Bilateral breast cancer: the first full study reveals that the tumors are independent of one another

Bilateral breast cancer affects between 2 and 11% of all breast cancers, and its incidence continues to rise. It is characterized by the occurrence of a tumor in both breasts, either exactly at the same time, or within a period of around six months. Until now, bilateral breast cancer has not been associated with a strong genetic determinant.

Conducted at Institut Curie by Dr. Joshua Waterfall, Inserm researcher and head of the team in the Cancer, Heterogeneity, Instability and Plasticity unit (Inserm/Institut Curie), Prof. Fabien Reyal, head of the Gynecological, Breast and Reconstructive Surgery department and Dr. Anne-Sophie Hamy-Petit, oncologist and researcher at Institut Curie in the Tumor Residue and Treatment Response team, this study includes a cohort of 17,500 patients of all ages, of which 404 (or 2%) had bilateral breast cancer.

First of all, the research team analyzed all 17,500 medical files. It thus characterized the nature of the tumors but also observed the immune system response and the response to neoadjuvant treatment (administered to patients before surgery). Researchers and physicians then discovered that the immune system did not react in the same way if the right and left tumors were from different sub-groups (luminal, triple negative or HER2). “For example, luminal breast cancers[1] do not usually respond to neoadjuvant treatment, but with a triple negative contralateral tumor, the immune response and the response to treatment are improved,” explains Joshua Waterfall. “A systemic mechanism for which there is as yet no explanation.”

In the second phase, a smaller cohort of 6 patients was analyzed and their tumors were characterized at the genomic level, comparing the patient profiles before and after neoadjuvant treatment. Using new-generation sequencing, the team managed to observe the order of nucleotides in the entire genome or in certain specific regions of the DNA or RNA. “This state-of-the-art technology has shown us that, from a genetic mutation standpoint, both tumors are completely independent of one another”, explains Joshua Waterfall.

Despite a very comprehensive sequencing tool, the very small size of the patient group makes it impossible to search for a gene common to all these tumors. “It’s a possibility that we cannot eliminate but we don’t see anything that confirms this. Bilateral tumors may be rare, but their occurrence appears to be independent and can be a matter of bad luck,” continues Joshua Waterfall. Independent from a genomics standpoint, in terms of mutations, copies of alterations and of expression, their occurrence could be influenced by factors from the microenvironment in the cells and tissues.

These new results help us better understand how to treat patients with bilateral breast cancer. The researchers and physicians involved in this work advise us to consider these tumors as two different entities before deciding on a treatment that would target both of them. “Given that these tumors are independent of one another but can influence one another, the choice of treatment can be a complex one. We hope that our results can guide healthcare professionals in their decisions and improve patient treatment,” continues Joshua Waterfall.

^{[1] Luminal breast cancer is the most common form of breast cancer, characterized by expression of the estrogen receptor.}