor negative (PR-) and HER2 negative. It can be more aggressive and harder to treat than other types of the disease. 

Understanding triple negative breast cancer

Not all triple negative breast cancers are the same. This makes it harder to create new treatments for the disease. Researchers are still looking for the best way to group these cancers and discover the best way to treat them.

In 2011, a group of scientists analysed the genetics of tumour samples from 587 patients with triple negative disease. They grouped these cancers into six groups, each with different genetic features. Understanding their features could help determine whether a treatment or therapy will be effective for each group. However, this is currently not used in clinical practice and more research is needed before this can be the case and treatment can be truly tailored based on subtype.

Different tumour features can be used to group triple negative breast cancers together. They can include changes to the ways cancer cells repair their DNA and changes to how cancer cells grow and multiply. New treatments can then be developed to target these features. Many researchers believe that further tailoring treatment is the key to successfully treating triple negative disease.

For instance, the 2011 study identified a group of triple negative breast cancers known as BL1. This group has a particularly high number of changes to the BRCA2 gene. This means that drugs like PARP inhibitors could be an effective treatment for patients with this type of triple negative disease. But more research is needed to confirm this and uncover treatments for other groups of triple negative disease.

Recent treatment advances

In recent years, research has brought hope of new treatments to people with triple negative breast cancer. While they don’t work for everyone, experts believe that the future lies with personalised treatment, whereby a person’s cancer is analysed to match the best treatment.

PARP inhibitors have been approved in the US to treat secondary triple negative breast cancer with changes in BRCA genes. Changes in BRCA genes are found in around 15% of triple negative breast cancers. PARP inhibitors have been shown to be well-tolerated with few side effects and the hope is that they could be used in combination with other treatments to improve outcomes. Breast Cancer Now researchers have contributed to PARP inhibitors becoming a breast cancer treatment.

The OlympiAD trial assessed the effectiveness of a PARP inhibitor olaparib for the treatment of secondary breast cancer with altered BRCA genes. The study included a group of people who had triple negative disease, for whom treatment with olaparib helped to slow the progression of the disease compared to standard chemotherapy. In the group which received olaparib, 59.9% saw their breast cancer shrink or disappear compared to the 28.8% group that received standard chemotherapy.

PD-L1 is a protein that stops the body’s immune system from attacking healthy cells in the body. Some cancers have a higher than normal level of PD-L1 which means that cancer cells can trick the immune system and avoid being destroyed.

Some immunotherapies that work by blocking PD-L1 and other similar molecules have shown some success in TNBC. Atezolizumab is available on the NHS in combination with nab-paclitaxel to treat certain people with triple negative secondary breast cancer. Pembrolizumab, a PD-L1 inhibitor, has had some positive results in the treatment of secondary triple negative breast cancer in combination with chemotherapy. Early data from the I-SPY trial showed that pembrolizumab in combination with paclitaxel had a positive response when used to treat people with triple negative breast cancer.

Anti-Trop 2 antibody therapies have also shown promise. Trop-2 is a protein that is present in many cancers, including breast cancer. It is thought to be involved in the growth of cancer cells.

The ASCENT trial was assessing the safety and effectiveness of a drug sacituzumab govitecan, targeting Trop-2. In the trial, the drug stopped the growth of breast cancer and improved overall survival when compared to standard chemotherapy. The drug was recently approved to treat some secondary triple negative breast cancers in the US. We hope this treatment will be licensed and assessed for use on the NHS as quickly as possible.

Emerging targeted therapies

There’s also ongoing research into new targeted treatments for triple negative breast cancer.

Treatments targeting PI3K/AKT

PI3K and AKT are proteins that interact with each other to help cells maintain a normal life cycle. It is thought that irregular changes to these proteins and their interactions occur in about 25% of primary triple negative breast cancers. Drugs that inhibit the PI3K and the proteins it interacts with have shown some effectiveness in treating breast cancers with changes in PIK3CA proteins, especially the drug alpelisib in combination with the chemotherapy nab-paclitaxel. A phase II clinical trial is currently looking to assess whether the combination of alpelisib in combination with nab-paclitaxel can be used to effectively treat people with TNBC who have changes to PIK3CA, as well as determine if this combination has any side effects.

AKT inhibitors have also shown some promise. The early stage LOTUS trial tested the AKT inhibitor ipatasertib in combination with paclitaxel to treat secondary triple negative disease. The trial found that the combination could halt the progression of the disease. Similar effects were also observed for the AKT inhibitor capiversertib in the PAKT trial. Now, these treatments need to be tested in phase 3 trials to fully understand their effectiveness and who would most benefit from the treatment.

Therapies targeting AR

Androgen receptor (AR) is found in high levels in about 10-43% of triple negative breast cancers. Some drugs blocking AR, such as bicalutamide, are being assessed to treat triple negative breast cancer. A phase II clinical trial suggested the drug had some success in slowing the growth of tumours. Other clinical trials are testing other AR inhibitors too. The progress of these drugs has been slower due to the lack of knowledge about exactly what role AR plays in breast cancer. Further studies are needed to understand this.

Researchers are making great strides in better understanding triple negative disease. It is only a matter of time before they find new ways to treat it, improving outcomes and saving lives.