Exposure to alendronate is associated with a lower risk of bone metastases in osteoporotic women with early breast cancer

Rouach, Vanessa; Goldshtein, Inbal; Wolf, Ido; Catane, Raphael; Chodick, Gabriel; Iton, Amit; Stern, Naftali; Cohen, Dani

doi:10.1016/j.jbo.2018.07.011

Cited by 21 publications

(20 citation statements)

References 32 publications

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“…(16) However, similar effects are seen in non-neoplastic cells, so this probably represents a nonspecific toxicity from high doses of these drugs. (24) The UK General Practice Database showed reduced risk of all cancers, and of breast and colorectal cancers specifically, in bisphosphonate users, (25) and a nationwide Danish database suggested protection against colon cancer with alendronate use. (17,18) Third, observational studies have reported that oral bisphosphonate use is associated with fewer first breast cancers (19)(20)(21) ; reduced risk of contralateral breast cancer (OR = 0.4) (22) ; reduced risk of a combined endpoint of recurrence, second primary breast cancer, and breast cancer mortality (23) ; and reduced risk of skeletal metastases in early breast cancer.…”

Section: Discussionmentioning

confidence: 99%

“…(17,18) Third, observational studies have reported that oral bisphosphonate use is associated with fewer first breast cancers (19)(20)(21) ; reduced risk of contralateral breast cancer (OR = 0.4) (22) ; reduced risk of a combined endpoint of recurrence, second primary breast cancer, and breast cancer mortality (23) ; and reduced risk of skeletal metastases in early breast cancer. (24) The UK General Practice Database showed reduced risk of all cancers, and of breast and colorectal cancers specifically, in bisphosphonate users, (25) and a nationwide Danish database suggested protection against colon cancer with alendronate use. (26) A meta-analysis of observational studies of colon cancer also found a protective effect.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Zoledronate on Cancer, Cardiac Events, and Mortality in Osteopenic Older Women

Reid

Horne

Mihov

et al. 2019

Journal of Bone and Mineral Research

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We recently showed that zoledronate prevented fractures in older women with osteopenia (hip T-scores between −1.0 and −2.5). In addition to fewer fractures, this study also suggested that women randomized to zoledronate had fewer vascular events, a lower incidence of cancer, and a trend to lower mortality. The present analysis provides a more detailed presentation of the adverse event data from that study, a 6-year, double-blind trial of 2000 women aged >65 years recruited using electoral rolls. They were randomly assigned to receive four infusions of either zoledronate 5 mg or normal saline at 18-month intervals. Supplements of vitamin D, but not calcium, were provided. There were 1017 serious adverse events in 443 participants in the placebo group, and 820 events in 400 participants in those randomized to zoledronate (relative risk = 0.90; 95% CI, 0.81 to 1.00). These events included fractures resulting in hospital admission. Myocardial infarction occurred in 39 women (43 events) in the placebo group and in 24 women (25 events) in the zoledronate group (hazard ratio 0.60 [95% CI, 0.36 to 1.00]; rate ratio 0.58 [95% CI, 0.35 to 0.94]). For a prespecified composite cardiovascular endpoint (sudden death, myocardial infarction, coronary artery revascularization, or stroke) 69 women had 98 events in the placebo group, and 53 women had 71 events in the zoledronate group (hazard ratio 0.76 [95% CI, 0.53 to 1.08]; rate ratio 0.72 [95% CI, 0.53 to 0.98]). Total cancers were significantly reduced with zoledronate (hazard ratio 0.67 [95% CI, 0.51 to 0.89]; rate ratio 0.68 [95% CI, 0.52 to 0.89]), and this was significant for both breast cancers and for non-breast cancers. Eleven women had recurrent or second breast cancers during the study, all in the placebo group. The hazard ratio for death was 0.65 (95% CI, 0.40 to 1.06; p = 0.08), and 0.51 (95% CI, 0.30 to 0.87) in those without incident fragility fracture. These apparent beneficial effects justify further appropriately powered trials of zoledronate with these nonskeletal conditions as primary endpoints.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of Zoledronate on Cancer, Cardiac Events, and Mortality in Osteopenic Older Women

Reid

Horne

Mihov

et al. 2019

Journal of Bone and Mineral Research

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“…In the clinical setting, the effect of these inhibitors of bone resorption are promising. For example, in patients with early breast cancer adjuvant therapy with bisphosphonates was shown to increase survival benefit and reduce bone metastatic burden [111][112][113]. Similarly, treatment with denosumab was found to increase bone metastasis-free survival in prostate cancer patients [114,115].…”

Section: Accepted Articlementioning

confidence: 99%

Targeting dormant tumor cells to prevent cancer recurrence

2020

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Over the years, developments in oncology led to significantly improved clinical outcome for cancer patients. However, cancer recurrence after initial treatment response still poses a major challenge, as it often involves more aggressive, metastatic disease. The presence of dormant cancer cells is associated with recurrence, metastasis, and poor clinical outcome, suggesting that these cells may play a crucial role in the process of disease relapse. Cancer cell dormancy typically presents as growth arrest while retaining proliferative capacity and can be induced or reversed by a wide array of cell-intrinsic and cell-extrinsic factors. Conventional therapies preferentially target fast-dividing cells, leaving dormant cancer cells largely insensitive to these treatments. In this review, we discuss the role of dormant cancer cells in cancer recurrence and highlight how novel therapy strategies based on cell-cycle modulation, modifications of existing drugs, or enhanced drugdelivery vehicles may be used to specifically target this subpopulation of tumor cells, and thereby have the potential to prevent disease recurrence.

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“…The EBCTCG meta-analysis on adjuvant use of bisphosphonates concluded there was insufficient evidence for the use of alendronate and risedronate in the adjuvant setting of breast cancer [7]. Nevertheless, non-prospective trials suggest this relationship also exists for these oral bisphosphonates [22,23]. Hopefully, future prospective trials will clarify this matter.…”

Section: Discussionmentioning

confidence: 99%

Breast cancer outcome in relation to bone mineral density and bisphosphonate use: a sub-study of the DATA trial

Hellemond

Smorenburg

Peer³

et al. 2020

Breast Cancer Res Treat

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Purpose The phase III DATA study compared 6 and 3 years of adjuvant anastrozole following 2-3 years of tamoxifen in postmenopausal breast cancer patients. This pre-planned side-study assessed the relationship between a reduced bone mineral density (BMD) and distant recurrence-free survival (DRFS), and evaluated the effect of bisphosphonates on DRFS. Methods We selected all patients with a BMD measurement within 3 years after randomisation (landmark) without any DRFS events. Kaplan-Meier methods and Cox proportional hazards models were used for analyses. Results Of 1860 eligible patients, 1142 had a DEXA scan before the landmark. The BMD was normal in 436 (38.2%) and showed osteopenia in 565 (49.5%) and osteoporosis in 141 (12.3%) patients. After a median follow-up of 5.0 years from the landmark, neither osteopenia nor osteoporosis (compared with normal BMD) were associated with DRFS in both the 6-year [osteopenia HR 0.82 (95% CI 0.45-1.49), osteoporosis HR 1.10 (95% CI 0.26-4.67)] and the 3-year arm [osteopenia HR 0.75 (95% CI 0.40-1.42), osteoporosis HR 1.86 (95% CI 0.43-8.01)]. Moreover, bisphosphonate use did not impact DRFS.Conclusion No association was observed between a reduced BMD and DRFS. Neither did we observe an impact of bisphosphonates on DRFS.Keywords Breast cancer · Tamoxifen · Aromatase inhibitor · Bone health · Osteoporosis · Bisphosphonates · Survival · Bone metastases · Distant recurrence-free survival Part of these results were presented at the poster session of the 2018 San Antonio Breast Cancer Symposium, abstract number 810.

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Exposure to alendronate is associated with a lower risk of bone metastases in osteoporotic women with early breast cancer

Cited by 21 publications

References 32 publications

Effects of Zoledronate on Cancer, Cardiac Events, and Mortality in Osteopenic Older Women

Effects of Zoledronate on Cancer, Cardiac Events, and Mortality in Osteopenic Older Women

Targeting dormant tumor cells to prevent cancer recurrence

Breast cancer outcome in relation to bone mineral density and bisphosphonate use: a sub-study of the DATA trial

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