Abstract P6-07-10: Luminal A vs. Basal-like Breast Cancer: time dependent changes in the risk of relapse in the absence of treatment
Bibliographic record
Abstract
Abstract Background: Numerous retrospective analyses of prospective randomized clinical trials of patients treated with adjuvant tamoxifen and chemotherapy have demonstrated that the breast cancer intrinsic subtype Luminal A tumors generally have favorable early initial outcomes, while basal-like tumors are associated with a marked risk of early relapse. To determine the extended natural history of the intrinsic subtypes across two decades of follow up the PAM50 “non-commercial open source bioinformatics” qPCR assay was conducted on node negative tumors accrued through the Cooperative Breast Cancer Tissue Registry (CBCTR) from patients who did not receive systemic therapy. Methods: Intrinsic subtype calls were obtained from 331 CBCTR cases treated with local interventions only. Tumors were classified into Luminal A (LumA), Luminal B (LumB), HER2-enriched (HER2-E) and Basal-like (BLBC), and correlated relapse-free (RFS). Patient survival and hazard rate were estimated using Kaplan-Meier plots and log-rank test. Multivariable Cox regression analyses were used to determine the significance of the intrinsic subtypes, adjusted with standard clinicopathological variables including tumor size, age at diagnosis, grade, radiation therapy treatment, centralized reviewed estrogen receptor, progesterone receptor and human epidermal growth factor 2 status measured by immunohistochemistry. Patients were diagnosed from 1978 to 1992, with a mean follow-up time of 13 years (range 0.5–31). Results: Of the 331 tumors tested, 51% of cases were classified as LumA, 18% as LumB, 11% as HER2-E and 20% as BLBC. Although LumA was associated with the best outcome for the first 10-year of follow-up, the final number of RFS events were eventually comparable with those observed for BLBC with prolonged follow up (Table 1). In the multivariable Cox model, only BLBC tumors were associated with worse prognosis than LumA with borderline significance (Hazard ratio: 2.0 (95% CI 0.9–5), p = 0.07). BLBC had the highest hazard rates for the first 5 years (7% at first year to 5% at 5 yr), consistent with previous observations. Interestingly, in the absence of treatment, the slow growing LumA subtype had a gradual increase of hazard for an RFS event from 3% at 5 yrs to 4% at 10 yrs to 7% at 20 yrs. The hazard rates of LumA cross with those of BLBC at 10 years. Conclusions: Basal-like breast cancers are associated with an early risk of relapse that decreases over time. In contrast, Luminal A breast cancer has a low risk of relapse at the outset but the risk of relapse increases over time and is responsible of the majority of the RFS events after 20 years of follow up. Luminal A breast cancers are therefore not truly low risk, particularly if they do not receive endocrine therapy; and may experience the consequences of inadequate treatment decades after diagnosis. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-10.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".