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Neoadjuvant chemotherapy in ER+ HER2- breast cancer: response prediction based on immunohistochemical and molecular characteristics.
Breast Cancer Res Treat. 2012 Feb; 131(3):827-36.BC

Abstract

A pathological complete remission (pCR) is rarely achieved by neoadjuvant chemotherapy in estrogen receptor-positive (ER+) HER2-negative (HER2-) tumors. Therefore, its use might be questionable in specific groups of this tumor type. To select which patients benefit and which could be spared neoadjuvant chemotherapy, we tested standard pathology and molecular markers in ER+ HER2- breast tumors. Pretreatment biopsies were available from 211 ER+ HER2- tumors, who had been treated with neoadjuvant chemotherapy (adriamycin/cyclophosphamide). mRNA expression data were available for 132 tumors. We determined progesterone receptor expression (PR), endocrine sensitivity, HER2 expression, histology, proliferation, and molecular subtypes. We correlated these data to chemotherapy response using pCR rates and the previously published neoadjuvant response index (NRI). PR-negative tumors (n = 65, 30.8%) and luminal B type tumors (n = 43, 20.4%) responded significantly better to chemotherapy than other tumors. These associations remained significant in multivariate analysis. However, even in the subgroup of patients with the lowest response rate, comprising tumors that had both a positive-PR expression and the luminal A subtype (n = 58, 44%), the majority of the patients had downstaging because of chemotherapy. For histology (lobular vs. ductal), endocrine sensitivity, and proliferation, no associations with chemotherapy response were observed. Gene expression array analysis resulted in 28 significant genes (FDR < 0.1). PR expression and luminal B status are associated with a better response to neoadjuvant chemotherapy. However, both markers had only weak response predictive power, and it was not possible to identify a subgroup with no or only minimal chemotherapy benefit. Therefore, the decision to refrain from neoadjuvant chemotherapy to ER+ HER2- breast tumors should not be based on predictive markers, but exclusively on estimates of prognosis.

Authors+Show Affiliations

Departments of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21472434

Citation

Lips, E H., et al. "Neoadjuvant Chemotherapy in ER+ HER2- Breast Cancer: Response Prediction Based On Immunohistochemical and Molecular Characteristics." Breast Cancer Research and Treatment, vol. 131, no. 3, 2012, pp. 827-36.
Lips EH, Mulder L, de Ronde JJ, et al. Neoadjuvant chemotherapy in ER+ HER2- breast cancer: response prediction based on immunohistochemical and molecular characteristics. Breast Cancer Res Treat. 2012;131(3):827-36.
Lips, E. H., Mulder, L., de Ronde, J. J., Mandjes, I. A., Vincent, A., Vrancken Peeters, M. T., Nederlof, P. M., Wesseling, J., & Rodenhuis, S. (2012). Neoadjuvant chemotherapy in ER+ HER2- breast cancer: response prediction based on immunohistochemical and molecular characteristics. Breast Cancer Research and Treatment, 131(3), 827-36. https://doi.org/10.1007/s10549-011-1488-0
Lips EH, et al. Neoadjuvant Chemotherapy in ER+ HER2- Breast Cancer: Response Prediction Based On Immunohistochemical and Molecular Characteristics. Breast Cancer Res Treat. 2012;131(3):827-36. PubMed PMID: 21472434.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neoadjuvant chemotherapy in ER+ HER2- breast cancer: response prediction based on immunohistochemical and molecular characteristics. AU - Lips,E H, AU - Mulder,L, AU - de Ronde,J J, AU - Mandjes,I A M, AU - Vincent,A, AU - Vrancken Peeters,M T F D, AU - Nederlof,P M, AU - Wesseling,J, AU - Rodenhuis,S, Y1 - 2011/04/07/ PY - 2010/12/03/received PY - 2011/03/25/accepted PY - 2011/4/8/entrez PY - 2011/4/8/pubmed PY - 2012/5/16/medline SP - 827 EP - 36 JF - Breast cancer research and treatment JO - Breast Cancer Res Treat VL - 131 IS - 3 N2 - A pathological complete remission (pCR) is rarely achieved by neoadjuvant chemotherapy in estrogen receptor-positive (ER+) HER2-negative (HER2-) tumors. Therefore, its use might be questionable in specific groups of this tumor type. To select which patients benefit and which could be spared neoadjuvant chemotherapy, we tested standard pathology and molecular markers in ER+ HER2- breast tumors. Pretreatment biopsies were available from 211 ER+ HER2- tumors, who had been treated with neoadjuvant chemotherapy (adriamycin/cyclophosphamide). mRNA expression data were available for 132 tumors. We determined progesterone receptor expression (PR), endocrine sensitivity, HER2 expression, histology, proliferation, and molecular subtypes. We correlated these data to chemotherapy response using pCR rates and the previously published neoadjuvant response index (NRI). PR-negative tumors (n = 65, 30.8%) and luminal B type tumors (n = 43, 20.4%) responded significantly better to chemotherapy than other tumors. These associations remained significant in multivariate analysis. However, even in the subgroup of patients with the lowest response rate, comprising tumors that had both a positive-PR expression and the luminal A subtype (n = 58, 44%), the majority of the patients had downstaging because of chemotherapy. For histology (lobular vs. ductal), endocrine sensitivity, and proliferation, no associations with chemotherapy response were observed. Gene expression array analysis resulted in 28 significant genes (FDR < 0.1). PR expression and luminal B status are associated with a better response to neoadjuvant chemotherapy. However, both markers had only weak response predictive power, and it was not possible to identify a subgroup with no or only minimal chemotherapy benefit. Therefore, the decision to refrain from neoadjuvant chemotherapy to ER+ HER2- breast tumors should not be based on predictive markers, but exclusively on estimates of prognosis. SN - 1573-7217 UR - https://www.unboundmedicine.com/medline/citation/21472434/Neoadjuvant_chemotherapy_in_ER+_HER2__breast_cancer:_response_prediction_based_on_immunohistochemical_and_molecular_characteristics_ L2 - https://doi.org/10.1007/s10549-011-1488-0 DB - PRIME DP - Unbound Medicine ER -