Retrospective Analysis of Time to Recurrence in the ATAC Trial According to Hormone Receptor Status: An Hypothesis-Generating Study

Dowsett, Mitch; Cuzick, Jack; Wale, Chris; Howell, Tony; Houghton, J; Baum, Michael

doi:10.1200/jco.2005.01.4829

Cited by 240 publications

(138 citation statements)

References 14 publications

Supporting

Mentioning

128

Contrasting

Unclassified

Order By: Relevance

“…This was particularly apparent in the ATAC trial where the hazard ratio was 0.43 for PgRÀ patients (n ¼ 880) and 0.83 for PgRþ patients (n ¼ 3834) (Dowsett et al, 2005). Smaller differences in this direction were seen in the ARNO/ ABCSG trial again using anastrozole, where the effect on PgRÀ tumours (n ¼ 564) was again very large (HR ¼ 0.42) (Jakesz et al, 2005a), and to a lesser extent in the IES trial using exemestane (Coombes et al, 2004a).…”

Section: Pgr Subgroupsmentioning

confidence: 95%

Should aromatase inhibitors be used as initial adjuvant treatment or sequenced after tamoxifen?

2006

View full text Add to dashboard Cite

A number of trials have studied the value of aromatase inhibitors (AIs) for the adjuvant treatment of early hormone-responsive postmenopausal breast cancer. Three different AIs have been used and they have been compared as initial treatment (two trials) or after 2 -3 years of tamoxifen (four trials), in both cases against a standard arm of 5 years of tamoxifen. In addition, two trials have evaluated AIs against no treatment after 5 years of tamoxifen. In all circumstances, the AIs have demonstrated superior efficacy. However, no results are currently available for the key question, that is -is it better to start initially with an AI or use it sequentially after 2 years of tamoxifen? Here, we review the trial results and present two models, which address this issue. The models clearly show that early treatment with an AI is superior to using it after 5 years of tamoxifen. They also favour an upfront strategy to sequencing after 2 years of tamoxifen, but in this case the differences are small and model-dependent. A key question is whether AIs have substantially better efficacy than tamoxifen for ER-positive -PgR-negative tumours, where the data are currently contradictory. A mechanism explaining why greater efficacy might be so is proposed. Further results from ongoing trials will be needed to resolve this issue.

show abstract

Section: Pgr Subgroupsmentioning

confidence: 95%

Should aromatase inhibitors be used as initial adjuvant treatment or sequenced after tamoxifen?

2006

View full text Add to dashboard Cite

show abstract

“…Previous studies have reported an estrogen receptornegative, progesterone receptor-positive rate between 1.5 and 10%. 3,20,[34][35][36][37][38][39][40][41][42][43][44] The methods used to determine estrogen and progesterone receptor status varied between these studies, with ligandbinding and laboratory-developed assays predominantly utilized. Of the more recent studies, the range of estrogen receptor-negative, progesterone receptorpositive is 1.5-4.0%; however, almost all of these studies were based on laboratory-developed assays.…”

Section: Discussionmentioning

confidence: 99%

A systematic comparison of three commercial estrogen receptor assays in a single clinical outcome breast cancer cohort

et al. 2016

View full text Add to dashboard Cite

Breast cancers are routinely assessed for estrogen receptor status using immunohistochemical assays to assist in patient prognosis and clinical management. Specific assays vary between laboratories, and several antibodies have been validated and recommended for clinical use. As numerous factors can influence assay performance, many laboratories have opted for ready-to-use assays using automated stainers to improve reproducibility and consistency. Three commonly used autostainer vendors-Dako, Leica, and Ventana-all offer such estrogen receptor assays; however, they have never been directly compared. Here, we present a systematic comparison of three platform-specific estrogen receptor ready-to-use assays using a retrospective, tamoxifen-treated, breast cancer cohort from patients who were treated in Calgary, Alberta, Canada from 1985 to 2000. We found all assays showed good intra-observer agreement. Inter-observer pathological scoring showed some variability: Ventana had the strongest agreement followed closely by Dako, whereas Leica only showed substantial agreement. We also analyzed each estrogen receptor assay with respect to 5-year disease-free survival, and found that all performed similarly in univariate and multivariate models. Determination of measures of test performance found that the Leica assay had a lower negative predictive value than Dako or Ventana, compared with the original ligand-binding assay, while other measures-sensitivity, specificity, positive predictive value, and accuracywere comparable between the three ready-to-use assays. When comparing against disease-free survival, the difference in negative predictive value between the vendor assays were not as extreme, but Dako and Ventana still performed slightly better than Leica. Despite some discordance, we found that all ready-to-use assays were comparable with or superior to the ligand-binding assay, endorsing their continued use. Our analysis also allowed for exploration of estrogen receptor-negative, progesterone receptor-positive cases, and we discovered that this phenotype was not consistent across the assays, suggesting this might be an artifact. Endocrine therapy is standard treatment for hormone receptor-positive breast cancers that can improve patient survival. 1-3 Estrogen receptor and progesterone receptor analysis is routinely performed by immunohistochemical assays on breast cancer specimens to classify hormone receptor status and determine patient prognosis and management. [1][2][3][4] Eventually, immunohistochemical-based testing replaced the ligand-binding assay as the standard method for determining hormone receptor status. 5 The switch from ligand-binding assay to immunohistochemistry did not occur at a specific time point, and varied by location and laboratories between the mid-90s and early 2000s. Although estrogen and progesterone receptor are both routinely evaluated, patient management decisions are typically made on the basis of estrogen receptor results alone as the role of progesterone receptor in breast cancer patie...

show abstract

“…The importance of aromatase in the pathogenesis of breast cancer has also clearly been shown in a clinical setting, as inhibitors of this enzyme have been regularly used in the treatment of postmenopausal breast cancer (6). A recent study suggested that aromatase inhibitors might be more effective than modulators of the estrogen receptor in slowing tumor progression (7).…”

Section: Introductionmentioning

confidence: 99%

Genetic Polymorphisms of the CYP19A1 Gene and Breast Cancer Survival

Long

Kataoka

Shu

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

The CYP19A1 protein (aromatase) plays a critical role in estrogen biosynthesis and thus may be related to the progression of breast cancer. We examined the association between CYP19A1 genetic polymorphisms and breast cancer survival in a cohort of 1,136 patients who were recruited as part of a population-based case-control study in Shanghai, China from 1996 to 1998 and who has donated a DNA sample to the study. Patients were followed for cancer recurrence and mortality through July 2005. Nineteen haplotype tagging single-nucleotide polymorphisms (SNP) in the CYP19A1 gene were evaluated. For each of the five SNPs located in haplotype block 2, patients homozygous for the minor alleles had a reduced 5-year disease-free survival rate compared with those carrying the major allele. The age-adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were

show abstract

Retrospective Analysis of Time to Recurrence in the ATAC Trial According to Hormone Receptor Status: An Hypothesis-Generating Study

Cited by 240 publications

References 14 publications

Should aromatase inhibitors be used as initial adjuvant treatment or sequenced after tamoxifen?

Should aromatase inhibitors be used as initial adjuvant treatment or sequenced after tamoxifen?

A systematic comparison of three commercial estrogen receptor assays in a single clinical outcome breast cancer cohort

Genetic Polymorphisms of the CYP19A1 Gene and Breast Cancer Survival

Contact Info

Product

Resources

About