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

NCT07617025 | Recruiting

• 1 other identifier: PAMBRACA
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Breast Cancer

Keywords

breast cancer; molecular characterization; Breast Cancer 360; CDK4/6 inhibitors; hormone receptor-positive; transcriptomic analysis; gene expression; BRCA1; BRCA2; germline

Outcome Measures

Primary Outcomes (2)

• Distribution of intrinsic subtypes in BRCA1 and BRCA2-associated HR+/HER2-negative tumors

  To evaluate the differences in intrinsic subtype distribution between BRCA1 and BRCA2-associated HR+/HER2-negative tumors.

  through study completion

• Overall survival depending on intrinsic subtype

  To explore the prognostic role of different intrinsic subtypes in terms of overall survival (OS) in HR+/HER2-negative BRCA-associated breast cancer

  through study completion

Secondary Outcomes (2)

• Benefit from CDK4/6 inhibitors depending on molecular subtype

  through study completion

• Molecular features of BRCA1-related and BRCA2-related breast cancers

  through study completion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Each enrolling center will be responsible for identifying patients eligible for the study. Information will be collected for each patient regarding: * Patient and treatment characteristics: age, date of diagnosis, and data relating to any treatments received. * Biological characteristics of the primary disease: histotype, grade, hormone receptor and HER2 expression, and cytoproliferative activity. The data collected reflect those normally collected in clinical practice for patients diagnosed with breast cancer. No additional specific visits or assessments are required.

You may qualify if:

• 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)

You may not qualify if:

• None

Sponsors & Collaborators

• Angela Toss: lead

Study Sites (6)

Ospedale San Martino di Genova

Genova, 16132, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori Milano

Milan, 20133, Italy

RECRUITING

Istituto Oncologico Europeo di Milano

Milan, 20141, Italy

RECRUITING

Azienda Ospedaliero-Universitaria Policlinico di Modena

Modena, 41124, Italy

RECRUITING

Istituto Oncologico Veneto IRCCS Padova

Padova, 35128, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli di Roma

Roma, 00168, Italy

RECRUITING

Related Publications (15)

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• 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 BACKGROUND

• 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, Lakhani SR, Yothers G, Campbell C, Geyer CE Jr; OlympiA Clinical Trial Steering Committee and Investigators. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. N Engl J Med. 2021 Jun 24;384(25):2394-2405. doi: 10.1056/NEJMoa2105215. Epub 2021 Jun 3.

  PMID: 34081848 BACKGROUND

• 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 BACKGROUND

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  PMID: 28578601 BACKGROUND

• 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 the WSG-ADAPT-TN trial. Int J Cancer. 2020 Jan 1;146(1):262-271. doi: 10.1002/ijc.32488. Epub 2019 Jun 19.

  PMID: 31162838 BACKGROUND

• 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 Neoadjuvant Pertuzumab/Trastuzumab vs. Trastuzumab Plus Standard Chemotherapy: An Analysis of Real-World Data. Front Oncol. 2019 Nov 5;9:1178. doi: 10.3389/fonc.2019.01178. eCollection 2019.

  PMID: 31750258 BACKGROUND

• 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: 10.3389/fonc.2019.00707. eCollection 2019.

  PMID: 31448227 BACKGROUND

• Cejalvo JM, Pascual T, Fernandez-Martinez A, Braso-Maristany F, Gomis RR, Perou CM, Munoz M, Prat A. Clinical implications of the non-luminal intrinsic subtypes in hormone receptor-positive breast cancer. Cancer Treat Rev. 2018 Jun;67:63-70. doi: 10.1016/j.ctrv.2018.04.015. Epub 2018 May 7.

  PMID: 29763779 BACKGROUND

• Lee S, Park K, Kim GM, Jung KH, Kang SY, Park IH, Kim JH, Ahn HK, Park WY, Im SA, Park YH. Exploratory analysis of biomarkers associated with clinical outcomes from the study of palbociclib plus endocrine therapy in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. Breast. 2022 Apr;62:52-60. doi: 10.1016/j.breast.2022.01.014. Epub 2022 Jan 29.

  PMID: 35124320 BACKGROUND

• Prat A, Chaudhury A, Solovieff N, Pare L, Martinez D, Chic N, Martinez-Saez O, Braso-Maristany F, Lteif A, Taran T, Babbar N, Su F. Correlative Biomarker Analysis of Intrinsic Subtypes and Efficacy Across the MONALEESA Phase III Studies. J Clin Oncol. 2021 May 1;39(13):1458-1467. doi: 10.1200/JCO.20.02977. Epub 2021 Mar 26.

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• Prat A, Brase JC, Cheng Y, Nuciforo P, Pare L, Pascual T, Martinez D, Galvan P, Vidal M, Adamo B, Hortobagyi GN, Baselga J, Ciruelos E. Everolimus plus Exemestane for Hormone Receptor-Positive Advanced Breast Cancer: A PAM50 Intrinsic Subtype Analysis of BOLERO-2. Oncologist. 2019 Jul;24(7):893-900. doi: 10.1634/theoncologist.2018-0407. Epub 2019 Jan 24.

  PMID: 30679318 BACKGROUND

• Prat A, Galvan P, Jimenez B, Buckingham W, Jeiranian HA, Schaper C, Vidal M, Alvarez M, Diaz S, Ellis C, Nuciforo P, Ferree S, Ribelles N, Adamo B, Ramon Y Cajal S, Peg V, Alba E. Prediction of Response to Neoadjuvant Chemotherapy Using Core Needle Biopsy Samples with the Prosigna Assay. Clin Cancer Res. 2016 Feb 1;22(3):560-6. doi: 10.1158/1078-0432.CCR-15-0630. Epub 2015 Jul 7.

  PMID: 26152740 BACKGROUND

• Prat A, Fan C, Fernandez A, Hoadley KA, Martinello R, Vidal M, Viladot M, Pineda E, Arance A, Munoz M, Pare L, Cheang MC, Adamo B, Perou CM. Response and survival of breast cancer intrinsic subtypes following multi-agent neoadjuvant chemotherapy. BMC Med. 2015 Dec 18;13:303. doi: 10.1186/s12916-015-0540-z.

  PMID: 26684470 BACKGROUND

• Zattarin E, Marra A, Palazzo A, Griguolo G, Vernieri C, Etessami J, Pontolillo L, Landa G, Daneri A, De Monte M, Cuoghi Costantini R, Tenedini E, Ponzoni O, Razeti MG, Sposetti C, Barbieri E, Manni M, Caggia F, Cortesi L, Curigliano G, Bria E, Dominici M, Guarneri V, Lambertini M, Toss A. Real-world effectiveness of PARP inhibitors after CDK4/6 inhibitor therapy in BRCA-mutated HR-positive/HER2-negative advanced breast cancer. NPJ Breast Cancer. 2025 Dec 13;11(1):145. doi: 10.1038/s41523-025-00859-z.

  PMID: 41390667 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

paraffin-embedded breast tumor tissue from which RNA is extracted

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: April 21, 2026
• First Posted: June 1, 2026
• Study Start: September 5, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 1, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (6)