Breast cancers: similarities between sub-families
Coupe histologique d'une tumeur du sein.
As Dr. Anne Vincent-Salomon, head of the Pathology, genetics, immunology division, is constantly explaining, “Breast cancer is not a single disease: it comes in many different forms” (http://curie.fr/soins/pole-medecine-diagnostique-theranostique). Now, another step has been taken toward classifying types of breast cancer, and particularly toward analysing HER2 breast cancers. Women who present with this type of cancer, i.e. approximately 15% of breast cancer patients, can now benefit from several types of targeted therapies. They do not all respond to the treatments in the same way, however. “This is undoubtedly due to the fact that there are different kinds of breast cancer, even among HER2 breast cancers,” explains Vincent-Salomon. “Thanks to the French group of the International Cancer Genome Consortium (ICGC), co-directed by Gilles Thomas (Fondation Synergie Lyon Cancer, France) and Michael Stratton (Welcome Trust, Sanger Institute, UK), and partly funded by the French National Cancer Institute (INCa), we were able to explore this family of breast cancers in detail.” Whole genome sequencing was conducted on 64 tumours and analysed along with the gene expression data.
Result: 4 sub-families of HER2 cancer were established based on their molecular characteristics.
“This family of cancers is identified in clinical practice by the overexpression of the HER2 gene, but this work shows that HER2 tumours can actually be broken down into four distinct molecular groups,” explains the pathologist, who jointly authored the study. One of these groups (Group A) is characterised by the expression of oestrogen receptors and the absence of mutations in the TP53 gene, a low number of genomic reorganisations, and relatively low overexpression of HER2. On the opposite end of the spectrum, another group (Group D) is characterised by the absence of oestrogen receptor expression, mutations of the TP53 gene, and a large number of genomic reorganisations characteristic of tumours showing an alteration to the BRCA1 gene. In addition, the study also identifies the specific genomic mechanisms that result in amplification of the HER2 gene with a level of precision not yet achieved elsewhere.
Ultimately, one consequence of this work will be that among patients with HER2-positive breast tumours, the transcriptomic profile of the tumour, the status of the TP53 gene, and the genomic profile of the tumour will be routinely characterised in order to adjust the combinations of treatment for patients with Group A, B, C, or D tumours. With the rise of targeted therapies and the need to assign the treatment most appropriate for each molecular profile, it is essential to define tumour sub-types. This better understanding will also open up new avenues of treatment, based o both existing and novel therapies.
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Anthony Ferrari, Anne Vincent-Salomon, Xavier Pivot, Anne-Sophie Sertier, Emilie Thomas, Laurie Tonon, Sandrine Boyault, Eskeatnaf Mulugeta, Isabelle Treilleux, Gaëtan MacGrogan, Laurent Arnould, Janice Kielbassa, Vincent Le Texier, Hélène Blanche, Jean-François Deleuze, Jocelyne Jacquemier, Marie-Christine Mathieu, Frederique Penault-Llorca, Frédéric Bibeau, Odette Mariani, Cécile Mannina, Jean-Yves Pierga, Olivier Trédan, Thomas Bachelot, Hervé Bonnefoi, Gilles Romieu, Pierre Fumoleau, Suzette Delaloge, Maria Rios, Jean-Marc Ferrero, Carole Tarpin, Catherine Bouteille, Fabien Calvo, Ivo Glynne Gut, Marta Gut, Sancha Martin, Serena Nik-Zaina, Michael R. Stratton, Iris Pauporté, Pierre Saintigny, Daniel Birnbaum, Alain Viari, Gilles Thomas
Nature Communications, DOI: 10.1038/ncomms12222, 13 juillet 2016