Factors associated with concordant estrogen receptor expression at diagnosis and centralized re-assay in a Danish population-based breast cancer study

Cronin‐Fenton, Deirdre; Hellberg, Ylva; Lauridsen, Kristina Lystlund; Ahern, Thomas P.; Garne, Jens Peter; Rosenberg, Carol L.; Silliman, Rebecca A.; Sørensen, Henrik Toft; Lash, Timothy L.; Hamilton-Dutoit, Stephen

doi:10.3109/0284186x.2011.633556

Cited by 8 publications

(9 citation statements)

References 28 publications

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“…The blocks derived from patients with centrally confirmed [94] ER+ stage II breast cancer diagnosed in 2000 or 2001. From each block, three 10-micron sections were cut to slides, the first of which was hematoxylin and eosin (H&E) stained to identify regions of highest tumor cellularity, which were then demarcated on the unstained slides.…”

Section: Methodsmentioning

confidence: 99%

Interactions between immunity, proliferation and molecular subtype in breast cancer prognosis

et al. 2013

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BackgroundGene expression signatures indicative of tumor proliferative capacity and tumor-immune cell interactions have emerged as principal biology-driven predictors of breast cancer outcomes. How these signatures relate to one another in biological and prognostic contexts remains to be clarified.ResultsTo investigate the relationship between proliferation and immune gene signatures, we analyzed an integrated dataset of 1,954 clinically annotated breast tumor expression profiles randomized into training and test sets to allow two-way discovery and validation of gene-survival associations. Hierarchical clustering revealed a large cluster of distant metastasis-free survival-associated genes with known immunological functions that further partitioned into three distinct immune metagenes likely reflecting B cells and/or plasma cells; T cells and natural killer cells; and monocytes and/or dendritic cells. A proliferation metagene allowed stratification of cases into proliferation tertiles. The prognostic strength of these metagenes was largely restricted to tumors within the highest proliferation tertile, though intrinsic subtype-specific differences were observed in the intermediate and low proliferation tertiles. In highly proliferative tumors, high tertile immune metagene expression equated with markedly reduced risk of metastasis whereas tumors with low tertile expression of any one of the three immune metagenes were associated with poor outcome despite higher expression of the other two metagenes.ConclusionsThese findings suggest that a productive interplay among multiple immune cell types at the tumor site promotes long-term anti-metastatic immunity in a proliferation-dependent manner. The emergence of a subset of effective immune responders among highly proliferative tumors has novel prognostic ramifications.

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Section: Methodsmentioning

confidence: 99%

Interactions between immunity, proliferation and molecular subtype in breast cancer prognosis

et al. 2013

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“…[39] A previous validation study using medical record review confirmed all recurrences, eliminating the potential for outcome misclassification, and showed perfect agreement for all covariates except one patient’s menopausal status. [40] Staining guidelines were designed to be clinically applicable to ensure that ApoD could be a practical predictive or prognostic indicator if an association was found.…”

Section: Discussionmentioning

confidence: 95%

Apolipoprotein D expression does not predict breast cancer recurrence among tamoxifen-treated patients

et al. 2017

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BackgroundApolipoprotein D (ApoD) has been proposed as a predictor of breast cancer recurrence among estrogen receptor-positive (ER+), tamoxifen-treated patients.MethodsWe conducted a population-based case-control study nested in a population of 11,251 women aged 35–69 years at diagnosis with Stage I–III breast cancer between 1985 and 2001 on Denmark’s Jutland Peninsula and registered with the Danish Breast Cancer Cooperative Group. We identified 541 recurrent or contralateral breast cancers cases among women with ER+ disease treated with tamoxifen for at least 1 year and 300 cases in women with ER– disease never treated with tamoxifen. We matched one control subject per case and assessed ApoD expression in the tumor cell nucleus and cytoplasm using tissue microarray immunohistochemistry. We computed the odds ratio (OR) associating ApoD expression with recurrence and adjusted for potential confounding using logistic regression.ResultsCytoplasmic ApoD expression was seen in 68% of ER+ tumors, in 66% of ER– tumors, and in 66% of controls across both groups. In women with ER+ tumors, the associations of cytoplasmic ApoD expression with recurrence (OR = 1.0; 95% CI = 0.7 to 1.4) and increasing cytoplasmic expression with recurrence (OR = 1.0; 95% CI = 0.996 to 1.003) were null, as were those for women with ER– tumors. Associations for nuclear ApoD expression and combined nuclear and cytoplasmic expression were similarly near-null.ConclusionApoD expression is likely not a predictor of recurrence in tamoxifen-treated patients.ImpactThis study eliminates the previously suggested marker ApoD as a predictor of recurrence among tamoxifen-treated women.

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“…Furthermore, data were of high quality: the positive predictive value of the DBCG Registry’s recurrence classification was reported to be 99.4% (26), and this finding was confirmed by medical record review for a subset of cases in this study (15). Since our study covered a time period of evolving ER assay methodologies, we centrally re-assayed ER status for cases and controls using current standard clinical methods (27). Our use of TMAs allowed Pak1 and ERαS305-P to be assayed in one batch with single reagent lots, eliminating two major sources of staining variability common to immunohistochemical assays.…”

Section: Discussionmentioning

confidence: 99%

Pak1, adjuvant tamoxifen therapy, and breast cancer recurrence risk in a Danish population-based study

et al. 2016

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Background Adjuvant tamoxifen therapy approximately halves the risk of estrogen receptor positive breast cancer recurrence, but many women do not respond to therapy. Observational studies nested in clinical trial populations suggest that overexpression or nuclear localization of p21-activated kinase 1 (Pak1) in primary tumors predicts tamoxifen failure. Materials and Methods We measured the association between Pak1 expression and breast cancer recurrence in a Danish population-based case-control study. Pak1 cytoplasmic expression level and nuclear positivity were determined by immunohistochemical staining of primary breast tumors from recurrence cases and matched controls from two breast cancer populations; women diagnosed with ER-positive tumors who received at least one year of tamoxifen therapy (ER+/TAM+), and women diagnosed with ER-negative tumors who survived for at least one year (ER−/TAM−). Pak1 staining was assessed by a single, blinded pathologist, and associations were estimated with conditional logistic regression models. Results We included 541 recurrence cases and 1:1 matched controls from the ER+/TAM+ group and 300 recurrence cases and 1:1 matched controls from the ER−/TAM− group. Pak1 cytoplasmic intensity was not associated with breast cancer recurrence in either group (ER+/TAM+ ORadj for strong vs. no cytoplasmic staining=0.91, 95% CI: 0.57, 1.5; ER−/TAM− ORadj for strong vs. no cytoplasmic staining=0.74, 95% CI: 0.39, 1.4). Associations between Pak1 nuclear positivity and breast cancer recurrence were similarly near-null in both groups. Conclusion Pak1 positivity in primary breast tumors was neither predictive nor prognostic in this prospective, population-based study.

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Factors associated with concordant estrogen receptor expression at diagnosis and centralized re-assay in a Danish population-based breast cancer study

Cited by 8 publications

References 28 publications

Interactions between immunity, proliferation and molecular subtype in breast cancer prognosis

Interactions between immunity, proliferation and molecular subtype in breast cancer prognosis

Apolipoprotein D expression does not predict breast cancer recurrence among tamoxifen-treated patients

Pak1, adjuvant tamoxifen therapy, and breast cancer recurrence risk in a Danish population-based study

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