How do you interpret the EBCTCG meta-analysis analyzing the magnitude of benefit of anthracyclines in early stage ER+ breast cancer?

The appreciation of studies testing the specific benefit of adding or substituting anthracyclines as adjuvant therapy for early stage breast cancer requires a historical overview (so my apologies for a very long response….). Several of the earlier trials comparing non-anthracycline therapies (primarily CMF) to anthracycline therapies and meta-analyses of these trials have consistently shown about a 10% relative reduction in the hazards of mortality (translating into about a 5% absolute benefit over 10 years). However, these trials were mostly conducted/completed prior to routine testing for HER2. (1) Subsequently, HER2 positivity has been shown to be associated with a higher anthracycline benefit in numerous trials, and HER2-negative cases ...

For HR+ breast cancer, the benefit of anthracyclines in patients with less than 4 positive lymph nodes is very small and I tend to avoid it in that scenario. In triple negative breast cancer patients, there is a benefit to anthracyclines compared to TC but it remains to be seen whether that benefit can also be obtained from carboplatin/taxotere per the positive results of NeoPACT Trial. A randomized study comparing this regimen vs. KEYNOTE 522 regimen is ongoing at this time.

I agree with Dr. @Dr. First Last that the benefit of using anthracyclines in ER+ N0 or N1 disease is not making a significant difference. The EBCTCG manuscript states that the relative risk reduction of these chemotherapy treatments is roughly 30% of whatever absolute risk is left over after appropriate endocrine therapy. In many of the older studies, this was tamoxifen instead of aromatase inhibitors. So, as the endocrine alone or endocrine + CDK4/6i therapies improve outcomes, there will likely be a less remaining risk to shave off with chemotherapy. Also, the supplemental data (Table S2B) from RxPONDER looking at anthracycline/taxane treated vs. TC treated patients showed an HR of .89 (95% CI .6-1.32) in postmenopausal and .93 (95% CI .5...