Researchers from the Clínic-IDIBAPS, the UB and the academic research group in oncology SOLTI have shown that the molecular classification of breast cancer, which divides it into four subtypes (Luminal A, Luminal B, HER2-enriched and Basal-like) is useful in predicting the benefit of treatment in patients with advanced hormone-dependent breast cancer. This is the largest study to demonstrate the value of the biomarker and the first to do so in the context of CDK4 / 6 inhibitors such as ribociclib.
The study, published in the journal Journal of Clinical Oncology from la American Society of Clinical Oncology (ASCO), has been coordinated by Prof. Aleix Prat, head of the Clinical Medical Oncology Service and of the Translational Genomics and targeted therapies in solid tumors group at IDIBAPS, professor of the Department of Medicine of the UB and president of SOLTI.
Breast cancer affects 2.3 million people and kills 571,000 each year. Among the different types of breast cancer, hormone dependent accounts for 70% of all cases. When the disease is in an early stage, local treatment, chemotherapy and hormonal treatment for 5 or 10 years have shown great long-term benefits in terms of survival. Even so, 20-30% of patients end up developing a metastasis during follow-up. In this context, survival is compromised and specific biomarkers and treatments are needed.
In recent years, new therapies have been incorporated for hormone-dependent disease in advanced stages, such as the introduction of new drugs that inhibit CDK4 / 6, a key protein in the cell cycle. “The recent introduction of CDK4 / 6 inhibitors such as ribociclib has improved the survival of patients with advanced hormone-dependent breast cancer. However, this disease is clinically and biologically heterogeneous and at least 4 molecular subtypes can be identified. Until now, we did not know the real value of this molecular classification in advanced hormone-dependent disease “, he points out Aleix Prat.
For 5 years, the research line of Dr. Aleix Prat has made it possible to describe the biological heterogeneity of hormone-dependent disease and to identify 4 molecular groups (Luminal A, Luminal B, HER2-enriched and Basal-like) with different prognoses and sensitivities to treatments. “The question we asked ourselves was how this biological classification behaved in advanced hormone-dependent breast cancer“, he points out Aleix Prat. “Two previous studies led by our group indicated that, among patients with advanced hormone-dependent breast cancer treated with hormone therapy, the Luminal A subtype has the best prognosis while the HER2-enriched and Basal-like subtypes have the worst prognosis. In contrast, the Luminal B subtype has a medium prognosis. In this context, it was necessary to validate these findings and, above all, to see the impact of CDK4 / 6 inhibitors as they are currently the standard treatment. “, Add.
In the article published in the Journal of Clinical Oncology, researchers analyzed the expression of 152 genes in 1,160 patients with advanced hormone-dependent breast cancer treated in 3 phase III clinical trials of the MONALEESA program, which led to the approval of ribociclib by health authorities.
A total of 488 patients received hormone therapy alone, and 672 patients received hormone therapy in combination with ribociclib. The molecular subtype Luminal A was the most frequent (47%), followed by Luminal B (24%), HER2-enriched (13%) and basal-like (3%). Compared with Luminal A, the risk of disease progression was higher in the rest of the molecular subtypes. For example, the risk of progression in the HER2-enriched and Basal-like subtypes was 2 and 4 times higher compared to Luminal A. Finally, the researchers observed that all molecular subtypes benefited from ribociclib, except Basal-like.
“On the one hand, our study definitively validates previous observations about the prognostic value of the molecular classification. Furthermore, we demonstrated for the first time the high clinical value of ribociclib in the HER2-enriched subtype, a very aggressive group of tumors when treated with hormonal therapy alone. Finally, our study makes it clear that knowing the molecular subtype is increasingly important “, concludes Aleix Prat.
Future studies will establish the predictive value of the molecular classification of hormone-dependent breast cancer in other contexts. Specific examples would be the search for new targeted therapies for aggressive HER2-enriched and Basal-like subtypes. Along these lines, the SOLTI cooperative group, chaired by Aleix Prat, is conducting multicenter clinical trials for each of these groups such as the trial DEEDS or the ARIANNA where innovative therapies such as immunotherapy are evaluated.
This study was funded by Novartis, the Carlos III Health Institute, the Breast Cancer Research Foundation, the foundation Breast Cancer Now, the Generalitat of Catalonia within the Peris program, the Fundació La Marató TV3, European funds Horizon 2020 (RESCUER project), the Scientific Foundation of the Spanish Association Against Cancer (AECC), and the associations Save the Mama, Pas a Pas and Metastatic Breast Cancer.
Study reference:
Prat A, Chaudhury A, Solovieff N, Paré L, Martinez D, Chic N, Martínez-Sáez O, Brasó-Maristany F, Lteif A, Taran T, Babbar N, Su F.
J Clin Oncol. 2021 Mar 26:JCO2002977. doi: 10.1200/JCO.20.02977.
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