Adjuvant oral clodronate improves the overall survival of primary breast cancer patients with micrometastases to the bone marrow—a long-term follow-up

Diel, Ingo J.; Jäschke, Anja; Solomayer, Erich; Gollan, Christina; Bastert, G.; Sohn, Christof; Schuetz, Florian

doi:10.1093/annonc/mdn429

Cited by 213 publications

(143 citation statements)

References 18 publications

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“…Bone metastasis-free survival and nonskeletal-free survival were most favorable for clodronate in the Diel et al study, less favorable in the Powles et al study, and unfavorable in the Saarto et al study. Similarly, for patients on clodronate, overall survival was considerably improved for the Diel et al study (HR0.50, P = 0.049), 124 was improved in the Powles et al study (HR 0.74, P = 0.041), 125 and was worse in the Saarto et al study (HR 1.33, P = 0.13). 123 The discrepancy in these trials may be explained by variability in sample size, study populations, and study methodology.…”

Section: Clinical Evidence In Adjuvant Breast Cancer Trialsmentioning

confidence: 84%

Optimal management of bone metastases in breast cancer patients

Wong

Pavlakis

2011

BCTT

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Bone metastasis in breast cancer is a significant clinical problem. It not only indicates incurable disease with a guarded prognosis, but is also associated with skeletal-related morbidities including bone pain, pathological fractures, spinal cord compression, and hypercalcemia. In recent years, the mechanism of bone metastasis has been further elucidated. Bone metastasis involves a vicious cycle of close interaction between the tumor and the bone microenvironment. In patients with bone metastases, the goal of management is to prevent further skeletal-related events, manage complications, reduce bone pain, and improve quality of life. Bisphosphonates are a proven therapy for the above indications. Recently, a drug of a different class, the RANK ligand antibody, denosumab, has been shown to reduce skeletal-related events more than the bisphosphonate, zoledronic acid. Other strategies of clinical value may include surgery, radiotherapy, radiopharmaceuticals, and, of course, effective systemic therapy. In early breast cancer, bisphosphonates may have an antitumor effect and prevent both bone and non-bone metastases. Whilst two important Phase III trials with conflicting results have led to controversy in this topic, final results from these and other key Phase III trials must still be awaited before a firm conclusion can be drawn about the use of bisphosphonates in this setting. Advances in bone markers, predictive biomarkers, multi-imaging modalities, and the introduction of novel agents have ushered in a new era of proactive management for bone metastases in breast cancer.

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Section: Clinical Evidence In Adjuvant Breast Cancer Trialsmentioning

confidence: 84%

Optimal management of bone metastases in breast cancer patients

Wong

Pavlakis

2011

BCTT

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“…The studies have reported mixed results, with 445 NCCN Guidelines Insights CE variable effects on DFS and OS. [54][55][56][57] However, in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-34 trial, although DFS was similar in older and younger women, improvements in skeletal metastasis-free interval (P=.027) and nonskeletal metastasis-free interval (P=.014) were noted with adjuvant clodronate in women >50 years of age. 57 Patients aged >60 years appeared to derive the most benefit from adjuvant clodronate, including an almost 60% reduction in skeletal metastases and a 40% to 50% reduction in nonskeletal metastases.…”

Section: Bisphosphonatesmentioning

confidence: 99%

NCCN Guidelines Insights: Breast Cancer, Version 1.2017

Gradishar¹,

Anderson

Balassanian

et al. 2017

J Natl Compr Canc Netw

396

346

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These NCCN Guidelines Insights highlight the important updates/changes to the surgical axillary staging, radiation therapy, and systemic therapy recommendations for hormone receptor-positive disease in the 1.2017 version of the NCCN Guidelines for Breast Cancer. This report summarizes these updates and discusses the rationale behind them. Updates on new drug approvals, not available at press time, can be found in the most recent version of these guidelines at NCCN.org.

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“…55,56 Several studies confirmed their efficacy in prophylaxis of bone metastasis and their positive impact on survival in selected subgroups of patients. 57 In vitro bisphosphonates were shown to influence the microenvironment by altered secretion of growth factors and cytokines; inhibit tumor cell adhesion, invasion, and proliferation; and induce apoptosis. 58 Furthermore, these drugs may act indirectly on cancer cells through microenvironmental changes using immunomodulatory and antiangiogenic effects.…”

Section: Targeting the Microenvironmentmentioning

confidence: 99%

Dormancy in breast cancer

Banys

Hartkopf

Krawczyk

et al. 2012

BCTT

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Tumor dormancy describes a prolonged quiescent state in which tumor cells are present, but disease progression is not yet clinically apparent. Breast cancer is especially known for long asymptomatic periods, up to 25 years, with no evidence of the disease, followed by a relapse. Factors that determine the cell's decision to enter a dormant state and that control its duration remain unclear. In recent years, considerable progress has been made in understanding how tumor cells circulating in the blood interact and extravasate into secondary sites and which factors might determine whether these cells survive, remain dormant, or become macrometastases. The mechanisms of tumor cell dormancy are still not clear. Two different hypotheses are currently discussed: tumor cells persist either by completely withdrawing from the cell cycle or by continuing to proliferate at a slow rate that is counterbalanced by cell death. Because dormant disseminated tumor cells may be the founders of metastasis, one hypothesis is that dormant tumor cells, or at least a fraction of them, share stem cell-like characteristics that may be responsible for their long half-lives and their suggested resistance to standard chemotherapy. Therefore, knowledge of the biology of tumor cell dormancy may be the basis from which to develop innovative targeted therapies to control or eliminate this tumor cell fraction. In this review, we discuss biological mechanisms and clinical implications of tumor dormancy in breast cancer patients.

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Adjuvant oral clodronate improves the overall survival of primary breast cancer patients with micrometastases to the bone marrow—a long-term follow-up

Abstract: These long-term survival data extend the survival advantage reported in previous studies with oral clodronate in breast cancer.

Cited by 213 publications

References 18 publications

Optimal management of bone metastases in breast cancer patients

Optimal management of bone metastases in breast cancer patients

NCCN Guidelines Insights: Breast Cancer, Version 1.2017

Dormancy in breast cancer

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