Drugs that block the cancer-promoting activity of oestrogen are known to reduce the risk of developing new breast cancers. A new computer modelling study in the Journal of Clinical Oncology has shown that these treatments could also reduce the risk of dying from the disease in women who are at high risk.
“Recent studies have shown that women diagnosed with oestrogen receptor (ER) positive tumours continue to experience breast cancer recurrence and death for as long as 30 years after their primary diagnosis,” says Claudine Issacs, MD, of the Georgetown Lombardi Comprehensive Cancer Center, one of the study’s two senior authors.
She says this new evidence prompted researchers to revisit the lifetime benefits and harms of risk-reducing medications developed for the primary prevention of breast cancer to see if the drugs could reduce the rate of death from the disease in the long term.
“Based on the available data, recommendations for preventing ER-positive breast cancer with tamoxifen or aromatase inhibitors presumed that women at elevated risk who took the drugs simply reduced their chances of developing the disease, but our modelling study found that, over the long run, there could also be a significant impact on mortality” Isaacs says. “Giving an oestrogen blocker to a woman in her 30s who is at high risk could potentially forestall death due to breast cancer for 20 years or more, which would be significant.”
Over the past several decades, a number of large, federally-funded randomised clinical trials have shown that risk-reducing antioestrogen medications such as tamoxifen and aromatase inhibitors could decrease the incidence of ER-positive breast cancer by 30 to 50% in women who are at high-risk of developing the disease. Despite evidence from these trials, the drugs have remained underutilised, perhaps due to the risk, albeit low, of endometrial cancer conferred by the drugs as well as other factors.
“What has been missing from our conversation until now is our ability to say to women that these drugs can not only prevent them from getting breast cancer but they can ultimately prevent them from dying of the disease,” Isaacs says.
Studies have shown that chemoprevention drugs are most effective if taken for five years and not longer. This latest study shows that the impact on mortality could confer a lasting benefit for a decade or more.
The study used computer models developed by the Cancer Intervention and Surveillance Modeling Network (CISNET), a National Cancer Institute sponsored consortium, to determine the lifetime benefits and harms of oestrogen blockers for women with a five-year risk of developing breast cancer equal to or greater than three percent. The researchers evaluated the effects of oestrogen blockers, along with annual screening with mammograms and MRI if necessary, to calculate the risk of invasive breast cancer, breast cancer death, side-effects, false positives and chances of overdiagnosis.
Tamoxifen, and the use of annual screening, reduced the risk of developing new invasive breast cancers by 40% and reduced the risk of breast cancer deaths by 57%. This translates to 95 fewer invasive breast cancers and 42 fewer breast cancer deaths per 1000 women compared to women who didn’t get screening or risk-reducing drugs. Tamoxifen was not without downsides, potentially increasing new endometrial cancers by up to 11 per 1000. Furthermore, a randomised clinical trial would be too large and take too long to generate results, Isaacs noted.
