Single-Agent Bisphosphonate, AI Offer Postmenopausal Breast Cancer Benefits

Bisphosphonate therapy and aromatase inhibitors individually combat postmenopausal breast cancer recurrence and mortality

medwireNews: The results of two separate meta-analyses published in The Lancet demonstrate that treatment with either a bisphosphonate or an aromatase inhibitor (AI) therapy significantly reduces the risk of recurrent breast cancer for postmenopausal women.

“About two-thirds of all women with breast cancer are postmenopausal with hormone-sensitive tumours, so could potentially benefit from both drugs”, commented Richard Gray, from the University of Oxford in the UK and lead statistician on both of the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) studies, in a press release.

“The drugs are complementary, because the main side effect of aromatase inhibitors is an increase in bone loss and fractures, while bisphosphonates reduce bone loss and fractures as well as improving survival.”

The meta-analysis on the risk of recurrence and breast cancer-specific mortality with use of 2 to 5 years of bisphosphonate therapy included data for 18,766 women with early breast cancer who were followed-up for a median of 5.6 years.

Bisphosphonate use in women who were postmenopausal when they started treatment was associated with “highly significant” reductions in the risk of recurrence (relative risk [RR]=0.86), distance recurrence (RR=0.82), bone recurrence (RR=0.72) and breast cancer-specific mortality (RR=0.82), as well as bone fracture (RR=0.85).

The reduced risk of bone recurrence was also found in women aged over 55 years, whereas those aged less than 45 years derived no significant reduction with bisphosphonate therapy.

“The use of bisphosphonates in breast cancer is mainly to reduce bone loss and risk of fracture in postmenopausal women with [oestrogen receptor]-positive disease treated with aromatase inhibitors”, the EBCTCG authors say.

“Our results show that such bisphosphonate treatment can, in addition, provide oncological benefit, and suggest that adjuvant bisphosphonates should be considered in a broader range of postmenopausal women.”

The meta-analysis on AI used data for 31,920 women with oestrogen receptor-positive early breast cancer who participated in one of nine trials comparing 5 years of endocrine treatment with an AI, tamoxifen or sequential 2 to 3 years of tamoxifen followed by an AI.

The risk of recurrence with an AI versus tamoxifen was significantly reduced for years 0 to 1 and 2 to 4, with RRs of 0.64 and 0.80, respectively, although not for later time points. And 10-year breast cancer-specific mortality was significantly lower with an AI than tamoxifen, with rates of 12.1% versus 14.2% and a RR of 0.85.

The RR for recurrence with an AI versus sequential treatment was a significant 0.74 for year 0 to 1 but not thereafter, and there was no significance difference in breast cancer-specific mortality between these regimens.

The recurrence results also favoured patients given 2 to 3 years of tamoxifen followed by an AI versus those given 5 years of tamoxifen, with a significant reduction for years 2 to 4 (RR=0.56) and a lower breast cancer-specific mortality, at 8.7% versus 10.1%.

When the results were aggregated, the risk of recurrence significantly differed only for the periods where the treatments differed (RR=0.70). However, the risk of breast cancer-specific mortality was lower with AI treatment during periods where treatments differed (RR=0.79), later periods (RR=0.89) and over the whole 5-year period (RR=0.86).

Writing in an accompanying comment, Erica Mayer and Harold Burstein, from Dana-Farber Cancer Institute in Boston, Massachusetts, USA, observe that patient experience is missing from the AI meta-analysis, citing anecdotal evidence that individual patients may have differing tolerances to AI and tamoxifen therapy.

Noting that the recommended endocrine therapy duration is likely to extend in the future, they emphasise: “Ultimately, the best choice for adjuvant endocrine therapy is a treatment the patient is willing to take.”


Early Breast Cancer Trialists’ Collaborative Group. Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet 2015; Advance online publication 24 July. DOI: S0140-6736(15)61074-1

Early Breast Cancer Trialists’ Collaborative Group. Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet 2015; Advance online publication 24 July. DOI:

Mayer EL, Burstein HJ. Postmenopausal breast cancer: a best endocrine strategy? Lancet 2015; Advance online publication 24 July. DOI:

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