TY - JOUR
T1 - Precision medicine in breast cancer
T2 - From clinical trials to clinical practice
AU - Crimini, Edoardo
AU - Repetto, Matteo
AU - Aftimos, Philippe
AU - Botticelli, Andrea
AU - Marchetti, Paolo
AU - Curigliano, Giuseppe
N1 - Funding Information:
GC reports honoraria from Ellipses Pharma, consulting or advisory role for Roche/Genentech, Pfizer, Novartis, Lilly, Foundation Medicine, Bristol Myers Squibb, Samsung, AstraZeneca, Daichi-Sankyo, Boehringer Ingelheim, GSK, Seattle Genetics, speakers’ bureau from Roche/Genentech, Novartis, Pfizer, Lilly, Foundation Medicine, Samsung, Daiichi Sankyo, research funding from Merck (Inst), and travel/accommodations expenses from Roche/Genentech, Pfizer.
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/7
Y1 - 2021/7
N2 - Introduction: Breast cancer (BC) is the most common cancer in women and, despite the undeniable improvements in the outcome of these patients obtained in the last decade, the discovery and the validation of new actionable molecular targets represent a priority. ESCAT permits to rank molecular alterations in different classes according to their evidence of actionability in a specific cancer type, assisting clinicians in their therapeutical decisions. Main: ERBB2, PIK3CA and germline BRCA1/2 alterations are biomarkers prospectively validated in BC, driving the selection of targeted therapies, and are therefore classified in the highest level of evidence (Ia). Agnostic biomarkers, namely microsatellite instability, NTRK fusions and high tumor mutational burden, demonstrated similar activity across different tumor types and are consequently ranked in tier Ic. In tier II are classified alterations that still need confirmatory prospective studies but for which evidence of efficacy is available. Somatic BRCA1/2 mutations, germline PALB2 mutations, HER2-low expression, ERBB2 mutations, PTEN deletions, AKT1 mutations, ESR1 resistance mutations satisfy the requirements to be classified in this tier. In tier III are ranked various molecular alterations for which there is evidence of actionability in other tumors (IIIa) or that have similar functional impact in the same gene or pathway of a tier I alteration, without clinical data (IIIb). In tier IV are listed the molecular alterations for which only preclinical studies are available. Conclusion: In this review we report the most relevant molecular targets in BC, ordered pursuant to their pathway and classified in concordance with ESCAT.
AB - Introduction: Breast cancer (BC) is the most common cancer in women and, despite the undeniable improvements in the outcome of these patients obtained in the last decade, the discovery and the validation of new actionable molecular targets represent a priority. ESCAT permits to rank molecular alterations in different classes according to their evidence of actionability in a specific cancer type, assisting clinicians in their therapeutical decisions. Main: ERBB2, PIK3CA and germline BRCA1/2 alterations are biomarkers prospectively validated in BC, driving the selection of targeted therapies, and are therefore classified in the highest level of evidence (Ia). Agnostic biomarkers, namely microsatellite instability, NTRK fusions and high tumor mutational burden, demonstrated similar activity across different tumor types and are consequently ranked in tier Ic. In tier II are classified alterations that still need confirmatory prospective studies but for which evidence of efficacy is available. Somatic BRCA1/2 mutations, germline PALB2 mutations, HER2-low expression, ERBB2 mutations, PTEN deletions, AKT1 mutations, ESR1 resistance mutations satisfy the requirements to be classified in this tier. In tier III are ranked various molecular alterations for which there is evidence of actionability in other tumors (IIIa) or that have similar functional impact in the same gene or pathway of a tier I alteration, without clinical data (IIIb). In tier IV are listed the molecular alterations for which only preclinical studies are available. Conclusion: In this review we report the most relevant molecular targets in BC, ordered pursuant to their pathway and classified in concordance with ESCAT.
KW - Agnostic therapy
KW - Breast cancer
KW - ESCAT
KW - Molecular tumor board
KW - Precision medicine
KW - Target therapy
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U2 - 10.1016/j.ctrv.2021.102223
DO - 10.1016/j.ctrv.2021.102223
M3 - Review article
C2 - 34049187
AN - SCOPUS:85107075338
VL - 98
JO - Cancer Treatment Reviews
JF - Cancer Treatment Reviews
SN - 0305-7372
M1 - 102223
ER -