The Breast Cancer Now Catalyst Programme

To achieve our aim that by 2050 everyone who develops breast cancer will live and be supported to live well, we need to speed up the translation of research in the lab into new and effective treatments for patients. We’re bringing together leading researchers and top pharmaceutical companies to pool ideas and resources and ultimately stop people dying from breast cancer.

As part of the Breast Cancer Now Catalyst Programme, we have collaborated with leading pharmaceutical company Pfizer to give researchers unprecedented access to a number of Pfizer’s licensed and investigative drugs as well as vital funding for researchers to test these drugs. This allows us to combine the expertise of our researchers with Pfizer’s compounds and deliver new treatments to patients more quickly.

Project details

Researcher: Dr Rachael Natrajan

Location: The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, London

The challenge

Around 15% of breast cancers are classed as triple negative. This form of breast cancer can be more aggressive than other forms of the disease. One of the key issues that patients face is that there are currently limited targeted treatments available for triple negative breast cancer. We urgently need to address this and find new and effective ways to treat this group of patients.

Drug: Palbociclib

  • Blocks the activity of proteins called CDK4 and CDK6, which prevents cells from multiplying
  • Currently in Phase III trials in combination with other drugs for high risk early breast cancer
  • Already used to treat oestrogen receptor positive (ER+) HER2 negative breast cancer that has spread, in combination with hormone (endocrine) therapy

The science behind the project

Dr Rachael Natrajan and her team are investigating whether patients with triple negative breast cancer could benefit from the drug palbociclib. Palbociclib belongs to a group of drugs called CDK4/6 inhibitors, originally designed to treat oestrogen receptor positive (ER+) breast cancer.

Rachael and her team have previously developed 3D ‘mini tumours’ grown in the lab from samples donated by patients. This enables researchers to study the genetic changes that occur in triple negative breast cancer. Through this, they discovered that a gene called CREBBP may influence how tumours respond to CDK4/6 inhibitor drugs. Researchers found that more aggressive tumours tend to have lower levels of CREBBP activity and are more likely to respond to CDK4/6 inhibitors such as palbociclib. The team also found that changes in the CREBBP gene in ER+ breast cancer may be linked to resistance to palbociclib.

Now, they want to find which patients could benefit most from palbociclib. They are using data from two ongoing clinical trials to find out whether measuring the levels of CREBBP activity in cancer cells can accurately predict whose cancer will respond to these drugs. The first trial, PALLET, is looking at the impact of palbociclib and another drug letrozole on post-menopausal women with ER+ breast cancer. The second, Chemo-NEAR, is collecting biopsy samples from breast cancer patients before, during and after pre-surgical chemotherapy.

Furthermore, Rachael and her team want to uncover how ER+ and triple negative tumours can become resistant to palbociclib. To do this, they are studying mice with tumours resistant to palbociclib. Researchers are looking for changes in the proteins made by the cancer cells which may be linked to this resistance.

What difference will this project make?

This research could lead to a much-needed new treatment option for some people with triple negative breast cancer and improve their chances of survival. We want to make sure that patients only receive the treatments that will benefit them. So being able to identify people who will benefit from palbociclib – as well as those whose cancers are likely to become resistant, is an important step towards personalised medicine.

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* Pfizer has provided funding and Pfizer compounds for this research study as an Independent Medical Research grant as part of the Breast Cancer Now Catalyst Programme. Pfizer has no other involvement in this research study.