The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index; 4 of the 24 sources its claims cite were checked for support.
Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study
Open accessAbstract
Whole-genome sequencing (WGS) brings comprehensive insights to cancer genome interpretation. To explore the clinical value of WGS, we sequenced 254 triple-negative breast cancers (TNBCs) for which associated treatment and outcome data were collected between 2010 and 2015 via the population-based Sweden Cancerome Analysis Network-Breast (SCAN-B) project (ClinicalTrials.gov ID:NCT02306096). Applying the HRDetect mutational-signature-based algorithm to classify tumors, 59% were predicted to have homologous-recombination-repair deficiency (HRDetect-high): 67% explained by germline/somatic mutations of BRCA1/BRCA2, BRCA1 promoter hypermethylation, RAD51C hypermethylation or biallelic loss of PALB2. A novel mechanism of BRCA1 abrogation was discovered via germline SINE-VNTR-Alu retrotransposition. HRDetect provided independent prognostic information, with HRDetect-high patients having better outcome on adjuvant chemotherapy for invasive disease-free survival (hazard ratio (HR) = 0.42; 95% confidence interval (CI) = 0.2-0.87) and distant relapse-free interval (HR = 0.31, CI = 0.13-0.76) compared to HRDetect-low, regardless of whether a genetic/epigenetic cause was identified. HRDetect-intermediate, some possessing potentially targetable biological abnormalities, had the poorest outcomes. HRDetect-low cancers also had inadequate outcomes: ~4.7% were mismatch-repair-deficient (another targetable defect, not typically sought) and they were enriched for (but not restricted to) PIK3CA/AKT1 pathway abnormalities. New treatment options need to be considered for now-discernible HRDetect-intermediate and HRDetect-low categories. This population-based study advocates for WGS of TNBC to better inform trial stratification and improve clinical decision-making.
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56 Own result · 22 Own interpretation · 14 Not checked yet · 5 Own method · 3 No basis given · 2 Partly supported · accuracy not yet measured
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In the paper
“We note that four HRDetect-low patients (4.7%) had mismatch-repair deficient (MMRd) tumors23”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Partly supportedcites [23] Davies, H. et al. Whole-genome sequencing reveals breast cancers with mismatch repair deficiency. Cancer Res. 77, 4755–4762 (2017). sourceExperimental — accuracy not yet measured
The Abstract reports 11 mismatch-repair-deficient tumors among 640 breast cancer patients. The paper does not report that four HRDetect-low patients had such tumors or give a 4.7% rate for that subgroup; HRDetect appears only in a cited reference (References, page unavailable). (LLM, conf=0.83)
plainn = 4- Asserted: passes — The authors put it forward as true.
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In the paper
“237 (93%) had WGS data of sufficient quality for comprehensive genomic profiling.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
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In the paper
“identified a germline SINE-VNTR-Alu (SVA) retrotransposon 1.8kb downstream of the first coding exon of BRCA1 in one patient, PD35958a.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plainSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“HRDetect-intermediate, some possessing potentially targetable biological abnormalities, had poorest outcomes.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“~4.7% were mismatch-repair-deficient”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Abstract
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“4665 patients were registered with invasive breast cancer in that period.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plainn = 4,665- Asserted: passes — The authors put it forward as true.
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In the paper
“of cases sequenced to 30-fold depth, 3% failed, whereas 11% of cases failed when sequenced to 15-fold coverage.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“distant relapse-free interval (HR=0.31, CI=0.13-0.76) compared to HRDetect-low”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“HRDetect-high patients having better outcome on adjuvant chemotherapy for invasive disease-free survival (Hazard Ratio, HR=0.42, 95% confidence interval, CI=0.2-0.87)”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“67% explained by germline/somatic mutations of BRCA1/BRCA2, BRCA1 promoter hypermethylation, RAD51C hypermethylation or biallelic loss of PALB2.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Probably not a substantial claim. 13
- It may state two separate claims as one. 40
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Cancer whole genome sequencing (WGS) is now feasible, with thousands of matched tumor-normal pairs successfully sequenced to date, revealing novel biological insights2–4.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Partly supportedcites [2] Nik-Zainal, S. et al. Mutational processes molding the genomes of 21 breast cancers. Cell 149, 979–993 (2012). sourceExperimental — accuracy not yet measured
The Results (“Sequencing of Breast Cancers”) report whole-genome sequencing of 21 cancers with matched normal DNA, and the Discussion says the analysis yielded new insights into mutational processes. The paper does not support the claim that thousands of matched pairs had already been sequenced; it describes analyses of thousands of cancers as future work. (LLM, conf=0.90)
- Partly supportedcites [3] Nik-Zainal, S. et al. The life history of 21 breast cancers. Cell 149, 994–1007 (2012). sourceExperimental — accuracy not yet measured
The Results (Inference of Cancer Genome Evolution; page not provided) report whole-genome sequencing of 21 breast cancers, and the Introduction describes insights into their genomic evolution. These passages support the feasibility and biological-insights parts of the claim, but they do not establish that thousands of matched tumor–normal pairs had been sequenced. (LLM, conf=0.88)
- Partly supportedcites [4] Ryden, L. et al. Minimizing inequality in access to precision medicine in breast cancer by real-time population-based molecular analysis in the SCAN-B initiative. Br. J. Surg. 105, e158–e168 (2018). sourceExperimental — accuracy not yet measured
The References list a study of 560 breast cancer whole-genome sequences, supporting the feasibility of cancer WGS. But this paper’s Results report more than 7,500 tissue specimens processed for mRNA sequencing, not thousands of matched tumor–normal pairs sequenced by WGS. The cited passages also do not report novel biological insights from such pairs. (LLM, conf=0.76)
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nine percent (n=408) were TNBCs, consistent with national TNBC incidence (~9% in 2015).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plainn = 408- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“High inclusion rates of ~85% have resulted in >13,500 patients recruited since 2010.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaindirectn = 13,500- Asserted: passes — The authors put it forward as true.
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In the paper
“These genomic features in the SCAN-B TNBC cohort were comparable to a previously reported WGS cohort8”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Not checked yetcites [8] Nik-Zainal, S. et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature 534, 47–54 (2016). source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“More than half of TNBCs (58.6%) were classified as HRDetect-high (exceeding predefined score of 0.7, predictive of BRCA1/BRCA2-deficiency9). 35.9% were classified as HRDetect-low (score <0.2), 5.5% fell within an HRD-intermediate category (score 0.2-0.7)”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Not checked yetcites [9] Davies, H. et al. HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Nat. Med. 23, 517–525 (2017). source
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, HRDetect-high scores were also observed in tumors with ER-staining (62.1% of cases with 1-10% ER-staining intensity), in middle-aged patients (58% of HRDetect-high were 50-70 years) and older patients (>70 years, 36.4% HRDetect-high cases), as well as tumors with non-basal-like gene expression profiles”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Among 254 patients, 2.4% had metastatic disease at diagnosis, and 6.7% received neoadjuvant treatment.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plainn = 254- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“HRDetect-high classification was enriched in expected subgroups such as young patients (88.5% of women <50 years), high-grade tumors and a basal-like expression subtype”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“340 had enrolled into SCAN-B. Clinical re-review and availability of material for genomic/transcriptomic sequencing left 254 cases for matched tumor-normal WGS/RNAseq analysis”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plainn = 254- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although not significant for OS (HR=0.46, CI=0.19-1.13), it implies a potential effect with longer follow-up time”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As part of routine oncogenetic clinical screening, 49 of 254 recruited patients were previously screened for pathogenic germline variants in BRCA1 and BRCA2, with 12 positive findings (nine BRCA1- and three BRCA2-carriers).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Online Methods > Patient cohort
plainn = 254- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“To note, the RNA sequencing cohort has a slightly lower inclusion of smaller tumors, due to that the SCAN-B tissue sampling is performed by a pathologist after enough tissue has been secured for routine diagnostics.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Extended Data
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Five tumors had pathogenic germline PALB2 variants, three cases with c.509_510delGA variant (two biallelic, one monoallelic), one c.3239_3240delAA variant, one c.1039G>T variant. Four had wild-type allele inactivation through somatic pathogenic mutation in three cases and loss-of-heterozygosity in one instance.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plainn = 5- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“340 of these patients were enrolled in the SCAN-B study5,33,34 (ClinicalTrials.gov ID NCT02306096), which is a prospective, observational, population-based cohort study, from which 254 with concurrent RNAseq were selected for extensive clinical review and WGS.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Online Methods > Patient cohort
What the sources say
- Not checked yetcites [5] Saal, L. H. et al. The Sweden Cancerome Analysis Network-Breast (SCAN-B) initiative: a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine. Genome Med. 7, 20 (2015). source
- Not checked yetcites [33] Brueffer, C. et al. Clinical value of RNA sequencing-based classifiers for prediction of the five conventional breast cancer biomarkers: a report from the population-based multicenter Sweden Cancerome Analysis Network–Breast initiative. JCO Prec. Oncol. 2, 1–18 (2018). source
- Not checked yetcites [34] Chen, X. et al. TNBCtype: a subtyping tool for triple-negative breast cancer. Cancer Inf. 11, 147–156 (2012).
plainn = 340- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“An improved OS was also observed (log-rank p=0.06, Figure 4C), albeit non-significant because of limited follow-up interval.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, wild-type allele LOH was noted and BRCA1 expression was markedly reduced.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelationalSingle case- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“E.g., for HRDetect-high cases (left heatmap) using a k=2 solution, >70% of these tumors are located in cluster 1, together with 40-70% of HRDetect-low samples (as seen in right heatmap).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Extended Data
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“(29% versus 14% for PTEN, 2.2% versus 25% for PIK3CA, and 0.7% versus 7.1% for AKT1 for HRDetect-high versus HRDetect-low, respectively).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that HRDetect classification amongst chemotherapy-treated patients provided independent prognostic information favouring a better outcome in HRDetect-high cases compared to HRDetect-low cases, for IDFS (Hazard ratio, HR=0.42, 95% confidence interval, CI=0.20-0.87) and DRFI (HR=0.31, CI=0.13-0.76).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For these patients, there were no differences observed in overall survival (OS), invasive disease-free survival (IDFS), or distant relapse-free interval (DRFI) between HRDetect-high and HRDetect-low categories (log-rank p>0.05).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we explored the HRDetect-intermediate cohort (scores 0.2-0.7, n=13, 5.5%).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plainn = 13- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on data from the national breast cancer quality registry in Sweden (NKBC), a background population of primary resectable breast cancers from the entire SCAN-B catchment region during September 1 2010 to March 31 2015 was identified (same time period from which the TNBC cases in the current study were selected), comprising of 8587 patients.”
- Also stated in: § Extended Data · plain
“Of these 8587 patients, 5417 were enrolled in SCAN-B, with 3520 patients having RNA sequencing data passing basic quality criteria.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Extended Data
plainn = 3,520- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Extended Data · plain
In the paper
“the four biallelic PALB2 and five RAD51C cases (6.5% of HRDetect-high cases) consistently showed a BRCA2-null phenotype16 including elevated Substitution Signature 3, elevated Rearrangement Signatures 2 and 5, and no Rearrangement Signature 3”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Not checked yetcites [16] Polak, P. et al. A mutational signature reveals alterations underlying deficient homologous recombination repair in breast cancer. Nat. Genet. 49, 1476–1486 (2017). source
plaincorrelationaln = 5- Asserted: passes — The authors put it forward as true.
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In the paper
“The intermediate category is also enriched for hypermutators of a rearrangement signature of long tandem-duplications (RS1) (where RS1 is predominant, exceeding 100 RS1 rearrangements)26.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Not checked yetcites [26] Glodzik, D. et al. A somatic-mutational process recurrently duplicates germline susceptibility loci and tissue-specific super-enhancers in breast cancers. Nat. Genet. 49, 341–348 (2017). source
plaincorrelationaln = 32- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“148 of 153 patients (97%) were eligible for relapse analysis, of which 20% developed a relapse of some type”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Online Methods > Patient cohort
plainn = 153- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The broadened HRDetect-intermediate group had high prevalence of driver amplifications (75%, 24/32 cases) and harbored 47% of all CCNE1 amplifications.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelationaln = 32- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“When compared with HRDetect as reference, the “HRD assay” has a false negative rate of 13%, and 16% of CNA-based HRD-high cases were false positives.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Not checked yetcites [10] Paquet, E. R. & Hallett, M. T. Absolute assignment of breast cancer intrinsic molecular subtype. J. Natl Cancer Inst. 107, 357 (2014).
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Neither was able to find distinct transcriptional patterns distinguishing HRDetect-high and HRDetect-low groups (Extended Data 4A-E). Likewise, exhaustive machine-learning-based exploration could also not achieve high prediction accuracy for HRDetect-high and HRDetect-low subgroups”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“HRDetect classification persisted as a meaningful independent positive prognostic indicator for IDFS (HR=0.38, CI=0.17-0.85, p=0.02).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We noted that 83.5% of HRDetect-high tumors had scores exceeding 0.99, and nearly all were BRCA1/BRCA2-null tumors.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eight substitution/indel driver genes were enriched, albeit non-discriminatory between groups (TP53, PTEN, ARID1B, MLLT4 for HRDetect-high, PIK3CA and AKT1 for HRDetect-low, and RB1 and FBXW7 for HRDetect-high and HRDetect-intermediate) (Chi-square test p<0.05”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“41% had ≥5 years of follow-up, 25% 4-5 years, 31% 2-4 years, and 4% <2 years of follow-up.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Online Methods > Patient cohort
plainn = 153- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Six were monoallelic for BRCA1/BRCA2 and had low tumor cellularity.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All patients with suspected breast cancer are offered recruitment without exception.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“The Sweden Cancerome Analysis Network – Breast (SCAN-B; ClinicalTrials.gov identifier NCT02306096)5 is an on-going population-based observational study currently involving nine hospitals in the South of Sweden serving nearly two million inhabitants or ~20% of the Swedish population.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Not checked yetcites [5] Saal, L. H. et al. The Sweden Cancerome Analysis Network-Breast (SCAN-B) initiative: a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine. Genome Med. 7, 20 (2015). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Consequently, the HRD phenotype identified by HRDetect is enriched for but not restricted to typical basal-like tumors characteristic of young patients in TNBC.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“we applied a mutational-signature-based algorithm, HRDetect9 designed to detect “BRCA”ness or Homologous-recombination-repair deficiency (HRD)10, using default breast-cancer-specific parameters.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Not checked yetcites [9] Davies, H. et al. HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Nat. Med. 23, 517–525 (2017). source
- Not checked yetcites [10] Paquet, E. R. & Hallett, M. T. Absolute assignment of breast cancer intrinsic molecular subtype. J. Natl Cancer Inst. 107, 357 (2014).
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“expression-based profiling (e.g., PAM50) and Integrative Clusters13,15 are not adequately able to discriminate HRDetect groups, suggesting that HRDetect provides a novel, independent angle to TNBC stratification.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Not checked yetcites [13] Lehmann, B. D. et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J. Clin. Invest. 121, 2750–2767 (2011). source
- Not checked yetcites [15] Telli, M. L. et al. Homologous recombination deficiency (HRD) score predicts response to platinum-containing neoadjuvant chemotherapy in patients with triple-negative breast cancer. Clin. Cancer Res. 22, 3764–3773 (2016). source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The SCAN-B study was approved by the Regional Ethical Review Board in Lund, Sweden (applicable registration numbers 2009/658, 2015/277, 2016/742, 2018/267, and 2019/01252 for this study). All patients provided written informed consent prior to enrolment.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Online Methods > Ethics approval and consent to participate
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we show that PIK3CA/AKT1/PTEN mutations identified through targeted sequencing are differentially enriched in HRDetect categories, with different survival likelihoods.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In short, this study argues for WGS to improve TNBC patient stratification.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the HRDetect-intermediate group is a subset of tumors that are difficult to distinguish using customary genomic scar approaches or individual substitution signatures but are important to recognize because their idiosyncratic tumor biology is a harbinger of poor outcome and may be differently targetable in terms of therapeutics.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“this suggests that HRDetect-low cases are deriving limited benefit from current standard-of-care, warranting a re-appraisal of systemic therapies for this now-identifiable subgroup with poor outcome.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Chemotherapy-treated and untreated HRDetect-low patients are comparable enough for their invasive disease-free survival to be compared.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Demonstration of the year to year representativity of molecular subtypes in breast cancer (PAM50, top panel) and administered treatments based on data from the NKBC (lower panel) for patients identified in D.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Extended Data
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“PAM50 subtyping was performed using the AIMS method (Paquet et al.) (as for the TNBC cases in the current study) as this classifier is a single sample classifier that does not rely on a mean centering of gene expression data across a cohort (thus is not sensitive to e.g. potential bias in year to year inclusion).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Extended Data
What the sources say
- Not checked yetcites Paquet et al.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The lower panels demonstrate the clinicopathological characteristics of the different subgroups in the consort diagram, demonstrating the representativity of the end RNA sequencing cohort compared to all enrolled SCAN-B patients and the total patient population in the catchment region.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Extended Data
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“HRDetect is therefore more specific than current substitution signature and CNA approaches, while extending identification of HRD to a wider set of samples”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
The 1000 Genomes dataset is a sufficient reference for judging whether the SVA insertion is novel.
“This specific mobile element has not been reported in the 1000 genomes dataset.”
The paper relies on this without support.
Chemotherapy-treated and untreated HRDetect-low patients are comparable enough for their invasive disease-free survival to be compared.
“chemotherapy-treated HRDetect-low patients had a similar IDFS to patients that did not receive adjuvant chemotherapy, in spite of superior fitness and lower age of diagnosis (75% <70 years)”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, we cannot formally exclude that these observations originate from differences in cohort inclusion criteria that could skew numbers (e.g. due to more recruitment of patients with triple negative breast cancer which has higher HRD rates12).”
From Pan-cancer landscape of homologous recombination deficiency. (2020) · cites this paper as [12]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“with RAD51C and PALB2 inactivation resulting in BRCA2-type HRD.”
From Pan-cancer landscape of homologous recombination deficiency. (2020) · cites this paper as [12]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
“237 (93%) had WGS data of sufficient quality for comprehensive genomic profiling. Failure rate was influenced by sequencing depth: of cases sequenced to 30-fold depth, 3% failed, whereas 11% of cases failed when sequenced to 15-fold coverage.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
“254 cases for matched tumor-normal WGS/RNAseq analysis (170 at 30-fold and 84 at 15-fold sequence depth)”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
“Of 139 HRDetect-high cases, 29 (21%) confirmed biallelic loss of BRCA1 or BRCA2 (i.e., 20 germline and 9 somatic with LOH of the wild-type parental allele) and 55 (40%) had BRCA1 hypermethylation with loss of the other parental allele (Figure 2A, note one case with concurrent BRCA2 biallelic alteration and BRCA1 hypermethylation).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
“Causes for HRDetect-high scores in the remaining 46 (33%) samples were unclear.”
Citations
Cites
The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups
METABRIC Group, Curtis, C., Shah, S. P., Chin, S.-F., Turashvili, G., Rueda, O. M., Dunning, M. J., Speed, D., Lynch, A. G., Samarajiwa, S., et al. (2012) · Nature · doi:10.1038/nature10983 · Cited by 6,097
Lehmann, B. D., Bauer, J. A., Chen, X., Sanders, M. E., Chakravarthy, A. B., Shyr, Y., & Pietenpol, J. A. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45014 · Cited by 5,592
Accurate whole human genome sequencing using reversible terminator chemistry
Bentley, D. R., Balasubramanian, S., Swerdlow, H. P., Smith, G. P., Milton, J., Brown, C. G., Hall, K. P., Evers, D. J., Barnes, C. L., Bignell, H. R., et al. (2008) · Nature · doi:10.1038/nature07517 · Cited by 3,684
Liedtke, C., Mazouni, C., Hess, K. R., André, F., Tordai, A., Mejia, J. A., Symmans, W. F., Gonzalez-Angulo, A. M., Hennessy, B., Green, M., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.4147 · Cited by 2,892
Landscape of somatic mutations in 560 breast cancer whole-genome sequences
Nik-Zainal, S., Davies, H., Staaf, J., Ramakrishna, M., Glodzik, D., Zou, X., Martincorena, I., Alexandrov, L. B., Martin, S., Wedge, D. C., et al. (2016) · Nature · doi:10.1038/nature17676 · Cited by 2,218
Self-citationOncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
Bartkova, J., Rezaei, N., Liontos, M., Karakaidos, P., Kletsas, D., Issaeva, N., Vassiliou, L.-V. F., Kolettas, E., Niforou, K., Zoumpourlis, V. C., et al. (2006) · Nature · doi:10.1038/nature05268 · Cited by 1,986
Mutational Processes Molding the Genomes of 21 Breast Cancers
Nik-Zainal, S., Alexandrov, L. B., Wedge, D. C., Van Loo, P., Greenman, C. D., Raine, K., Jones, D., Hinton, J., Marshall, J., Stebbings, L. A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.024 · Cited by 1,909
Self-citationAn Oncogene-Induced DNA Damage Model for Cancer Development
Halazonetis, T. D., Gorgoulis, V. G., & Bartek, J. (2008) · Science · doi:10.1126/science.1140735 · Cited by 1,851
Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication
Di Micco, R., Fumagalli, M., Cicalese, A., Piccinin, S., Gasparini, P., Luise, C., Schurra, C., Garre’, M., Giovanni Nuciforo, P., Bensimon, A., et al. (2006) · Nature · doi:10.1038/nature05327 · Cited by 1,821
The Life History of 21 Breast Cancers
Nik-Zainal, S., Van Loo, P., Wedge, D. C., Alexandrov, L. B., Greenman, C. D., Lau, K. W., Raine, K., Jones, D., Marshall, J., Ramakrishna, M., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.023 · Cited by 1,443
Self-citation
Cited by
Sorted by citations
Adjuvant Olaparib for Patients with BRCA1 - or BRCA2 -Mutated Breast Cancer
Tutt, A. N. J., Garber, J. E., Kaufman, B., Viale, G., Fumagalli, D., Rastogi, P., Gelber, R. D., de Azambuja, E., Fielding, A., Balmaña, J., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2105215 · Cited by 1,729
Treatment landscape of triple-negative breast cancer — expanded options, evolving needs
Bianchini, G., Angelis, C. D., Licata, L., & Gianni, L. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00565-2 · Cited by 1,450
Pathogenesis of Triple-Negative Breast Cancer
Derakhshan, F., & Reis-Filho, J. S. (2022) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-042420-093238 · Cited by 714
Pan-cancer landscape of homologous recombination deficiency.
Nguyen, L., W. M. Martens, J., Van Hoeck, A., & Cuppen, E. (2020) · Nature communications · doi:10.1038/s41467-020-19406-4 · Cited by 532
“RAD51C and PALB2 deficient patients shared the BRCA2type HRD phenotype (absence of duplications) with BRCA2 deficient patients (clusters 1-3; Figure 3c), consistent with previous studies[11, 12].”
BackgroundResultInfluentialMiller, R. E., Leary, A. F., Scott, C. L., Serra, V., Lord, C. J., Bowtell, D. D. L., Chang, D. K.-F., Garsed, D. W., Jonkers, J., Ledermann, J. A., et al. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.08.2102 · Cited by 507
Self-citation
Metadata
- Authors
- Staaf, J., Glodzik, D., Bosch, A., Vallon-Christersson, J., Reuterswärd, C., Häkkinen, J., Degasperi, A., Amarante, T. D., Saal, L. H., Hegardt, C., Stobart, H., Ehinger, A., Larsson, C., Rydén, L., Loman, N., Malmberg, M., Kvist, A., Ehrencrona, H., Davies, H. R., Borg, Å., & Nik-Zainal, S.
- Affiliations
- Lund University (SE)
- University of Cambridge (GB)
- Corresponding author
- Staaf, Johan
- ORCID
- Venue
- Nature Medicine
- Published
- 2019-09-30
- Volume
- 25
- Issue
- 10
- Pages
- 1526-1533
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC6859071
- OpenAlex
- W2976898289
- Cited by
- 307
- References
- 38
- Citations by year
- 2026: 27 · 2025: 33 · 2024: 50 · 2023: 41 · 2022: 56 · 2021: 58 · 2020: 41 · 2019: 1
- FWCI
- 23.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Wellcome Trust (WT100183MA)
- Cancer Research UK (C60100/A25274, C60100/A23916)
- Cancerfonden (SIA190013)
- Sveriges Regering ((ALF) 2018/40612)
- Fru Berta Kamprads Stiftelse (FBKS-2018-4-146)
- Crafoordska Stiftelsen (20180543)
- Stiftelsen Konung Gustaf V:s Jubileumsfond (174271)
- Vetenskapsrådet
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- triple-negative breast cancer, whole genome sequencing, homologous recombination deficiency, mismatch repair deficiency, BRCA1, BRCA2, BRCA1 promoter hypermethylation, PALB2, adjuvant chemotherapy, disease-free survival, distant recurrence-free survival, prognostic factors, trial stratification
- MeSH terms
- Whole Genome Sequencing, Adult, Aged, Aged, 80 and over, Female, Genetics, Population, Humans, Middle Aged, Neoplasm Recurrence, Local, Prognosis, Promoter Regions, Genetic, Germ-Line Mutation, Disease-Free Survival, DNA Methylation, Triple Negative Breast Neoplasms
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-01, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-01 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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