The importance of estrogen receptor concentration as a prognostic factor in postmenopausal breast cancer patients

Objective. While the value of Ki-67 has been recognized in breast cancer, controversy also exists. The goal of this study is to show the prognostic value of Ki-67 according to progesterone receptor (PgR) expression in patients who have estrogen receptor- (ER-) positive, human epidermal growth factor receptor 2- (HER2-) negative early breast cancer. Methods. The records of nonmetastatic invasive breast cancer patients who underwent surgery at a single institution between 2009 and 2012 were reviewed. Primary end point was recurrence-free survival (RFS), and secondary end point was overall survival (OS). Ki-67 and PgR were assessed with immunohistochemistry for the tumor after surgery. Results. A total of 1848 patients were enrolled in this study. 223 (12%) patients had high (≥10%) Ki-67, and 1625 (88%) had low Ki-67 expression. Significantly worse RFS and OS were observed in the high vs. low Ki-67 expression only when the PgR was low (<20%) (p<0.001 and 0.005, respectively, for RFS and OS). There was no significant difference in RFS and OS according to Ki-67 when the PgR was high (p=0.120 and 0.076). RFS of four groups according to high/low Ki-67 and PgR expression was compared. The low PgR and high Ki-67 expression group showed worst outcome among them (p<0.001). In a multivariate analysis, high Ki-67 was an independent prognostic factor when the PgR was low (HR 3.05; 95% CI 1.50–6.19; p=0.002). Conclusions. Ki-67 had a value as a prognostic factor only under low PgR expression level in early breast cancer. PgR should be considered in evaluating the prognosis of breast cancer patients using Ki-67.

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Association of the phosphorylation of the estrogen receptor at serine 118 and 167 with prognosis in postmenopausal breast cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.562 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 562-562

Author(s):

Karin J. Beelen ◽

Mark Opdam ◽

Rutger H.T. Koornstra ◽

Andrew D. Vincent ◽

Jan Baptist Vermorken ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Cancer Patients ◽

Estrogen Therapy ◽

Postmenopausal Breast Cancer ◽

Tamoxifen Treatment ◽

Adjuvant Tamoxifen ◽

Breast Cancer Patients ◽

Premenopausal Breast Cancer ◽

Cox Models

562 Background: The sensitivity of the estrogen receptor (ERα) to anti-estrogen therapy can be affected by phosphorylation events. In premenopausal breast cancer patients, phosphorylation of the ERα at serine 118 (ERαS118-p) is predictive for benefit from adjuvant tamoxifen. Since ERαS118-p represents the common hallmark of different signaling cascades that differ in E2 dependency, the resulting effect on estrogen sensitivity may differ between pre- and postmenopausal patients. Phosphorylation of serine 167 (ERαS167-p) has been associated with favorable disease outcome, but whether ERαS167-p can predict tamoxifen sensitivity is currently unknown. We tested the predictive value of both ERαS118-p and ERαS167-p for benefit from adjuvant tamoxifen in postmenopausal breast cancer patients. Methods: We collected primary tumor blocks from 563 ERα positive (stage I-III) postmenopausal patients who had been randomized between tamoxifen (1 to 3 years) vs. no adjuvant therapy (IKA trial). The median follow-up of patients without a recurrence event was 9.4 years. Immunohistochemistry was performed on a TMA using monoclonal antibodies for ERαS118-p and ERαS167-p. The percentage of positive nuclei was scored and a score of ≥ 10 % was considered as positive. Multivariate Cox models were used to assess hazard ratios (HRs) for recurrence free interval and the interaction between these phosphorylations and tamoxifen treatment. Results: We did not find a significant interaction between either ERαS118-p (p=0.99) or ERαS167-p (p=0.44) and tamoxifen, suggesting that the relative benefit from adjuvant tamoxifen in postmenopausal patients is not dependent on the presence of one of these phosphorylations. Both tamoxifen treated patients as well as control patients had a better prognosis when their tumor was positive for ERαS118-p (adjusted HR 0.60 p=0.02) or ERαS167-p (adjusted HR 0.62, p=0.02) compared to patients whose tumor did not express these ERα phosphorylations. Conclusions: In postmenopausal patients ERαS118-p and ERαS167-p are both associated with better prognosis, but do not predict differential benefit from tamoxifen.

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Abstract P2-10-06: Serum protein peak 3144m/z is a potential prognostic factor for postmenopausal breast cancer patients

10.1158/0008-5472.sabcs13-p2-10-06 ◽

2013 ◽

Author(s):

Y Gao ◽

X-J Wang ◽

S-H Xu ◽

H-J Yang ◽

Z-H Chen ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Factor ◽

Cancer Patients ◽

Serum Protein ◽

Postmenopausal Breast Cancer ◽

Breast Cancer Patients ◽

Protein Peak ◽

Potential Prognostic Factor

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Association between breast cancer and estrogen receptor gene polymorphism PVU II

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.643 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 643-643

Author(s):

K. Neuss ◽

D. Elling ◽

I. Cascorbi ◽

D. Lueftner

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Cancer Patients ◽

Receptor Gene ◽

White Blood Cells ◽

Postmenopausal Breast Cancer ◽

Receptor Expression ◽

Restriction Enzyme Digestion ◽

Breast Cancer Patients ◽

Receptor Polymorphism

643 Background: The estrogen receptor (ER) is well acknowledged as a prognostic factor in breast cancer, and it is a prerequisite to use the predictive information for hormonal therapy. We investigated whether that the different polymorphisms of the estrogen receptor could influence its expression or functionality. Methods: DNA was extracted from white blood cells of 236 breast cancer patients and 236 healthy, matched controls. The ER genotypes were determined by polymerase chain reaction (PCR) amplification followed by restriction enzyme digestion of the PCR product. Results were shown by electrophoreses. Clinical data such as histologic types, pTNM stage and patients age were available for statistical analyses. Results: We found a statistically significant correlation between the estrogen receptor polymorphism pattern and breast cancer. The receptor type PP was detected statistically significantly more often in postmenopausal breast cancer patients (PP vs pp+Pp, p =0.03). However, there was no correlation to the histobiochemical receptor status or UICC-Stadium. Conclusions: These results show an association between the estrogen receptor polymorphism and breast cancer. It seems to be that a complete lack of the p-allel is a risk factor to develop breast cancer at postmenopausal age. There was no influence on estrogen receptor expression or clinical tumor stage. Thus, we propose that there is no clinical use for estrogen receptor polymorphism analyses at this stage. No significant financial relationships to disclose.

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Prognostic value of gene expression of p63 by microarray analysis in estrogen receptor positive and negative breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.566 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 566-566

Author(s):

L. C. Hanker ◽

T. Karn ◽

A. Rody ◽

E. Ruckhäberle ◽

C. Solbach ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Prognostic Factor ◽

Cancer Patients ◽

Receptor Expression ◽

Prognostic Impact ◽

Breast Cancer Patients ◽

Cox Regression Analysis ◽

Significant Difference ◽

Er Positive

566 Background: The protein 63 (p63) represents a member of the p53 family (p53/p63/p73) located on chromosome 3q27. This gene family seems to play an important role in carcinogenesis and its members may act as oncogenes or tumor suppressor genes. P63 is overexpressed in many different tumors like head and neck cancer, lung cancers, uterine tumors and breast cancer, and has been associated with poor prognosis in some studies. P63 was found to be overexpressed in a subset of highly aggressive breast cancers that represent a basal and myoepithelial phenotype and have a poor clinical outcome. This protein seems to be a specific myoepithelial cell marker in normal breast tissue and might represent a prognostic factor in breast cancer. Methods: Large scale analysis was performed using Affymetrix microarray data from n=1581 breast cancer patients to evaluate p63 expression. Results: P63 expression showed a strong correlation with patient's age (χ2-test, p < 0.001), tumor size (p < 0.003), proliferation rate (p < 0.001), Topo2α expression (p = 0.001) and estrogen receptor expression (p = 0.017). Survival analysis of all patients with available follow up data (n = 1263) showed a significant difference due to high and low p63 expression (log rank p < 0.001). Patients with a low p63 expression had the worst prognosis. In univariate Cox regression analysis p63 showed a hazard ratio (HR) of 1.61 (95% CI 1.31–2.00, p < 0.001) for disease free survival. This prognostic impact remained significant when samples were stratified by estrogen receptor status. High expression of p63 was significantly associated with longer OS in both ER negative (n = 334, log rank p = 0.022) and ER positive (n = 929, log rank p < 0,001) breast cancer. The prognostic impact of p63 expression was independent of Ki67 expression (p = 0.011 and p = 0.001 for high and low Ki67, respectively). Moreover a worse prognosis of low p63 expressing tumors was found in both subgroups of ErbB2 positive tumors (p < 0.001) and ErbB2 negative tumors (p < 0.001). Conclusions: P63 expression is a prognostic factor in both ER positive and negative breast cancer and could be helpful for risk assessment in breast cancer patients. No significant financial relationships to disclose.

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