Targeted therapy to improve outcomes for triple negative breast cancer patients

Project Description:

Triple negative breast cancer (TNBC) accounts for around 10-15% of newly diagnosed breast cancer cases but leads to about 30% of breast cancer related deaths. Palbociclib, a targeted cancer therapy, is a well-tolerated drug that slows the growth of cancer cells and is currently used for the treatment of advanced and metastatic estrogen receptor positive breast cancer. However, it is yet to be prescribed for the treatment of TNBC even though about 12% of TNBC patients have had their tumour growth slowed by this drug in clinical trials. In this NBCF-funded study A/Prof Liz Caldon will investigate the potential of using palbociclib to treat TNBC patients. Additionally, the research aims to develop a novel biomarker test to identify patients who are most likely to respond to treatment with palbociclib.

Why is this work needed:

Triple negative breast cancer (TNBC) is a breast cancer subtype with poor prognosis. This is partly due to the lack of targeted therapies, with surgery, radiotherapy and chemotherapy been the primary treatment approach. Hence, there is a need to develop new treatment options to reduce the deaths of patients diagnosed with TNBC.

Expected outcomes:

The successful outcomes of this study will establish the feasibility of a new biomarker test to identify patients diagnosed with TNBC that will benefit from palbociclib treatment. This personalised approach for the treatment of TNBC has the potential to prevent or delay some of the 1000 deaths from TNBC per year in Australia.

Project description:

Triple negative breast cancer (TNBC) is an aggressive form of cancer with the lowest survival outcomes relative to other breast cancer subtypes and has a higher prevalence among younger women. TNBC accounts for up to 15% of all newly diagnosed breast cancer cases and in Australia this is around 3000 new cases every year. TNBC is estimated to contribute to about 30% of all breast cancer-related deaths. This is partly due to the lack of targeted therapies, with surgery, radiotherapy and chemotherapy been the primary treatment approach.

Palbociclib, a targeted cancer therapy, has been established as an effective therapy and the standard of care for the treatment of advanced and metastatic estrogen receptor positive breast cancer. However, it is yet to be prescribed for the treatment of TNBC even though about 12% of TNBC patients have had their tumour growth slowed by this drug in clinical trials.

Prior research led by A/Prof Liz Caldon at the Garvan Institute of Medical Research identified a positive correlation between the effectiveness of palbociclib and the presence of two protein biomarkers, p16 and RB, in samples derived from patients with TNBC.

With NBCF support, the team aims to establish the specific levels of the protein biomarkers, p16 and RB, that can lead to a favourable response to palbociclib in preclinical models of TNBC. Pathology laboratories currently use this biomarker test to evaluate patients with other types of cancer, enabling the identification of the most effective therapies for their treatment. Moreover, palbociclib will be evaluated as a standalone therapy or in combination with standard of care therapy on TNBC preclinical models to determine the most effective therapeutic approach for this cancer type.

This personalised approach for the treatment of TNBC has the potential to prevent or delay a proportion of the 30% of breast cancer related deaths that are due to TNBC.