Breast Cancer Subtypes and Response to Docetaxel in Node-Positive Breast Cancer: Use of an Immunohistochemical Definition in the BCIRG 001 Trial

Hugh, Judith; Hanson, John; Cheang, Maggie C.U.; Nielsen, Torsten O.; Perou, Charles M.; Dumontet, Charles; Reed, John C.; Krajewska, Maryla; Treilleux, Isabelle; Rupin, Matthieu; Magherini, E.; Mackey, John R.; Martín, Miguel; Vogel, Charles L.

doi:10.1200/jco.2008.18.1024

Cited by 476 publications

(349 citation statements)

References 46 publications

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“…In the BCIRG 001 adjuvant study, an improved 3-year DFS with TAC versus FAC treatment schemes was shown in the luminal B group (p=0.025), with a marginal trend in the triple negatives (p=0.051) and HER2 (p=0.068) subtypes. No DFS advantage was seen in the luminal A population [22]. Similarly, the GEICAM 9906 trial comparing FEC to FEC followed by weekly paclitaxel, found that the paclitaxel benefit was mainly concentrated in the triple negative/basal-like patient population [65].…”

Section: Discussionmentioning

confidence: 98%

“…Tumors were classified into molecular intrinsic subtypes based either on IHC/FISH parameters or using gene expression profiles [20][21][22] .The first method was based on an immunopanel of 4 biomarkers previously described by Hugh et al [22] The second approach was based on the "gold-standard" of gene expression profiles as assayed by DNA microarrays. The background subtracted Lowess normalized log2 ratio of Cy3 and Cy5 intensity values were retrieved and used for all subsequent analyses.…”

Section: Ihc and Fish Techniquesmentioning

confidence: 99%

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Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer

Martín

Romero

Cheang

et al. 2011

Breast Cancer Res Treat

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Section: Discussionmentioning

confidence: 98%

Section: Ihc and Fish Techniquesmentioning

confidence: 99%

Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer

Martín

Romero

Cheang

et al. 2011

Breast Cancer Res Treat

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“…Previous studies have also shown an association with ER expression 23 and some reports indicated AR expression in ER-negative tumors. 24,26 In the last few years our understanding of breast carcinoma has significantly improved with discovery of breast cancer molecular classes using the 14,29 We designed this study to analyze AR expression in breast carcinoma with respect to IHC-defined molecular classes and also its relationship to other clinical-pathological factors.…”

Section: Discussionmentioning

confidence: 99%

Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation

et al. 2010

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Androgens exert growth inhibitory effects on estrogen receptor and progesterone receptor-negative breast cancer cell lines that show androgen receptor expression. These laboratory findings may be translated into inexpensive alternative therapies for hormone receptor-negative invasive breast cancers. Our aim was to systematically evaluate androgen receptor expression by immunohistochemistry in invasive breast cancers. Androgen receptor (clone AR441, Dako) expression was analyzed on 189 well-characterized consecutive invasive breast carcinomas represented with threefold redundancy on tissue microarrays. Androgen receptor expression was semi-quantitated using a histochemical score-like method and a score 410 was considered positive. Of the 189 consecutive invasive breast cancers, 151 (80%) were positive and 38 (20%) were negative for androgen receptor. The majority (95%) of estrogen receptor-positive tumors were also androgen receptor positive. Of the estrogen receptor-negative tumors, androgen receptor reactivity was seen in 3 of 30 (10%) triple-negative cases and in 5/8 (63%) estrogen receptor-negative/progesterone receptor-negative/HER2 þ cases. Six of eight estrogen receptor-negative/androgen receptor-positive cases showed apocrine differentiation. Androgen receptor expression in estrogen receptor-positive cases was associated with smaller tumor size (P ¼ 0.0001), lower Nottingham grade (P ¼ 0.002) and less frequent tumor cell necrosis (P ¼ 0.0001). Androgen receptor expression in estrogen receptor-negative tumors was associated with lower Nottingham grade (P ¼ 0.005) and apocrine differentiation (P ¼ 0.039). In conclusion, most estrogen receptor-positive breast tumors also express androgen receptor. Androgen receptor expression in estrogen receptor-negative/ progesterone receptor-negative/HER2 þ tumors (which commonly show apocrine differentiation) and a subset of triple -negative apocrine tumors suggest that these tumors together comprises the 'molecular apocrine' group described previously. However, these findings should be further confirmed on larger series of triplenegative and estrogen negative/progesterone negative/HER2 þ tumors. Androgen receptor-targeted therapy in estrogen/progesterone receptor-negative tumors may provide an inexpensive alternative to usual high-dose chemotherapy with or without trastuzumab. Keywords: androgen receptor; breast carcinoma; apocrine differentiation Breast cancer represents a diverse group of tumors that vary in clinical behavior and response to therapy. Currently, invasive breast cancer is treated by multi-modality therapy. Approximately 75% of breast cancers are positive for estrogen (ER) and/or progesterone (PR) receptor protein expression. This group of tumors is generally responsive to selective estrogen receptor modulators, 1 with relative resistance seen in a subset of tumors co-expressing HER2. 2 The remaining 20-25% of breast cancers are ER and PR negative and are not amenable to selective estrogen receptor modulators. This hormone receptor-negative group include...

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“…Notably, many of the neoadjuvant and adjuvant chemotherapeutic interventions approved for clinical use include agents targeting either replicating cells (in S phase) or dividing cells (M phase), and will therefore only be effective against cells progressing through the cell cycle. In support of this concept, in breast cancer, high Ki67 levels appear to predict benefit for an adjuvant taxane regime (M phase agent docetaxel) compared with non-taxane regimes [104,105]. However, although Ki67 has emerged as a prognostic marker of potential interest, its introduction into routine clinical practice has been compromised by conflicting data from meta-analysis studies [106].…”

Section: Tumour Cell Cycle Phase Analysismentioning

confidence: 99%

The cell cycle and cancer

Williams

Stoeber

2011

The Journal of Pathology

540

396

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Deregulation of the cell cycle underlies the aberrant cell proliferation that characterizes cancer and loss of cell cycle checkpoint control promotes genetic instability. During the past two decades, cancer genetics has shown that hyperactivating mutations in growth signalling networks, coupled to loss of function of tumour suppressor proteins, drives oncogenic proliferation. Gene expression profiling of these complex and redundant mitogenic pathways to identify prognostic and predictive signatures and their therapeutic targeting has, however, proved challenging. The cell cycle machinery, which acts as an integration point for information transduced through upstream signalling networks, represents an alternative target for diagnostic and therapeutic interventions. Analysis of the DNA replication initiation machinery and mitotic engine proteins in human tissues is now leading to the identification of novel biomarkers for cancer detection and prognostication, and is providing target validation for cell cycle-directed therapies.

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Breast Cancer Subtypes and Response to Docetaxel in Node-Positive Breast Cancer: Use of an Immunohistochemical Definition in the BCIRG 001 Trial

Abstract: A simple immunopanel can divide breast cancers into biologic subtypes with strong prognostic effects. TAC significantly complements endocrine therapy in patients with luminal B subtype and, in the absence of targeted therapy, is effective in the triple-negative population.

Cited by 476 publications

References 46 publications

Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer

Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer

Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation

The cell cycle and cancer

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