Abstract P2-10-23: ASSESSING CLINICAL FEATURES AND OUTCOME OF BREAST CANCER IN PALB2 MUTATION CARRIERS: AN EUROPEAN MULTICENTRIC RETROSPECTIVE HOSPITAL-BASED COHORT CONTROL STUDY (PALBREAST)

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Abstract Background: PALB2 is a breast cancer susceptibility gene that encodes the BRCA2-interacting protein. Mono-allelic mutations of PALB2 are associated with an increased risk for breast and ovarian cancer in women, prostate cancer in men, and pancreatic cancer in both genders. Women with no family history of breast cancer have a cumulative risk of 33%, compared to 58% in women with two or more family members with breast cancer. Several studies aimed to describe breast cancer phenotypic characteristics in PALB2 mutation carriers. Some of these studies suggested an association with triple-negative phenotype, older age at diagnosis (>60 years), tumor size > 2 cm, negative HER2 status, lymph nodes positive and bilaterality. Nevertheless, results among different studies are contradictory and no data on prognosis of these patients are reported. Furthermore, the clinical potential of PARP inhibition beyond currently approved indications to additional patients whose tumors have (epi)genetic changes affecting homologous recombination repair (HRR) raises new interest in PALB2 mutations as molecular target. So far, the study is aimed to collect, in an European dataset, a large number of PALB2 related BC characteristics starting from 2010 until now and to evaluate the outcome of those patients. This database will be useful for establishing the clincal needs for PALB2 patients, particularly in order to design new interventional studies with target therapies Trial design: PALBREAST is a multicenter hospital-based retrospective cohort control study conducted across several Institutions with known expertise in managing hereditary breast cancer. It is planned to enroll at least 300 PALB2-related BC diagnosed at the different Units and 300 BC as control group tested for multigene panel and resulted negative for mutations. It is expected to complete the accrual in one year; furthermore, a minimum follow-up of one more year is required for the final analysis of primary and secondary endpoints. Each participant with PALB2 mutations and BC will be registered in the database where age and modality at diagnosis, type of surgery (quadrantectomy vs. mastectomy vs bilateral mastectomy), tumor characteristics (grading, histology, carcinoma in situ vs invasive, multifocal vs multicentric, proliferation rate, hormonal receptors, nodal status) stage, age at relapse, treatment (neoadjuvant vs adjuvant, chemotherapy vs hormonal treatment), follow-up status will be inserted. A CT/PET for the last follow-up will be performed at the end of the study. All participants will be followed by telephone for overall survival until the end of the study. The primary end-points are incidence and mortality rates of gPALB2-BC. Secondary end-points are to evaluate the modalities of diagnosis and the imaging characteristics, the type of surgery (bilateral vs. monolateral), the somatic PALB2 mutations rates evaluated by centralized RAD51 assay in the control group, the Disease Free Survival (DFS), and Overall Survival (OS) in comparison with patients with somatic mutations and wild-type PALB2 breast cancer, adjusted for age, stage and period of diagnosis, matched for age, stage, subtype and diagnosis period. Also, the type of therapy (chemotherapy, hormonal treatments and target therapies) and the rate of second BC and other tumors in the patients and in the family will be evaluated. Planned statistical analyses of DFS and OS will be conducted using a stratified log-rank test. Participant enrolment is ongoing. Ninety-seven patients have been already registered in three different centers in Italy. Clinical trial identification: NCT06403904 Funding: This study was supported by AstraZeneca. Citation Format: Laura Cortesi, Benedetta Pellegrino, Federica Caggia, Martina Manni, Marta Venturelli, Isabella Marchi, Elena Barbieri, Angela Toss, Ugo de Giorgi, Elisa Gasparini, Claudia Degli Esposti, Chiara Casarini, Geertruida H de Bock, Elen Vettus, Evandro de Azambuja, Mateja Krajc, Lazar Popovic, Hayane Akopyan, Aleksander Myszka, Alonso Atanasio Pandiella, Katarzyna Pogoda, Svetlana Bajalica Lagercrantz, Massimo Dominici. ASSESSING CLINICAL FEATURES AND OUTCOME OF BREAST CANCER IN PALB2 MUTATION CARRIERS: AN EUROPEAN MULTICENTRIC RETROSPECTIVE HOSPITAL-BASED COHORT CONTROL STUDY (PALBREAST) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-10-23.

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