Zoledronic acid preserves bone mineral density in premenopausal women who develop ovarian failure due to adjuvant chemotherapy: Final results from CALGB trial 79809

Shapiro, Charles L.; Halabi, Susan; Hárs, Vera; Archer, Linda L.; Weckstein, Douglas; Kirshner, Jeffrey J.; Sikov, W.; Winer, Eric P.; Burstein, Harold J.; Hudis, Clifford A.; Isaacs, Claudine; Schilsky, Richard L.; Paskett, Electra D.

doi:10.1016/j.ejca.2010.11.024

Cited by 87 publications

(70 citation statements)

References 38 publications

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“…Few trials have evaluated the efficacy of bisphosphonates to attenuate chemotherapy-induced bone loss in young women [156][157][158][159][160][161][162][163][164]. The administration of oral clodronate at daily doses of 1,600 mg, oral risedronate at a dose of 30 mg/day, cyclical intravenous pamidronate at doses of 60 mg every 3 months and intravenous zoledronic acid at a dose of 4 mg every 3 months prevented chemotherapy-induced bone loss in these studies.…”

Section: Breast Cancermentioning

confidence: 99%

Cancer-associated bone disease

Rizzoli

Body²,

Brandi³

et al. 2013

Osteoporos Int

122

103

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Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancerassociated bone disease. This has led to the development of guidelines by several societies and working groups to assist physicians in clinical decision making, providing them with evidencebased care pathways to prevent skeletal-related events and bone loss. The goal of this paper is to put forth an IOF position paper addressing bone diseases and cancer and summarizing the position papers of other organizations. Epidemiology of cancer-associated bone disease Bone metastasisCancer affects nearly 12.7 million people and is associated with over 7 million deaths in 2008 [1]. Cancer is a rising global health burden and it is estimated that in 2030, cancer deaths will be tallied at over 13 million (World Health Organization (WHO) 2010 Global Status Report [2]). Addressing the morbidity and mortality of cancer is an important public health concern. On purpose, we are limiting our analysis to cancer bone involvement in adults and do not discuss cancer in children.Metastases from cancer are associated with 90 % of cancer deaths [3]. It was estimated that one half of people who die from cancer in the USA have bone involvement [4][5][6]. Different tumou...

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Section: Breast Cancermentioning

confidence: 99%

Cancer-associated bone disease

Rizzoli

Body²,

Brandi³

et al. 2013

Osteoporos Int

122

103

View full text Add to dashboard Cite

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“…Tamoxifen and other SERMs are an exception and exert a bone-protective effect in postmenopausal, but not premenopausal, women with BC [23][24][25]. Indeed, SERMS inhibit estradiol signaling, causing subsequent decrease in BMD in premenopausal women [16,18]. Ovarian ablation in premenopausal women causes immediate, artificial menopause.…”

Section: Bone Effects Of Breast Cancer Treatmentmentioning

confidence: 99%

“…Adjuvant hormonal therapies (e.g, ovarian suppression, AIs) dramatically decrease estrogen levels in pre-and postmenopausal women, resulting in increased osteoclast-mediated bone resorption and subsequent BMD decrease [16,18,23]. Tamoxifen and other SERMs are an exception and exert a bone-protective effect in postmenopausal, but not premenopausal, women with BC [23][24][25].…”

Section: Bone Effects Of Breast Cancer Treatmentmentioning

confidence: 99%

“…Bisphosphonates are a well-established treatment option for patients with bone metastases from BC, wherein they reduce the risk of skeletal-related events (SREs; i.e, pathologic fracture, spinal cord compression, radiation to bone, hypercalcemia of malignancy, and surgery to bone) [7]. Furthermore, BPs may help preserve bone in the adjuvant BC setting [14][15][16][17][18].…”

Section: Bisphosphonatesmentioning

confidence: 99%

“…Furthermore, chemotherapy can lead to ovarian failure in premenopausal women with BC. The ensuing sudden decrease in estrogen levels during chemotherapy and hormonal therapy causes rapid imbalances in bone remodeling and a sudden loss in BMD in women with BC [16,18,23].…”

Section: Bone Effects Of Breast Cancer Treatmentmentioning

confidence: 99%

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The role of antiresorptive therapies in improving patient care in early and metastatic breast cancer

Candelaria-Quintana

Dayao

Royce

2011

Breast Cancer Res Treat

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Breast cancer is the second most common cancer among American women and has a high rate of metastasis to bone. Patients regularly undergo adjuvant therapy (chemotherapy or hormonal therapy) following surgical resection of the tumor. In addition to potential direct effects on bone cells, both chemotherapy and hormonal therapy induce ovarian dysfunction and dramatically decrease estrogen levels in both pre- and postmenopausal women. This leads to decreased bone mineral density and increased fracture risk. Antiresorptive therapies (e.g, zoledronic acid and denosumab) have demonstrated efficacy in preventing cancer therapy-induced bone loss in patients with breast cancer and are approved for the prevention of skeletal-related events in patients with bone metastases from breast cancer. This review will focus on the evolving role of these antiresorptive therapies in the care of women with early or metastatic breast cancer.

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Prognosis of Patients With Early Breast Cancer Receiving 5 Years vs 2 Years of Adjuvant Bisphosphonate Treatment

et al. 2021

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IMPORTANCEBisphosphonate treatment in patients with early breast cancer has become part of care, but the optimal treatment duration is still unclear.OBJECTIVE To compare 2 vs 5 years of zoledronate treatment following adjuvant chemotherapy in patients with early breast cancer. DESIGN, SETTING, AND PARTICIPANTSThe SUCCESS A phase 3 multicenter randomized open-label clinical trial with a 2 × 2 factorial design enrolled 3754 patients from September 21, 2005, to March 12, 2007 (last patient out, May 7, 2014. Final data analysis was conducted from September 2019 to October 2020. In 250 German study centers, patients were eligible for participation in the SUCCESS A trial if they had either node-positive or high-risk node-negative (defined as at least 1 of the following: tumor size Ն pT2, histologic grade 3, negative hormone receptor status, or age Յ35 years) primary invasive breast cancer.INTERVENTIONS Patients were first randomized to adjuvant chemotherapy with 3 cycles of fluorouracil, epirubicin, and cyclophosphamide followed by 3 cycles of docetaxel with or without gemcitabine (not presented in this report). After chemotherapy, patients underwent a second randomization of 5 years of zoledronate treatment (4 mg intravenously every 3 months for 2 years, followed by 4 mg intravenously every 6 months for 3 years) vs 2 years of zoledronate treatment (4 mg intravenously every 3 months for 2 years). MAIN OUTCOMES AND MEASURESThe primary end point of the study was disease-free survival; secondary end points were overall survival, distant disease-free survival, and the incidence of skeletal-related adverse events. Survival times were measured from 2 years after the start of zoledronate treatment (landmark analysis).RESULTS Overall, data on 2987 patients were available for analysis; median age was 53 (range, 21-86) years. Disease-free survival, overall survival, and distant disease-free survival did not differ significantly between the 2 treatment arms (5 vs 2 years) as shown by adjusted multivariable Cox proportional hazards regression models (disease-free survival: hazard ratio [HR], 0.97; 95% CI, 0.75-1.25; P = .81; overall survival: HR, 0.98; 95% CI, 0.67-1.42; P = .90; distant disease-free survival: HR, 0.87; 95% CI, 0.65-1.18; P = .38). Adverse events were observed more often in the 5-year (46.2%) vs 2-year (27.2%) zoledronate treatment arm, which was particularly true for the skeletal-related events bone pain (5 years, 8.3% vs 2 years, 3.7%) and arthralgia (5 years, 5.1% vs 2 years, 3.1%). CONCLUSIONS AND RELEVANCEThe results of this phase 3 randomized clinical trial indicate that extending the zoledronate treatment beyond 2 years does not improve the prognosis of high-risk patients with early breast cancer receiving chemotherapy, suggesting that the currently recommended bisphosphonate treatment duration of 3 to 5 years could be reduced.

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Zoledronic acid preserves bone mineral density in premenopausal women who develop ovarian failure due to adjuvant chemotherapy: Final results from CALGB trial 79809

Cited by 87 publications

References 38 publications

Cancer-associated bone disease

Cancer-associated bone disease

The role of antiresorptive therapies in improving patient care in early and metastatic breast cancer

Prognosis of Patients With Early Breast Cancer Receiving 5 Years vs 2 Years of Adjuvant Bisphosphonate Treatment

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