E60: Incidence of high-risk lesions in women with germline pathogenic variants in BRCA1/2, PALB2 and other breast cancer susceptibility genes undergoing risk-reducing mastectomy

ePoster Abstract Author(s)

Sarah Al Ben Ali, MD

General Surgery Resident
Department of Surgery, McGill University Medical School, Montreal, QC, Canada
Montreal, Quebec, Canada

Submitter(s)

Sarah Al Ben Ali, MD

General Surgery Resident
Department of Surgery, McGill University Medical School, Montreal, QC, Canada
Montreal, Quebec, Canada

Author(s)

Sarah Al Ben Ali, MD

General Surgery Resident
Department of Surgery, McGill University Medical School, Montreal, QC, Canada
Montreal, Quebec, Canada
Carla Apostolova, MD (she/her/hers)

Medical student
Department of Surgery, McGill University Medical School, Montreal, QC, Canada
Kirkland, Quebec, United States
AF

Amina Ferroum, MD

Medical Student
Department of Surgery, McGill University Medical School, Montreal, QC, Canada, United States
Basmah Alhassan, MD MSc

Fellow
Department of Surgery, McGill University Medical School, Montreal, QC, Canada
Montreal, Quebec, United States
Ipshita Prakash, MD MSc

Assistant Professor
Department of Surgery, McGill University Medical School, Montreal, QC, Canada, Quebec, United States
MB

Mark Basik, MD

Associate Professor of Surgery and Oncology
Department of Surgery, McGill University Medical School, Montreal, QC, Canada, United States
JB

Jean Francois Boileau, MD MSc

Assistant Professor
Department of Surgery, McGill University Medical School, Montreal, QC, Canada, United States
KM

Karyne Martel, MD

Associate Professor
Department of Surgery, McGill University Medical School, Montreal, QC, Canada, United States
Sarkis Meterissian, MD Msc (he/him/his)

Professor
Department of Surgery, McGill University Medical School, Montreal, QC, Canada
Montreal, Quebec, United States
NW

Nora Wong, MS CCGC

Genetics Counselor
Department of Human Genetics, McGill University Medical School, Montreal, QC, Canada, United States
WF

William D. D. Foulkes, MBBS PhD

Director, Program in Cancer Genetics, McGill University
Department of Human Genetics, McGill University Medical School, Montreal, QC, Canada, United States
Stephanie M. M. Wong, MD, MPH

Assistant Professor
Department of Surgery, McGill University Medical School, Montreal, QC, Canada; Sir Mortimer B. Davis Jewish General Hospital, QC, Montreal, Canada
Montreal, Quebec, United States

Introduction: The goal of this study was to evaluate the incidence of high-risk lesions such as atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), or atypical ductal hyperplasia (ADH) in risk reducing mastectomy (RRM) specimens of women with germline pathogenic variants in breast cancer susceptibility genes.

Methods: We retrospectively reviewed the incidence of high-risk lesions in all female patients with a confirmed pathogenic variant in a breast cancer susceptibility gene (BRCA1/2, PALB2, TP53, CHEK2, ATM, PTEN, RAD51D, or CDH1) who underwent bilateral or contralateral RRM at our institution between 2004 to 2023. Univariate analyses were then performed to identify factors associated with the presence of high-risk lesions (ALH, ADH, or LCIS) on final RRM pathology.

Results: Of 679 germline pathogenic variant carriers, RRM were performed in 305 (45%) patients at a median age of 45 years (IQR, 37-53 years), including 278 BRCA1/2, 15 PALB2, and 12 carriers of other breast cancer susceptibility genes. Overall, 161 women underwent bilateral RRM (52.8%) and 144 (47.2%) underwent contralateral RRM, of which, 39 (12.7%) had high-risk lesions on final pathology. Of 466 mastectomies, 7 (1.5%) contained occult invasive cancer, 18 (3.9%) occult ductal carcinoma in situ, 20 (4.3%) ADH and 20 (4.3%) ALH or LCIS. The incidence of high-risk lesions was similar across BRCA1 (12.7%), BRCA2 (13.3%), PALB2 (6.7%) and other carriers (16.7%) undergoing RRM (p=0.87). Older age at the time of RRM was associated with an increased incidence of high-risk lesions identified on RRM pathology (< 40 years, 4.9%; >40-50 years, 18.2%; 50 years, 15.5%; p=0.01). Personal history of breast cancer, history of benign breast biopsies, prior oophorectomy, and prior exposure to endocrine therapy did not significantly alter the incidence of high-risk lesions (all p >0.05). In 142 carriers with breast cancer undergoing unilateral therapeutic and contralateral RRM as part of index treatment, the use of neoadjuvant therapy was associated with a decreased incidence of high-risk lesions in the contralateral RRM at the time of surgery (6.9% vs. 19.7%, p= 0.02).

Conclusions: The incidence of high-risk lesions in germline pathogenic variant carriers undergoing RRM is approximately 13%.

Learning Objectives:

To evaluate the incidence of high-risk lesions such as atypical lobular hyperplasia, lobular carcinoma in situ, or atypical ductal hyperplasia in germline pathogenic variant carriers undergoing risk reducing mastectomy.
To identify factors associated with the presence of high-risk lesions such as, atypical lobular hyperplasia, lobular carcinoma in situ, or atypical ductal hyperplasia on final risk reducing mastectomy pathology.
To describe the clinical significance of high-risk lesions such as, atypical lobular hyperplasia, lobular carcinoma in situ, or atypical ductal hyperplasia among germline pathogenic variant carriers.