A systematic review and meta-analysis examining the effects of neoadjuvant endocrine therapy (NET) on surgical outcomes in early breast cancer was recently published in BJS Open. The study, conducted by researchers from the University of Southampton and other UK institutions, aimed to evaluate whether NET is associated with reduced extent of surgery compared to upfront surgery in patients with estrogen receptor (ER)-positive early breast cancer.
The meta-analysis included 20 studies (12 cohort studies and 8 randomized controlled trials) published between 1946 and March 2024, with a total of 6,382 patients. The primary outcome was the comparison of mastectomy rates between NET and upfront surgery groups. Secondary outcomes included the optimal duration of NET and comparison of aromatase inhibitors (AIs) versus selective estrogen receptor modulators and downregulators (SERM/Ds).
To be included, studies had to investigate mastectomy rates in postmenopausal women with ER-positive early breast cancer treated with NET versus upfront surgery. The researchers excluded studies that included patients with ER-negative breast cancer, metastatic breast cancer, preclinical studies, window of opportunity studies, and studies where primary endocrine therapy was given as the only treatment without intent for surgery. Studies with a sample size of less than 30 patients were also excluded.
The meta-analysis revealed that NET was associated with a 47% reduction in mastectomy rate compared to the baseline surgical decision (risk ratio 0.53, 95% CI 0.44-0.64). This effect was consistent across both randomized controlled trials and cohort studies. Subgroup analysis showed no significant difference in mastectomy rates based on the duration of NET (more than 4 months versus 4 months or less).
Additionally, the use of AIs was associated with a 21% higher breast-conserving surgery rate compared to SERM/Ds (risk ratio 1.21, 95% CI 1.09-1.34). This finding aligns with previous meta-analyses showing superior outcomes with AIs in the neoadjuvant setting.
The study had several limitations, including significant heterogeneity between the included studies. This heterogeneity likely stemmed from differences in patient characteristics, tumor features, and variations in NET type and duration. The definition of ER-positivity was not uniform across studies, and not all studies included HER2 status, which are known factors affecting response to NET.
Another limitation was the lack of standardization in how surgical decisions were made and by whom. Most studies did not explicitly describe the decision-making process for surgery type, potentially introducing bias. Furthermore, using the baseline surgical decision as a comparator may have underestimated the number of mastectomies that would have been required, as some patients might have been converted from breast-conserving surgery to mastectomy due to positive margins on final histology.
Despite these limitations, the authors concluded that NET is associated with a reduction in mastectomy rates in patients with ER-positive early breast cancer. They emphasized that the findings support current guidelines from the National Institute for Health and Care Excellence (NICE) and the American Society of Clinical Oncology (ASCO), which recommend considering NET to downstage ER-positive, HER2-negative tumors and increase local treatment options in postmenopausal women when there is no definite indication for chemotherapy.
The potential clinical impact of this study is significant. It provides further evidence supporting the use of NET as a strategy to increase breast conservation rates in suitable patients. This is particularly important given that mastectomy has been associated with impaired quality of life compared to breast-conserving surgery. The study also highlights the superior performance of AIs over SERM/Ds in the neoadjuvant setting, which may guide clinicians in their choice of endocrine therapy.
However, the authors note that further research is needed to address the limitations of current evidence. They call for well-designed randomized controlled trials that specifically evaluate the role of NET in improving surgical outcomes, with type of surgery as a primary outcome. Such trials could provide more robust evidence to guide clinical decision-making and potentially increase the adoption of NET in suitable patients.
The study also raises questions about the optimal duration of NET, as no significant difference was found between treatments lasting more or less than 4 months. This finding suggests that shorter durations of NET might be sufficient to achieve surgical downstaging, potentially reducing treatment time and improving patient convenience.
In conclusion, this meta-analysis provides valuable insights into the potential benefits of NET in reducing mastectomy rates for patients with ER-positive early breast cancer. While the results are promising, they should be interpreted with caution due to the heterogeneity and methodological limitations of the included studies. As the field of breast cancer treatment continues to evolve, further research in this area could help refine treatment strategies and improve outcomes for patients with ER-positive early breast cancer.
References
Brett B, Savva C, Mirshekar-Syahkal B, et al. Surgical outcomes of neoadjuvant endocrine treatment in early breast cancer: meta-analysis. BJS Open. 2024;8(5):zrae100. doi:10.1093/bjsopen/zrae100
