| Autor: |
Tsoulos N; Genekor Medical S.A., 15344 Athens, Greece., Papadopoulou E; Genekor Medical S.A., 15344 Athens, Greece., Agiannitopoulos K; Genekor Medical S.A., 15344 Athens, Greece., Grigoriadis D; Genekor Medical S.A., 15344 Athens, Greece., Tsaousis GN; Genekor Medical S.A., 15344 Athens, Greece., Bouzarelou D; Genekor Medical S.A., 15344 Athens, Greece., Gogas H; First Department of Internal Medicine, Laikon General Hospital, School of Medicine, National Kapodistrian University of Athens, 11527 Athens, Greece., Troupis T; School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece., Venizelos V; Metropolitan Hospital, 18547 Athens, Greece., Fountzilas E; Second Department of Medical Oncology, Euromedica General Clinic, 54645 Thessaloniki, Greece., Theochari M; Oncology Unit, 'Hippokrateion' General Hospital of Athens, 11527 Athens, Greece., Ziogas DC; First Department of Internal Medicine, Laikon General Hospital, School of Medicine, National Kapodistrian University of Athens, 11527 Athens, Greece., Giassas S; Second Oncology Clinic IASO, General Maternity and Gynecology Clinic, 15123 Athens, Greece., Koumarianou A; Hematology Oncology Unit, 4th Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, 12462 Athens, Greece., Christopoulou A; Oncology Unit, ST Andrews General Hospital of Patras, 26332 Patras, Greece., Busby G; Allelica Inc., 447 Broadway, New York, NY 10013, USA., Nasioulas G; Genekor Medical S.A., 15344 Athens, Greece., Markopoulos C; School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece. |
| Abstrakt: |
Breast cancer (BC) is the most prominent tumor type among women, accounting for 32% of newly diagnosed cancer cases. BC risk factors include inherited germline pathogenic gene variants and family history of disease. However, the etiology of the disease remains occult in most cases. Therefore, in the absence of high-risk factors, a polygenic basis has been suggested to contribute to susceptibility. This information is utilized to calculate the Polygenic Risk Score (PRS) which is indicative of BC risk. This study aimed to evaluate retrospectively the clinical usefulness of PRS integration in BC risk calculation, utilizing a group of patients who have already been diagnosed with BC. The study comprised 105 breast cancer patients with hereditary genetic analysis results obtained by NGS. The selection included all testing results: high-risk gene-positive, intermediate/low-risk gene-positive, and negative. PRS results were obtained from an external laboratory (Allelica). PRS-based BC risk was computed both with and without considering additional risk factors, including gene status and family history. A significantly different PRS percentile distribution consistent with higher BC risk was observed in our cohort compared to the general population. Higher PRS-based BC risks were detected in younger patients and in those with FH of cancers. Among patients with a pathogenic germline variant detected, reduced PRS values were observed, while the BC risk was mainly determined by a monogenic etiology. Upon comprehensive analysis encompassing FH, gene status, and PRS, it was determined that 41.90% (44/105) of the patients demonstrated an elevated susceptibility for BC. Moreover, 63.63% of the patients with FH of BC and without an inherited pathogenic genetic variant detected showed increased BC risk by incorporating the PRS result. Our results indicate a major utility of PRS calculation in women with FH in the absence of a monogenic etiology detected by NGS. By combining high-risk strategies, such as inherited disease analysis, with low-risk screening strategies, such as FH and PRS, breast cancer risk stratification can be improved. This would facilitate the development of more effective preventive measures and optimize the allocation of healthcare resources. |
