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


This study conducted by Institut Curie, in collaboration with Inserm and the German Breast Cancer Group, is the first to describe bilateral breast cancer with such advanced sequencing technologies. Although the two tumors in each breast have different origins, the type of each tumor (luminal, HER2, triple negative) influences the tumor microenvironment in the other breast, in particular the immune system, and alters the response to treatment.


Marquage immunofluorescent sur les différents sous types de cellules immunitaires du microenvironnement tumoral (marquage CD68 (jaune) – CD 163 (violet) – CD138 (orange)– CKIT (vert)– AE1/AE3 (bleu…

Published in Nature Medicine in March 6, 2023, this study offers clinical perspectives to improve the treatment of patients with bilateral breast cancer.

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 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. A systemic mechanism for which there is as yet no explanation.

Explains Joshua Waterfall.

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.

Evolution of synchronous female bilateral breast cancers and response to treatment. Anne-Sophie Hamy, Judith Abecassis, Keltouma Driouch, Lauren Darrigues, Mathias Vandenbogaert, Cecile Laurent, Francois Zaccarini, Benjamin Sadacca, Myriam Delomenie, Enora Laas, Odette Mariani, Than Lam, Beatriz Grandal, Marick Laé, Ivan Bieche, Sophie Vacher, Jean-Yves Pierga, Etienne Brain, Celine Vallot, Judicael Hotton, Wilfrid Richer, Dario Rocha, Zakia Tariq, Veronique Becette, Didier Meseure, Laetitia Lesage, Anne Vincent-Salomon, Natalie Filmann, Jenny Furlanetto, Sibylle Loibl, Elise Dumas, Joshua J. Waterfall, Fabien Reyal. Nature medicine, March 6, 2023.

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