4: Germline Genetic Mutations in a Prospective Multi-Center Cohort of 241 Phyllodes Tumors; Time to Expand Testing Criteria

Friday, March 24, 2023

4:31 PM – 4:41 PM

Location: Veterans Memorial Auditorium

Abstract Presenter(s)

Laura H. Rosenberger, MD, MS (she/her/hers)

Associate Professor of Surgery
Duke University Medical Center
Durham, North Carolina, United States

Disclosure(s): No financial relationships to disclose

Author(s)

Laura H. Rosenberger, MD, MS (she/her/hers)

Associate Professor of Surgery
Duke University Medical Center
Durham, North Carolina, United States

Disclosure(s): No financial relationships to disclose
ST

Samantha M. Thomas, MS

Biostatistician
Biostatistics and Bioinformatics, Duke University, United States

Disclosure information not submitted.
Tina J. Hieken, MD

Professor of Surgery
Mayo Clinic
Rochester, Minnesota, United States

Disclosure information not submitted.
Kristalyn K. Gallagher, DO (she/her/hers)

Associate Professor of Surgery
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States

Disclosure information not submitted.
Heather B. Neuman, MD, MS

Associate Professor
University of Wisconsin School of Medicine and Public Health
Madison, WI, United States

Disclosure information not submitted.
Anna Weiss, MD

Associate Surgeon
Brigham and Women's Hospital
Boston, Massachusetts, United States

Disclosure information not submitted.
Tari A. King, MD, FSSO, FASCO (she/her/hers)

Chief, Division of Breast Surgery
Brigham and Womens Hospital, Dana Farber/Brigham Cancer Center
Boston, Massachusetts, United States

Disclosure(s): Exact Sciences/Genomic Health: Advisor (Ongoing), Speaker (Ongoing)
JW

Jasmine Wong, MD

Associate Professor
Department of Surgery, University of California, San Francisco, United States

Disclosure information not submitted.
BT

Barry S. Tong, MS, MPH

Genetic Counselor
University of California, San Francisco, United States

Disclosure information not submitted.
Amanda L. Nash, MD

Resident
Duke University School of Medicine
Durham, North Carolina, United States

Disclosure information not submitted.
CM

Carolyn S. Menendez, MD

Assistant Professor
Department of Surgery, Duke University, United States

Disclosure information not submitted.
Shelley Hwang, MD MPH

Vice Chair of Research, Chief of Breast Surgical Oncology
Duke University
Durham, North Carolina, United States

Disclosure information not submitted.
James W. Jakub, MD

Division of Breast and Melanoma Surgical Oncology; Professor of Surgery
Mayo Clinic
Rochester, Minnesota, United States

Disclosure information not submitted.
Jennifer K. Plichta, MD, MS

Associate Professor of Surgery
Duke University Medical Center
Durham, North Carolina, United States

Disclosure(s): No financial relationships to disclose

Disclosure(s):

Laura H. Rosenberger, MD, MS: No financial relationships to disclose

Tari A. King, MD, FSSO, FASCO: Exact Sciences/Genomic Health: Advisor (Ongoing), Speaker (Ongoing)

Jennifer K. Plichta, MD, MS: No financial relationships to disclose

Introduction: Germline genetic mutations in women with phyllodes tumors (PT) are understudied, although a few have described associations with TP53, BRCA1, and RB1 mutations. Our previous work demonstrated that very few women with PT undergo germline testing. We sought to determine the prevalence of pathogenic/likely pathogenic (P/LP) variants in women with PT in a contemporary cohort.

Methods: A prospective, multi-center germline genetic testing study of women with a PT (benign, borderline, or malignant) was initiated at 6 Comprehensive Cancer Centers, then expanded to include national enrollment through an online “Phyllodes Support Group” (PSG). All women underwent 84-gene panel testing (Invitae Corporation, San Francisco, CA). Participants’ demographics, pathology, family history, and testing results were recorded. Variants were determined as actionable if national guidelines on management were available. We defined eligibility for genetic testing based on family history, according to select 2022 NCCN (National Comprehensive Cancer Network) criteria. Logistic regression was used to estimate the association of select covariates with the likelihood of a P/LP variant.

Results: 266 women were enrolled; 160 (60.2%) through multi-center recruitment and 106 (39.8%) through the online PSG. Of the 241 women with available results, 36 (14.9%) had a P/LP variant, nearly all of which are considered actionable (N=34, 14.1%; Table 1). Of the women without a P/LP variant, at least one VUS was identified in 100 (41.5%). Numerically, a P/LP variant was more frequent in higher grade PT (benign=10.3%, borderline=14.5%, malignant=16.9%, p=0.47). Of the 106 with available family history, only 27 patients (25.5%) met NCCN criteria for germline genetic testing. Presence of P/LP variants was not associated with age at diagnosis (OR=1.00, p=0.93) or NCCN Genetic Testing Eligibility (OR=0.79, p=0.71), but was associated with malignant PT type (malignant vs. benign, OR=1.26, p=0.003).

Conclusions: Our study demonstrates that a significant number of women with PT harbor P/LP variants that are clinically actionable, for which the majority have national guidelines regarding management and may impact adjuvant therapy decision making. National guidelines for germline genetic testing should be expanded to include women with PT.
Learning Objectives:
Upon completion, participants will be able to recognize that phyllodes tumors are currently omitted as criteria from National Comprehensive Cancer Network guidelines for germline genetic testing.
Upon completion, participants will be able to identify the high rate of pathogenic/ likely pathogenic variants identified in women with phyllodes tumors, regardless of presence of family history of cancer.
Upon completion, participants will be prepared to take a comprehensive family history of cancer and refer women with phyllodes tumors to genetic counselors for consideration of testing.