To evaluate the outcomes of germline pathogenic or likely pathogenic variants (PVs) associated with increased breast cancer risk in women diagnosed with primary invasive lobular carcinoma (ILC) and to assess the potential of polygenic risk scores (PRS) as prognostic markers.
Approach:
Study Design: A longitudinal, prospective cohort study analyzing 113 genes through blood samples from women with postoperative histopathologic diagnosis of ILC.
Sample Collection: Blood samples were collected from 219 women prospectively and 195 women retrospectively, with clinical and family history data recorded.
Genetic Analysis: Genomic DNA was extracted and analyzed using a cancer solution panel targeting hereditary cancer-associated genes.
Variant Classification: Variants were classified according to established guidelines, and patients were grouped based on germline variant status.
Key Findings:
Germline PVs in CDH1 and BRCA2 are strongly associated with increased ILC risk, particularly in women diagnosed before age 40.
CHEK2, ATM, and PALB2 are associated with moderate risk for ILC, while BRCA1 PVs are not significantly associated.
CDH1 PVs are more frequent in ILC compared to invasive ductal carcinoma.
Interpretation:
The study aims to improve genetic risk stratification in ILC, which could inform tailored surveillance strategies and personalized risk-reduction interventions.
Limitations:
The study is limited to women diagnosed with primary ILC and may not be generalizable to other breast cancer subtypes.
The outcomes are based on a single cohort from the European Institute of Oncology.
Conclusion:
The findings may have implications for genetic counseling and targeted therapies in ILC patients.
by Giovanni Corso, Elena Marino, Francesca Fava, Fabrizio Natali, Paolo Peterlongo, Matteo Dal Molin, Irene Feroce, Cristina Zanzottera, Giulia Massari, Susanna Di Silvestre, Micol Moscatiello, Andrea Franceschini, Vincenzo Bagnardi, Giuseppe Curigliano, Bernardo Bonanni, Paolo Veronesi, Francesco Bertolini
