Pathological non-response to chemotherapy in a neoadjuvant setting of breast cancer: an inter-institutional study

Abstract

To identify markers of non-response to neoadjuvant chemotherapy (NAC) that could be used in the adjuvant setting. Sixteen pathologists of the European Working Group for Breast Screening Pathology reviewed the core biopsies of breast cancers treated with NAC and recorded the clinico-pathological findings (histological type and grade; estrogen, progesterone receptors, and HER2 status; Ki67; mitotic count; tumor-infiltrating lymphocytes; necrosis) and data regarding the pathological response in corresponding surgical resection specimens. Analyses were carried out in a cohort of 490 cases by comparing the groups of patients showing pathological complete response (pCR) and partial response (pPR) with the group of non-responders (pathological non-response: pNR). Among other parameters, the lobular histotype and the absence of inflammation were significantly more common in pNR (p < 0.001). By ROC curve analyses, cut-off values of 9 mitosis/2 mm2 and 18 % of Ki67-positive cells best discriminated the pNR and pCR + pPR categories (p = 0.018 and < 0.001, respectively). By multivariable analysis, only the cut-off value of 9 mitosis discriminated the different response categories (p = 0.036) in the entire cohort. In the Luminal B/HER2− subgroup, a mitotic count <9, although not statistically significant, showed an OR of 2.7 of pNR. A lobular histotype and the absence of inflammation were independent predictors of pNR (p = 0.024 and <0.001, respectively). Classical morphological parameters, such as lobular histotype and inflammation, confirmed their predictive value in response to NAC, particularly in the Luminal B/HER2− subgroup, which is a challenging breast cancer subtype from a therapeutic point of view. Mitotic count could represent an additional marker but has a poor positive predictive value.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-014-3192-3) contains supplementary material, which is available to authorized users.

Neoadjuvant endocrine therapy with exemestane followed by response‐guided combination therapy with low‐dose cyclophosphamide in postmenopausal patients with estrogen receptor‐positive breast cancer: A multicenter, open‐label, phase II study

“…[16][17][18][19] In several studies, changes in Ki67 index were used to evaluate the effects of neoadjuvant chemotherapy on prognosis in breast cancer patients. [20][21][22] However, few equivalent studies have been carried out for neoadjuvant endocrine therapy. 6,23,24 A Ki67-based scoring system has recently been developed to monitor the response to neoadjuvant endocrine therapy.…”

Evaluación de la clasificación molecular por inmunohistoquímica en cáncer de mama avanzado tratado con epirubicina docetaxel: diferencias clínicas, patológicas, terapéuticas y pronósticas

“…Es el tumor más frecuente registrado en diversos estudios (39 a 67%) 6,[8][9][10][11][21][22][23][24] . Los tumores con fenotipo RH+ y HER2-de moderado grado histológico (G2) o grado 1 (42 a 89%) 6,10,21 son más probables que sean LA.…”

“…Los tumores con fenotipo RH+ y HER2-de moderado grado histológico (G2) o grado 1 (42 a 89%) 6,10,21 son más probables que sean LA. Presentan características clínicas favorables, es el subtipo que incluye mayor porcentaje de CLI (15 a 23%) 22 . Al momento del diagnóstico son relativamente tumores pequeños (< 2 cm) o en estadio I-II (44 a 47%) 6,11,21 .…”

“…Es frecuente la alta expresión de enfermedad RH+ (RE alfa y/o RPg), sobre todo el CLI muestra positividad a los RE (60 a 90%), genes relacionados con la activación de los RE (p. ej., LIV1, ciclina D1) 3,25 , expresan altos niveles de BCL-2 y GATA3 26 y bajos índices de Ki-67 (7 a 33.9%) 5,10,11,22,24 . Expresan bajo índice mitótico (69%) 6 y menor frecuencia de Tabla 3.…”

“…La mayoría de los casos cursan con buen pronóstico al mostrar mayor supervivencia y baja tasa de recurrencias 2,3,[9][10][11] . La tasa de RPc varía de 3 a 8.9%, indicaría que la RPc no sería un marcador de supervivencia para este subtipo 8,11,22,25,27,28 .…”