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BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Ovarian Cancer | Research article

Extended genetic analysis and tumor characteristics in over 4600 women with suspected hereditary breast and ovarian cancer

Authors: Anna Öfverholm, Therese Törngren, Anna Rosén, Brita Arver, Zakaria Einbeigi, Karin Haraldsson, Anne Kinhult Ståhlbom, Ekaterina Kuchinskaya, Annika Lindblom, Beatrice Melin, Ylva Paulsson-Karlsson, Marie Stenmark-Askmalm, Emma Tham, Anna von Wachenfeldt, Anders Kvist, Åke Borg, Hans Ehrencrona

Published in: BMC Cancer | Issue 1/2023

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Abstract

Background

Genetic screening for pathogenic variants (PVs) in cancer predisposition genes can affect treatment strategies, risk prediction and preventive measures for patients and families. For decades, hereditary breast and ovarian cancer (HBOC) has been attributed to PVs in the genes BRCA1 and BRCA2, and more recently other rare alleles have been firmly established as associated with a high or moderate increased risk of developing breast and/or ovarian cancer. Here, we assess the genetic variation and tumor characteristics in a large cohort of women with suspected HBOC in a clinical oncogenetic setting.

Methods

Women with suspected HBOC referred from all oncogenetic clinics in Sweden over a six-year inclusion period were screened for PVs in 13 clinically relevant genes. The genetic outcome was compared with tumor characteristics and other clinical data collected from national cancer registries and hospital records.

Results

In 4622 women with breast and/or ovarian cancer the overall diagnostic yield (the proportion of women carrying at least one PV) was 16.6%. BRCA1/2 PVs were found in 8.9% of women (BRCA1 5.95% and BRCA2 2.94%) and PVs in the other breast and ovarian cancer predisposition genes in 8.2%: ATM (1.58%), BARD1 (0.45%), BRIP1 (0.43%), CDH1 (0.11%), CHEK2 (3.46%), PALB2 (0.84%), PTEN (0.02%), RAD51C (0.54%), RAD51D (0.15%), STK11 (0) and TP53 (0.56%). Thus, inclusion of the 11 genes in addition to BRCA1/2 increased diagnostic yield by 7.7%. The yield was, as expected, significantly higher in certain subgroups such as younger patients, medullary breast cancer, higher Nottingham Histologic Grade, ER-negative breast cancer, triple-negative breast cancer and high grade serous ovarian cancer. Age and tumor subtype distributions differed substantially depending on genetic finding.

Conclusions

This study contributes to understanding the clinical and genetic landscape of breast and ovarian cancer susceptibility. Extending clinical genetic screening from BRCA1 and BRCA2 to 13 established cancer predisposition genes almost doubles the diagnostic yield, which has implications for genetic counseling and clinical guidelines. The very low yield in the syndrome genes CDH1, PTEN and STK11 questions the usefulness of including these genes on routine gene panels.
Appendix
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Metadata
Title
Extended genetic analysis and tumor characteristics in over 4600 women with suspected hereditary breast and ovarian cancer
Authors
Anna Öfverholm
Therese Törngren
Anna Rosén
Brita Arver
Zakaria Einbeigi
Karin Haraldsson
Anne Kinhult Ståhlbom
Ekaterina Kuchinskaya
Annika Lindblom
Beatrice Melin
Ylva Paulsson-Karlsson
Marie Stenmark-Askmalm
Emma Tham
Anna von Wachenfeldt
Anders Kvist
Åke Borg
Hans Ehrencrona
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11229-y

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