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Record W2970862661 · doi:10.1093/jncics/pkz063

PTHrP, A Biomarker for CNS Metastasis in Triple-Negative Breast Cancer and Selection for Adjuvant Chemotherapy in Node-Negative Disease

2019· article· en· W2970862661 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueJNCI Cancer Spectrum · 2019
Typearticle
Languageen
FieldMedicine
TopicBone health and treatments
Canadian institutionsMcGill UniversityUniversity of AlbertaMcGill University Health Centre
FundersFondation de l'Hôpital Général de MontréalJewish General HospitalUniversity of ChittagongAlberta Cancer FoundationMcGill University Health CentreAmerican Association for Cancer ResearchMcGill UniversityU.S. Department of Defense
KeywordsMedicineBreast cancerOncologyTriple-negative breast cancerInternal medicineHazard ratioProportional hazards modelBiomarkerTrastuzumabCancerMetastasisUnivariate analysisConfidence intervalMultivariate analysisBiology

Abstract

fetched live from OpenAlex

Abstract Background Triple-negative breast cancer (TNBC) is characterized by poor prognosis and lack of targeted therapies and biomarkers to guide decisions on adjuvant chemotherapy. Parathyroid hormone-related protein (PTHrP) is frequently overexpressed in breast cancer and involved in proliferation and metastasis, two hallmarks of poor prognosis for node-negative breast cancer. We investigated the prognostic value of PTHrP with respect to organ-specific metastasis and nodal status in TNBC. Methods We assessed PTHrP expression using immunohistochemistry in a clinically annotated tissue microarray for a population-based study of 314 patients newly diagnosed with TNBC, then analyzed its correlation to progression and survival using Kaplan-Meier and Cox regression analyses. The Cancer Genome Atlas (TCGA) validation analysis was performed through Bioconductor. All statistical tests were two-sided. Results PTHrP overexpression (160 of 290 scorable cases, 55.2%) was statistically significantly associated in univariate analysis with decreased overall survival (OS) in our cohort (P = .0055) and The Cancer Genome Atlas (P = .0018) and decreased central nervous system (CNS)-progression-free survival (P = .0029). In multivariate analysis, PTHrP was a statistically significant independent prognostic factor for CNS-progression-free survival in TNBC (hazard ratio [HR] = 5.014, 95% confidence interval [CI] = 1.421 to 17.692, P = .0122) and for OS selectively in node-negative TNBC (HR = 2.423, 95% CI = 1.129 to 5.197, P = .0231). Strikingly, PTHrP emerged as the only statistically significant prognostic factor (HR = 2.576, 95% CI = 1.019 to 6.513, P = .0456) for OS of low-clinical risk node-negative patients who did not receive adjuvant chemotherapy. Conclusions PTHrP is a novel independent prognostic factor for CNS metastasis and adjuvant chemotherapy selection of low-clinical risk node-negative TNBC. Its predictive value needs to be prospectively assessed in clinical trials.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.053
Threshold uncertainty score0.992

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.021
GPT teacher head0.338
Teacher spread0.316 · 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