Estrogen receptor, Progesterone receptor, HER2 status and Ki67 index and responsiveness to adjuvant tamoxifen in postmenopausal high-risk breast cancer patients enrolled in the DBCG 77C trial

TY - JOUR

T1 - Estrogen receptor, Progesterone receptor, HER2 status and Ki67 index and responsiveness to adjuvant tamoxifen in postmenopausal high-risk breast cancer patients enrolled in the DBCG 77C trial

AU - Knoop, Ann S

AU - Lænkholm, Anne-Vibeke

AU - Jensen, Maj-Britt

AU - Nielsen, Kirsten V

AU - Andersen, Jørn

AU - Nielsen, Dorte

AU - Ejlertsen, Bent

AU - Danish Breast Cancer Cooperative Group

N1 - Copyright © 2014 Elsevier Ltd. All rights reserved.

PY - 2014/5

Y1 - 2014/5

N2 - The DBCG 77C trial compared one year of tamoxifen in postmenopausal, steroid-receptor unknown, high-risk breast cancer patients to no adjuvant systemic therapy. After a potential follow-up of 30 years we report overall efficacy of the study and results according to subtypes subsequently assessed by immunohistochemistry and fluorescent in situ hybridisation (FISH). Methods Between 1977 and 1982, 1716 postmenopausal patients with tumours larger than 5 cm or positive axillary nodes were randomly assigned to no systemic therapy or tamoxifen 30 mg daily for one year. Archival tumour tissue from 1515 patients was analysed and the hormone receptor positive (estrogen receptor (ER) and/or progesterone receptor (PR)) cancers were defined as luminal A if Ki67 low and HER2-negative; as luminal B if Ki67 high or HER2-positive; and otherwise as non-luminal-HER2 positive or triple negative. Findings In the intent-to-treat (ITT) population one year of tamoxifen improved the disease-free-survival (DFS) (hazard ratio (HR) = 0.87; 95% confidence interval (CI) 0.77-0.98), the Breast Cancer Recurrence Rate (BCRR) (HR = 0.79; 0.69-0.90) and reduced the breast-cancer-specific-mortality (BCM) (HR = 0.83; 0.73-0.93). BCRR were improved significantly by tamoxifen in luminal A (HR = 0.66; 0.53-0.84) and luminal B/HER2- (HR = 0.54; 0.39-0.74) but not in the other subsets, and with similar results for BCM with 30 years follow-up. Interpretation One year of treatment with tamoxifen significantly improves BCRR and BCM in postmenopausal patients with ER positive breast cancers. The relative benefit from tamoxifen was not significantly different in luminal A and B subtypes. Funding The Danish Breast Cancer Cooperative Group (DBCG) prepared the original protocol (DBCG 77C) and was the sponsor of the study. Funding was not provided to the participating departments. The biomarker study was supported by grants from the Clinical Institute, Odense University.

AB - The DBCG 77C trial compared one year of tamoxifen in postmenopausal, steroid-receptor unknown, high-risk breast cancer patients to no adjuvant systemic therapy. After a potential follow-up of 30 years we report overall efficacy of the study and results according to subtypes subsequently assessed by immunohistochemistry and fluorescent in situ hybridisation (FISH). Methods Between 1977 and 1982, 1716 postmenopausal patients with tumours larger than 5 cm or positive axillary nodes were randomly assigned to no systemic therapy or tamoxifen 30 mg daily for one year. Archival tumour tissue from 1515 patients was analysed and the hormone receptor positive (estrogen receptor (ER) and/or progesterone receptor (PR)) cancers were defined as luminal A if Ki67 low and HER2-negative; as luminal B if Ki67 high or HER2-positive; and otherwise as non-luminal-HER2 positive or triple negative. Findings In the intent-to-treat (ITT) population one year of tamoxifen improved the disease-free-survival (DFS) (hazard ratio (HR) = 0.87; 95% confidence interval (CI) 0.77-0.98), the Breast Cancer Recurrence Rate (BCRR) (HR = 0.79; 0.69-0.90) and reduced the breast-cancer-specific-mortality (BCM) (HR = 0.83; 0.73-0.93). BCRR were improved significantly by tamoxifen in luminal A (HR = 0.66; 0.53-0.84) and luminal B/HER2- (HR = 0.54; 0.39-0.74) but not in the other subsets, and with similar results for BCM with 30 years follow-up. Interpretation One year of treatment with tamoxifen significantly improves BCRR and BCM in postmenopausal patients with ER positive breast cancers. The relative benefit from tamoxifen was not significantly different in luminal A and B subtypes. Funding The Danish Breast Cancer Cooperative Group (DBCG) prepared the original protocol (DBCG 77C) and was the sponsor of the study. Funding was not provided to the participating departments. The biomarker study was supported by grants from the Clinical Institute, Odense University.

KW - Adult

KW - Aged

KW - Antineoplastic Agents, Hormonal

KW - Breast Neoplasms

KW - Chemotherapy, Adjuvant

KW - Disease-Free Survival

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Immunohistochemistry

KW - In Situ Hybridization, Fluorescence

KW - Intention to Treat Analysis

KW - Ki-67 Antigen

KW - Middle Aged

KW - Postmenopause

KW - Receptor, ErbB-2

KW - Receptors, Estrogen

KW - Receptors, Progesterone

KW - Risk Factors

KW - Survival Analysis

KW - Tamoxifen

KW - Treatment Outcome

U2 - 10.1016/j.ejca.2014.02.022

DO - 10.1016/j.ejca.2014.02.022

M3 - Journal article

C2 - 24675287

SN - 0959-8049

VL - 50

SP - 1412

EP - 1421

JO - European journal of cancer (Oxford, England : 1990)

JF - European journal of cancer (Oxford, England : 1990)

IS - 8

ER -