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Use of Molecular Tools to Identify Patients With Indolent Breast Cancers With Ultralow Risk Over 2 Decades
University of Calif San Francisco, CA 94115 USA.
University of Calif San Francisco, CA 94115 USA; Buck Institute Research Aging, CA USA.
University of Calif San Francisco, CA 94115 USA.
University of Calif San Francisco, CA 94115 USA.
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2017 (Engelska)Ingår i: JAMA Oncology, ISSN 2374-2437, E-ISSN 2374-2445, Vol. 3, nr 11, s. 1503-1510Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
AMER MEDICAL ASSOC , 2017. Vol. 3, nr 11, s. 1503-1510
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
URN: urn:nbn:se:liu:diva-143248DOI: 10.1001/jamaoncol.2017.1261ISI: 000414801500013PubMedID: 28662222OAI: oai:DiVA.org:liu-143248DiVA, id: diva2:1160426
Anmärkning

Funding Agencies|California Breast Cancer Research Program BCRP award [180B-0065]; Modeling the Impact of Targeted Therapy Based on Breast Cancer Subtypes [U01CA187945]; Elucidating the Molecular and Contextual Basis for Indolent Tumors and the Tumor Immune Microenvironment, Swedish Research Council [U01CA196404, 521-2014-2057]; Swedish Research Council for Health, Working life and Welfare, FORTE [2014-1962]; Gosta Milton Donation Fund (Stiftelsen Gosta Miltons donationsfond); Breast Cancer Research Foundation

Tillgänglig från: 2017-11-27 Skapad: 2017-11-27 Senast uppdaterad: 2017-11-27

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