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Somatic and Germline Genomic Alterations in Very Young Women with Breast Cancer.

Authors
  • Waks, Adrienne G1, 2
  • Kim, Dewey1, 3
  • Jain, Esha1, 3
  • Snow, Craig1
  • Kirkner, Gregory J1
  • Rosenberg, Shoshana M1, 2
  • Oh, Coyin2
  • Poorvu, Philip D1, 2
  • Ruddy, Kathryn J4
  • Tamimi, Rulla M5
  • Peppercorn, Jeffrey2, 6
  • Schapira, Lidia7
  • Borges, Virginia F8
  • Come, Steven E2, 9
  • Brachtel, Elena F6, 10
  • Warner, Ellen11
  • Collins, Laura C2, 9
  • Partridge, Ann H1, 2
  • Wagle, Nikhil1, 2, 3
  • 1 Dana-Farber Cancer Institute, Boston, Massachusetts.
  • 2 Harvard Medical School, Boston, Massachusetts.
  • 3 The Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
  • 4 Mayo Clinic, Rochester, Minnesota.
  • 5 Weill Cornell Medicine, New York, New York.
  • 6 Massachusetts General Hospital, Boston, Massachusetts.
  • 7 Stanford Cancer Institute, Stanford University, Palo Alto, California.
  • 8 University of Colorado Denver, Aurora, Colorado.
  • 9 Beth Israel Deaconess Medical Center, Boston, Massachusetts. , (Israel)
  • 10 Maastricht University Medical Center, Maastricht, the Netherlands. , (Netherlands)
  • 11 Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. , (Canada)
Type
Published Article
Journal
Clinical Cancer Research
Publisher
American Association for Cancer Research
Publication Date
Jun 01, 2022
Volume
28
Issue
11
Pages
2339–2348
Identifiers
DOI: 10.1158/1078-0432.CCR-21-2572
PMID: 35101884
Source
Medline
Language
English
License
Unknown

Abstract

Young age at breast cancer diagnosis correlates with unfavorable clinicopathologic features and worse outcomes compared with older women. Understanding biological differences between breast tumors in young versus older women may lead to better therapeutic approaches for younger patients. We identified 100 patients ≤35 years old at nonmetastatic breast cancer diagnosis who participated in the prospective Young Women's Breast Cancer Study cohort. Tumors were assigned a surrogate intrinsic subtype based on receptor status and grade. Whole-exome sequencing of tumor and germline samples was performed. Genomic alterations were compared with older women (≥45 years old) in The Cancer Genome Atlas, according to intrinsic subtype. Ninety-three tumors from 92 patients were successfully sequenced. Median age was 32.5 years; 52.7% of tumors were hormone receptor-positive/HER2-negative, 28.0% HER2-positive, and 16.1% triple-negative. Comparison of young to older women (median age 61 years) with luminal A tumors (N = 28 young women) revealed three significant differences: PIK3CA alterations were more common in older patients, whereas GATA3 and ARID1A alterations were more common in young patients. No significant genomic differences were found comparing age groups in other intrinsic subtypes. Twenty-two patients (23.9%) in the Young Women's Study cohort carried a pathogenic germline variant, most commonly (13 patients, 14.1%) in BRCA1/2. Somatic alterations in three genes (PIK3CA, GATA3, and ARID1A) occur at different frequencies in young versus older women with luminal A breast cancer. Additional investigation of these genes and associated pathways could delineate biological susceptibilities and improve treatment options for young patients with breast cancer. See related commentary by Yehia and Eng, p. 2209. ©2022 The Authors; Published by the American Association for Cancer Research.

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