Two classes of generic drugs, aromatase inhibitors and bisphosphonates, can reduce deaths in postmenopausal women with early breast cancer suggest the results of meta-analyses conducted by Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) and published in The Lancet. The studies analyzed the results of several previously conducted randomized clinical trials and found that aromatase inhibitors, a newer class of drugs for breast cancer with fewer side effects and bisphosphonates which are used to treat ostoporosis can both reduce the risk of cancer recurrence and improve survival rates in postmenopausal women.
Dr. Claudine Isaacs, Professor of Medicine and Oncology, Lombardi Comprehensive Cancer Center, Georgetown University (webpage):
Expertise: genetic testing, medical management, and prevention strategies for women at high risk for breast cancer; clinical trials in early stage and metastatic breast cancer. Dr Isaacs is the co-director of the breast cancer program at Georgetown Lombardi.
“This study is a meta-analysis of a number of large randomized clinical trials that examined the role of bisphosphonates as adjuvant therapy for breast cancer. They include a heterogeneous group of patients, but a number of them suggested on unplanned analysis that the benefit was only seen in postmenopausal women. So what this study did was to perform a meta-analysis of these trials, and examine the benefits in different subsets – including, importantly, looking at the difference in pre- and postmenopausal women.
“In this analysis there were over 11,000 postmenopausal women and what the study demonstrated is that the use of bisphosphonates, which are general quite well-tolerated medications, for somewhere from 2 to 5 years was associated with a very significant reduction in risk of bone recurrence and, even more impressively, overall survival. The absolute benefit was a little over than 3% for overall survival.
“Again, this benefit was only seen in postmenopausal women and not in premenopausal women. There are some preclinical data that suggest a rationale for this.
“My sense is that this is very important and clinically relevant. These medications are widely available. They are used and approved for the treatment of osteoporosis in postmenopausal women so we know the safety profile and overall, these drugs are well-tolerated. There are some rare side effects seen with them that are concerning. There is about a 1% incidence, particularly in the intravenous version, of osteonecrosis of the jaw, which is a very painful side effect.
“I think bisphosphonates are something that we need to be integrating into the treatment of our postmenopausal patients with breast cancer.”
Dr. Parvin Peddi, Assistant Clinical Professor of Medicine, Division of Hematology/Oncology; Member, Jonsson Comprehensive Cancer Center, University of California, Los Angeles (webpage):
Expertise: Dr Peddi leads the medical oncology aspect of the multidisciplinary team at the Revlon Breast Center and is involved in clinical and translational breast cancer research
“These are large, well conducted meta analysis trials. In the aromatase therapy meta-analysis, aromatase inhibitors were found to be superior to tamoxifen in the post menopausal women, confirming earlier studies. Aromatase inhibitors are already the drug of choice in treatment of postmenopausal patients with breast cancer so I don’t see changes on this front.
“In the study of use of bisphosphonates in patients with breast cancer, as the authors state, benefit was seen in postmenopausal women and in that population, was seen restricted to reducing risk of cancer recurrence in the bone that probably translated to increase in survival. The reduction in spread of cancer to bone is consistent with studies in the metastatic setting where bisphosphonates are known to help in treatment of cancer that has already spread to the bone. What is unclear is why the benefit is not seen in premenopausal patients in the this study as these medications are beneficial in both pre and post menopausal women in the metastatic setting.
“Currently, bisphosphonates are used in postmenopausal patients treated for localized breast cancer, only for bone health if they are also found to have pre-existing osteopenia or osteoporosis. This large meta-analysis however, shows their benefit for reducing cancer recurrence as well. Combined with their general safety, more postmenopausal patients will be offered these medications if they do not have contraindications, for not only bone health as it is currently being practiced but also for benefit in reducing the risk of cancer recurrence in the bone. Various bisphosphonates on varying schedules were administered in the trials analyzed so the optimal regimen is not established at this point. More research is also needed on why no benefit was seen in premenopausal women with localized breast cancer.”
Declared interests (see GENeS register of interests policy):
Dr Claudine Isaacs: Dr. Isaacs receives research support from Novartis.
No further interests declared