Stromal lymphocyte infiltration after neoadjuvant chemotherapy is associated with aggressive residual disease and lower disease-free survival in HER2-positive breast cancer.
Ann Oncol
; 28(9): 2233-2240, 2017 Sep 01.
Article
en En
| MEDLINE
| ID: mdl-28911063
ABSTRACT
BACKGROUND:
The role of tumor-infiltrating lymphocytes (TILs) in breast cancer has been extensively studied over the last decade. High TILs levels have been associated with pathological response rate in the neoadjuvant setting and with better outcomes in the adjuvant setting. However, little attention has been paid to changes in TILs and residual TIL levels after neoadjuvant chemotherapy (NAC). We investigated TIL levels before, after chemotherapy, and their dynamics during treatment; and we assessed the correlation of these levels with response to NAC and prognosis. MATERIALS ANDMETHODS:
We identified 175 patients with primary HER2-positive breast cancers receiving NAC+/- trastuzumab between 2002 and 2011. Microbiopsy specimens and paired surgical samples were evaluated for stromal lymphocyte infiltration. Univariate and multivariate analyses were carried out to assess the association of clinical and pathological factors with pathological complete response (pCR) and disease-free survival.RESULTS:
Baseline TIL levels were not significantly associated with pCR. TIL levels decreased during treatment in 78% of the patients. The magnitude of the decrease was strongly associated with pCR. After chemotherapy, TIL levels were high in tumors displaying aggressive patterns (high residual cancer burden score, mitotic index >22, tumor cellularity >5%). In the population with residual disease, TIL levels >25% at the end of NAC were significantly associated with an adverse outcome (TILs >25%, HR = 7.98, P = 0.009) after multivariate analyses including BMI, post-NAC mitotic index and tumor grade.CONCLUSION:
A decrease in TIL levels during chemotherapy was positively associated with response to treatment. In tumor failing to achieve pCR, post-NAC lymphocytic infiltration was associated with higher residual tumor burden and adverse clinical outcome. Further studies are required to characterize immune infiltration in residual disease to identify candidates who could benefit from second-line therapy trials including immune checkpoint inhibitors.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Linfocitos Infiltrantes de Tumor
/
Células del Estroma
/
Genes erbB-2
/
Terapia Neoadyuvante
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Ann Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2017
Tipo del documento:
Article