Oral Bisphosphonates and Improved Survival of Breast Cancer.
Purpose:Bisphosphonates are used for treatment or prevention of osteoporosis and of bone metastases. The use of oral bisphosphonates was suggested to be associated with reduced risk of developing breast cancer, and their positive influence on breast cancer survival was only demonstrated with third-generation bisphosphonates. We studied the association of use of oral bisphosphonates after breast cancer diagnosis on overall and breast cancer survival.Experimental Design:A nested case-control analysis was performed using data from the population-based Breast Cancer in Northern Israel Study (BCINIS). Participants were postmenopausal women with newly diagnosed breast cancer insured by Clalit. Use of second-generation bisphosphonates (alendronate and/or risedronate) was identified using computerized prescription records. The analysis was restricted to women who did not use bisphosphonates prior to diagnosis.Results:In a cohort of 3,731 postmenopausal women with breast cancer, followed up for an average of 70 months, there were 799 cases of death which were matched to 15,915 control periods of living breast cancer cases. Use of bisphosphonates after diagnosis for at least 18 months was significantly more common among survivors than among their matched controls who died, adjusted for tumor stage/grade (overall survival: OR = 0.63, 0.41-0.96,P= 0.03; breast cancer-specific survival: OR = 0.28, 0.09-0.91,P= 0.035). A similar advantageous effect, but statistically underpowered, was found in estrogen receptor (ER)-positive, ER-negative, and HER2neu-positive tumors.Conclusions:The use of oral bisphosphonates, by postmenopausal, probably osteoporotic, women initiated after diagnosis of breast cancer was associated with a significant improvement in overall and breast-specific odds of survival.Clin Cancer Res; 23(7); 1684-9. ©2016 AACR.
Department of Community Medicine and Epidemiology, Carmel Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and Clalit National Cancer Control Center, Haifa, Israel. rennert@tx.technion.ac.il.
Gad
G
Rennert
Department of Community Medicine and Epidemiology, Carmel Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and Clalit National Cancer Control Center, Haifa, Israel.
Mila
M
Pinchev
Department of Community Medicine and Epidemiology, Carmel Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and Clalit National Cancer Control Center, Haifa, Israel.
Naomi
N
Gronich
Department of Community Medicine and Epidemiology, Carmel Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and Clalit National Cancer Control Center, Haifa, Israel.
Walid
W
Saliba
Department of Community Medicine and Epidemiology, Carmel Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and Clalit National Cancer Control Center, Haifa, Israel.
Anath
A
Flugelman
Department of Community Medicine and Epidemiology, Carmel Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and Clalit National Cancer Control Center, Haifa, Israel.
Idit
I
Lavi
Oncology Institute, Western Galilee Hospital, Naharia, Israel.
Hadassah
H
Goldberg
Oncology Institute, Rambam Medical Center, Haifa, Israel.
Georgeta
G
Fried
Lynn Medical Center, Clalit Health Services, Haifa, Israel.
Mariana
M
Steiner
Department of Surgery A, Carmel Medical Center, Haifa, Israel.
Arie
A
Bitterman
Department of Community Medicine and Epidemiology, Carmel Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and Clalit National Cancer Control Center, Haifa, Israel.
Keren
K
Landsman
Department of Community Medicine and Epidemiology, Carmel Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and Clalit National Cancer Control Center, Haifa, Israel.
Hedy S
HS
Rennert
D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D004164:Diphosphonates / Q000627:therapeutic use*; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010024:Osteoporosis / Q000188:drug therapy* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics
D004164:Diphosphonates; D047628:Estrogen Receptor alpha; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human