Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials

Bergh, Jonas; Pritchard, Kathleen I.; Albain, Kathy S.; Anderson, Stewart J.; Arriagada, R.; Barlow, William E.; Bergsten-Nordström, W.; Bliss, Judith; Boccardo, Francesco; Bradley, Rosie; Buyse, Marc; Cameron, David; Clarke, Michael; Coates, Michael R.; Coleman, Robert E.; Correa, Candace R.; Costantino, Joseph P.; Cuzick, Jack; Davidson, N.; Davies, Claire; Leo, Angelo Di; Dowsett, Mitch; Ewertz, Marianne; Forbes, JF; Gelber, R.D.; Geyer, Russell; Gianni, Luca; Gnant, Michael; Goldhirsch, Aron; Gray, Richard; Hayes, Daniel; Hill, Catherine; Ingle, James N.; Janni, W; MacKinnon, Elizabeth; Martín, Miguel; McGale, Paul; Norton, Larry; Ohashi, Yasuo; Paik, Soon Young; Pan, H; Pérez, E. González; Pető, Richárd; Piccart, R.; Pierce, Lori J.; Raina, Vinod; Ravdin, Peter M.; Robertson, J. F. R.; Rutgers, Emiel J.; Sparano, Joseph A.; Swain, Sandra M.; Taylor, Carolyn; Viale, Giuseppe; Minckwitz, Gϋnter von; Wang, X; Whelan, Timothy J.; Wilcken, Nicholas; Winer, Eric P.; Wolmark, Norman; Wood, William C.

doi:10.1016/s0140-6736(15)60908-4

Cited by 601 publications

(213 citation statements)

References 29 publications

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“…However, these therapeutic approaches which decrease skeletal-related events and in post-menopausal breast cancer patients increase overall survival [79] are still directly targeting tumor osteolysis and not tumor cells. The targeting of osteolytic factors (e.g., PTHrP) and bone resorption has provided much needed advances in patient care, but alternative approaches that translate in vivo tumor biology findings to breast cancer patients with bone metastatic disease are needed.…”

Section: Hallmarks Of Breast Cancer Bone Metastasismentioning

confidence: 99%

Hallmarks of Bone Metastasis

Johnson

Suva

2017

Calcif Tissue Int

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Breast cancer bone metastasis develops as the result of a series of complex interactions between tumor cells, bone marrow cells, and resident bone cells. The net effect of these interactions are the disruption of normal bone homeostasis, often with significantly increased osteoclast and osteoblast activity, which has provided a rational target for controlling tumor progression, with little or no emphasis on tumor eradication. Indeed, the clinical course of metastatic breast cancer is relatively long, with patients likely to experience sequential skeletal-related events (SREs), often over lengthy periods of time, even up to decades. These SREs include bone pain, fractures, and spinal cord compression, all of which may profoundly impair a patient’s quality-of-life. Our understanding of the contributions of the host bone and bone marrow cells to the control of tumor progression has grown over the years, yet the focus of virtually all available treatments remains on the control of resident bone cells, primarily osteoclasts. In this perspective, our focus is to move away from the current emphasis on the control of bone cells and focus our attention on the hallmarks of bone metastatic tumor cells and how these differ from primary tumor cells and normal host cells. In our opinion, there remains a largely unmet medical need to develop and utilize therapies that impede metastatic tumor cells while sparing normal host bone and bone marrow cells. This perspective examines the impact of metastatic tumor cells on the bone microenvironment and proposes potential new directions for uncovering the important mechanisms driving metastatic progression in bone based on the hallmarks of bone metastasis.

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Section: Hallmarks Of Breast Cancer Bone Metastasismentioning

confidence: 99%

Hallmarks of Bone Metastasis

Johnson

Suva

2017

Calcif Tissue Int

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“…Such cancers are commonly breast, prostate, and lung cancers and, to a lesser degree, renal, thyroid, and gastrointestinal cancers 2. A National Institute for Health and Care Excellence (NICE) guideline now recommends bisphosphonates as adjuvant treatment for breast cancer in postmenopausal women 1213. This is likely to have a substantial impact on the UK population at risk of medication-related osteonecrosis of the jaw.…”

Section: What Medications Can Have This Adverse Effect?mentioning

confidence: 99%

Preventing medication-related osteonecrosis of the jaw

Zebic

Patel

2019

BMJ

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“…A second meta-analysis performed a decade later deconvoluted this result by demonstrating that bisphosphonate treatment is only effective in preventing skeletal-related events in patients who were post-menopausal when treatment began (Coleman et al 2015). This was experimentally validated by a study demonstrating that Zoledronate slowed osteolysis only in ovariectomized mice compared to sham when injected with a triple negative breast cancer line, thereby mimicking the post-menopausal state and showing that Zoledronate is only effective in low estrogen individuals (Ottewell et al 2014a).…”

Section: From Colonization To the Vicious Cycle Of Metastatic Expansimentioning

confidence: 99%

The Biology of Bone Metastasis

Esposito

Guise

Kang

2017

Cold Spring Harb Perspect Med

137

110

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Summary Bone metastasis, or the development of secondary tumors within the bone of cancer patients, is a debilitating and incurable disease. Despite its morbidity, the biology of bone metastasis represents one of the most complex and intriguing of all oncogenic processes. This complexity derives from the intricately organized bone microenvironment in which the various stages of hematopoiesis, osteogenesis, and osteolysis are jointly regulated but spatially restricted. Disseminated tumor cells (DTCs) from various common malignancies such as breast, prostate, lung, and kidney cancers or myeloma are uniquely primed to subvert these endogenous bone stromal elements to grow into pathological osteolytic or osteoblastic lesions. This colonization process can be separated into three key steps: seeding, dormancy, and outgrowth. Targeting the processes of dormancy and initial outgrowth offers the most therapeutic promise. Here we discuss the concepts of the bone metastasis niche from controlling tumor cell survival to growth into clinically detectable disease.

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Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials

Abstract: Cancer Research UK, Medical Research Council.

Cited by 601 publications

References 29 publications

Hallmarks of Bone Metastasis

Hallmarks of Bone Metastasis

Preventing medication-related osteonecrosis of the jaw

The Biology of Bone Metastasis

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