Messaggi chiave
- Gli autori del presente studio hanno analizzato le associazioni esistenti tra i tassi di risposta patologica completa (pCR)/sopravvivenza libera da recidiva a distanza (DRFS) e una serie di caratteristiche cliniche/molecolari in 379 pazienti con carcinoma mammario precoce HR+/HER2- arruolate in otto bracci di trattamento neoadiuvante nel contesto dello studio I-SPY2.
- Considerando tutti i bracci di trattamento, il tasso di pCR osservato è stato del 17%. I tassi sono stati significativamente più alti nelle pazienti con malattia in stadio II rispetto a III (21 vs 9%, p = 0,0013), istologia duttale rispetto a lobulare (19 vs 11%, p = 0,049), positività ER ≤66 rispetto a >66% (35 vs 9%, p = 3,4E-09), classe di rischio MP-High2 rispetto a MP-High1 (31 vs 11%, p = 1,1E-05), sottotipo BluePrint basale (BP-Basal) rispetto a luminale (34 vs 10%, p = 1,62E-07) e firma immunitaria ImPrint-positiva rispetto a negativa (38 vs 10%, p = 1,64E-09). A un follow-up mediano di 4,8 anni, il raggiungimento della pCR è stato associato a esiti eccellenti, a prescindere dal profilo clinico-molecolare. In assenza di pCR, gli eventi di DRFS sono stati più frequenti nelle pazienti con malattia MP-High2 e di tipo basale rispetto alle pazienti MP-High1 e con tumore luminale.
- In questa analisi, le firme MP-High2, BP-Basal e ImPrint+ hanno identificato un sottogruppo parzialmente sovrapposto di pazienti con maggiori probabilità di raggiungere la pCR in risposta a un trattamento neoadiuvante con chemioterapia ± agenti mirati o immunoterapia ed emergono quindi come biomarcatori potenzialmente utili ai fini della selezione e personalizzazione del trattamento.
Abstract
Background
- 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.
Patients and methods
- 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.
Results
- 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.
Conclusions
- 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.