Pathologic complete response (pCR) rates for patients with HR+/HER2- high-risk, early-stage breast cancer (EBC) by clinical and molecular features in the phase II I-SPY2 clinical trial

• Published in: Annals of oncology
• Main Authors: Huppert, L.A., Wolf, D., Yau, C., Brown-Swigart, L., Hirst, G.L., Isaacs, C., Pusztai, L., Pohlmann, P.R., DeMichele, A., Shatsky, R., Yee, D., Thomas, A., Nanda, R., Perlmutter, J., Heditsian, D., Hylton, N., Symmans, F., Veer, L.J. van ’t, Esserman, L., Rugo, H.S.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 28.10.2024
• Subjects: basal; intrinsic subtype; luminal; MammaPrint; molecular subtype; Neoadjuvant therapy; Neoadjuvant therapy; intrinsic subtype; luminal; basal; molecular subtype; MammaPrint
• ISSN: 0923-7534; 1569-8041; 1569-8041
• DOI: 10.1016/j.annonc.2024.10.018

Hormone receptor positive (HR+), HER2- early-stage breast cancer (EBC) is a heterogenous disease. Identification of better clinical and molecular biomarkers is essential to guide optimal therapy for each patient. We analyzed rates of pathologic complete response (pCR) and distant recurrence-free survival (DRFS) for patients with HR+/HER2- EBC in 8 neoadjuvant arms in the I-SPY2 trial by clinical/molecular features: age, stage, histology, percentage ER positivity, ER/PR status, MammaPrint (MP)-High1 (0 to -0.57) versus MP-High2 (<-0.57), BluePrint (BP)-Luminal-type versus BP-Basal-type, and ImPrint immune signature. We quantified the clinical/molecular heterogeneity, assessed overlap among these biomarkers, and evaluated associations with pCR and DRFS. 379 patients with HR+/HER2- EBC were included in this analysis, with an observed pCR rate of 17% across treatment arms. pCR rates were higher in patients with stage II versus III disease (21% versus 9%, p=0.0013), ductal versus lobular histology (19% versus 11%, p=0.049), lower %ER positivity (≤66% versus >66%) (35% versus 9%, p=3.4E-09), MP-High2 versus MP-High1 disease (31% versus 11%, p=1.1E-05), BP-Basal-type versus BP-Luminal-type disease (34% versus 10%, p=1.62E-07), and ImPrint positive versus negative disease (38% versus 10%, p=1.64E-09). Patients with lower %ER were more likely to have MP-High2 and BP-Basal-type disease. At a median follow-up of 4.8 years, patients who achieved pCR had excellent outcomes irrespective of clinical/molecular features. Among patients who did not achieve pCR, DRFS events were more frequent in patients with MP-High2 and BP-Basal-type disease than those with MP-High1 and BP-Luminal-type disease. Among patients with high molecular-risk HR+/HER2- EBC, the MP-High2, BP-Basal-type, and ImPrint positive signatures identified a partially overlapping subset of patients who were more likely to achieve pCR in response to neoadjuvant chemotherapy +/- targeted agents or immunotherapy compared to patients with MP-High1, BP-Luminal-type, and ImPrint negative disease. I-SPY2.2 is incorporating the use of these biomarkers to molecularly define specific patient populations and optimize treatment selection. •We characterized the clinical and molecular heterogeneity of patients with HR+/HER2- early-stage breast cancer in ISPY2•We quantified overlap in MammaPrint (MP), BluePrint (BP), and ImPrint signatures and associations with rates of pCR and DRFS•The MP-High2, BP-Basal, and ImPrint+ signatures identify a partially overlapping subset of patients with higher rate of pCR•Patients who achieved pCR had low rates of DRFS events at 4.8 years irrespective of clinical or molecular features•Among patients who did not achieve pCR, DRFS events were more frequent in patients with MP-High2 and BP-Basal disease