Pathogenic variants among females with breast cancer and a non-breast cancer reveal opportunities for cancer interception

Sep 24, 2026

Uploaded by Rowan

Reports the frequency and distribution of germline pathogenic variants (PVs) among females with breast cancer who also had at least one other non-breast primary cancer and underwent multi-gene panel testing. Includes patients tested with a multi-gene panel through Ambry Genetics between 2012 and 2016. Finds PVs in 14.1% overall and 16.4% among those diagnosed first with breast cancer, with many having actionable PVs linked to subsequent PV-associated cancers. Concludes that combined-cancer patients show high germline PV frequency and highlights interception opportunities.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Abstract

Purpose

Methods

Results

Conclusions

Introduction

Breast Cancer Research and Treatment (2023) 200:63–72 [https://doi.org/10.1007/s10549-023-06870-x](https://doi.org/10.1007/s10549-023-06870-x) Pathogenic variants among females with breast cancer and a non‑breast cancer reveal opportunities for cancer interception Brittany L. Bychkovsky1,2,3,4 · Min‑Tzu Lo5 · AmalYussuf5 · Carrie Horton5 · Parichehr Hemyari5 · Holly LaDuca5 · Judy E. Garber1,2,3,4 · Rochelle Scheib1,2,3,4 · Huma Q. Rana1,3,4 Received: 22 February 2022 / Accepted: 21 January 2023 / Published online: 1 March 2023 © The Author(s) 2023, corrected publication 2023 Abstract Purpose Herein, we report the frequency and distribution of germline pathogenic variants (PVs) among females with breast cancer (BC) and at least one other non-BC who underwent multi-gene panel testing (MGPT) . Among females with PVs diagnosed first with BC or ovarian cancer (OC), we sought to enumerate the frequency of subsequent PV-associated cancers. Methods Females with BC and cancer of ≥ 1 other site (multiple primary cancers, MPC) who underwent MGPT through Ambry Genetics from March 2012 to December 2016 were included if they had testing of at least 21 genes of interest (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53). Phenotypic data were abstracted from test requisition forms and clinical notes. Results Of 6,617 evaluable patients, most were White (70.8%) and median age at first cancer, second cancer, and MGPT was 49 (interquartile range [IQR]: 18), 59 (IQR: 16), and 63 (IQR: 16) years, respectively. PVs were found among 14.1%(932/6617) of the overall cohort and in 16.4%(440/2687) of females who were diagnosed first with BC. Among those, 55.2%(243/440) had an actionable PV associated with a subsequent cancer diagnosis including 150 OCs. Of the 2443 females with breast and ovarian cancer, few (n = 97, 9.5%) were diagnosed first with OC, limiting our analysis. Conclusions Females with MPC, including BC, have a high frequency of germline PVs (14.1%) . These data delineate the opportunities for intercepting subsequent cancers associated with genetic risk among females diagnosed first with BC. Keywords Multiple primary cancers · Breast cancer · Genetics · Germline · Pathogenic variants · Cancer interception · Survivorship Previous presentation: These data were presented at the SABCS 2021 Annual Meeting. * Brittany L. Bychkovsky [Brittany_Bychkovsky@dfci.harvard.edu](Brittany_Bychkovsky@dfci.harvard.edu) 1 Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA 2 Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA 3 Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA, USA 4 Harvard Medical School, Boston, MA, USA 5 Ambry Genetics, Aliso Viejo, CA, USA Introduction Multiple primary cancers (MPCs) and, notably, subsequent cancer diagnoses among breast cancer survivors are multifactorial. While some are due to receipt of chemotherapy or radiation or exposure to a common carcinogen, others can be attributed to a genetic risk [1] . In prior work, we found that patients with MPCs who underwent germline genetic testing had a high rate of pathogenic variants (PVs) (> 10%) regardless of age at their second cancer diagnosis (< 50, 50–70 or >70) [2] . Patients with breast cancer (BC) who develop a second BC are more likely to have PVs in germline BC genes (ATM, BRCA1, BRCA2, CHEK2, CDH1, NBN, NF1, PABL2, PTEN, and TP53) than those with one BC [3] . Additionally, patients with BC and any other primary cancer diagnosis are more likely to have a PV in a variety of cancer genes than those with a BC only (8.5% vs. 4.9%) [4] . Data remain limited on the frequency of PVs among BC survivors who develop a subsequent cancer diagnosis. Germline genetic testing of female patients with BC is often limited to those with a strong cancer

FAQs

What was the purpose of the study?

To report how often germline pathogenic variants occur among females with breast cancer and at least one other non-breast primary cancer, and to quantify subsequent PV-associated cancers.

What testing approach and gene set were used?

Females underwent multi-gene panel testing through Ambry Genetics, with inclusion requiring testing of at least 21 genes of interest.

What were the main findings on PV frequency and actionable variants?

PVs were found in 14.1% of the overall cohort and 16.4% among females diagnosed first with breast cancer; among those, many had actionable PVs associated with subsequent cancer diagnoses.

Sep 24, 2026

Uploaded by Rowan