Prognostic value of steroid receptors after long-term follow-up of 2257 operable breast cancers

Pichon, M.; Broet, Philippe; Magdelénat, H.; Delarue, J; Spyratos, Frédérique; Basuyau, J.P.; Saez, S.; Rallet, A.; Courrière, Philippe; Millon, Régine; Asselain, Bernard

doi:10.1038/bjc.1996.291

Cited by 122 publications

(79 citation statements)

References 15 publications

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“…However, the association found in our study is time-dependent. Nonetheless, in some breast cancer studies, several prognosis factors have been identified with a time-dependent effect that decreases during the follow-up [24][25][26]. On the contrary, we found that CBC hazard is increased during the long term follow-up among overweight and obese patients.…”

Section: Discussioncontrasting

confidence: 61%

Increased risk of contralateral breast cancers among overweight and obese women: a time-dependent association

Majed

Dozol

Ribassin-Majed

et al. 2010

Breast Cancer Res Treat

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Section: Discussioncontrasting

confidence: 61%

Increased risk of contralateral breast cancers among overweight and obese women: a time-dependent association

Majed

Dozol

Ribassin-Majed

et al. 2010

Breast Cancer Res Treat

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“…13 There has been strong evidence of a nonproportional effect of ER as indicated by the loss of its predictive value over long periods of patient follow-up. 28 For this study, tests of proportionality of PR on disease-free and overall survival over the follow-up period were performed using hypothesis tests of PR as a time-dependent variable in the Cox model, as well as examining plots of the beta coefficients of PR from the Cox model vs follow-up time. 29 For this study population, evidence of nonproportionality of PR was not detected, and Cox models were therefore developed without adjustment for PR as a time-dependent variable.…”

Section: Methodsmentioning

confidence: 99%

Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study

et al. 2004

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Progesterone receptor is a surrogate marker of estrogen receptor activity in breast cancer and its utility in helping predict clinical outcome has been established using biochemical assays. However, most laboratories worldwide have switched to immunohistochemistry to assess progesterone receptor, but unfortunately no validated immunohistochemical assay exists for progesterone receptor. The purpose of this study was to develop and validate an immunohistochemical assay for progesterone receptor in breast cancer. The assay was based on monoclonal antibody 1294 (DakoCytomation) and slides were scored microscopically using the 'Allred score' on a scale of 0-8. The assay was compared to ligand-binding assay in 1235 breast cancers, and a subset (n ¼ 362) that received only hormonal therapy was used to define a cutoff for progesterone receptorpositive. Clinical utility was validated in an independent set of samples (n ¼ 423) from a clinical trial randomizing premenopausal breast cancer patients to tamoxifen þ oophorectomy vs observation following surgery. A cutoff of 42 (corresponding to 41% positive cells) dichotomized patients with significantly better or worse clinical outcome (P ¼ 0.0014). Progesterone receptor by immunohistochemistry provided significantly better results than progesterone receptor by ligand-binding assay in predicting clinical outcome. In the clinical trial, a positive result in univariate analyses was associated with significantly improved disease-free and overall survival both in untreated (hazard ratios/P ¼ 0.656/0.060 and 0.479/0.005, respectively) and hormonally treated patients (hazard ratios/P ¼ 0.529/0.017 and 0.451/0.007, respectively). Positive progesterone receptor remained significant for improved disease-free and overall survival (hazard ratios/P ¼ 0.666/0.038 and 0.549/0.007, respectively) in multivariate analyses including the standard variables of tumor size, nodal status, treatment, histological grade, and HER-2/neu status. Estrogen and progesterone receptors are codependent variables and progesterone receptor was a weaker predictor of response to endocrine therapy than estrogen receptor when both were included in multivariate analysis. This is the first comprehensive study assessing the clinical usefulness of progesterone receptor by immunohistochemistry in archival tissue in breast cancer. Progesterone receptor assessed by immunohistochemistry provides useful information about clinical outcome and it is better than progesterone receptor measured by ligand-binding assay.

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“…A weakness in our study is the median FU period which consisted of 3.5 years only and which allows us only short-term DFI interpretations. Others have referred to ER and PR as only being short-term prognostic factors whereas little data are available on HER-2 as a prognostic factor beyond five years of FU [6,54,55].…”

Section: Discussionmentioning

confidence: 99%

“…The prognostic value of these predictive biomarkers can be summarized as follows. Women with an ER-positive tumor have a better prognosis than those with an ER-negative tumor, although this is not true for very young women and not after approximately eight years of follow-up (FU) when survival curves of ER-positive and ER-negative cases cross [5][6][7]. The combination of ER with PR further refines the short-term prognostic value of ER.…”

Section: Introductionmentioning

confidence: 99%

Short-term outcome of primary operated early breast cancer by hormone and HER-2 receptors

Brouckaert

Pintens

Belle

et al. 2008

Breast Cancer Res Treat

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Introduction Prognostic subgroup classification of operable breast cancers using cDNA clustering of breast cancer-related genes resembles the classification based on the combined immunohistochemical (IHC) expression of the hormone and HER-2 receptors. We here report the shortterm disease-free interval (DFI) of operable breast cancers by their joint hormone receptor/HER-2 phenotype. Patients and methods Short-term follow-up (FU) of a prospective cohort of 1,958 breast-cancer patients primary operated at our institution between 2000 and 2005. Receptors were evaluated using IHC. Steroid receptors were considered positive for any nuclear staining; HER-2 for strong (3+) membrane staining or positive fluorescence in situ hybridization (FISH). Kaplan-Meier (KM) DFI curves were calculated for any relapse defined as a local, regional, contralateral, or distant breast cancer event for the six predefined breast cancer subgroups: ER + PR + HER-2 -(PPN), ER + PR -HER-2 -(PNN), ER + PR + HER-2 + (PPP), ER -PR -HER-2 -(NNN), ER -PR -HER-2 + (NNP), and ER + PR -HER-2 + (PNP). P-values were calculated for comparison of the six different survival curves using two possible adaptations for multiple testing. A multivariate model for the receptors predicting DFI did incorporate local and systemic adjuvant therapy. Results Median patient age was 57 years (ranges 26-96) and median FU was 3.35 years. Overall, DFI at median FU was 91%; 94% for PPN, 89% for PNN, 86% for NNN, 81% for PPP, 80% for PNP, and 76% for NNP cases. Some receptor subgroups had a significantly better DFI than others based on multiple testing, especially when the PPN group was compared against the four most frequent subtypes. The multivariate model with local and systemic adjuvant therapy confirmed the prognostic value of ER, PR, and HER-2 for short-term DFI. Conclusion It is possible to distinguish short-term prognostic breast cancer subgroups only on the basis of ER, PR, and HER-2 even when stratified for local and systemic adjuvant therapy. While gene expression profiles based on microarray data of over hundreds of genes will probably teach us much about breast cancer biology, heterogeneity, and prognosis, we emphasize the important short-term prognostic value of currently used IHC markers for ER, PR, and HER-2.

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Prognostic value of steroid receptors after long-term follow-up of 2257 operable breast cancers

Abstract: S_inary The prognostic value of oestrogen receptor (ER) and progesterone receptor (PR) was estimated through a multicentric study of 2257 operable breast cancer patients followed up for a median of 8.5 years. None of the patients had received adjuvant therapy.

Cited by 122 publications

References 15 publications

Increased risk of contralateral breast cancers among overweight and obese women: a time-dependent association

Increased risk of contralateral breast cancers among overweight and obese women: a time-dependent association

Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study

Short-term outcome of primary operated early breast cancer by hormone and HER-2 receptors

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