• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7959-7964
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• 2014

The significance of the single hormone receptor positive phenotype of breast cancer is still poorly understood. The use of hormone therapy has been found to be less effective for this type, which has a survival outcome midway between double positive and double negative phenotypes. The aim of this study was to investigate differences in patient and tumor characteristics and survival between double-receptor positive (ER+PR+), double receptor negative (ER-PR-) and single receptor positive (ER+PR- and ER-PR+) breast cancer in an Asian setting. A total of 1,992 patients with newly diagnosed stage I to IV breast cancer between 2003 and 2008, and where information on ER and PR were available, were included in this study. The majority of patients had ER+PR+ tumors (n=903: 45.3%), followed by 741 (37.2%) ER-PR-, 247 (12.4%) ER+PR-, and 101 (5.1%) ER-PR+ tumors. Using multivariate analysis, ER+PR- tumors were 2.4 times more likely to be grade 3 compared to ER+PR+ tumors. ER+PR- and ER-PR+ tumors were 82% and 86% respectively less likely to be grade 3 compared with ER-PR- tumors. ER-PR+ tumours were associated with younger age. There were no survival differences between patients with ER+PR+ and ER-PR+ tumors. However, ER+PR- tumors have poorer survival compared with ER+PR+ tumours. ER-PR- tumours had the worst survival. Adjuvant hormonal therapy with tamoxifen was found to have identical survival advantage in patients with ER+PR+ and ER-PR+ tumors whereas impact was slightly lower in patients with ER+PR- tumors. In conclusion, we found ER+PR- tumors to be more aggressive and have poorer survival when compared to ER+PR+ tumors, while patients with ER-PR+ tumours were younger, but had a similar survival to their counterparts with ER+PR+ tumours.

• Korean Journal of Clinical Laboratory Science
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• v.36 no.2
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• pp.185-192
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• 2004

Overexpressions of the estrogen receptors(ER), progesterone receptors(PR) and C-erbB-2 protein are important determiners of the response to chemotherapy in the breast cancer. For detecting ER, PR and C-erbB-2, immunohistochemistry are currently regarded as standard method. The purposes of this study compared to histologic grade and expression of the ER, PR and C-erbB-2 in breast cancer. We examined overexpression of ER, PR and C-erbB-2 protein in 84 breast carcinomas by using immunohistochemical stains. The following results were obtained. For histologic grade, 10 cases(11.9%) showed carcinoma in situ, 16 cases(19%) showed grade I, 36 cases (42.9%) showed grade II, and 22 cases(26.2%) showed grade III among the 84 test samples. The average positive rate ER and PR was 63%, 46% showed carcinoma in situ, 80%, 60% showed grade I, 64%, 41% showed grade II, 34%, 23% showed grade III, respectively. The induction of PR increased when induction of ER increased, thus showing significant relationship(p<0.05). The expression of C-erbB-2 protein was 9 cases(10.7%) in one positive(1+), 9 cases(10.7%) in two positive(2+), and 9 cases(10.7%) in three positive(3+). C-erbB-2 protein expression showed no statistical significance. In conclusion, ER and PR positive rates were inversely associated with histologic grades significantly(p<0.05). C-erbB-2 showed no significant difference with histologic grade. However ER, PR and C-erbB-2 showed significant relationship with each other(p<0.05). Therefore, these findings might be an important prognostic factor and might be arranged as a regular pathological examination in cases of breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8395-8400
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• 2014

In Saudi Arabia, cancer of breast is ranked the most frequent neoplasm and second source of cancer death in the female population. Breast cancer (BC) fast diagnosis, prognosis and medication management necessitate, these days, immunohistochemistry (IHC) assessment of hormone receptors and HER2 expression profile. The present report defines the IHC profile of ER, PR and HER2 in Saudi female breast neoplasms of ductal and lobular types and associations ER, PR and HER2 expression patterns with various clinicopathological factors (age, type of tumor, size, laterality, histological grade, and involvement of axillaries lymph nodes). Ninety nine cases of breast tumors were recruited from the pathology department archive of King Abdulaziz University Hospital, Kingdom of Saudi Arabia. ER, PR and HER2 expression was assessed using IHC staining. Ductal carcinomas with a variety of histological grades constituted 88 (88.8%) of total cases. Seventy four (77.8%), 59 (62.1%), and 35 (36.8%) of ductal carcinomas showed positive staining for ER, PR and HER2, in that order. Remaining breast cancer cases were four (4%) lobular carcinomas and two (2%) mixed form of ductal and lobular types, which were ER+, PR+, and HER2-. Breast cancer expression pattern of ER, PR and HER2 in Saudi female is different from that of Tunisian and Jordanian female populations and closer to the expression pattern of Egyptian, Lebanese, Iraqi and western country females. Furthermore, the present study found two IHC patterns of breast cancer ER+/PR-/HER2+ (5%) and ER+/PR-/HER2- (11.1%), which had not been reported in other Arabic studies. Thus the rates of IHC expression patterns in breast cancer show some variation among Arabic female populations.

• Journal of Yeungnam Medical Science
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• v.28 no.2
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• pp.153-164
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• 2011

Background: It has been reported that estrogen receptor beta ($ER{\beta}$) mRNA expression was down-regulated during carcinogenesis and was inversely related to estrogen receptor alpha ($ER{\alpha}$) expression in breast cancer. The association of $ER{\beta}$ mRNA expression to tamoxifen resistance has also been reported. In this study, the expression of $ER{\alpha}$ and $ER{\beta}$ via immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) was prompted, and an attempt was made to find out the relationship between $ER{\beta}$ expression and recurrence in the hormonal therapy group, and between $ER{\beta}$ expression and known prognostic factors. Methods: Tumor specimens were obtained at surgery from 67 female breast cancer patients during the period of September 1995 to December 2000. All the specimens were frozen in liquid nitrogen and kept at $-70^{\circ}C$ until they were used. The medical records were analyzed retrospectively. The expressions of ER were analyzed using IHC and RT-PCR methods. Results: The median follow-up was at 93.0 months (range: 14-157 months). The percentage of $ER{\alpha}+/ER{\beta}+$, $ER{\alpha}+/ER{\beta}-$, $ER{\alpha}-/ER{\beta}+$, and $ER{\alpha}-/ER{\beta}$ group were 35.9% 9.4%, 47.2%, and 7.5%, respectively, in 53 patients with hormonal therapy. $ER{\beta}$ was positive in 42 (82.3%) of 51 ER-positive patients. In the hormonal therapy group, the recurrence rates of each group was 15.8%, 0%, 40.0%, and 0%, respectively. In this group, the $ER{\beta}$ expression tended to recur, but there was no clinical significance (p=0.084). Conclusion: The $ER{\beta}$ expression may be a predictive marker of a poor response to endocrine therapy in breast cancer patients, although this needs to be confirmed in additional studies.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1077-1082
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• 2016

Background: The three standard biomarkers used in breast cancer are the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The Ki-67 index, a proliferative marker, has been shown to be associated with a poorer outcome, and despite absence of standardization of pathological assessment, is widely used for therapy decision making. We aim to study the role of the Ki-67 index in a group of Asian women with breast cancer. Materials and Methods: A total of 450 women newly diagnosed with Stage 1 to 3 invasive breast cancer in a single centre from July 2013 to Dec 2014 were included in this study. Univariable and multivariable logistic regression was used to determine the association between Ki-67 (positive defined as 14% and above) and age, ethnicity, grade, mitotic index, ER, PR, HER2, lymph node status and size. All analyses were performed using SPSS Version 22. Results: In univariable analysis, Ki -67 index was associated with younger age, higher grade, ER and PR negativity, HER2 positivity, high mitotic index and positive lymph nodes. However on multivariable analysis only tumour size, grade, PR and HER2 remained significant. Out of 102 stage 1 patients who had ER positive/PR positive/HER2 negative tumours and non-grade 3, only 5 (4.9%) had a positive Ki-67 index and may have been offered chemotherapy. However, it is interesting to note that none of these patients received chemotherapy. Conclusions: Information on Ki67 would have potentially changed management in an insignificant proportion of patients with stage 1 breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.873-877
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• 2012

MicroRNAs (miRNAs) are short non-coding RNA molecules characterized by their regulatory roles in cancer and gene expression. We analyzed the expression of miR-21, miR-205, and miR-342 in 59 patients with breast cancer. Samples were divided into three different groups according to their immunohistochemistry (IHC) classification: ER- positive and/or PR-positive group ($ER^+$ and/or $PR^+$; group I); HER2-positive group ($HER^{2+}$; group II); and ER/ PR/ HER2- negative ($ER^-$/ $PR^-$/ $HER^{2-}$; group III) as the triple negative group. The expression levels of the 3 miRNAs were analyzed in the tumor samples and the compared with the normal neighboring dissected tumor (NNDT) samples in all three groups. The expression of miR-21 was similar in all three groups. In patients positive for P53 by IHC, positive for axillary lymph node metastasis and higher tumor stages, it appeared to have significantly elevated. However, significant increase was not found among the 18 fibroadenoma samples. Both miR-205 and miR-342 expressions were significantly down regulated in group III. We conclude that miR-21 does not discriminate between different breast cancer groups. In contrast, miR-205 and miR-342 may be used as potential biomarkers for diagnosis of triple negative breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1707-1713
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• 2015

Eighty six cases of invasive ductal breast carcinomas were utilized to investigate GSTP1 polymorphisms in certain immunohistochemistry (IHC) subtypes of breast cancer with respect to ER, PR and HER2 expression. The frequency of wild allele homozygote, heterozygote and variant allele homozygote genotypes were 46.5%, 52.3% and 1.16% respectively; Whereas 54.3% of the control subjects were GSTP1 wild type allele homozygous, 40.0% were heterozygous and 5.71% mutant allele homozygous. There was dramatic inverted relation between positive IHC ER staining and increasing grade of tumors in general (100%, 88.6%, 40.4%) and especially among tumors with heterozygote genotype of GSTP1 (70%, 35.4%, 22.7). There was increase in positive IHC HER2 staining consistent with higher grades in general (20%, 29.6%, 50.0%), especially among tumors with GSTP1 wild allele homozygote genotype (5.0%, 9.1%, 31.8%). A remarkable reverse relation was also observed between the fraction of IHC hormone receptor phenotype ER+/PR+/ HER2- and increased grade of tumors (60.0%, 45.5%, and 27.3%) especially among tumors with GSTP1 heterozygote genotype, and a similar link was noted regarding ER+/PR-/ HER2- and tumor grade. There was increase in frequency of ER-/PR-/ HER2- (0.0%, 6.8%, and 18.2%) and ER-/PR-/ HER2+ (0.0%, 4.54%, and 40.9%) consistent with the higher grades of tumors in general and especially GSTP1 heterozygote genotype tumors. As a conclusion, there is no correlation between GSTP1 polymorphism and increased risk of breast cancer i.e. the mutant allele is randomly distributed in cancer and control cases. However, there is a link between GSTP1 genotypes and hormone receptor expression status and certain phenotypes of breast cancer, which may have clinical importance.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2729-2734
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• 2012

Despite clinical advances in anticancer therapy, there is still a need for novel anticancer metabolites, with higher efficacy and lesser side effects. Oroxylum indicum (L.) Vent. is a small tree of the Bignoniaceae family which is well known for its food and medicinal properties. In present study, the chemopreventive properties of O. indicum hot and cold non-polar extracts (petroleum ether and chloroform) were investigated with MDA-MB-231 (cancer cells) and WRL-68 (non-tumor cells) by XTT assay. All the extracts, and particularly the petroleum ether hot extract (PHO), exhibited significantly (P<0.05) higher cytotoxicity in MDA-MB-231 when compared to WRL-68 cells. PHO was then tested for apoptosis induction in estrogen receptor (ER)-negative (MDA-MB-231) and ER-positive (MCF-7) breast cancer cells by cellular DNA fragmentation ELISA, where it proved more efficient in the MDA-MB-231 cells. Further, when PHO was tested for anti-metastatic potential in a cell migration inhibition assay, it exhibited beneficial effects. Thus non-polar extracts of O. indicum (especially PHO) can effectively target ER-negative breast cancer cells to induce apoptosis, without harming normal cells by cancer-specific cytotoxicity. Hence, it could be considered as an extract with candidate precursors to possibly harness or alleviate ER-negative breast cancer progression even in advanced stages of malignancy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9233-9239
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• 2014

Background: We aimed to evaluate the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression discordance in matched pairs of primary breast cancer and lymph node metastasis specimens and determine the effect of discordance on prognosis. Materials and Methods: Among all patients diagnosed with lymph node metastases from 2004 to 2007, primary tumors and paired lymph node metastases were resected from 209 patients. The status of ER, PR, and HER2 expression was analyzed immunohistochemically in 200, 194, and 193 patients, respectively. Discordance was correlated with prognosis. Results: Biomarker discordance between primary tumors and paired lymph node metastases was 25.0% (50/200) for ER status, 28.9% (56/194) for PR status, and 14.0% (27/193) for HER2 status. ER positivity was a significant independent predictor of improved survival when analyzed in primary tumors and lymph node metastases. Patients with PR-positive primary tumors and paired lymph node metastases displayed significantly enhanced survival compared to patients with PR-positive primary tumors and PR-negative lymph node metastases. Patients with ER- and PR-positive primary tumors and paired lymph node metastases who received endocrine therapy after surgery displayed significantly better survival than those not receiving endocrine therapy. Similalry treated patients with PR-negative primary tumors and PR-positive paired lymph node metastases also displayed better survival than those not receiving endocrine therapy. Conclusions: Biomarker discordance was observed in matched pairs of primary tumors and lymph node metastases. Such cases displayed poor survival. Thus, it is important to reassess receptor biomarkers used for lymph node metastases.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3459-3463
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• 2016

Background: Breast cancer is the second most common cancer in women in Cambodia, a low income country in South-East Asia. The Sihanouk Hospital Centre of Hope (SHCH) is a charity hospital set up by an international non-governmental organisation, HOPE Worldwide. In 2008, SHCH partnered with AmeriCares, a global health organisation to set up and deliver a breast cancer programme to provide education, diagnosis and treatment for women with breast cancer. The objective of this study is to characterise the presentation, diagnosis, treatment and outcomes of women treated under this program. Materials and Methods: A total of 215 women newly diagnosed with breast cancer from 1 March 2008 until 31 March 2011 were studied. Age at diagnosis, tumour size, histological type, tumour grade, ER, lymph node involvement, treatment modalities (surgery, radiotherapy, chemotherapy, hormone therapy) were recorded. Data on mortality at 3 years were obtained whenever possible. Results: The median age was 47 years old. Some 77.8% were diagnosed with stage 3 and 4 lesions, and 78.5% underwent mastectomy, of which 28.4% the intent was palliative. Of those whose ER status were known, only 48.3% were ER positive. Only 6 patients could afford chemotherapy while only 1 patient had radiotherapy. Hormone therapy was provided free for those who were ER positive. The overall survival rate at 3 years was 39.1%. Conclusions: Breast cancer presents at a late stage, and because treatment is suboptimal, survival is poor in Cambodia. A more aggressive approach to early detection and treatment needs to be developed to improve outcome from this potentially curable disease.