For years the holy grail of breast cancer research has been prevention. The first hint that there could be a meaningful strategy was discovered years ago when women who had undergone oophorectomy (removal of the ovaries) at an early age had a lower incidence of breast cancer later in life.
More recently the drug raloxifene, studied to see whether it could prevent fractures, was found to reduce the incidence of breast cancer by 45%. Then tamoxifen, a drug used to treat breast cancer for over thirty years, was found to reduce the incidence of new breast cancer by 38% on average in several different studies.
The increased risk of uterine cancer and blood clots with tamoxifen impacted upon its widespread acceptance as a prevention measure.
In 2004 a study was started to see whether the next generation of breast cancer hormonal drugs, aromatase inhibitors (AI’s) could prevent breast cancer. These drugs are more effective in preventing breast cancer metastasis in post-menopausal women so there was hope they could be more effective in prevention.
Now we have the results. At the recent annual meeting of the American Society of Clinical Oncology, and in the New England Journal of Medicine, the results from this trial, involving over 4000 patients, were revealed. As shown in the accompanying graph the incidence of ductal carcinoma (the top curves) and lobular cancer (the bottom curves) were dramatically reduced. Overall there was a 65% reduction in the incidence of breast cancer in the women enrolled in this trial, all of whom had at least a slightly increased risk of breast cancer over the general population.
There was concern at the beginning of the trial that there would be an increased incidence of fractures in the treatment group because exemestane is known to cause a reduction in bone mineral density in people so treated. All patients in this trial were treated with bisphosphonates (e.g., Fosamax) and there was no excess fracture rate.
Unanswered by this trial is the optimal duration of therapy with aromatase inhibitors and whether the other two commercially available AI’s, which have a slightly different profile of side effects, would be equally effective at prevention. Follow-up in this study was short, and no substantial time has elapsed after the end of the trial to see whether the effects of five years of exemestane would result in long-lasting or only temporary protection.
Nonetheless, this study could be a game changer and physicians will be under some pressure by women to be treated. This class of drug is expensive (brand name aromatase inhibitors cost $250-300.month; some patents expire soon) and there are no long-term follow up studies that might uncover unexpected side effects.