Influence of tumor estrogen and progesterone receptor levels on the response to tamoxifen and chemotherapy in primary breast cancer.

Fisher, Bernard; Redmond, Carol; Brown, A; Wickerham, D. Lawrence; Wolmark, Norman; Allegra, Joseph C.; Escher, George C.; Lippman, Marc E.; Savlov, Edwin D.; Wittliff, James L.

doi:10.1200/jco.1983.1.4.227

Cited by 244 publications

(99 citation statements)

References 9 publications

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“…In current clinical practice, the response to hormone therapy is associated with the levels of both estrogen receptors (ERs) and progesterone receptors (PRs) in both primary (Fisher et al, 1983;Rose et al, 1985;Harvey et al, 1999) and advanced (Valavaara et al, 1990;Harvey et al, 1999;Elledge et al, 2000) breast cancers. In the current receptor.…”

Section: Discussionmentioning

confidence: 99%

Loss of Expression and Aberrant Methylation of the CDH1 (E-cadherin) Gene in Breast Cancer Patients from Kashmir

Asiaf

Ahmad²,

Aziz³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Aberrant promoter hypermethylation has been recognized in human breast carcinogenesis as a frequent molecular alteration associated with the loss of expression of a number of key regulatory genes and may serve as a biomarker. The E-cadherin gene (CDH1), mapping at chromosome 16q22, is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. The aim of our study was to assess the methylation pattern of CDH1 and to correlate it with the expression of E-cadherin, clinicopathological parameters and hormone receptor status in breast cancer patients of Kashmir. Materials and Methods: Methylation specific PCR (MSP) was used to determine the methylation status of CDH1 in 128 invasive ductal carcinomas (IDCs) paired with the corresponding normal tissue samples. Immunohistochemistry was used to study the expression of E-cadherin, ER and PR. Results: CDH1 hypermethylation was detected in 57.8% of cases and 14.8% of normal adjacent controls. Reduced levels of E-cadherin protein were observed in 71.9% of our samples. Loss of E-cadherin expression was significantly associated with the CDH1 promoter region methylation (p<0.05, OR=3.48, CI: 1.55-7.79). Hypermethylation of CDH1 was significantly associated with age at diagnosis (p=0.030), tumor size (p=0.008), tumor grade (p= 0.024) and rate of node positivity or metastasis (p=0.043). Conclusions: Our preliminary findings suggest that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast cancers associated with a decrease in E-cadherin expression. We found significant differences in tumor-related CDH1 gene methylation patterns relevant to tumor grade, tumor size, nodal involvement and age at diagnosis of breast tumors, which could be extended in future to provide diagnostic and prognostic information.

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Section: Discussionmentioning

confidence: 99%

Loss of Expression and Aberrant Methylation of the CDH1 (E-cadherin) Gene in Breast Cancer Patients from Kashmir

Asiaf

Ahmad²,

Aziz³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…1,2 Accurate determination of biomarkers is essential for the proper management of breast cancer patients. [3][4][5][6][7][8] The HER2 is overexpressed in B15-20% of breast carcinomas. [9][10][11] HER2 positivity is associated with higher rate of recurrence and mortality in newly diagnosed breast cancer patients, and agents that target HER2 are found to be effective in both the metastatic and adjuvant settings, reducing the risk of recurrence and mortality in patients with early stage disease.…”

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confidence: 99%

The effect of cold ischemic time on the immunohistochemical evaluation of estrogen receptor, progesterone receptor, and HER2 expression in invasive breast carcinoma

2012

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The American Society of Clinical Oncology/College of American Pathologist (ASCO/CAP) guidelines on breast cancer currently recommend a cold ischemic time of o1 h, although data are limited. Breast resection specimens were subjected to variable cold ischemic time periods (0.5, 1, 2, 3, 4, 24, and 48 h) within the refrigerator and at room temperature. The study included 25 tumors, all of which had refrigerated samples. Nonrefrigerated samples (samples at room temperature) were present on 23 cases. Hormone receptors were semiquantitatively scored using the H-score method. Human epidermal growth factor receptor 2 gene ERBB2 (HER2) was scored using the ASCO/CAP guidelines. The results were compared with the core biopsy scores, which have negligible cold ischemic time period before fixation. Mild reduction in staining for hormone receptors was judged present if the H-score on the resection specimen was between one-half and three-fourth of the H-score at core biopsy. Significant reduction was judged present when the H-score on resection was less than one-half of the core biopsy H-score. Mild reduction in HER2 staining was judged present if there was one-step reduction; and significant reduction was judged present if there was two-step reduction in staining. A true reduction was judged present only when the reduction was consistently present for the increasing time interval. A focal reduction for a particular time sample was attributed to the heterogeneity of the tumor sample. Non-refrigerated samples are affected more by prolonged cold ischemic time than refrigerated samples. Cold ischemic time period of as short as one-half hour may occasionally impact the immunohistochemical (IHC) staining for progesterone receptor. Significant reduction in IHC staining for hormone receptors, and HER2, however, generally does not result until 4 h for refrigerated samples and 2 h for non-refrigerated samples. The ASCO/CAP guideline of cold ischemic time period of o1 h is a prudent guideline to follow. Modern Pathology (2012Pathology ( ) 25, 1098Pathology ( -1105 doi:10.1038/modpathol.2012 published online 30 March 2012 Keywords: breast carcinoma; cold ischemic time; ER/PR/HER2 All invasive primary breast cancers are analyzed for at least estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 gene ERBB2 (HER2), as these markers have been shown to be the most important prognostic and predictive factors in breast cancer. The patients with ER þ primary invasive breast cancer derive considerable benefit from endocrine therapy, while ER-negative tumors do not. Similarly to ER expression, PR expression by immunohistochemistry also provides prognostic and predictive information. 1,2 Accurate determination of biomarkers is essential for the proper management of breast cancer patients. [3][4][5][6][7][8] The HER2 is overexpressed in B15-20% of breast carcinomas. 9-11 HER2 positivity is associated with higher rate of recurrence and mortality in newly diagnosed breast cancer patients, and agents that t...

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“…Among postmenopausal women, earlier studies have shown a significant trend in reduction of recurrence rate with higher ER levels among tamoxifen treated, supporting the significance of stronger ER content in endocrine treatment [5][6][7][8].…”

Section: Discussionmentioning

confidence: 91%

“…Remaining research questions include the benefit of LHRH agonists, in addition to tamoxifen, and if LHRH agonists have a role among those not achieving amenorrhea during cytotoxic chemotherapy. Moreover, efficacy of endocrine treament in relation to estrogen receptor (ER) status is mainly established among postmenopausal women, and the different endocrine milieu in premenopausal women may affect the predictive ability of ER status [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Interaction between goserelin and tamoxifen in a prospective randomised clinical trial of adjuvant endocrine therapy in premenopausal breast cancer

Sverrisdóttir

Johansson

et al. 2011

Breast Cancer Res Treat

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Interaction between goserelin and tamoxifen in a prospective randomised clinical trial of adjuvant endocrine therapy in premenopausal breast cancer. Breast Cancer Research and Treatment, Springer Verlag, 2011, 128 (3) Abstract: Ovarian ablation improves survival in premenopausal early breast cancer, but the potential added value by luteinizing hormone-releasing hormone (LHRH) agonists to tamoxifen, is still not clear. The purpose of our study is to examine the efficacy of the LHRH agonist goserelin for adjuvant therapy of premenopausal breast cancer, the role of interaction between goserelin and tamoxifen, and the impact of estrogen receptor (ER) content. A total of 927 patients were included in the Stockholm part of the Zoladex in Premenopausal Patients (ZIPP) trial. They were randomly allocated in a 2 x 2 factorial study design to goserelin, tamoxifen, the combination of goserelin and tamoxifen or no endocrine therapy for 2 years, with or without chemotherapy. This is formally not a preplanned subset analysis presenting the endpoint first event. In this Stockholm sub-study, at a median follow up of 12.3 years, goserelin reduced the risk of first event by 32 % (P = 0.005) in the absence of tamoxifen, and tamoxifen reduced the risk by 27 % (P = 0.018) in the absence of goserelin. The combined goserelin and tamoxifen treatment reduced the risk by 24 % (P = 0.021) compared to no endocrine treatment. In highly ER positive tumours, there were 29% fewer events among goserelin treated (P = 0.044) and a trend towards greater risk reduction depending on the level of ER content. The greatest risk reduction from goserelin treatment was observed among those not receiving tamoxifen (HR: 0.52, P = 0.007). In conclusion, goserelin as well as tamoxifen, reduces the risk of recurrence in endocrine responsive premenopausal breast cancer. Women with strongly ER positive tumours may benefit more from goserelin treatment. The combination of goserelin and tamoxifen is not superior to either modality alone. With the limitations of a subset trial, these data have to be interpreted cautiously.

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Influence of tumor estrogen and progesterone receptor levels on the response to tamoxifen and chemotherapy in primary breast cancer.

Cited by 244 publications

References 9 publications

Loss of Expression and Aberrant Methylation of the CDH1 (E-cadherin) Gene in Breast Cancer Patients from Kashmir

Loss of Expression and Aberrant Methylation of the CDH1 (E-cadherin) Gene in Breast Cancer Patients from Kashmir

The effect of cold ischemic time on the immunohistochemical evaluation of estrogen receptor, progesterone receptor, and HER2 expression in invasive breast carcinoma

Interaction between goserelin and tamoxifen in a prospective randomised clinical trial of adjuvant endocrine therapy in premenopausal breast cancer

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