The effects of anti-estrogen therapy on lymphocyte functions in breast cancer patients

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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Challenges of measuring accurate estradiol levels in aromatase inhibitor-treated postmenopausal breast cancer patients on vaginal estrogen therapy

Pharmacology Research & Perspectives ◽

10.1002/prp2.330 ◽

2017 ◽

Vol 5 (4) ◽

pp. e00330 ◽

Cited By ~ 3

Author(s):

Polly Niravath ◽

Raksha Bhat ◽

Mohamed Al-Ameri ◽

Ahmed AlRawi ◽

Claudette Foreman ◽

...

Keyword(s):

Breast Cancer ◽

Aromatase Inhibitor ◽

Cancer Patients ◽

Estrogen Therapy ◽

Postmenopausal Breast Cancer ◽

Breast Cancer Patients ◽

Vaginal Estrogen ◽

Vaginal Estrogen Therapy ◽

Estradiol Levels

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Divergence from osteoporosis screening guidelines in older breast cancer patients treated with anti-estrogen therapy: A population-based cohort study

Bone ◽

10.1016/j.bone.2018.06.005 ◽

2018 ◽

Vol 116 ◽

pp. 94-102 ◽

Cited By ~ 1

Author(s):

David Henault ◽

Tracy Westley ◽

Sinziana Dumitra ◽

Sue-Ling Chang ◽

Richard Kremer ◽

...

Keyword(s):

Breast Cancer ◽

Cohort Study ◽

Cancer Patients ◽

Estrogen Therapy ◽

Population Based ◽

Breast Cancer Patients ◽

Osteoporosis Screening ◽

Screening Guidelines

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Circulating levels of the breast cancer growth factor GP88 in the serum of breast cancer (BC) patients

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.20050 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 20050-20050

Author(s):

G. Serrero ◽

K. Tkaczuk ◽

N. Tait ◽

O. Golubeva ◽

H. Dai ◽

...

Keyword(s):

Breast Cancer ◽

Growth Factor ◽

Serum Level ◽

Healthy Volunteers ◽

Cancer Patients ◽

Critical Role ◽

Estrogen Therapy ◽

Breast Adenocarcinoma ◽

P Value ◽

Breast Cancer Patients

20050 Background: The 88 kDa autocrine growth factor PC-Cell Derived Growth Factor (GP88) plays a critical role in breast tumorigenesis. GP88 expression was low in estrogen receptor positive cells, whereas in ER negative cells, it was constitutively overexpressed. Increased GP88 expression was associated with anti-estrogen therapy resistance in ER+ cells and Herceptin resistance in Her-2 overexpressing breast tumors. Antisense inhibition of GP88 expression in human breast adenocarcinoma lead to inhibition of tumor growth in vivo. Immunohistochemical studies have shown that GP88 was expressed in 80% of invasive ductal carcinomas in correlation with expression of poor prognosis markers whereas normal tissues and benign breast lesions were negative. Since GP88 is secreted by breast cancer cells, we examined whether GP88 was found in the circulation at an elevated level in the sera of breast cancer patients when compared to healthy individuals. Methods: A blood sampling study was conducted to determine the serum level of GP88 in healthy volunteers (HV) and breast cancer patients (BC pts). Ten ml of blood was drawn every three months to obtain serum. GP88 serum concentration was determined in triplicate by quantitative enzyme immunoassay using human GP88 as standard. 126 BC pts were accrued. . In addition, sera from 53 healthy volunteers were obtained to establish a GP88 baseline in HV. BC pts characteristics: race: Caucasian- 61, African American-60, Asian-5; median age: 52.5 (range 26–84), stage I-32, II-34, III-18, IV-42. Results: Circulating GP88 was measurable in the serum. Median level of GP88 was 32.8 ng/ml (range 15.3–42.8) in HV and 43.8 ng/ml (range 15.4–158.4) in BC pts, (p-value = 0.0007). Conclusions: GP88 is measurable in the sera of HV and BC pts. Comparison between the two groups indicates that GP88 level is significantly higher in the sera of BC pts. These studies are important since it identifies GP88 as a measurable biomarker that is also a therapeutic target of malignant transformation or malignant progression of breast carcinoma (BC). Future studies will examine the correlation of GP88 level with BC prognostic factors. Correlation between the serum level of GP88 and therapeutic response to systemic therapy in breast cancer patients will also be assessed. [Table: see text]

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Methylation ESR1 as a potential factor of resistence to HER2/neu therapy in patients with breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.26_suppl.24 ◽

2013 ◽

Vol 31 (26_suppl) ◽

pp. 24-24

Author(s):

Joaquina Martínez-Galán ◽

Cynthia S. González Rivas ◽

Julia Ruiz Vozmediano ◽

Lucia Portellano ◽

Juan Ramón Delgado

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Strong Association ◽

Estrogen Therapy ◽

Therapy Resistance ◽

Healthy Controls ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Luminal A ◽

Luminal B

24 Background: Estrogen receptor (ER)-positive breast cancers are considered prognostically more favorable than ER-negative tumors and are often responsive to anti-estrogen therapy. Whereas tumors overexpressing HER2 are endocrine resistant and they require the blockage of the HER2 pathway in addition to estrogen deprivation. To evaluate epigenetics differences in tumor-related genes to ESR1 and HER2/neu status in primary breast cancer is the objective of this study. Methods: We quantified methylation levels of promoter of ERS1 which are to confer growth adventage to cells in 107 women with breast cancer. Real Time QMS-PCR SYBR green (methylation-specific PCR) was used to analyze the hypermethylation. Tumours were classified as phenotype basal, luminal A, Luminal B, and phenotype HER2+. Results: Presence of methylated ESR1 in serum of breast cancer patients was associated with ER-negative phenotype (p=0.0179). Of the available cases, 60 pts (56%) were Luminal A, 10 pts (9.3%) Luminal B, 13 pts (12%) Basal like, and 9 pts (8.4%) HER2+. We observed that methylated ERS1 was preferably associated with phenotype Basal Like and worse interval progression free and survival global though p > 0.05 and the amplification HER2+ was correlation with significant more frequent methylation gene (p<0.05). Thet hypermethylation of normal ERS1 and 14-3-3σ combined differentiated between breast cancer patients and healthy controls (p = 0.0001) with a sensitivity of 81% (95% CI: 72–88%) and specificity of 88% (95% CI: 78–94%). Conclusions: This study identifies the presence of variations in global levels of methylation promoters genes in healthy controls and breast cancer with different phenotype classes and shows that these differences have clinical significance. These showed that frequent methylation had a strong association with molecular phenotype of breast cancer and perhaps in the future can explain therapy resistance related to RE and HER2/neu status and this may be of significance in the assessment of targeted therapy resistance related to ER and HER2/neu status in breast cancer patients.

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