Clinical and fertility outcomes in lynch syndrome patients with endometrial carcinoma or endometrial Intraepthelial neoplasia treated with fertility sparing management

Objectives: Provide evidence on fertility-sparing treatment for patients with Lynch Syndrome (LS) and early-stage low grade endometrioid endometrial cancer (EC) or endometrial intraepithelial neoplasia (EIN). Methods: We conducted a retrospective chart review of patients with EC or EIN, LS pathogeni...

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Main Authors: Hadley W. Reid, Alexandria N. Young, Sophia H. Yin, Isabela Covelli Velez, Mary Kathryn Abel, David L. Kolin, Elizabeth S. Ginsburg, Matthew B. Yurgelun, Colleen Feltmate, Jessica D. St Laurent
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Gynecologic Oncology Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352578925000931
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author Hadley W. Reid
Alexandria N. Young
Sophia H. Yin
Isabela Covelli Velez
Mary Kathryn Abel
David L. Kolin
Elizabeth S. Ginsburg
Matthew B. Yurgelun
Colleen Feltmate
Jessica D. St Laurent
author_facet Hadley W. Reid
Alexandria N. Young
Sophia H. Yin
Isabela Covelli Velez
Mary Kathryn Abel
David L. Kolin
Elizabeth S. Ginsburg
Matthew B. Yurgelun
Colleen Feltmate
Jessica D. St Laurent
author_sort Hadley W. Reid
collection DOAJ
description Objectives: Provide evidence on fertility-sparing treatment for patients with Lynch Syndrome (LS) and early-stage low grade endometrioid endometrial cancer (EC) or endometrial intraepithelial neoplasia (EIN). Methods: We conducted a retrospective chart review of patients with EC or EIN, LS pathogenic germline variant, and treatment with progestin therapy without upfront hysterectomy due to desire to preserve fertility. Demographic, clinical, and reproductive variables were collected. Results: Of the 273 patients who met criteria for LS with EIN (38) or EC (235) there were seven patients, three with an initial diagnosis of EIN and four with an initial diagnosis of EC who underwent fertility sparing treatment. The median age was 36 (range 31–44) at diagnosis with the following mutations MLH1 (2), PMS2 (1), MSH2 (1) and MSH6 (3). Four out of 7 (53%) patients responded to progestin therapy with a 33% (1/3) and 75% (3/4) regression rate for EIN and EC respectively. Two out of 4 patients (50%) subsequently recurred. There were three pregnancies and two live births. Five patients ultimately underwent hysterectomy. Two patients, both with mutant p53 expression on immunohistochemistry, had higher grade or stage pathology, one with stage 1A grade 2 EC and one with stage 1B grade 3 EC. Conclusion: Fertility sparing management for LS patients with an EIN or EC diagnosis is uncommon. Progesterone response rates appear to be lower than those in sporadic cases, though similar clinical and histologic factors (age, BMI, and p53 expression pattern) may predict disease regression and fertility outcomes. A larger sample and standardized treatment paradigm are needed to provide more evidence on fertility sparing management for LS patients.
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spelling doaj-art-a7f077e9daad4fbcae1894865ac79e762025-08-20T02:36:23ZengElsevierGynecologic Oncology Reports2352-57892025-06-015910176810.1016/j.gore.2025.101768Clinical and fertility outcomes in lynch syndrome patients with endometrial carcinoma or endometrial Intraepthelial neoplasia treated with fertility sparing managementHadley W. Reid0Alexandria N. Young1Sophia H. Yin2Isabela Covelli Velez3Mary Kathryn Abel4David L. Kolin5Elizabeth S. Ginsburg6Matthew B. Yurgelun7Colleen Feltmate8Jessica D. St Laurent9Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Massachusetts General Hospital, Boston, MA, USA; Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, USADepartment of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, USADivision of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Massachusetts General Hospital, Boston, MA, USA; Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, USADivision of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Massachusetts General Hospital, Boston, MA, USA; Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, USADivision of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Massachusetts General Hospital, Boston, MA, USA; Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, USADepartment of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USADivision of Reproductive Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Massachusetts General Hospital, Boston, MA, USADepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USADivision of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Massachusetts General Hospital, Boston, MA, USA; Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, USADivision of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Massachusetts General Hospital, Boston, MA, USA; Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, USA; Corresponding author at: Brigham and Women’s Hospital, 221 Longwood Avenue, Building BLI-139, Boston, MA 02115, USA.Objectives: Provide evidence on fertility-sparing treatment for patients with Lynch Syndrome (LS) and early-stage low grade endometrioid endometrial cancer (EC) or endometrial intraepithelial neoplasia (EIN). Methods: We conducted a retrospective chart review of patients with EC or EIN, LS pathogenic germline variant, and treatment with progestin therapy without upfront hysterectomy due to desire to preserve fertility. Demographic, clinical, and reproductive variables were collected. Results: Of the 273 patients who met criteria for LS with EIN (38) or EC (235) there were seven patients, three with an initial diagnosis of EIN and four with an initial diagnosis of EC who underwent fertility sparing treatment. The median age was 36 (range 31–44) at diagnosis with the following mutations MLH1 (2), PMS2 (1), MSH2 (1) and MSH6 (3). Four out of 7 (53%) patients responded to progestin therapy with a 33% (1/3) and 75% (3/4) regression rate for EIN and EC respectively. Two out of 4 patients (50%) subsequently recurred. There were three pregnancies and two live births. Five patients ultimately underwent hysterectomy. Two patients, both with mutant p53 expression on immunohistochemistry, had higher grade or stage pathology, one with stage 1A grade 2 EC and one with stage 1B grade 3 EC. Conclusion: Fertility sparing management for LS patients with an EIN or EC diagnosis is uncommon. Progesterone response rates appear to be lower than those in sporadic cases, though similar clinical and histologic factors (age, BMI, and p53 expression pattern) may predict disease regression and fertility outcomes. A larger sample and standardized treatment paradigm are needed to provide more evidence on fertility sparing management for LS patients.http://www.sciencedirect.com/science/article/pii/S2352578925000931Lynch syndromeEndometrial cancerEndometrial intraepithelial neoplasiaOncofertility
spellingShingle Hadley W. Reid
Alexandria N. Young
Sophia H. Yin
Isabela Covelli Velez
Mary Kathryn Abel
David L. Kolin
Elizabeth S. Ginsburg
Matthew B. Yurgelun
Colleen Feltmate
Jessica D. St Laurent
Clinical and fertility outcomes in lynch syndrome patients with endometrial carcinoma or endometrial Intraepthelial neoplasia treated with fertility sparing management
Gynecologic Oncology Reports
Lynch syndrome
Endometrial cancer
Endometrial intraepithelial neoplasia
Oncofertility
title Clinical and fertility outcomes in lynch syndrome patients with endometrial carcinoma or endometrial Intraepthelial neoplasia treated with fertility sparing management
title_full Clinical and fertility outcomes in lynch syndrome patients with endometrial carcinoma or endometrial Intraepthelial neoplasia treated with fertility sparing management
title_fullStr Clinical and fertility outcomes in lynch syndrome patients with endometrial carcinoma or endometrial Intraepthelial neoplasia treated with fertility sparing management
title_full_unstemmed Clinical and fertility outcomes in lynch syndrome patients with endometrial carcinoma or endometrial Intraepthelial neoplasia treated with fertility sparing management
title_short Clinical and fertility outcomes in lynch syndrome patients with endometrial carcinoma or endometrial Intraepthelial neoplasia treated with fertility sparing management
title_sort clinical and fertility outcomes in lynch syndrome patients with endometrial carcinoma or endometrial intraepthelial neoplasia treated with fertility sparing management
topic Lynch syndrome
Endometrial cancer
Endometrial intraepithelial neoplasia
Oncofertility
url http://www.sciencedirect.com/science/article/pii/S2352578925000931
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