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Tamoxifen therapy benefit for patients with 70-gene signature high and low risk
University of Calif San Francisco, CA 94115 USA.
University of Calif San Francisco, CA 94115 USA; Buck Institute Research Aging, CA 94945 USA.
Karolinska Institute, Sweden.
Buck Institute Research Aging, USA; University of Calif San Francisco,USA.
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2017 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 166, no 2, 593-601 p.Article in journal (Refereed) Published
Abstract [en]

Breast cancer molecular prognostic tools that predict recurrence risk have mainly been established on endocrine-treated patients and thus are not optimal for the evaluation of benefit from endocrine therapy. The Stockholm tamoxifen (STO-3) trial which randomized postmenopausal node-negative patients to 2-year tamoxifen (followed by an optional randomization for an additional 3-year tamoxifen vs nil), versus no adjuvant treatment, provides a unique opportunity to evaluate long-term 20-year benefit of endocrine therapy within prognostic risk classes of the 70-gene prognosis signature that was developed on adjuvantly untreated patients. We assessed by Kaplan-Meier analysis 20-year breast cancer-specific survival (BCSS) and 10-year distant metastasis-free survival (DMFS) for 538 estrogen receptor (ER)-positive, STO-3 trial patients with retrospectively ascertained 70-gene prognosis classification. Multivariable analysis of long-term (20 years) BCSS by STO-3 trial arm in the 70-gene high-risk and low-risk subgroups was performed using Cox proportional hazard modeling adjusting for classical patient and tumor characteristics. Tamoxifen-treated, 70-gene low- and high-risk patients had 20-year BCSS of 90 and 83%, as compared to 80 and 65% for untreated patients, respectively (log-rank p amp;lt; 0.0001). Notably, there is equivalent tamoxifen benefit in both high (HR 0.42 (0.21-0.86), p = 0.018) and low (HR 0.46 (0.25-0.85), p = 0.013) 70-gene risk categories even after adjusting for clinico-pathological factors for BCSS. Limited tamoxifen exposure as given in the STO-3 trial provides persistent benefit for 10-15 years after diagnosis in a time-varying analysis. 10-year DMFS was 93 and 85% for low- and high-risk tamoxifen-treated, versus 83 and 70% for low- and high-risk untreated patients, respectively (log-rank p amp;lt; 0.0001). Patients with ER-positive breast cancer, regardless of high or low 70-gene risk classification, receive significant survival benefit lasting over 10 years from adjuvant tamoxifen therapy, even when given for a relatively short duration.

Place, publisher, year, edition, pages
SPRINGER , 2017. Vol. 166, no 2, 593-601 p.
Keyword [en]
70-gene signature; Tamoxifen benefit; Endocrine therapy; Breast cancer; Long-term survival
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-143077DOI: 10.1007/s10549-017-4428-9ISI: 000414472400025PubMedID: 28776283OAI: oai:DiVA.org:liu-143077DiVA: diva2:1159445
Note

Funding Agencies|California Breast Cancer Research Program BCRP award [180B-0065]; Breast Cancer Research Foundation [BCRF]; Swedish Research Council [521-2014-2057]; FORTE [2014-1962]; Stiftelsen Gosta Miltons Donationsfond [The Gosta Milton Donation Fund]; Cancerforeningen i Stockholm [Stockholm Cancer Society]

Available from: 2017-11-22 Created: 2017-11-22 Last updated: 2017-11-22

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Nordenskjöld, BoStål, Olle
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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of Oncology
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CiteExportLink to record
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