Prognostic and Predictive Role of Intrinsic Molecular Subtypes in BRCA-associated Breast Cancer

Overview

This study is an observational study being carried out in several hospitals. No extra tests or procedures are required beyond those already part of normal medical care. The study is sponsored by the University of Modena and Reggio Emilia and aims to include about 100 patients. The main goal of the study is to better understand the different biological types of breast cancer in patients who have hormone receptor-positive (HR-positive), HER2-negative breast cancer related to BRCA gene mutations. In particular, the study will explore whether these cancers tend to belong to molecular types that may respond less to endocrine or CDK4/6 inhibitor therapy. The study also compares cancers linked to BRCA1 and BRCA2 mutations and investigates whether the different biological types are associated with differences in disease outcomes and response to treatment.

Primary outcome measures

• Distribution of intrinsic subtypes in BRCA1 and BRCA2-associated HR+/HER2-negative tumors [Time frame: through study completion]
• Overall survival depending on intrinsic subtype [Time frame: through study completion]

Secondary outcome measures (2)

• Benefit from CDK4/6 inhibitors depending on molecular subtype [Time frame: through study completion]
• Molecular features of BRCA1-related and BRCA2-related breast cancers [Time frame: through study completion]

Eligibility criteria

Inclusion criteria

• Age 18 years or older
• Patients carrying a pathogenic or likely pathogenic germline variant in BRCA1 or BRCA2 with a histologically confirmed diagnosis of HR+/HER2-negative breast cancer
• Patients with available hospital and/or outpatient medical records for clinical data collection
• Presence of available formally fixed paraffin-embedded (FFPE) breast tumor tissue (primary or metastatic site)

Exclusion criteria

• None

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Italy · 6 centers

• Ospedale San Martino di Genova — Genova
• Fondazione IRCCS Istituto Nazionale dei Tumori Milano — Milan
• Istituto Oncologico Europeo di Milano — Milan
• Azienda Ospedaliero-Universitaria Policlinico di Modena — Modena
• Istituto Oncologico Veneto IRCCS Padova — Padova
• Fondazione Policlinico Universitario Agostino Gemelli di Roma — Roma

Publications

• Hequet D, Harrissart G, Krief D, Maumy L, Lerebours F, Menet E, Callens C, Rouzier R. Prosigna test in breast cancer: real-life experience. Breast Cancer Res Treat. 2021 Jul;188(1):141-147. doi: 10.1007/s10549-021-06191-x. Epub 2021 Apr 15. PMID 33860387
• Collins JM, Nordstrom BL, McLaurin KK, Dalvi TB, McCutcheon SC, Bennett JC, Murphy BR, Singhal PK, McCrea C, Shinde R, Briceno JM. A Real-World Evidence Study of CDK4/6 Inhibitor Treatment Patterns and Outcomes in Metastatic Breast Cancer by Germline BRCA Mutation Status. Oncol Ther. 2021 Dec;9(2):575-589. doi: 10.1007/s40487-021-00162-4. Epub 2021 Jul 25. PMID 34308518
• Tutt ANJ, Garber JE, Kaufman B, Viale G, Fumagalli D, Rastogi P, Gelber RD, de Azambuja E, Fielding A, Balmana J, Domchek SM, Gelmon KA, Hollingsworth SJ, Korde LA, Linderholm B, Bandos H, Senkus E, Suga JM, Shao Z, Pippas AW, Nowecki Z, Huzarski T, Ganz PA, Lucas PC, Baker N, Loibl S, McConnell R, Piccart M, Schmutzler R, Steger GG, Costantino JP, Arahmani A, Wolmark N, McFadden E, Karantza V, La PMID 34081848
• Litton JK, Rugo HS, Ettl J, Hurvitz SA, Goncalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roche H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl J Med. 2018 Aug 23;379(8):753-763. doi: 10.1056/NEJMoa1802905. Epub 2018 Aug 15. PMID 30110579
• Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. doi: 10.1056/NEJMoa1706450. Epub 2017 Jun 4. PMID 28578601
• Gluz O, Kolberg-Liedtke C, Prat A, Christgen M, Gebauer D, Kates R, Pare L, Grischke EM, Forstbauer H, Braun M, Warm M, Hackmann J, Uleer C, Aktas B, Schumacher C, Kuemmel S, Wuerstlein R, Pelz E, Nitz U, Kreipe HH, Harbeck N. Efficacy of deescalated chemotherapy according to PAM50 subtypes, immune and proliferation genes in triple-negative early breast cancer: Primary translational analysis of th PMID 31162838
• Diaz-Redondo T, Lavado-Valenzuela R, Jimenez B, Pascual T, Galvez F, Falcon A, Alamo MDC, Morales C, Amerigo M, Pascual J, Sanchez-Munoz A, Gonzalez-Guerrero M, Vicioso L, Laborda A, Ortega MV, Perez L, Fernandez-Martinez A, Chic N, Jerez JM, Alvarez M, Prat A, Ribelles N, Alba E. Different Pathological Complete Response Rates According to PAM50 Subtype in HER2+ Breast Cancer Patients Treated With PMID 31750258
• Pernas S, Petit A, Climent F, Pare L, Perez-Martin J, Ventura L, Bergamino M, Galvan P, Falo C, Morilla I, Fernandez-Ortega A, Stradella A, Rey M, Garcia-Tejedor A, Gil-Gil M, Prat A. PAM50 Subtypes in Baseline and Residual Tumors Following Neoadjuvant Trastuzumab-Based Chemotherapy in HER2-Positive Breast Cancer: A Consecutive-Series From a Single Institution. Front Oncol. 2019 Aug 6;9:707. doi: PMID 31448227

Identifiers

NCT: NCT07617025 · PAMBRACA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗