The impact of menopause on bone, zoledronic acid, and implications for breast cancer growth and metastasis.
Recent data from the AZURE, ABCSG-12, and ZO-FAST clinical trials have challenged our understanding of the potential anticancer activity of zoledronic acid (ZOL). Although the results of these studies may appear to be conflicting on the surface, a deeper look into commonalities among the patient populations suggest that some host factors (i.e. patient age and endocrine status) may contribute to the anticancer activity of ZOL. Indeed, data from these large clinical trials suggest that the potential anticancer activity of ZOL may be most robust in a low-estrogen environment. However, this may be only part of the story and many questions remain to be answered to fully explain the phenomenon. Does estrogen override the anticancer activity of ZOL seen in postmenopausal women? Are hormones other than estrogen involved that contribute to this effect? Does the role of bone turnover in breast cancer (BC) growth and progression differ in the presence of various estrogen levels? Here, we present a review of the multitude of factors affected by different endocrine environments in women with BC that may influence the potential anticancer activity of ZOL.
Department of Gynecology, Endocrinology, and Oncology, Philipps-University of Marburg, Marburg, Germany.
P
P
Hadji
Academic Unit of Clinical Oncology, Weston Park Hospital, CR-UK/YCR Sheffield Cancer Research Centre, Sheffield, UK.
R
R
Coleman
Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
M
M
Gnant
Department of Oncology, Novartis Pharma AG, Basel, Switzerland. Electronic address: jonathan.green@novartis.com.
J
J
Green
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy*; D004164:Diphosphonates / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008593:Menopause; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid