Dataset Information

Use of Molecular Tools to Identify Patients With Indolent Breast Cancers With Ultralow Risk Over 2 Decades.

ABSTRACT:

Importance

The frequency of cancers with indolent behavior has increased with screening. Better tools to identify indolent tumors are needed to avoid overtreatment.

Objective

To determine if a multigene classifier is associated with indolent behavior of invasive breast cancers in women followed for 2 decades.

Design, setting, and participants

This is a secondary analysis of a randomized clinical trial of tamoxifen vs no systemic therapy, with more than 20-year follow-up. An indolent threshold (ultralow risk) of the US Food and Drug Administration-cleared MammaPrint 70-gene expression score was established above which no breast cancer deaths occurred after 15 years in the absence of systemic therapy. Immunohistochemical markers (n = 727 women) and Agilent microarrays, for MammaPrint risk scoring (n = 652 women), were performed from formalin-fixed paraffin-embedded primary tumor blocks. Participants were postmenopausal women with clinically detected node-negative breast cancers treated with mastectomy or lumpectomy and radiation enrolled in the Stockholm tamoxifen (STO-3) trial, 1976 to 1990.

Exposures

After 2 years of tamoxifen vs no systemic therapy, regardless of hormone receptor status, patients without relapse who reconsented were further randomized to 3 additional years or none.

Main outcomes and measures

Breast cancer-specific survival assessed by Kaplan-Meier analyses and multivariate Cox proportional hazard modeling, adjusted for treatment, patient age, year of diagnosis, tumor size, grade, hormone receptors, and ERBB2/HER2 and Ki67 status.

Results

In this secondary analysis of node-negative postmenopausal women, conducted in the era before mammography screening, among the 652 women with MammaPrint scoring available (median age, 62.8 years of age), 377 (58%) and 275 (42%) were MammaPrint low and high risk, respectively, while 98 (15%) were ultralow risk. At 20 years, women with 70-gene high and low tumors but not ultralow tumors had a significantly higher risk of disease-specific death compared with ultralow-risk patients by Cox analysis (hazard ratios, 4.73 [95% CI, 1.38-16.22] and 4.54 [95% CI, 1.40-14.80], respectively). There were no deaths in the ultralow-risk tamoxifen-treated arm at 15 years, and these patients had a 20-year disease-specific survival rate of 97%, whereas for untreated patients the survival rate was 94%. Recursive partitioning identified ultralow risk as the most significant predictor of good outcome. In tumors "not ultralow risk," tumor size greater than 2 cm was the most predictive of outcome.

Conclusions and relevance

The ultralow-risk threshold of the 70-gene MammaPrint assay can identify patients whose long-term systemic risk of death from breast cancer after surgery alone is exceedingly low.

SUBMITTER: Esserman LJ

PROVIDER: S-EPMC5710197 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Publications

Use of Molecular Tools to Identify Patients With Indolent Breast Cancers With Ultralow Risk Over 2 Decades.

Esserman Laura J LJ Yau Christina C Thompson Carlie K CK van 't Veer Laura J LJ Borowsky Alexander D AD Hoadley Katherine A KA Tobin Nicholas P NP Nordenskjöld Bo B Fornander Tommy T Stål Olle O Benz Christopher C CC Lindström Linda S LS

JAMA oncology 20171101 11

<h4>Importance</h4>The frequency of cancers with indolent behavior has increased with screening. Better tools to identify indolent tumors are needed to avoid overtreatment.<h4>Objective</h4>To determine if a multigene classifier is associated with indolent behavior of invasive breast cancers in women followed for 2 decades.<h4>Design, setting, and participants</h4>This is a secondary analysis of a randomized clinical trial of tamoxifen vs no systemic therapy, with more than 20-year follow-up. An ...[more]

PMID: 28662222

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Project description:ImportanceEfficient screening tools that effectively identify substance use disorders (SUDs) among youths are needed.ObjectiveTo evaluate the psychometric properties of 3 brief substance use screening tools (Screening to Brief Intervention [S2BI]; Brief Screener for Tobacco, Alcohol, and Drugs [BSTAD]; and Tobacco, Alcohol, Prescription Medication, and Other Substances [TAPS]) with adolescents aged 12 to 17 years.Design, setting, and participantsThis cross-sectional validation study was conducted from July 1, 2020, to February 28, 2022. Participants aged 12 to 17 years were recruited virtually and in person from 3 health care settings in Massachusetts: (1) an outpatient adolescent SUD treatment program at a pediatric hospital, (2) an adolescent medicine program at a community pediatric practice affiliated with an academic institution, and (3) 1 of 28 participating pediatric primary care practices. Participants were randomly assigned to complete 1 of the 3 electronic screening tools via self-administration, followed by a brief electronic assessment battery and a research assistant-administered diagnostic interview as the criterion standard measure for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnoses of SUDs. Data were analyzed from May 31 to September 13, 2022.Main outcomes and measuresThe main outcome was a DSM-5 diagnosis of tobacco/nicotine, alcohol, or cannabis use disorder as determined by the criterion standard World Mental Health Composite International Diagnostic Interview Substance Abuse Module. Classification accuracy of the 3 substance use screening tools was assessed by examining the agreement between the criterion, using sensitivity and specificity, based on cut points for each tool for use disorder, chosen a priori from previous studies.ResultsThis study included 798 adolescents, with a mean (SD) age of 14.6 (1.6) years. The majority of participants identified as female (415 [52.0%]) and were White (524 [65.7%]). High agreement between screening results and the criterion standard measure was observed, with area under the curve values ranging from 0.89 to 1 for nicotine, alcohol, and cannabis use disorders for each of the 3 screening tools.Conclusions and relevanceThese findings suggest that screening tools that use questions on past-year frequency of use are effective for identifying adolescents with SUDs. Future work could examine whether these tools have differing properties when used with different groups of adolescents in different settings.

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Dataset Information

Use of Molecular Tools to Identify Patients With Indolent Breast Cancers With Ultralow Risk Over 2 Decades.

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Conclusions and relevance

Publications

Use of Molecular Tools to Identify Patients With Indolent Breast Cancers With Ultralow Risk Over 2 Decades.

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