Two new studies suggest that two different classes of drugs, aromatase inhibitors (AIs) and bisphosphonates, can each improve survival prospects for postmenopausal women with early breast cancer. Moreover, the researchers suggest that the two types of drugs can be used together, increasing the benefits while also decreasing some side effects.
The studies were both published in The Lancet (2015; doi:10.1016/S0140-6736(15)61074-1 and doi:10.1016/S0140-6736(15)60908-4).
Most women are postmenopausal when breast cancer develops. Surgery can remove all detectable disease when breast cancer is found early, dangerous undetected micrometastases (small secondary tumors) may be left behind. Approximately 80% of breast cancers are hormone sensitive (ER-positive), which means that they can be stimulated by the body’s own hormones, such as estrogen. Endocrine treatments, which act to stop hormone stimulation of cancer cells, can help protect against breast cancer recurrence.
The Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) is a worldwide collaboration set up 30 years ago by researchers at the University of Oxford, United Kingdom, to collate the evidence from all randomized trials on the treatment of early breast cancer every few years. The two reports provide the best evidence yet for the effects of AIs and bisphosphonates on postmenopausal women with early breast cancer.
The first study brings together evidence from 30,000 postmenopausal women in nine randomized trials, showing that 5 years of treatment with the newer endocrine therapy (ie, an AI) produces somewhat better survival than 5 years of standard endocrine therapy (tamoxifen).
Compared with tamoxifen, taking AIs for 5 years further reduced the likelihood of the cancer recurring by almost one-third (30%), and the risk of dying from breast cancer by approximately 15% throughout the decade after beginning treatment. The researchers estimate that, compared with no endocrine treatment, the risk of dying from breast cancer for women who took AIs would be reduced by approximately 40% in the decade after beginning treatment.
The second study brings together evidence from another 20,000 women in 26 randomized trials, showing that 2 to 5 years of treatment with bisphosphonates, which are usually used to treat osteoporosis, reduces the risk of breast cancer recurrence in postmenopausal women, and also significantly extends survival. However, bisphosphonate treatment appears to have little effect in premenopausal women.
The most common site for breast cancer metastasis is bone. Tumor cells released from the primary breast cancer can remain dormant in the bone for years before spreading to other parts of the body. Bisphosphonates alter the bone microenvironment, which could make it less favorable for cancer cells and so reduce the risk of cancer recurrence in the bone and in other organs. Taken separately, previous clinical trials of bisphosphonates in early breast cancer have shown mixed results, but taking all their results together, a clearer picture emerges.
The meta-analysis included individual patient data on 18,766 women in 26 randomized trials, comparing 2 to 5 years of bisphosphonates versus no bisphosphonate. In the overall study population, the only clear benefit of bisphosphonates was a 17% reduction in recurrence of cancer in the bone. However, among postmenopausal women, bisphosphonate treatment produced a larger reduction in bone recurrence of 28% and also reduced the risk of dying from breast cancer by 18% during the first decade after diagnosis.