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Sökning: onr:"swepub:oai:DiVA.org:liu-143248" > Use of Molecular To...

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

Esserman, Laura J. (författare)
University of Calif San Francisco, CA 94115 USA
Yau, Christina (författare)
University of Calif San Francisco, CA 94115 USA; Buck Institute Research Aging, CA USA
Thompson, Carlie K. (författare)
University of Calif San Francisco, CA 94115 USA
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vant Veer, Laura J. (författare)
University of Calif San Francisco, CA 94115 USA
Borowsky, Alexander D. (författare)
University of Calif Davis, CA 95616 USA
Hoadley, Katherine A. (författare)
University of N Carolina, NC USA
Tobin, Nicholas P. (författare)
Karolinska Institute, Sweden; University Hospital, Sweden
Nordenskjöld, Bo (författare)
Linköpings universitet,Avdelningen för Kirurgi, Ortopedi och Onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US
Fornander, Tommy (författare)
Karolinska Institute, Sweden; University Hospital, Sweden
Stål, Olle (författare)
Linköpings universitet,Avdelningen för Kirurgi, Ortopedi och Onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US
Benz, Christopher C. (författare)
University of Calif San Francisco, CA 94115 USA; Buck Institute Research Aging, CA USA
Lindstrom, Linda S. (författare)
University Hospital, Sweden; Karolinska Institute, Sweden
Thompson, CK (författare)
Benz, CC (författare)
Yau, C (författare)
Stal, O (författare)
van't Veer, LJ (författare)
Tobin, NP (författare)
Karolinska Institutet
Esserman, LJ (författare)
Borowsky, AD (författare)
Nordenskjold, B (författare)
Fornander, T (författare)
Karolinska Institutet
Lindstrom, LS (författare)
Karolinska Institutet
Hoadley, KA (författare)
visa färre...
 (creator_code:org_t)
AMER MEDICAL ASSOC, 2017
2017
Engelska.
Ingår i: JAMA Oncology. - : AMER MEDICAL ASSOC. - 2374-2437 .- 2374-2445. ; 3:11, s. 1503-1510
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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.

Ämnesord

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

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