Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials
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چکیده
BACKGROUND Bisphosphonates have profound effects on bone physiology, and could modify the process of metastasis. We undertook collaborative meta-analyses to clarify the risks and benefits of adjuvant bisphosphonate treatment in breast cancer. METHODS We sought individual patient data from all unconfounded trials in early breast cancer that randomised between bisphosphonate and control. Primary outcomes were recurrence, distant recurrence, and breast cancer mortality. Primary subgroup investigations were site of first distant recurrence (bone or other), menopausal status (postmenopausal [combining natural and artificial] or not), and bisphosphonate class (aminobisphosphonate [eg, zoledronic acid, ibandronate, pamidronate] or other [ie, clodronate]). Intention-to-treat log-rank methods yielded bisphosphonate versus control first-event rate ratios (RRs). FINDINGS We received data on 18,766 women (18,206 [97%] in trials of 2-5 years of bisphosphonate) with median follow-up 5·6 woman-years, 3453 first recurrences, and 2106 subsequent deaths. Overall, the reductions in recurrence (RR 0·94, 95% CI 0·87-1·01; 2p=0·08), distant recurrence (0·92, 0·85-0·99; 2p=0·03), and breast cancer mortality (0·91, 0·83-0·99; 2p=0·04) were of only borderline significance, but the reduction in bone recurrence was more definite (0·83, 0·73-0·94; 2p=0·004). Among premenopausal women, treatment had no apparent effect on any outcome, but among 11 767 postmenopausal women it produced highly significant reductions in recurrence (RR 0·86, 95% CI 0·78-0·94; 2p=0·002), distant recurrence (0·82, 0·74-0·92; 2p=0·0003), bone recurrence (0·72, 0·60-0·86; 2p=0·0002), and breast cancer mortality (0·82, 0·73-0·93; 2p=0·002). Even for bone recurrence, however, the heterogeneity of benefit was barely significant by menopausal status (2p=0·06 for trend with menopausal status) or age (2p=0·03), and it was non-significant by bisphosphonate class, treatment schedule, oestrogen receptor status, nodes, tumour grade, or concomitant chemotherapy. No differences were seen in non-breast cancer mortality. Bone fractures were reduced (RR 0·85, 95% CI 0·75-0·97; 2p=0·02). INTERPRETATION Adjuvant bisphosphonates reduce the rate of breast cancer recurrence in the bone and improve breast cancer survival, but there is definite benefit only in women who were postmenopausal when treatment began. FUNDING Cancer Research UK, Medical Research Council.
منابع مشابه
Adjuvant bisphosphonate treatment in early breast cancer: meta- analyses of individual patient data from randomised trials
متن کامل
Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials
Methods We sought individual patient data from all unconfounded trials in early breast cancer that randomised between bisphosphonate and control. Primary outcomes were recurrence, distant recurrence, and breast cancer mortality. Primary subgroup investigations were site of fi rst distant recurrence (bone or other), menopausal status (postmenopausal [combining natural and artifi cial] or not), a...
متن کاملAdjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials
Methods We sought individual patient data from all unconfounded trials in early breast cancer that randomised between bisphosphonate and control. Primary outcomes were recurrence, distant recurrence, and breast cancer mortality. Primary subgroup investigations were site of fi rst distant recurrence (bone or other), menopausal status (postmenopausal [combining natural and artifi cial] or not), a...
متن کاملAre adjuvant bisphosphonates now standard of care of women with early stage breast cancer? A debate from the Canadian Bone and the Oncologist New Updates meeting
The 9th Bone and the Oncologist New Updates conference was held in Ottawa, Canada during 2014. This annual meeting focuses on innovative research into the mechanisms and consequences of treatment-induced and metastatic bone disease. Given the recent presentation of the Oxford overview's "Effects of bisphosphonate treatment on recurrence and cause-specific mortality in women with early breast ca...
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ورودعنوان ژورنال:
- The Lancet
دوره 386 شماره
صفحات -
تاریخ انتشار 2015