Dataset Information

Estimating Breast Cancer Survival by Molecular Subtype in the Absence of Screening and Adjuvant Treatment.

ABSTRACT: BACKGROUND:As molecular subtyping of breast cancer influences clinical management, the evaluation of screening and adjuvant treatment interventions at the population level needs to account for molecular subtyping. Performing such analyses are challenging because molecular subtype-specific, long-term outcomes are not readily accessible; these markers were not historically recorded in tumor registries. We present a modeling approach to estimate historical survival outcomes by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status. METHOD:Our approach leverages a simulation model of breast cancer outcomes and integrates data from two sources: the Surveillance Epidemiology and End Results (SEER) databases and the Breast Cancer Surveillance Consortium (BCSC). We not only produce ER- and HER2-specific estimates of breast cancer survival in the absence of screening and adjuvant treatment but we also estimate mean tumor volume doubling time (TVDT) and mean mammographic detection threshold by ER/HER2-status. RESULTS:In general, we found that tumors with ER-negative and HER2-positive status are associated with more aggressive growth, have lower TVDTs, are harder to detect by mammography, and have worse survival outcomes in the absence of screening and adjuvant treatment. Our estimates have been used as inputs into model-based analyses that evaluate the effects of screening and adjuvant treatment interventions on population outcomes by ER and HER2 status developed by the Cancer Intervention and Surveillance Modeling Network (CISNET) Breast Cancer Working Group. In addition, our estimates enable a re-assessment of historical trends in breast cancer incidence and mortality in terms of contemporary molecular tumor characteristics. CONCLUSION:Our approach can be generalized beyond breast cancer and to more complex molecular profiles.

SUBMITTER: Munoz DF

PROVIDER: S-EPMC6635303 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Estimating Breast Cancer Survival by Molecular Subtype in the Absence of Screening and Adjuvant Treatment.

Munoz Diego F DF Plevritis Sylvia K SK

Medical decision making : an international journal of the Society for Medical Decision Making 20180401 1_suppl

<h4>Background</h4>As molecular subtyping of breast cancer influences clinical management, the evaluation of screening and adjuvant treatment interventions at the population level needs to account for molecular subtyping. Performing such analyses are challenging because molecular subtype-specific, long-term outcomes are not readily accessible; these markers were not historically recorded in tumor registries. We present a modeling approach to estimate historical survival outcomes by estrogen rece ...[more]

PMID: 29554464

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Project description:PurposeGastric cancer (GC) is the third-leading cause of cancer-related deaths. Several pivotal clinical trials of adjuvant treatments were performed during the previous decade; however, the optimal regimen for adjuvant treatment of GC remains controversial.Patients and methodsWe developed a novel deep learning-based survival model (survival recurrent network [SRN]) in patients with GC by including all available clinical and pathologic data and treatment regimens. This model uses time-sequential data only in the training step, and upon being trained, it receives the initial data from the first visit and then sequentially predicts the outcome at each time point until it reaches 5 years. In total, 1,190 patients from three cohorts (the Asian Cancer Research Group cohort, n = 300; the fluorouracil, leucovorin, and radiotherapy cohort, n = 432; and the Adjuvant Chemoradiation Therapy in Stomach Cancer cohort, n = 458) were included in the analysis. In addition, we added Asian Cancer Research Group molecular classifications into the prediction model. SRN simulated the sequential learning process of clinicians in the outpatient clinic using a recurrent neural network and time-sequential outcome data.ResultsThe mean area under the receiver operating characteristics curve was 0.92 ± 0.049 at the fifth year. The SRN demonstrated that GC with a mesenchymal subtype should elicit a more risk-adapted postoperative treatment strategy as a result of its high recurrence rate. In addition, the SRN found that GCs with microsatellite instability and GCs of the papillary type exhibited significantly more favorable survival outcomes after capecitabine plus cisplatin chemotherapy alone.ConclusionOur SRN predicted survival at a high rate, reaching 92% at postoperative year 5. Our findings suggest that SRN-based clinical trials or risk-adapted adjuvant trials could be considered for patients with GC to investigate more individualized adjuvant treatments after curative gastrectomy.

Project description:Importance:Given recent advances in screening mammography and adjuvant therapy (treatment), quantifying their separate and combined effects on US breast cancer mortality reductions by molecular subtype could guide future decisions to reduce disease burden. Objective:To evaluate the contributions associated with screening and treatment to breast cancer mortality reductions by molecular subtype based on estrogen-receptor (ER) and human epidermal growth factor receptor 2 (ERBB2, formerly HER2 or HER2/neu). Design, Setting, and Participants:Six Cancer Intervention and Surveillance Network (CISNET) models simulated US breast cancer mortality from 2000 to 2012 using national data on plain-film and digital mammography patterns and performance, dissemination and efficacy of ER/ERBB2-specific treatment, and competing mortality. Multiple US birth cohorts were simulated. Exposures:Screening mammography and treatment. Main Outcomes and Measures:The models compared age-adjusted, overall, and ER/ERBB2-specific breast cancer mortality rates from 2000 to 2012 for women aged 30 to 79 years relative to the estimated mortality rate in the absence of screening and treatment (baseline rate); mortality reductions were apportioned to screening and treatment. Results:In 2000, the estimated reduction in overall breast cancer mortality rate was 37% (model range, 27%-42%) relative to the estimated baseline rate in 2000 of 64 deaths (model range, 56-73) per 100?000 women: 44% (model range, 35%-60%) of this reduction was associated with screening and 56% (model range, 40%-65%) with treatment. In 2012, the estimated reduction in overall breast cancer mortality rate was 49% (model range, 39%-58%) relative to the estimated baseline rate in 2012 of 63 deaths (model range, 54-73) per 100?000 women: 37% (model range, 26%-51%) of this reduction was associated with screening and 63% (model range, 49%-74%) with treatment. Of the 63% associated with treatment, 31% (model range, 22%-37%) was associated with chemotherapy, 27% (model range, 18%-36%) with hormone therapy, and 4% (model range, 1%-6%) with trastuzumab. The estimated relative contributions associated with screening vs treatment varied by molecular subtype: for ER+/ERBB2-, 36% (model range, 24%-50%) vs 64% (model range, 50%-76%); for ER+/ERBB2+, 31% (model range, 23%-41%) vs 69% (model range, 59%-77%); for ER-/ERBB2+, 40% (model range, 34%-47%) vs 60% (model range, 53%-66%); and for ER-/ERBB2-, 48% (model range, 38%-57%) vs 52% (model range, 44%-62%). Conclusions and Relevance:In this simulation modeling study that projected trends in breast cancer mortality rates among US women, decreases in overall breast cancer mortality from 2000 to 2012 were associated with advances in screening and in adjuvant therapy, although the associations varied by breast cancer molecular subtype.

Project description:BackgroundThe relation between breast cancer molecular subtype and survival has been studied in several jurisdictions, but limited information is available for Ontario. The aim of this study was to determine breast cancer survival by molecular subtype and to assess the effect on survival of selected demographic and tumour-based characteristics.MethodsWe extracted 29 833 breast cancer cases (in 26 538 girls and women aged ≥ 15 yr) diagnosed between 2010 and 2012 from the Ontario Cancer Registry. Cancers were categorized into 4 molecular subtypes: 1) luminal A (estrogen-receptor-positive and/or progesterone-receptor-positive [ER+ and/or PR+] and negative for human epidermal growth factor receptor 2 [HER2-]), 2) luminal B (ER+ and/or PR+/HER2+), 3) HER2-enriched (ER- and PR-/HER2+) and 4) triple-negative (ER- and PR-/HER2-). We estimated associations with predictor variables (age, stage at diagnosis, histologic type, comorbidity and place of residence [urban or rural]) using a multivariate Cox proportional hazards model. Likelihood ratio testing was used to evaluate differences in risk of death.ResultsLuminal A was the most commonly diagnosed subtype (59.0%) and had the greatest survival, whereas triple-negative had the poorest survival. For all subtypes, a dose-response effect was observed between the hazard of death and age and stage at diagnosis, with the greatest effect found for the HER2-enriched subtype (age: hazard ratio [HR] 7.87 [95% confidence interval (CI) 3.68-11.81]; stage at diagnosis: HR 37.71 [95% CI 34.64-41.27]). Moderate comorbidity (Charlson Comorbidity Index score 1 or 2) was associated with increased risk of death for triple-negative cancers (HR 2.42 [95% CI 1.36-4.31]), and severe comorbidity (Charlson Comorbidity Index score ≥ 3) increased the risk for all molecular subtypes.InterpretationThe results indicate the importance of including molecular subtype, along with age, stage at diagnosis and comorbidity, in assessing breast cancer survival. They highlight the need to address outcomes related to hormone-receptor-negative cancers, for which survival lags behind that for hormone-receptor-positive cancers.

Dataset Information

Estimating Breast Cancer Survival by Molecular Subtype in the Absence of Screening and Adjuvant Treatment.

Publications

Estimating Breast Cancer Survival by Molecular Subtype in the Absence of Screening and Adjuvant Treatment.

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