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Record W4361943653 · doi:10.1158/1078-0432.c.6519033

Data from Lynch Syndrome–Associated Breast Cancers: Clinicopathologic Characteristics of a Case Series from the Colon Cancer Family Registry

2023· preprint· en· W4361943653 on OpenAlexaff
Michael D. Walsh, Daniel D. Buchanan, Margaret C. Cummings, Sally‐Ann Pearson, Sven Arnold, Mark Clendenning, Rhiannon Walters, Diane McKeone, Amanda B. Spurdle, John L. Hopper, Mark A. Jenkins, Kerry Phillips, Graeme Suthers, Jill George, Jack Goldblatt, Amanda B. Muir, Kathy Tucker, Elise Pelzer, Michael Gattas, Sonja Woodall, Susan Parry, Finlay Macrae, Robert W. Haile, John A. Baron, John D. Potter, Loı̈c Le Marchand, Bharati Bapat, Stephen N. Thibodeau, Noralane M. Lindor, Michael A. McGuckin, Joanne Young

Bibliographic record

Venuenot available
Typepreprint
Languageen
FieldMedicine
TopicGenetic factors in colorectal cancer
Canadian institutionsLunenfeld-Tanenbaum Research InstituteUniversity of TorontoMount Sinai Hospital
FundersCancer Council Queensland
KeywordsLynch syndromeBreast cancerMicrosatellite instabilityMSH2MedicineMLH1Colorectal cancerInternal medicineOncologyMSH6CancerDNA mismatch repairBiologyGeneGenetics

Abstract

fetched live from OpenAlex

Abstract Purpose: The recognition of breast cancer as a spectrum tumor in Lynch syndrome remains controversial. The aim of this study was to explore features of breast cancers arising in Lynch syndrome families. Experimental Design: This observational study involved 107 cases of breast cancer identified from the Colorectal Cancer Family Registry (Colon CFR) from 90 families in which (a) both breast and colon cancer co-occurred, (b) families met either modified Amsterdam criteria, or had at least one early-onset (<50 years) colorectal cancer, and (c) breast tissue was available within the biospecimen repository for mismatch repair (MMR) testing. Eligibility criteria for enrollment in the Colon CFR are available online. Breast cancers were reviewed by one pathologist. Tumor sections were stained for MLH1, PMS2, MSH2, and MSH6, and underwent microsatellite instability testing. Results: Breast cancer arose in 35 mutation carriers, and of these, 18 (51%) showed immunohistochemical absence of MMR protein corresponding to the MMR gene mutation segregating the family. MMR-deficient breast cancers were more likely to be poorly differentiated (P = 0.005) with a high mitotic index (P = 0.002), steroid hormone receptor–negative (estrogen receptor, P = 0.031; progesterone receptor, P = 0.022), and to have peritumoral lymphocytes (P = 0.015), confluent necrosis (P = 0.002), and growth in solid sheets (P < 0.001) similar to their colorectal counterparts. No difference in age of onset was noted between the MMR-deficient and MMR-intact groups. Conclusions: MMR deficiency was identified in 51% of breast cancers arising in known mutation carriers. Breast cancer therefore may represent a valid tissue option for the detection of MMR deficiency in which spectrum tumors are lacking. Clin Cancer Res; 16(7); 2214–24. ©2010 AACR.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.004
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Case report · Consensus signal: none
GenreCandidate signal: Dataset · Consensus signal: none
Teacher disagreement score0.009
Threshold uncertainty score0.018

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.004
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0020.002
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.151
GPT teacher head0.363
Teacher spread0.212 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designCase report
Domainnot available
GenreDataset

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2023
Admission routes1
Has abstractyes

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