Assessing Clinical Features and Outcome of Breast Cancer in PALB2 Mutation Carriers: the Palbreast Study

The Modena hereditary breast cancer group identified 3498 BRCA test candidates affected by breast cancer (BC). Among those, 392 were BRCA1/2 positive (11.2%). Since 2018, the site started to analyze eligible BC patients by multi gene panel (MGP) test. Fifty hundred sixty BRCA negative patients have been recalled, whereas other 934 were firstly analyzed by MGP. Totally, among 1494 BC patients analyzed by MGP test, 33 were PALB2 mutation carriers (2%). By involving the Italian Society of Genetic Oncology and 11 European Institutions, it is calculated to identify about 300 PALB2 mutation carriers. 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 gender. 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 with populations ranging from to 54 to 362 individuals 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 (\>30 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 raises new interest in PALB2 mutations as molecular target. Primary objectives is to study the incidence and mortality rates of gPALB2 Breast Cancer.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

\- 1. Has a histologically or cytologically confirmed breast cancer 2. Has any stage of BC 3. Has documented mutation in PALB2 gene (germline or somatic) that is predicted to be deleterious or suspected deleterious.

4\. Has a multigene test performed and resulted negative for alterations. 5. Has information on tumours characteristics, modality of diagnosis, type of surgical treatment, medical therapy, family history and eventually second primary tumours

Demographics Is male or female, who is at least 18 years of age at the time of signing the informed consent.

Exclusion Criteria:

Has a benign variant of PALB2 gene or variant of uncertain (or unknown) significance (VUS) Is involved in the planning and/or conduct of the study Is judged by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.

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