April 13, 2017

Could diagnosing cancer as rare diseases improve outcomes for patients?

Dr. John Bartlett

Breast cancer is the most common form of cancer amongst women in Canada and worldwide, but despite its prevalence, a group of researchers believes that it should often be treated as a rare disease. Doing so would change clinical approaches and improve treatment for patients.

Next-generation sequencing technologies have deepened understanding of the biology of breast cancer subtypes and allowed pathologists to better define cancers based on their molecular makeup (called ‘molecular stratification’) rather then their site of origin in the body. When looking at breast cancer at this level of detail it is no longer one disease, but many different subtypes of disease, some of which are more prevalent than others. There are at least 11 different subtypes of breast cancer, with each having a unique response to treatment and varying patient outcomes.

Drs. John Bartlett, Director of the Ontario Institute for Cancer Research’s (OICR) Diagnostic Development Program and Wendy Parelukar, a Senior Investigator at Queen’s University argue in a recent editorial that some breast cancer subtypes would easily qualify as rare, even using the most stringent definition of two to three incidences per 100,000 people, established by the International Rare Cancers Initiative. Increasing our knowledge of breast cancer subtypes and using this information to inform preclinical and clinical strategies would allow for a more personalized approach to breast cancer treatments.

The piece, recently published in Nature Partner Journals Breast Cancer, outlines the relevance of subtyping breast cancers and the challenges that will need to be overcome to effectively target these diseases. “To improve care for breast cancer patients we will have to change our preclinical and clinical approaches,” says Bartlett. “To do this we will have to develop new diagnostics to better identify subtypes, validate targeted therapeutics against these subtypes and integrate molecular stratification into clinical trial design.” The authors point out that technological advancements mean that our understanding of breast cancer subtypes will continue to evolve and research and care will need to keep pace.

Bartlett and Parelukar believe that more resources need to be committed to developing robust diagnostic approaches to molecularly stratify cancers. If these tests can be implemented in diagnostic laboratories it will enable the selection of those patients who are most likely to benefit from novel therapeutics in a clinical trial.

The authors also argue that since there are many targeted drugs under evaluation that act on the same target or pathway, that the selection of the right one is essential. Researchers will have to be careful in their choice of preclinical evaluation strategies for these therapeutics, say Bartlett and Parelukar.

Clinical trials are at the centre of efforts to bring a more personalized approach to breast cancer. For the authors, molecular stratification is almost always a must in clinical trial design. They conceptualize a two stage molecular screening process to first identify patients for whom conventional treatments are predicted to be effective, and can therefore be spared unnecessary treatment toxicity, and then identify patients at high risk of relapse who could benefit from more targeted therapeutics matched to their cancer’s molecular signature. 

In their editorial Bartlett and Parelukar make a strong case for using molecular subtyping of breast cancer to inform research priorities and strategies to ultimately provide better patient outcomes.

OICR is a collaborative, not-for-profit research institute focused on accelerating the translation of new cancer research discoveries to patients around the world. Bartlett’s program is developing new diagnostic assays to enable the use of precision medicine through personalized diagnosis and treatment.

Read the editorial in Nature Partner Journals Breast Cancer:Breast cancers are rare diseases—and must be treated as such