scholarly journals Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report

2020 ◽  
Author(s):  
Mev Dominguez-Valentin ◽  
Emma J. Crosbie ◽  
Christoph Engel ◽  
Stefan Aretz ◽  
Finlay Macrae ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Decision Making ◽  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Mismatch Repair ◽  
Cancer Incidence ◽  
Gynecological Cancer ◽  
Different Ages ◽  
Aid Decision ◽  
Risk Reducing

Abstract Purpose To determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR (path_MMR) variants. Methods The Prospective Lynch Syndrome Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages. Results Risk-reducing hysterectomy at 25 years of age prevents endometrial cancer before 50 years in 15%, 18%, 13%, and 0% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 heterozygotes and death in 2%, 2%, 1%, and 0%, respectively. Risk-reducing BSO at 25 years of age prevents ovarian cancer before 50 years in 6%, 11%, 2%, and 0% and death in 1%, 2%, 0%, and 0%, respectively. Risk-reducing hysterectomy at 40 years prevents endometrial cancer by 50 years in 13%, 16%, 11%, and 0% and death in 1%, 2%, 1%, and 0%, respectively. BSO at 40 years prevents ovarian cancer before 50 years in 4%, 8%, 0%, and 0%, and death in 1%, 1%, 0%, and 0%, respectively. Conclusion Little benefit is gained by performing RRS before 40 years of age and premenopausal BSO in path_MSH6 and path_PMS2 heterozygotes has no measurable benefit for mortality. These findings may aid decision making for women with LS who are considering RRS.

scholarly journals Risk-reducing surgery in hereditary gynecological cancer: Clinical applications in Lynch syndrome and hereditary breast and ovarian cancer

2014 ◽  
Vol 3 (2) ◽  
pp. 267-273 ◽  
Author(s):  
MASATAKA ADACHI ◽  
KOUJI BANNO ◽  
MEGUMI YANOKURA ◽  
MIHO IIDA ◽  
KANAKO NAKAMURA ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lynch Syndrome ◽  
Gynecological Cancer ◽  
Clinical Applications ◽  
Breast And Ovarian Cancer ◽  
Risk Reducing

THE RISK OF DEVELOPING GYNECOLOGICAL CANCER IN WOMEN AFTER AN IN VITRO FERTILIZATION PROGRAM

2021 ◽  
pp. 7-13
Author(s):  
Allakhyarov D.Z. ◽  
Petrov Yu.A. ◽  
Palieva N.V.
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Endometrial Cancer ◽  
In Vitro Fertilization ◽  
Gynecological Cancer ◽  
The Body ◽  
Fertilization Program ◽  
Vitro Fertilization ◽  
Increased Risk

This article presents reviews of literature sources on the issue of assessing the risk of developing gynecological cancer in women after an in vitro fertilization program. Infertility and infertile marriages have now become quite a big problem of modern medicine. Against the background of the unfavorable demographic situation in the Russian Federation, this problem is becoming quite urgent. The main way to solve this situation is assisted reproductive technologies, among which the most common is in vitro fertilization. The in vitro fertilization program is accompanied by a hormonal ovulation stimulation procedure to obtain a female germ cell capable of fertilization. Against the background of the active use of the in vitro fertilization procedure, many patients had concerns related to the risk of developing gynecological cancer after the IVF procedure, which is due to the use of hormonal drugs to stimulate the ovaries. Also of concern is the fact that certain types of cancer, including ovarian cancer, endometrial cancer and breast cancer, are hormone-dependent. In this regard, multiple large-scale studies were conducted, which showed that the risk of developing gynecological cancer is really increased in patients after the in vitro fertilization program. In particular, breast cancer in women after the in vitro fertilization program is more common by 10%, and in women without a history of pregnancy and over the age of 40, it is more common by 31%. The increased risk may be due to age-related vulnerability to the effects of hormones or higher doses of hormones during the IVF procedure. Ovarian cancer and endometrial cancer are also more common in patients after IVF. According to the research results, it is suggested that it is not the IVF procedure itself that causes the development of cancer, but excessive hormonal load of the body, which leads to the launch of carcinogenesis.

Factors affecting surgical decision-making in carriers of BRCA1/2 pathogenic variants undergoing risk-reducing surgery at a dedicated hereditary ovarian cancer clinic

Menopause ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Michelle R. Jacobson ◽  
Melissa Walker ◽  
Gabrielle E.V. Ene ◽  
Courtney Firestone ◽  
Marcus Q. Bernardini ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Decision Making ◽  
Hereditary Ovarian Cancer ◽  
Surgical Decision ◽  
Factors Affecting ◽  
Pathogenic Variants ◽  
Risk Reducing ◽  
Surgical Decision Making ◽  
Cancer Clinic

scholarly journals Increased Overall Mortality Even after Risk Reducing Surgery for BRCA-Positive Women in Western Sweden

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 1046
Author(s):  
Anna Öfverholm ◽  
Zakaria Einbeigi ◽  
Antonia Wigermo ◽  
Erik Holmberg ◽  
Per Karsson
Keyword(s):  
Ovarian Cancer ◽  
General Population ◽  
Cancer Incidence ◽  
Population Based ◽  
Pathology Report ◽  
Breast And Ovarian Cancer ◽  
Incidence And Mortality ◽  
Incidence Risk ◽  
Risk Reducing ◽  
Overall Mortality

Women with BRCA variants have a high lifetime risk of developing breast and ovarian cancer. The aim of this study was to investigate the standard incidence ratios (SIR) for breast and ovarian cancer and standard mortality ratios (SMR) in a population-based cohort of women in Western Sweden, under surveillance and after risk reducing surgery. Women who tested positive for a BRCA variant between 1995–2016 (n = 489) were prospectively registered and followed up for cancer incidence, risk reducing surgery and mortality. The Swedish Cancer Register was used to compare breast and ovarian cancer incidence and mortality with and without risk reducing surgery for women with BRCA variants in comparison to women in the general population. SIR for breast cancer under surveillance until risk-reducing mastectomy (RRM) was 14.0 (95% CI 9.42–20.7) and decreased to 1.93 (95% CI 0.48–7.7) after RRM. The SIR for ovarian cancer was 124.6 (95% CI 59.4–261.3) under surveillance until risk reducing salpingo-oophorectomy (RRSO) and decreased to 13.5 (95% CI 4.34–41.8) after RRSO. The SMR under surveillance before any risk reducing surgery was 5.56 (95% 2.09–14.8) and after both RRM and RRSO 4.32 (95% CI 1.62–11.5). Women with cancer diagnoses from the pathology report after risk reducing surgery were excluded from the analyses. Risk reducing surgery reduced the incidence of breast and ovarian cancer in women with BRCA variants. However, overall mortality was significantly increased in comparison to the women in the general population and remained elevated even after risk reducing surgery. These findings warrant further research regarding additional measures for these women.

scholarly journals Understanding Inherited Risk in Unselected Newly Diagnosed Patients With Endometrial Cancer

2019 ◽  
pp. 1-15
Author(s):  
Karen A. Cadoo ◽  
Diana L. Mandelker ◽  
Semanti Mukherjee ◽  
Carolyn Stewart ◽  
Deborah DeLair ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Next Generation Sequencing ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Cancer Predisposition ◽  
Next Generation ◽  
Germline Variants ◽  
Predisposition Genes ◽  
Generation Sequencing

PURPOSE Mutations in DNA mismatch repair genes and PTEN, diagnostic of Lynch and Cowden syndromes, respectively, represent the only established inherited predisposition genes in endometrial cancer to date. The prevalence of other cancer predisposition genes remains unclear. We determined the prevalence of pathogenic germline variants in unselected patients with endometrial cancer scheduled for surgical consultation. PATIENTS AND METHODS Patients prospectively consented (April 2016 to May 2017) to an institutional review board–approved protocol of tumor-normal sequencing via a custom next-generation sequencing panel—the Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets—that yielded germline results for more than 75 cancer predisposition genes. Tumors were assessed for microsatellite instability. Per institutional standards, all tumors underwent Lynch syndrome screening via immunohistochemistry (IHC) for mismatch repair proteins. RESULTS Of 156 patients who consented to germline genetic testing, 118 (76%) had stage I disease. In 104 patients (67%), tumors were endometrioid, and 60 (58%) of those tumors were grade 1. Twenty-four pathogenic germline variants were identified in 22 patients (14%): seven (4.5%) had highly penetrant cancer syndromes and 15 (9.6%) had variants in low-penetrance, moderate-penetrance, or recessive genes. Of these, five (21%) were in Lynch syndrome genes (two MSH6, two PMS2, and one MLH1). All five tumors had concordant IHC staining; two (40%) were definitively microsatellite instability–high by next-generation sequencing. One patient had a known BRCA1 mutation, and one had an SMARCA4 deletion. The remaining 17 variants (71%) were incremental findings in low- and moderate-penetrance variants or genes associated with recessive disease. CONCLUSION In unselected patients with predominantly low-risk, early-stage endometrial cancer, germline multigene panel testing identified cancer predisposition gene variants in 14%. This finding may have implications for future cancer screening and risk-reduction recommendations. Universal IHC screening for Lynch syndrome successfully identifies the majority (71%) of high-penetrance germline mutations.

Mismatch Repair Genes and Microsatellite Instability as Molecular Markers for Gynecological Cancer Detection

2002 ◽  
Vol 227 (8) ◽  
pp. 579-586 ◽  
Author(s):  
Roman Miturski ◽  
Michał Bogusiewicz ◽  
Carmella Ciotta ◽  
Margherita Bignami ◽  
Marek Gogacz ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Mismatch Repair ◽  
Cancer Detection ◽  
Xeroderma Pigmentosum ◽  
Gynecological Cancer ◽  
Epidemiological Studies ◽  
Mismatch Repair Genes ◽  
The Past ◽  
Repair Genes

Due to major developments in genetics over the past decade, molecular biology tests are serving promising tools in early diagnosis and follow-up of cancer patients. Recent epidemiological studies revealed that the risk for each individual to develop cancer is closely linked to his/her own genetic potentialities. Some populations that are defective in DNA repair processes, for example in Xeroderma pigmentosum or in the Lynch syndrome, are particularly prone to cancer due to the accumulation of mutations within the genome. Such populations would benefit from the development of tests aimed at identifying people who are particularly at risk. Here, we review some data suggesting that the inactivation of mismatch repair is often found in endometrial cancer and we discuss molecular-based strategies that would help to identify the affected individuals in families with cases of glandular malignancies.

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