Premenopausal women with ER+ breast cancer have new options for endocrine (hormone) therapy. Studies show that aromatase inhibitors are more effective than tamoxifen in preventing cancer from coming back if ovarian function is suppressed. This research was presented in two sessions on December 8 at the San Antonio Breast Cancer Symposium (SABCS).
Tamoxifen and aromatase inhibitors are two different kinds of endocrine therapy. They are typically given to women with ER+ breast cancer after treatment has ended to prevent recurrence.
Tamoxifen has long been the mainstay in women with ER+ breast cancer. A 2011 study in Lancet found that it reduced 15-year breast cancer mortality by one-third.
Aromatase inhibitors (AIs) are even more effective than tamoxifen in postmenopausal women, as reported in a 2015 study in Lancet. Premenopausal women typically do not benefit from AIs.
Dana-Farber Cancer Institute’s SOFT trial found that tamoxifen plus OFS works better than tamoxifen alone in preventing recurrence. SOFT, and a second trial (TEXT), compared tamoxifen with OFS to AIs with OFS in premenopausal women with early-stage, ER+ breast cancer. The findings from these two studies were recently combined with findings from two other major trials in a major meta-analysis.
Two presentations at SABCS addressed this work. The first reported on a meta-analysis of four randomized trials. The second updated findings from SOFT and TEXT, two of the four trials. The results were consistent.
The meta-analysis included 7,030 women in the ABCSG 12, TEXT, SOFT, and HOBOE trials. These trials started between 1999 and 2004. The median followup across trials was eight years. Some participants were treated with chemotherapy prior to or concurrently with the trial.
The trial randomized participant data into two groups – those who received AI and OFS and those who received tamoxifen and OFS. The study looked at recurrence and death.
They found that recurrence was more common in the tamoxifen group than the AI group. AI reduced the overall risk of recurrence by 21 percent and the risk of distant recurrence by 17 percent. Most of the benefit was seen in years two to four. There were no increases in deaths.
Subgroup analysis did not show differences by age, BMI, tumor size, tumor grade, or experience with chemotherapy. There was, however, a difference among node groups. Women with four or more nodes (N4+ disease) did not benefit from AI. In the subgroups with no nodes (N0) or fewer nodes (N1-3), AI worked well, improving over time even more than expected.
In terms of side effects, women who received AI experienced more bone fractures than those who took tamoxifen (5 percent compared to 3.8 percent).
The second presentation was an update on the TEXT and SOFT trials. The SOFT trial established the value of OFS plus tamoxifen. Both trials supported the meta-analysis finding that AI plus OFS did better at preventing recurrence than tamoxifen plus OFS. These women have already been followed for 12 to 13 years. Researchers continue to follow them to learn more about the impact of these medicines over time.
What it means for young women with early-stage disease
Premenopausal women with early-stage ER+ breast cancer with OFS now have an even better option for preventing recurrence. AI proved significantly more effective at keeping cancer from coming back than tamoxifen, which is highly effective as well. Tamoxifen continues to be recommended for premenopausal women with very low-risk, early-stage ER+ disease.
These studies did not show any differences in mortality. Researchers will continue to follow participants.
The side effects of the medicines are similar, but AI is more likely to cause bone fractures. The impact of this on quality of life needs to be factored into treatment decisions. Women choosing AI may want to take steps to improve or protect bone density.
AI was not effective for women with four or more cancerous nodes. This finding was unexpected. Based on prior research, the research team anticipated a strong response among women with high-risk disease. They do not have an explanation for this.