Aromatase inhibitors and bisphosphonates can improve survival in postmenopausal early-stage breast cancer, and combining the two drug classes can help negate their individual adverse effects, according to two studies published online in The Lancet.
The research offers “the best evidence yet for the effects of aromatase inhibitors and bisphosphonates on postmenopausal women with early breast cancer,” according to a news release by The Lancet that accompanied the reports.
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Breast cancer typically occurs after menopause and is usually detected early enough to be operable, but can metastasize years later in bone or other sites if dormant malignant cells become activated, noted researchers from the Early Breast Cancer Trialists’ Collaborative Group, which conducted both meta-analyses.
For the aromatase inhibitor (AI) study, researchers analyzed data from almost 32,000 postmenopausal women with estrogen receptor–positive (ER-positive) early breast cancer who had participated in nine randomized, multiyear trials comparing AIs with standard tamoxifen-based endocrine therapy. Compared with tamoxifen, AI therapy cut the chances of breast cancer recurrence by about 30% during years 0-1 and 2-4 (P less than .001), they reported. “However, in the 2014 ASCO guidelines on endocrine treatment of postmenopausal women with ER-positive early breast cancer, three of the four recommended options start with tamoxifen; a review seems appropriate,” the investigators noted (Lancet 2015 July 24 [doi:10.1016/S0140-6736(15)61074-1]). Treatment with AIs also appeared to cut 10-year breast cancer mortality by about 15% compared with tamoxifen, and to lower the risk of dying of breast cancer by about 40% compared with no endocrine therapy, the researchers reported. “The impact of AIs is particularly remarkable given how specific these drugs are – removing only the tiny amount of estrogen that remains in the circulation of women after the menopause – and given the extraordinary molecular differences between ER-positive tumors,” Dr. Mitch Dowsett, the lead author, said in a statement.
“But AI treatment is not free of side effects, and it’s important to ensure that women with significant side effects are supported to try to continue to take treatment and fully benefit from it,” added Dr. Dowsett of The Royal Marsden and The Institute of Cancer Research, both in London.
Because AIs can increase fracture risk, clinicians need to monitor treated patients’ bone health and should consider using bisphosphonates when indicated, Dr. Dowsett and his associates added. The study also linked AIs to a slightly lower rate of endometrial cancer compared with tamoxifen therapy, helping offset the increased fracture risk, they said.
For the second study, investigators analyzed data from more than 18,700 women who had participated in 26 randomized controlled trials of bisphosphonates that assessed breast cancer recurrence, distant metastasis, and mortality. Bisphosphonate treatment did not seem to affect outcomes in premenopausal women, they found. But in postmenopausal patients, treatment led to “highly significant reductions” in local recurrence (risk ratio, 0.86, 95% confidence interval, 0.78 to 0.94; P = .002), distant recurrence (P = .0003), bone recurrence (P = .0002) and breast cancer mortality (P = .002), they reported (Lancet 2015 July 24 [doi:10.1016/S0140-6736(15)60908-4]).
Use of bisphosphonates also was tied to a small drop in fracture rates, which was probably real based on studies of other groups of patients, they noted. While bisphosphonates have been used primarily to help prevent bone loss and fractures in postmenopausal women with ER-positive disease who are receiving AIs, the findings show an additional oncological benefit “and suggest that adjuvant bisphosphonates should be considered in a broader range of postmenopausal women,” the researchers concluded. They were unable to assess rates of osteonecrosis of the jaw, but past reports point to rates of about 1% of patients on clodronate, ibandronate, or 6-monthly zoledronic acid therapy, and about 2% of those receiving more intensive zoledronic acid treatment, they noted.
Cancer Research UK and the UK Medical Research Council funded both studies. Ten authors from the AI study and eight authors from the bisphosphonate study reported financial relationships with a number of pharmaceutical companies.