Germline Pathogenic Variants in Cancer Predisposition Genes Among Women With Invasive Lobular Carcinoma of the Breast

Overview

Journal J Clin Oncol

Specialty Oncology

Date 2021 Oct 21

PMID 34672684

Citations 21

Authors

Siddhartha Yadav

Chunling Hu

Katherine L Nathanson

Jeffrey N Weitzel

David E Goldgar

Peter Kraft

Rohan D Gnanaolivu

Jie Na

Hongyan Huang

Nicholas J Boddicker

Nicole Larson

Chi Gao

Song Yao

Clarice Weinberg

Celine M Vachon

Amy Trentham-Dietz

Jack A Taylor

Dale R Sandler

Alpa Patel

Julie R Palmer

Janet E Olson

Susan Neuhausen

Elena Martinez

Sara Lindstrom

James V Lacey

Allison W Kurian

Esther M John

Christopher Haiman

Leslie Bernstein

Paul W Auer

Hoda Anton-Culver

Christine B Ambrosone

Rachid Karam

Elizabeth Chao

Amal Yussuf

Tina Pesaran

Jill S Dolinsky

Steven N Hart

Holly LaDuca

Eric C Polley

Susan M Domchek

Fergus J Couch

Affiliations

Soon will be listed here.

Abstract

Purpose: To determine the contribution of germline pathogenic variants (PVs) in hereditary cancer testing panel genes to invasive lobular carcinoma (ILC) of the breast.

Materials And Methods: The study included 2,999 women with ILC from a population-based cohort and 3,796 women with ILC undergoing clinical multigene panel testing (clinical cohort). Frequencies of germline PVs in breast cancer predisposition genes (, , , , , , , , , , , and ) were compared between women with ILC and unaffected female controls and between women with ILC and infiltrating ductal carcinoma (IDC).

Results: The frequency of PVs in breast cancer predisposition genes among women with ILC was 6.5% in the clinical cohort and 5.2% in the population-based cohort. In case-control analysis, and PVs were associated with high risks of ILC (odds ratio [OR] > 4) and , , and PVs were associated with moderate (OR = 2-4) risks. PVs and p.Ile157Thr were not associated with clinically relevant risks (OR < 2) of ILC. Compared with IDC, PVs were > 10-fold enriched, whereas PVs in were substantially reduced in ILC.

Conclusion: The study establishes that PVs in , , , , and are associated with an increased risk of ILC, whereas PVs are not. The similar overall PV frequencies for ILC and IDC suggest that cancer histology should not influence the decision to proceed with genetic testing. Similar to IDC, multigene panel testing may be appropriate for women with ILC, but should be specifically discussed because of low prevalence and gastric cancer risk.

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