A simple system for grading the response of breast cancer to neoadjuvant chemotherapy

Rodenhuis, S.; Mandjes, Ingrid A.M.; Wesseling, Jelle; Vijver, Marc J. van de; Peeters, M; Sonke, Gabe S.; Linn, Sabine C.

doi:10.1093/annonc/mdp348

Cited by 47 publications

(53 citation statements)

References 18 publications

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“…As pCRs (situations in which after chemotherapy, no invasive tumor cells remain in the breast and axilla) are rare in ER? HER2-tumors, we have also employed a novel and simple measure of downstaging of the tumor by chemotherapy, the ''Neoadjuvant Response Index'' (NRI) [17]. We show that the presence of PR expression and the ''luminal A'' classification are the best predictors of nonresponse and retain significance in multivariate analysis.…”

Section: Introductionmentioning

confidence: 99%

“…In prognostically more favorable cases, clinicians are often hard-pressed to make educated guesses about the chemosensitivity of the tumor. Many opinion leaders in the field state that they will not use neoadjuvant chemotherapy in lobular breast cancer, will recommend no chemotherapy in N 0 tumors that are ''highly endocrine sensitive'' [14,15], or believe that luminal A tumors should receive endocrine adjuvant therapy only [10,16,17]. Should these parameters be unreliable, however, withholding chemotherapy could lead to an increase in preventable breast cancer deaths.…”

Section: Introductionmentioning

confidence: 99%

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Neoadjuvant chemotherapy in ER+ HER2− breast cancer: response prediction based on immunohistochemical and molecular characteristics

Lips

Mulder

Ronde

et al. 2011

Breast Cancer Res Treat

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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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neoadjuvant chemotherapy in ER+ HER2− breast cancer: response prediction based on immunohistochemical and molecular characteristics

Lips

Mulder

Ronde

et al. 2011

Breast Cancer Res Treat

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“…The relative weight assigned to the breast response and the axilla response has little effect on the NRI, as a sensitivity analysis confirmed. This definition of NRI also ensures that widely accepted response measure cpCR is incorporated in a natural way as '1' [8] NRI uses information that can more or less be obtained from records of patients undergoing standard management for LABC. The only non standard parameter is MRI for tumor size and if this is not available, an individualized NRI could be adopted that should yield comparable outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…Calculation of NRI will always yield a score between 0 and 1. A score of 0 represents no response (or even progression in exceptional cases), while a score of 1 indicates a pCR of both primary tumor and axilla [8]. This prospective study was contemplated to evaluate and validate NRI and its correlation with other biomarkers estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), Her-2/neu receptor status and also RECIST in patients with LABC.…”

Section: Introductionmentioning

confidence: 99%

“…The NRI is calculated from a breast response and an axillary response score as described by S. Rodenhuis et al [8] The initial staging in clinical stages cT4, cT3, cT2 and cT1 is based on contrast-enhanced MRI. Following surgery, the diameter of the residual tumor as indicated by the pathology report is considered to determine the T-stage (pT).…”

Section: Introductionmentioning

confidence: 99%

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Evaluation and Validation of Neo-Adjuvant Response Index (NRI) and It’s Correlation with Various Predictive Biomarkers and RECIST in Locally Advanced Breast Cancer

Bamal

Chintamani

Tandon

et al. 2014

Indian J Surg Oncol

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Background Response evaluation following neo-adjuvant chemotherapy in breast cancer is usually done without taking in to account the axillary response and the available tools like 'response evaluation criteria in solid tumors' (RECIST) have this limitation. These criteria rely solely on the response observed in the primary tumour. Neoadjuvant response index is one such attempt to have a comprehensive assessment of response both in the primary tumour and the axilla.

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Clinical and Molecular Methods in Drug Development: Neoadjuvant Systemic Therapy in Breast Cancer as a Model

Braga

2016

Methods in Molecular Biology

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Neoadjuvant chemotherapy (NACT), neoadjuvant endocrine therapy (NAET), and neoadjuvant targeted therapy (NATT), more recently, have been adopted worldwide as standard of care in locally advanced and inoperable BC. These modalities, collectively called neoadjuvant systemic therapy (NAST), are also used for organ preservation and for mechanistic biological studies on drug response and resistance, drug development, and clinical trials. Furthermore, the response to NACT is a valuable indicator of long-term survival. In this work, the advantages and pitfalls of using NAST in BC for studying drug response and resistance for drug development and clinical trials are discussed as well as practical points on how to set up a NAST clinical trial in BC.

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A simple system for grading the response of breast cancer to neoadjuvant chemotherapy

Cited by 47 publications

References 18 publications

Neoadjuvant chemotherapy in ER+ HER2− breast cancer: response prediction based on immunohistochemical and molecular characteristics

Neoadjuvant chemotherapy in ER+ HER2− breast cancer: response prediction based on immunohistochemical and molecular characteristics

Evaluation and Validation of Neo-Adjuvant Response Index (NRI) and It’s Correlation with Various Predictive Biomarkers and RECIST in Locally Advanced Breast Cancer

Clinical and Molecular Methods in Drug Development: Neoadjuvant Systemic Therapy in Breast Cancer as a Model

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