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23-01-2024 | Breast Cancer | Breast Oncology

Upgrade Rates and Breast Cancer Development Among Germline Pathogenic Variant Carriers with High-Risk Breast Lesions

Authors: Alison Laws, MD, MPH, Saskia Leonard, BS, Emma Hershey, BS, Samantha Stokes, BS, MPA, Julie Vincuilla, BS, MPH, Eshita Sharma, BS, Kara Milliron, MS, CGC, Judy E. Garber, MD, MPH, Sofia D. Merajver, MD, PhD, Tari A. King, MD, Melissa L. Pilewskie, MD

Published in: Annals of Surgical Oncology | Issue 5/2024

Abstract

Background

High-risk lesions (HRL) of the breast are risk factors for future breast cancer development and may be associated with a concurrent underlying malignancy when identified on needle biopsy; however, there are few data evaluating HRLs in carriers of germline pathogenic variants (PVs) in breast cancer predisposition genes.

Methods

We identified patients from two institutions with germline PVs in high- and moderate-penetrance breast cancer predisposition genes and an HRL in an intact breast, including atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), and lobular neoplasia (LN). We calculated upgrade rates at surgical excision and used Kaplan–Meier methods to characterize 3-year breast cancer risk in patients without upgrade.

Results

Of 117 lesions in 105 patients, 65 (55.6%) were ADH, 48 (41.0%) were LN, and 4 (3.4%) were FEA. Most PVs (83.8%) were in the BRCA1/2, CHEK2 and ATM genes. ADH and FEA were excised in most cases (87.1%), with upgrade rates of 11.8% (95% confidence interval [CI] 5.5–23.4%) and 0%, respectively. LN was selectively excised (53.8%); upgrade rate in the excision group was 4.8% (95% CI 0.8–22.7%), and with 20 months of median follow-up, no same-site cancers developed in the observation group. Among those not upgraded, the 3-year risk of breast cancer development was 13.1% (95% CI 6.3–26.3%), mostly estrogen receptor-positive (ER +) disease (89.5%).

Conclusions

Upgrade rates for HRLs in patients with PVs in breast cancer predisposition genes appear similar to non-carriers. HRLs may be associated with increased short-term ER+ breast cancer risk in PV carriers, warranting strong consideration of surgical or chemoprevention therapies in this population.

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Title: Upgrade Rates and Breast Cancer Development Among Germline Pathogenic Variant Carriers with High-Risk Breast Lesions
Authors: Alison Laws, MD, MPH
Saskia Leonard, BS
Emma Hershey, BS
Samantha Stokes, BS, MPA
Julie Vincuilla, BS, MPH
Eshita Sharma, BS
Kara Milliron, MS, CGC
Judy E. Garber, MD, MPH
Sofia D. Merajver, MD, PhD
Tari A. King, MD
Melissa L. Pilewskie, MD
Publication date: 23-01-2024
Publisher: Springer International Publishing
Keywords: Breast Cancer
Breast Cancer
Published in: Annals of Surgical Oncology / Issue 5/2024
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-024-14947-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Upgrade Rates and Breast Cancer Development Among Germline Pathogenic Variant Carriers with High-Risk Breast Lesions

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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