Should women with Lynch syndrome be offered gynaecological cancer surveillance?

BMJ ◽  
2021 ◽  
pp. n2020
Author(s):  
NAJ Ryan ◽  
T Snowsill ◽  
E McKenzie ◽  
KJ Monahan ◽  
D Nebgen
2008 ◽  
Vol 26 (35) ◽  
pp. 5783-5788 ◽  
Author(s):  
Heather Hampel ◽  
Wendy L. Frankel ◽  
Edward Martin ◽  
Mark Arnold ◽  
Karamjit Khanduja ◽  
...  

Purpose Identifying individuals with Lynch syndrome (LS) is highly beneficial. However, it is unclear whether microsatellite instability (MSI) or immunohistochemistry (IHC) should be used as the screening test and whether screening should target all patients with colorectal cancer (CRC) or those in high-risk subgroups. Patients and Methods MSI testing and IHC for the four mismatch repair proteins was performed on 500 tumors from unselected patients with CRC. If either MSI or IHC was abnormal, complete mutation analysis for the mismatch repair genes was performed. Results Among the 500 patients, 18 patients (3.6%) had LS. All 18 patients detected with LS (100%) had MSI-high tumors; 17 (94%) of 18 patients with LS were correctly predicted by IHC. Of the 18 probands, only eight patients (44%) were diagnosed at age younger than 50 years, and only 13 patients (72%) met the revised Bethesda guidelines. When these results were added to data on 1,066 previously studied patients, the entire study cohort (N = 1,566) showed an overall prevalence of 44 of 1,566 patients (2.8%; 95% CI, 2.1% to 3.8%) for LS. For each proband, on average, three additional family members carried MMR mutations. Conclusion One of every 35 patients with CRC has LS, and each has at least three relatives with LS; all of whom can benefit from increased cancer surveillance. For screening, IHC is almost equally sensitive as MSI, but IHC is more readily available and helps to direct gene testing. Limiting tumor analysis to patients who fulfill Bethesda criteria would fail to identify 28% (or one in four) cases of LS.


2012 ◽  
Vol 30 (35) ◽  
pp. 4409-4415 ◽  
Author(s):  
Christoph Engel ◽  
Markus Loeffler ◽  
Verena Steinke ◽  
Nils Rahner ◽  
Elke Holinski-Feder ◽  
...  

Purpose Patients with Lynch syndrome are at high risk for colon and endometrial cancer, but also at an elevated risk for other less common cancers. The purpose of this retrospective cohort study was to provide risk estimates for these less common cancers in proven carriers of pathogenic mutations in the mismatch repair (MMR) genes MLH1, MSH2, and MSH6. Patients and Methods Data were pooled from the German and Dutch national Lynch syndrome registries. Seven different cancer types were analyzed: stomach, small bowel, urinary bladder, other urothelial, breast, ovarian, and prostate cancer. Age-, sex- and MMR gene–specific cumulative risks (CRs) were calculated using the Kaplan-Meier method. Sex-specific incidence rates were compared with general population incidence rates by calculating standardized incidence ratios (SIRs). Multivariate Cox regression analysis was used to estimate the impact of sex and mutated gene on cancer risk. Results The cohort comprised 2,118 MMR gene mutation carriers (MLH1, n = 806; MSH2, n = 1,004; MSH6, n = 308). All cancers were significantly more frequent than in the general population. The highest risks were found for male small bowel cancer (SIR, 251; 95% CI, 177 to 346; CR at 70 years, 12.0; 95% CI, 5.7 to 18.2). Breast cancer showed an SIR of 1.9 (95% CI, 1.4 to 2.4) and a CR of 14.4 (95% CI, 9.5 to 19.3). MSH2 mutation carriers had a considerably higher risk of developing urothelial cancer than MLH1 or MSH6 carriers. Conclusion The sex- and gene-specific differences of less common cancer risks should be taken into account in cancer surveillance and prevention programs for patients with Lynch syndrome.


Author(s):  
Amanda Veiga-Fernández ◽  
Monica Moran Carreira ◽  
María Ángeles Oyonarte ◽  
AMANDA LOPEZ PICADO ◽  
Ivan Marquez-Rodas ◽  
...  

2019 ◽  
Author(s):  
A Veiga-Fernández ◽  
M Móran ◽  
MÁ Oyonarte ◽  
A López Picado ◽  
I Marquez-Rodas ◽  
...  

Author(s):  
Fay Kastrinos ◽  
Myles A. Ingram ◽  
Elisabeth R. Silver ◽  
Aaron Oh ◽  
Monika Laszkowska ◽  
...  

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12536-e12536
Author(s):  
Rohini Rau-Murthy ◽  
Christopher Anrig ◽  
Emily Glogowski ◽  
Erin E. Salo-Mullen ◽  
Megan Harlan Fleischut ◽  
...  

e12536 Background: Lynch syndrome (LS) requires a lifelong commitment to multi-organ cancer surveillance and/or prophylactic surgery. Emotional and informational support for LS patients is not readily available. Through an LS Educational Workshop (LSEW) we assessed the need and interest in an educational and support group for LS families. Methods: LS patients identified at Memorial Sloan-Kettering Cancer Center (MSKCC) were sent LSEW invitations and a pre-workshop survey. All patients underwent prior genetic counseling. Though family members could attend, only index patients completed the surveys. All attendees were asked to complete both an evaluation of the LSEW and a needs assessment regarding implementation of a support group. Results: Invitations to 213 LS patients were mailed. Of 8 potential discussion topics, the most desired were chemoprevention and cancer screening recommendations. Thus, the 1st hour of the LSEW was a didactic session by physicians on these topics and LS research. The 2nd hour was a panel on patient experiences, family communication and Q&A. Fifty-three patients (25% of those invited) and 22 family members attended. The LSEW evaluation was completed by 26 index attendees, with 88% overall satisfied or extremely satisfied. Common requests for improvement were better division of informational and support aspects, and more Q&A. Of 23 who completed the needs assessment, 73% considered an LS support group as either somewhat or extremely useful. The group was equally divided on preference for a free-flow vs topic-focused approach; 57% felt a support group would have increased utility immediately after genetic testing. An in person venue was preferred by 87% over a virtual one, and 73% preferred every 3-6 month meetings. Respondents preferred a group inclusive of gender and cancer history. Based on this, the MSKCC Lynch Syndrome Patient Advocacy Network was created in 2012 with an in-person, every 4 month meeting facilitated by a social worker. Conclusions: Following genetic counseling, there is a continued need for informational sessions and support groups for LS patients/family members. Implementation of an in-person support group is feasible and responsive to the needs of our LS population.


2020 ◽  
Vol 148 (1) ◽  
pp. 106-114
Author(s):  
Swetlana Ladigan‐Badura ◽  
Deepak B. Vangala ◽  
Christoph Engel ◽  
Karolin Bucksch ◽  
Robert Hueneburg ◽  
...  

Author(s):  
Kathleen F. Mittendorf ◽  
Jessica Ezzell Hunter ◽  
Jennifer L. Schneider ◽  
Elizabeth Shuster ◽  
Alan F. Rope ◽  
...  

Abstract Background Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome. This study assesses trends in diagnosis of LS and adherence to recommended LS-related care in a large integrated healthcare organization (~ 575,000 members). Methods Electronic medical record (EMR) data (1999–2015) were examined to identify patients with a diagnosis of LS. We examined their LS-associated care recommendations and adherence to these recommendations. Qualitative patient and provider interviews were conducted with the aim of identifying opportunities for improved care delivery. Results We identified 74 patients with a diagnosis of LS; 64% were diagnosed with a LS-related malignancy prior to their diagnosis of LS. The time to LS diagnosis following development of a LS-related cancer decreased over time: before 2009 11% of individuals received a diagnosis of LS within 1 year of developing a LS-related cancer compared to 83% after 2009 (p < 0.0001). Colonoscopy recommendations were documented in the EMR for almost all patients with LS (96%). Documentation of other recommendations for cancer surveillance was less commonly found. Overall, patient adherence to colonoscopy was high (M = 81.5%; SD = 32.7%), and adherence to other recommendations varied. To improve care coordination, patients and providers suggested providing automated reminder prompts for LS-related surveillance, adding a LS-specific diagnosis code, and providing guidelines for LS-related surveillance in the EMR. Conclusions We identified fewer than expected patients with LS in our large care system, indicating that there is still a diagnostic care gap. However, patients with LS were likely to receive and follow CRC surveillance recommendations. Recommendations for and adherence to extracolonic surveillance were variable. Improved care coordination and clearer documentation of the LS diagnosis is needed.


2019 ◽  
Vol 37 (4) ◽  
pp. 286-295 ◽  
Author(s):  
Alicia Latham ◽  
Preethi Srinivasan ◽  
Yelena Kemel ◽  
Jinru Shia ◽  
Chaitanya Bandlamudi ◽  
...  

PURPOSE Microsatellite instability (MSI) and/or mismatch repair deficiency (MMR-D) testing has traditionally been performed in patients with colorectal (CRC) and endometrial cancer (EC) to screen for Lynch syndrome (LS)–associated cancer predisposition. The recent success of immunotherapy in high-frequency MSI (MSI-H) and/or MMR-D tumors now supports testing for MSI in all advanced solid tumors. The extent to which LS accounts for MSI-H across heterogeneous tumor types is unknown. Here, we establish the prevalence of LS across solid tumors according to MSI status. METHODS MSI status was determined using targeted next-generation sequencing, with tumors classified as MSI-H, MSI-indeterminate, or microsatellite-stable. Matched germline DNA was analyzed for mutations in LS-associated mismatch repair genes ( MLH1, MSH2, MSH6, PMS2, EPCAM). In patients with LS with MSI-H/I tumors, immunohistochemical staining for MMR-D was assessed. RESULTS Among 15,045 unique patients (more than 50 cancer types), LS was identified in 16.3% (53 of 326), 1.9% (13 of 699), and 0.3% (37 of 14,020) of patients with MSI-H, MSI-indeterminate, and microsatellite-stable tumors, respectively ( P < .001). Among patients with LS with MSI-H/I tumors, 50% (33 of 66) had tumors other than CRC/EC, including urothelial, prostate, pancreas, adrenocortical, small bowel, sarcoma, mesothelioma, melanoma, gastric, and germ cell tumors. In these patients with non-CRC/EC tumors, 45% (15 of 33) did not meet LS genetic testing criteria on the basis of personal/family history. Immunohistochemical staining of LS-positive MSI-H/I tumors demonstrated MMR-D in 98.2% (56 of 57) of available cases. CONCLUSION MSI-H/MMR-D is predictive of LS across a much broader tumor spectrum than currently appreciated. Given implications for cancer surveillance and prevention measures in affected families, these data support germline genetic assessment for LS for patients with an MSI-H/MMR-D tumor, regardless of cancer type or family cancer history.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 533-533
Author(s):  
Ashish Sharma ◽  
Johanna Chan ◽  
Tony Trang ◽  
Milena Gould Suarez

533 Background: Lynch Syndrome (LS) is the most common cause of inherited colorectal cancer (CRC). Universal testing is recommended as a cost effective strategy for screening for LS in all patients with CRC diagnosed < 70 years of age. This has shown to be beneficial in clinical decision making and cancer surveillance of both the patient and at risk relatives. According to a study in 2012, 71% of NCI institutions were performing universal testing versus 15%-36% of programs in the community. The aim of our study was to determine the outcomes of Universal Testing for LS in CRC in a County Hospital System. Methods: IRB-approved retrospective chart review of all patients diagnosed with colorectal cancer from cancer registry at Harris County Hospital District from March 2010 to Dec 2013. Patients between 18-70 yr were included. We collected data on patient characteristics, universal testing [immunohistochemistry (IHC) at our institution], and LS diagnosis (confirmed with germline testing for mismatch repair gene) in our patient cohort diagnosed with CRC. Descriptive statistics were performed using t-test for continuous variables. Results: Overall, 430 patients had CRC diagnosis in our study period, and 54 years was median age of diagnosis. IHC was performed in 359/430 (83.4%) CRC cases. IHC was positive in overall 26/430 (6%) cases of CRC. LS was confirmed in 9/430 (2%) CRC cases. IHC was more often positive with CRC diagnosed in patients younger than 50 years than in patients 50 years or older (7.91% vs 3.09%; p = 0.04). Conclusions: Universal testing for screening of LS amongst patients with CRC can result in significant rates of detection. In this study we have shown that this is possible in a largely safety-net setting.


Sign in / Sign up

Export Citation Format

Share Document