Prior to surgery, breast cancer patients are often treated with neoadjuvant chemotherapy to reduce their tumors. A new study suggests that patients with localized, estrogen receptor (ER)-positive breast cancer should be given neoadjuvant endocrine therapy instead, as it provides similar benefits but considerably fewer side effects.
The study, “Neoadjuvant Endocrine Therapy for Estrogen Receptor–Positive Breast Cancer: A Systematic Review and Meta-analysis,” published in The JAMA Network, was conducted by researchers at the Massachusetts General Hospital (MGH) Cancer Center.
“Estrogen-receptor-positive tumors are generally highly receptive to endocrine therapy with drugs such as tamoxifen and aromatase inhibitors. But while endocrine therapy is the most important component of adjuvant or postsurgical therapy, use of neoadjuvant endocrine therapy has been low in the U.S.” and chemotherapy more common, Aditya Bardia, MD, MPH, of the MGH Cancer Center, an assistant professor of Medicine at Harvard Medical School and the study’s senior author, said in a press release.
Although endocrine therapy is approved as neoadjuvant therapy for ER-positive breast cancer, studies assessing its efficacy are generally small, offering limited statistical power.
To address whether neoadjuvant endocrine therapy was an effective treatment option for these patients, researchers conducted a meta-analysis of 20 randomized clinical trials, evaluating data on 3,490 women. They not only compared the results of neoadjuvant endocrine therapy and chemotherapy, but also assessed whether some endocrine therapies were better than others.
Findings showed that neoadjuvant therapy with either endocrine therapies or chemotherapy was associated with similar response rates and breast conservation surgery rates. However, endocrine therapy induced far fewer side effects.
Importantly, the researchers found that treatment with aromatase inhibitors, which inhibit estrogen production, was associated with a significantly higher response rate and breast conservation surgery rate, compared to treatment with tamoxifen, which blocks estrogen signaling by binding to the receptor.
“Endocrine therapy is an approved option for neoadjuvant treatment of localized estrogen-receptor-positive breast cancer, so there’s no reason our findings cannot be applied to treatment right now,” said Laura Spring, MD, the lead author and a senior oncology fellow at the MGH Cancer Center. “With the spurt in development of new targeted therapies, particularly CDK4/6 inhibitors, more research is needed to look at combining endocrine therapy with those drugs for neoadjuvant treatment.”
CDK4/6 inhibitors, like Ibrance (palbociclib), abemaciclib, or ribociclib, act upon the cell proliferation mechanisms and have been showing promise in combination with endocrine therapies. A clinical trial (NCT02712723) assessing the efficacy of combining endocrine therapies with ribociclib is currently underway in ER-positive, HER2-negative early breast cancer patients in the U.S. The study is recruiting patients, and more information is available on its clinical trials.gov webpage.