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Should bisphosphonates be utilized in the adjuvant setting for breast cancer?

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Abstract

Adjuvant therapies for early breast cancer are associated with substantial decreases in bone mineral density. Bisphosphonates are antiresorptive agents that have an established role in preventing skeletal morbidity in patients with bone metastases and in the treatment of osteoporosis. Recently, several trials have demonstrated the efficacy of bone-directed agents for prevention of cancer treatment-induced bone loss in both premenopausal and postmenopausal women with early stage breast cancer. Moreover, it is now becoming evident that bisphosphonates may also exert anticancer effects in the adjuvant setting. For example, long-term follow-up of a study in patients with bone marrow micrometastases from breast cancer revealed overall survival benefits for clodronate versus placebo, and an ongoing large trial may provide further insights. Addition of twice-yearly zoledronic acid to standard adjuvant endocrine therapy significantly improved disease-free survival and decreased disease recurrence compared with standard therapy alone in 3 clinical trials involving nearly 3,500 patients with stage I-IIIA breast cancer, and monthly zoledronic acid during neoadjuvant therapy decreased residual tumor volume and improved pathologic response in patients with stage II/III breast cancer. Overall, a large and growing body of evidence suggests the potential adjuvant benefits of bisphosphonates in early breast cancer.

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Abbreviations

ABCSG-12:

Austrian Breast and Colorectal Cancer Study Group Trial 12

AI:

Aromatase inhibitor

AIBL:

Aromatase inhibitor-associated bone loss

BC:

Breast cancer

BMD:

Bone mineral density

BMFS:

Bone-metastases-free survival

BP:

Bisphosphonate

CTIBL:

Cancer therapy-induced bone loss

DFS:

Disease-free survival

DTCs:

Disseminated tumor cells

EBC:

Early breast cancer

HR:

Hazard ratio

IV:

Intravenous(ly)

LS:

Lumbar spine

NNT:

Number needed to treat

ONJ:

Osteonecrosis of the jaw

q3mo:

Every 3 months

q6mo:

Every 6 months

RANKL:

Receptor activator of nuclear factor kappa B ligand

RFS:

Recurrence-free survival

SRE:

Skeletal-related event

TAM:

Tamoxifen

TH:

Total hip

ZOL:

Zoledronic acid

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Acknowledgments

Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. I thank Shalini Murthy, PhD, for her medical editorial assistance with this manuscript. She helped draft the manuscript according to my direction and integrated the revisions I provided. The sponsor (Novartis Pharmaceuticals) had no influence over the content of the manuscript at any stage.

Conflict of interest statement

Dr. Lipton has participated as a consultant for Amgen and Novartis; received honoraria from Amgen, Novartis, and Genentech; received research funding from Novartis, Monogram Biosciences, and Oncogene Sciences; and provided expert testimony for Novartis.

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  1. Division of Hematology/Oncology, Milton S. Hershey Medical Center, Pennsylvania State University Cancer Institute, Room C6830, Hershey, PA, 17033, USA

    Allan Lipton

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Lipton, A. Should bisphosphonates be utilized in the adjuvant setting for breast cancer?. Breast Cancer Res Treat 122, 627–636 (2010). https://doi.org/10.1007/s10549-010-0935-7

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