Title: MammaPrint and BluePrint predict anthracycline chemosensitivity in patients with HR+HER2- early-stage breast cancer enrolled in FLEX

Publication: Miami Breast 2024, Poster 36

Authors: William Audeh, Nicole Chmielewski-Stivers, Harshini Ramaswamy, Andrea Menicucci, FLEX Investigators Group

Background

Hormone receptor-positive (HR+), HER2-negative early-stage breast cancer (EBC) often yields low (<10%) pathologic Complete Response (pCR) rates to neoadjuvant chemotherapy (NCT). NBRST and I–SPY 2 neoadjuvant trials showed that the MammaPrint (MP) risk of distant recurrence and BluePrint (BP) molecular subtyping signatures identify cohorts of HR+HER2- EBC patients with a high likelihood of achieving pCR to NCT. To identify potential patients likely to benefit from anthracycline-based NCT, we examined MP and BP utility to predict pCR rates for taxane and cyclophosphamide (TC) vs TC with anthracycline (AC-T) standard of care NCT regimens. 

Methods

Patients with HR+HER2-, MP High Risk tumors, treated with NCT, and enrolled in the ongoing prospective, observational FLEX Trial (NCT03053193) were included (N = 214). MP High Risk tumors were further classified as High 1 (H1; index 0.000 to -0.569) or High 2 (H2; index -0.570 to -1.000). BP subtypes were classified as either Luminal B–Type or Basal–Type. The associations between MP and BP, NCT regimen, and pCR outcomes were assessed.  

Results

Of all HR+HER2- tumors, 66% were H1 and 34% were H2. Age, menopausal status, race, tumor stage, and lymph node status were comparable between both groups. Most H1 tumors were Luminal B-Type, while similar proportions of H2 tumors were Basal-Type (47%) and Luminal B-Type (53%). Among H1 tumors, pCR rates to AC-T vs TC were comparable. In contrast, no H2 tumors achieved pCR to TC, whereas AC-T was significantly more effective for H2 compared to H1 (p < 0.001) tumors. Among H2 tumors, Basal-Type achieved the highest pCR rates with AC-T.  

Table: pCR rates among MP and BP subtypes in HR+HER2- FLEX patients with NCT 

*H1 Basal-Type excluded from analysis due to small sample size 

Conclusions

These data indicate that patients with MP H2 tumors, including Luminal B and Basal subtypes, are more likely to achieve a pCR in response to anthracycline–based NCT. In contrast, including anthracycline does not appear to improve pCR rates for patients with MP H1, Luminal B–Type tumors. These data are novel in demonstrating utility of MP and BP for optimizing specific NCT regimens for HR+HER2- EBC.