Multi-drug resistance protein 2 (MRP2) expression, adjuvant tamoxifen therapy, and risk of breast cancer recurrence: a Danish population-based nested case-control study

TY - JOUR

T1 - Multi-drug resistance protein 2 (MRP2) expression, adjuvant tamoxifen therapy, and risk of breast cancer recurrence: a Danish population-based nested case-control study

AU - Hjorth, Cathrine F

AU - Nielsen, Anja S

AU - Sørensen, Henrik T

AU - Lash, Timothy L

AU - Damkier, Per

AU - Hamilton-Dutoit, Stephen

AU - Cronin-Fenton, Deirdre

PY - 2019

Y1 - 2019

N2 - BACKGROUND: Adjuvant tamoxifen therapy approximately halves the risk of recurrence in estrogen receptor-positive (ER+) breast cancer patients, but many women respond insufficiently to therapy. Expression of multi-drug resistance protein 2 (MRP2) in breast cancer may potentiate tamoxifen resistance. Thus, we investigated the expression of MRP2 in breast cancer as a predictor of tamoxifen therapy effectiveness.MATERIAL AND METHODS: We conducted a case-control study nested in the Danish Breast Cancer Group clinical database. The study included women aged 35-69 years diagnosed with stage l-lll breast cancer during 1985-2001, in Jutland, Denmark. We identified 541 recurrent breast cancers (cases) among women with estrogen receptor positive (ER+) disease treated with tamoxifen for at least 1 year (ER+/TAM+) and 300 cases among women with estrogen receptor-negative (ER-) disease, never treated with tamoxifen (ER-/TAM-). We matched one recurrence-free control to each recurrent case. We retrieved paraffin-embedded primary tumor tissue for all patients, and all available recurrent tumor tissue from pathology archives. MRP2 expression was evaluated using immunohistochemistry. We computed odds ratios (ORs) and 95% confidence intervals (95% CIs) associating MRP2 expression (positive vs. none) with breast cancer recurrence in conditional logistic regression models. We compared MRP2 expression in paired primary- and recurrent tumors.RESULTS: MRP2 expression was more prevalent in the ER+/TAM + group, than in the ER-/TAM - group. No predictive utility of MRP2 for breast cancer recurrence was found in the ER+/TAM + group (ORadj = 0.96, 95% CI 0.70, 1.33). Further, no prognostic utility was found in the ER-/TAM - group (ORadj = 0.81, 95% CI 0.53, 1.23). MRP2 expression was not increased in recurrent versus primary tumors.CONCLUSIONS: MRP2 expression is neither a predictive marker of tamoxifen effectiveness nor a prognostic marker in breast cancer.

AB - BACKGROUND: Adjuvant tamoxifen therapy approximately halves the risk of recurrence in estrogen receptor-positive (ER+) breast cancer patients, but many women respond insufficiently to therapy. Expression of multi-drug resistance protein 2 (MRP2) in breast cancer may potentiate tamoxifen resistance. Thus, we investigated the expression of MRP2 in breast cancer as a predictor of tamoxifen therapy effectiveness.MATERIAL AND METHODS: We conducted a case-control study nested in the Danish Breast Cancer Group clinical database. The study included women aged 35-69 years diagnosed with stage l-lll breast cancer during 1985-2001, in Jutland, Denmark. We identified 541 recurrent breast cancers (cases) among women with estrogen receptor positive (ER+) disease treated with tamoxifen for at least 1 year (ER+/TAM+) and 300 cases among women with estrogen receptor-negative (ER-) disease, never treated with tamoxifen (ER-/TAM-). We matched one recurrence-free control to each recurrent case. We retrieved paraffin-embedded primary tumor tissue for all patients, and all available recurrent tumor tissue from pathology archives. MRP2 expression was evaluated using immunohistochemistry. We computed odds ratios (ORs) and 95% confidence intervals (95% CIs) associating MRP2 expression (positive vs. none) with breast cancer recurrence in conditional logistic regression models. We compared MRP2 expression in paired primary- and recurrent tumors.RESULTS: MRP2 expression was more prevalent in the ER+/TAM + group, than in the ER-/TAM - group. No predictive utility of MRP2 for breast cancer recurrence was found in the ER+/TAM + group (ORadj = 0.96, 95% CI 0.70, 1.33). Further, no prognostic utility was found in the ER-/TAM - group (ORadj = 0.81, 95% CI 0.53, 1.23). MRP2 expression was not increased in recurrent versus primary tumors.CONCLUSIONS: MRP2 expression is neither a predictive marker of tamoxifen effectiveness nor a prognostic marker in breast cancer.

KW - ABCC2

KW - COOPERATIVE GROUP

KW - CYP2D6

KW - DBCG

KW - IMPACT

KW - POLYMORPHISMS

KW - PROGNOSIS

KW - RECEPTOR

KW - TRANSPORTERS

KW - WOMEN

UR - http://www.scopus.com/inward/record.url?scp=85057518234&partnerID=8YFLogxK

U2 - 10.1080/0284186X.2018.1537508

DO - 10.1080/0284186X.2018.1537508

M3 - Journal article

C2 - 30458661

SN - 0284-186X

VL - 58

SP - 168

EP - 174

JO - Acta Oncologica

JF - Acta Oncologica

IS - 2

ER -