Title: Prediction of chemotherapy benefit by MammaPrint in patients with HR+HER2- early-stage breast cancer from real-world evidence studies

Publication: Miami Breast 2024, Poster 29

Authors: William Audeh, Harshini Ramaswamy, Andrea Menicucci, FLEX Investigators’ Group

Background

A need exists to identify biomarkers that predict chemotherapy (CT) benefit among patients with HR+HER2- early-stage breast cancer. The 70-gene signature, MammaPrint (MP), determines distant recurrence (DR) risk in early-stage breast cancer. MP has demonstrated utility in predicting adjuvant and neoadjuvant chemotherapy response. Here, we examined MP utility in predicting pathological Complete Response (pCR) to neoadjuvant CT and 5-year follow-up comparisons among patients who received adjuvant CT or endocrine therapy (ET) alone.

Methods

Of 901 pts with HR+HER2- EBC included, 426 enrolled in NBRST received NCT. The remaining 475 pts were enrolled in the prospective FLEX study with 5-yr follow–up: 181 received CT (+/-ET) and 294 received ET only. Logistic regression was used to estimate likelihood of pCR and 5-yr DR risk (including breast cancer specific death) for CT vs ET, as a continuous function of the MP index, defined as UltraLow (UL: +1.000 to +0.356), Low Risk (LR: +0.355 to +0.001), High 1 (H1: 0.000 to -0.569), and High 2 (H2: -0.570 to -1.000).

Results

NCT treated pts were significantly more likely to achieve pCR as MP risk increased, with up to 30% pCR observed in H2 tumors (p < 0.001). The MP index demonstrated effective performance for predicting 5-yr DR risk in the ET group, with an Area under the ROC Curve (AUC) of 0.73 (p=0.005), and the CT group, with an AUC of 0.77 (p=0.008). ET only treated pts had greater 5-yr DR risk with increasing MP risk compared to those with CT. Comparing ET vs CT groups, <1.5% and <1.0% difference in 5-yr DR risk was observed for MP indices in the LR and UL range, respectively. In contrast, CT benefit increased with increasing MP risk, with 2-7% absolute risk difference observed in H1, and 8-16% difference among H2 tumors. 

Table: Range (%) of pCR to NCT and 5-yr DR risk in CT and ET groups 

Conclusions

These data show that MP indices within LR and UL ranges exhibit low chemosensitivity and do not derive significant CT benefit, consistent with results in MINDACT. Conversely, the increasing CT benefit observed with increasing MP risk is consistent with the 50% relative reduction in recurrence risk reported by Knauer et al. Overall these findings indicate the utility of MammaPrint to predict neoadjuvant and adjuvant CT benefit in pts with HR+HER2– EBC.