-
[show abstract]
[hide abstract]
ABSTRACT: Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that hydrolyzes ubiquitin. Previous reports have shown both tumorigenic and antitumorigenic roles for UCHL1. However, the expression patterns of UCHL1 protein, an area that is critical for validating its clinicopathologic roles among subtypes of breast cancer, is still lacking. Here we examined the expression of UCHL1 by immunohistochemistry in 243 breast carcinomas of various subtypes. We found expression of UCHL1 in 8.3% of invasive ductal carcinomas but not in other carcinoma subtypes, except for metaplastic carcinomas of the breast, which showed UCHL1 staining in 61.9% of cases, with the sarcomatous components being more intensely stained. UCHL1 expression in invasive ductal carcinomas significantly correlated with a high histologic grade (P = .001), the triple-negative phenotype (P = .02), and the basal-like phenotype (P <.001); furthermore, it was associated with poorer overall survival by univariate and multivariate analyses. Knockdown of UCHL1 in an invasive Snail variant-transfected MCF7 cells with high endogenous UCHL1 protein level significantly reduced invasion and anchorage-independent growth. Conclusively, our results demonstrate a role for UCHL1 in aggressive phenotypes in breast carcinoma. The high expression of UCHL1 in metaplastic carcinomas of the breast, which is pathogenically related to epithelial-mesenchymal transition, may implicate an association between UCHL1 expression and the epithelial-mesenchymal transition in breast cancer.
Human pathology 05/2013; · 3.03 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: The abundance of circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPs), which serve as surrogate markers for angiogenesis, may be affected by chemotherapy. We studied their dynamic change during consecutive cycles of chemotherapy. METHODS: We collected blood samples from 15 breast cancer patients, who received a total of 56 courses of systemic chemotherapy, and measured the CECs, viable CECs (V-CECs), and CEPs by six-color flow cytometry within the seven days prior to chemotherapy, twice a week during the first and second cycles of chemotherapy, and then once a week during the subsequent cycles. RESULTS: The CEC, V-CEC, and CEP levels all significantly decreased from day 1 of treatment to the first week of chemotherapy. After one week of chemotherapy, the CEC and V-CEC levels returned to a level similar to day 1. The CEP level remained significantly reduced after the first week of chemotherapy, but gradually rebounded until the next course of chemotherapy. After six cycles of chemotherapy, the total number of CEC and V-CEC cells trended toward a decrease and the CEP cells toward an increase. Clinical factors, including the existence of a tumor, chemotherapy regimens, and the use of granulocyte colony stimulating factor, did not significantly affect these results. CONCLUSIONS: The CEC and CEP counts change dynamically during each course of chemotherapy and after the chemotherapy cycles, providing background data for any future study planning to use CECs and CEPs as surrogate markers of angiogenesis in antiangiogenesis treatments combined with chemotherapy.
BMC Cancer 12/2012; 12(1):620. · 3.01 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: AIMS: The ESR1 gene encodes for oestrogen receptor (ER) α, which plays a crucial role in mammary carcinogenesis and clinical outcome in patients with breast cancer. However, the clinical significance of the ESR1 gene copy number change for breast cancer has not been clarified. METHODS: ESR1 gene copy number was determined by fluorescence in situ hybridisation (FISH) on tissue sections. A minimum of 20 tumour cells were counted per section, and a FISH ratio of ESR1 gene to CEP6 ≥2.0 was considered ESR1 amplification. A ratio >1.2 but <2.0 was considered ESR1 gain. The ESR1 copy number was further measured by quantitative real-time PCR (Q-PCR) with ASXL2 as a reference. RESULTS: FISH revealed ESR1 amplification in six cases (4.0%) and ESR1 gain in 13 cases (8.7%) from a total of 150 cases. ESR1 gain and amplification were more common in older patients (p<0.001), and correlated well with ER protein expression (p=0.03) measured by immunohistochemistry, and ESR1 copy number (p<0.001) measured by Q-PCR. Furthermore, the multivariate analysis revealed that ESR1 amplification was associated with a shorter disease-free survival (HR=5.56, p=0.03) and a shorter overall survival (HR=5.11, p=0.04). CONCLUSIONS: In general, the frequency of ESR1 amplification in breast cancer is low when measured by FISH in large sections. ESR1 gain and amplification in breast cancer may be associated with older age and poorer outcomes.
Journal of clinical pathology 12/2012; · 2.43 Impact Factor
-
Journal of Clinical Oncology 10/2012; · 18.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Diabetes mellitus (DM) has been implicated in influencing the survival duration of patients with breast cancer. However, less is known about the impact of DM and other comorbidities on the breast cancer-specific survival (BCS) and overall survival (OS) outcomes of Asian patients with early-stage breast cancer.
The characteristics of female patients with newly diagnosed, early-stage breast cancer were collected from the Taiwan Cancer Registry database for 2003-2004. DM status and other comorbidities were retrieved from Taiwan's National Health Insurance database. The BCS and OS times of patients according to DM status were estimated via the Kaplan-Meier method. Cox's proportional hazard model was used to estimate adjusted hazard ratios (HRs) for the effects of DM, comorbidities, and other risk factors on mortality.
In total, 4,390 patients were identified and 341 (7.7%) presented with DM. The 5-year BCS and OS rates were significantly greater in DM patients than in non-DM patients (BCS, 85% versus 91%; OS, 79% versus 90%). Furthermore, after adjusting for clinicopathologic variables and comorbidities, DM remained an independent predictor of shorter BCS (adjusted HR, 1.53) and OS (adjusted HR, 1.71) times. Subgroup analyses also demonstrated a consistent prognostic influence of DM across different groups.
In Asian patients with early-stage breast cancer, DM is an independent predictor of lower BCS and OS rates, even after adjusting for other comorbidities. The integration of DM care as part of the continuum of care for early-stage breast cancer should be emphasized.
The Oncologist 04/2012; 17(4):485-91. · 3.91 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Moesin belongs to the ERM (ezrin, radixin and moesin) family. Recent in-vitro studies have shown the possible involvement of moesin in epithelial-mesenchymal transition (EMT), but correlating in-vivo evidence is lacking.
To study the biological significance of moesin, we used immunohistochemistry to investigate the in-situ expression profiles of moesin in 322 breast carcinomas of different subtypes, including 23 cases of metaplastic carcinoma (MCB) which is pathogenetically considered to involve EMT. Moesin was highly expressed in 95.7% of cases of MCB, and in 16% of cases of invasive ductal carcinoma (IDC), but was negative in all other subtypes of breast carcinomas. In IDCs, moesin expression correlated positively with a high histological grade (P < 0.001), basal-like phenotype (P < 0.001) and poor overall survival (P = 0.0263). Transfection of MCF7 cells with Snail, one of the key regulators of EMT, showed up-regulation of moesin at the transcriptional level. Finally, mRNA level of moesin correlated positively with Snail and EMT-related genes in a microarray data set using primary breast cancer samples.
These results offer biological evidence of moesin as an EMT marker, support the association between moesin, Snail and EMT and suggest a role for moesin in breast cancer prognostication.
Histopathology 03/2012; 61(1):78-87. · 3.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Radiotherapy is integrated into the multimodal treatment of localized hepatocellular carcinoma (HCC) refractory to conventional treatment. Tumor control remains unsatisfactory and the sublethal effect associates with secondary spread. The use of an effective molecularly targeted agent in combination with radiotherapy is a potential therapeutic approach. Our aim was to assess the effect of combining a phenylbutyrate-derived histone deacetylase (HDAC) inhibitor, AR-42, with radiotherapy in in vitro and in vivo models of human HCC.
Human HCC cell lines (Huh-7 and PLC-5) were used to evaluate the in vitro synergism of combining AR-42 with irradiation. Flow cytometry analyzed the cell cycle changes, whereas Western blot investigated the protein expressions after the combined treatment. Severe combined immunodeficient (SCID) mice bearing ectopic and orthotopic HCC xenografts were treated with AR-42 and/or radiotherapy for the in vivo response.
AR-42 significantly enhanced radiation-induced cell death by the inhibition of the DNA end-binding activity of Ku70, a highly versatile regulatory protein for DNA repair, telomere maintenance, and apoptosis. In ectopic xenografts of Huh-7 and PLC-5, pretreatment with AR-42 significantly enhanced the tumor-suppressive effect of radiotherapy by 48% and 66%, respectively. A similar combinatorial effect of AR-42 (10 and 25 mg/kg) and radiotherapy was observed in Huh-7 orthotopic model of tumor growth by 52% and 82%, respectively. This tumor suppression was associated with inhibition of intratumoral Ku70 activity as well as reductions in markers of HDAC activity and proliferation, and increased apoptosis.
AR-42 is a potent, orally bioavailable inhibitor of HDAC with therapeutic value as a radiosensitizer of HCC.
International journal of radiation oncology, biology, physics 02/2012; 83(2):e181-9. · 4.59 Impact Factor
-
Wen-Hong Kuo,
Po-Han Lin,
Ai-Chu Huang,
Yin-Hsiu Chien,
Tsang-Pai Liu, Yen-Shen Lu,
Li-Yuan Bai,
Aaron M Sargeant,
Ching-Hung Lin,
Ann-Lii Cheng,
Fon-Jou Hsieh,
Wuh-Liang Hwu,
King-Jen Chang
[show abstract]
[hide abstract]
ABSTRACT: Although evidence suggests an importance of genetic factors in the development of breast cancer in Taiwanese (ethnic Chinese) women, including a high incidence of early-onset and secondary contralateral breast cancer, a major breast cancer predisposition gene, BRCA1, has not been well studied in this population. In fact, the carcinogenic impacts of many genetic variants of BRCA1 are unknown and classified as variants of uncertain significance (VUS). It is therefore important to establish a method to characterize the BRCA1 VUSs and understand their role in Taiwanese breast cancer patients. Accordingly, we developed a multimodel assessment strategy consisting of a prescreening portion and a validated functional assay to study breast cancer patients with early-onset, bilateral or familial breast cancer. We found germ-line BRCA1 mutations in 11.1% of our cohort and identified one novel missense mutation, c.5191C>A. Two genetic variants were initially classified as VUSs (c.1155C>T and c.5191C>A). c.1155C>T is not predicted to be deleterious in the prescreening portion of our assessment strategy. c.5191C>A, on the other hand, causes p.T1691K, which is predicted to have high deleterious probability because of significant structural alteration, a high deleterious score in the predictive programs and, clinically, triple negative characteristics in breast tumors. This mutant is confirmed by transcription activation and yeast growth-inhibition assays. In conclusion, we show as high a prevalence of germ-line BRCA1 mutation in high-risk Taiwanese patients as in Caucasians and demonstrate a useful strategy for studying BRCA1 VUSs.
Journal of Human Genetics 02/2012; 57(2):130-8. · 2.57 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Thalidomide has been shown to have antitumor activity in some patients with advanced hepatocellular carcinoma (HCC). We initiated a phase II study to determine the safety and efficacy of adding metronomic chemotherapy to thalidomide as first-line therapy.
This open- labeled, single-arm, multicentered, investigator-initiated study enrolled patients with treatment-naïve advanced HCC not amenable to locoregional therapies. Treatment included oral thalidomide (100 mg twice daily) and tegafur/uracil [125 mg/m(2) (based on tegafur) twice daily]. Tumor assessment was performed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. Pretreatment plasma levels of angiogenesis factors were correlated with patient outcomes.
Forty-three patients were included. Sixteen (37%) patients had a Cancer of the Liver Italian Program (CLIP) score of 4, and 31 (72%) patients had chronic hepatitis B virus infection. The objective response rate was 9%, and the disease stabilization rate was 33%. The median progression-free survival was 1.9 months (95% CI 1.7-2.1 months), and the median OS was 4.6 months (95% CI 2.3-6.9 months). Treatment was generally tolerable. High baseline plasma levels of interleukin (IL)-6 and IL-8 were adversely correlated with patient survivals.
The combination of thalidomide and tegafur/uracil was safe and demonstrated modest activity in patients with advanced HCC.
Oncology 01/2012; 82(1):59-66. · 2.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The incidence of breast and genital tract cancers is increasing among Taiwanese women, but the age specificity and histopathological features of these cancers have not been determined. We used a descriptive epidemiological method and data from the Taiwan Cancer Registry (1979-2007) to examine secular trends in the age-specific incidences of female breast cancer, three major female genital tract cancers and the histopathological subtypes of these cancers. Age-specific incidence rates in the United States (1978-2002) were used as an external reference, and the incidence rates of all malignancies and of malignant brain tumors were used as internal references. We found that age-adjusted incidence rates of female breast, uterine, and ovarian cancers increased in Taiwan from 1979 to 2007, whereas the incidence of cervical cancer decreased after 1998. The largest increase was observed for ductal and lobular carcinomas of the breast and endometrioid carcinomas of the uterus and ovary in women ≤55 years, all of these tumors show a high prevalence of hormone receptor expressions. In addition, hormone-receptor-positive rates of breast cancer were uniquely higher in younger, as opposed to older, Taiwanese women. These findings indicate that estrogen-related cancers rapidly emerge in young women in Taiwan and that incidence rates are catching up with that of women living in the United States.
International Journal of Cancer 06/2011; 130(11):2629-37. · 5.44 Impact Factor
-
JAMA The Journal of the American Medical Association 06/2011; 305(22):2288-9; author reply 2290-1. · 30.03 Impact Factor
-
Ching-Hung Lin, Yen-Shen Lu,
Chiun-Sheng Huang,
Kuan-Ting Kuo,
Chung-Chieh Wang,
San-Lin You,
Po-Han Lin,
Dwan-Ying Chang,
Wen-Hung Kuo,
King-Jen Chang,
Ann-Lii Cheng
[show abstract]
[hide abstract]
ABSTRACT: Women aged ≤ 35 years with breast cancer have a poor prognosis, but their prognostic factors have not been clearly defined.
To evaluate whether the molecular markers used in age-unspecified breast cancer could also be applied to women ≤ 35 years.
Archival tumours from patients aged ≤ 35 years with stage I-III breast cancer were collected. Oestrogen receptor (ER), progesterone receptor (PR), HER2, Ki67 and P53 protein expression profiles in paraffin-embedded tissue sections were determined by immunohistochemistry. Tumours with an HER2 score of 2+ were further evaluated by fluorescence in situ hybridisation. Mutational analysis of exons 4-9 of the TP53 gene and exons 9 and 20 of the PIK3CA gene was carried out using direct sequencing analysis.
116 patients with a median follow-up duration of 62.7 months were included. In addition to tumour size and axillary lymph node status, univariate analysis showed that high Ki67 expression, ER-negative, HER2 overexpression, and TP53 mutations were associated with shorter overall survival. Multivariate analysis showed that high Ki67 expression (HR=3.93, p=0.005), HER2 overexpression (HR=3.21, p=0.013) and TP53 mutations (HR=4.44, p=0.005) were associated with shorter overall survival. PR expression and PIK3CA mutations were not associated with survival.
For women ≤ 35 years, TP53 mutations, Ki67 and HER2 expressions are strong prognostic factors. The limited prognostic value of hormone receptors suggests that the prognostic markers used in age-unspecified breast cancer may not be completely fit for this population.
Journal of clinical pathology 06/2011; 64(9):781-7. · 2.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Docetaxel, capecitabine, and cisplatin are effective chemotherapeutic agents for breast cancer with significant synergistic cytotoxicity demonstrated by in vitro studies. The purpose of this study was to assess the efficacy of a combination of docetaxel, capecitabine, and cisplatin (TXP) in patients diagnosed with locally advanced breast cancer (LABC).
Patients (n = 42) with chemotherapy-naïve LABC (stage IIIa or IIIb) were enrolled. The chemotherapeutic regimen consisted of 4-6 cycles of intravenous docetaxel (60 mg/m(2)) and cisplatin (50 mg/m(2)) on day 1, plus oral capecitabine (1,800 mg/m(2)/day) on day 1-14, repeated every 3 weeks. Upon completion of therapy, the primary tumor was resected when not contraindicated.
Median patient age was 48.5 years (range 31-66 years). Median tumor size was 6.8 cm (range 2.7-15 cm), 29 patients were node-positive, and 12 patients were hormone receptor positive. A total of 216 cycles (median 5; range 3-6 cycles) were administered without prophylactic G-CSF. The predominant toxicities were grade 3/4 neutropenia (30%/28%) and no grade 3/4 thrombocytopenia, febrile neutropenia, or grade 4 non-hematological toxicities were observed. Grade 3 non-hematological toxicities included hand-foot syndrome (5.6%) and vomiting (0.5%). The overall clinical response rate was 97.6% (41/42). Six of the 42 patients (14.3%) achieved a complete pathological response. Of 22 patients who completed 6 cycles of combination treatment, the complete pathological response was 27.3% (6/22).
A combination of TXP can be administered safely without prophylactic G-CSF, and appears to be an effective neoadjuvant regimen in patients with LABC.
Cancer Chemotherapy and Pharmacology 06/2011; 67(6):1257-63. · 2.83 Impact Factor
-
Jane Wang,
Tiffany Ting-Fang Shih,
Ruoh-Fang Yen, Yen-Shen Lu,
Chin-Yu Chen,
Tsui-Lien Mao,
Ching-Hung Lin,
Wen-Hung Kuo,
Yuh-Show Tsai,
King-Jen Chang,
Kuo-Liong Chien
[show abstract]
[hide abstract]
ABSTRACT: Evidence on breast infrared (IR) imaging and its association with estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) statuses of breast cancers is limited. The aim of this study was to investigate the association of IR imaging findings and ER, PR, and HER2 status in breast cancers.
A total of 163 women with 171 pathologically proven breast cancers underwent IR imaging of the breast before surgery. Five IR signs were used to score the lesions: IR1, the temperature difference (ΔT) of the lesion site from that of the contralateral mirror image site; IR2, ΔT of the lesion site from that of the adjacent normal breast tissue in the same breast; IR3, abnormal vascular morphologic patterns; IR4, focal bulge or edge sign with back heat at the lesion site; and IR5, asymmetric thermographic pattern between the lesion site and the contralateral breast. The association of different IR signs with ER, PR, and HER2 status was evaluated using Fisher's exact test.
IR1 was inversely associated with ER (P = .010) and PR status (P = .039). IR2 was inversely related to PR status (P = .020). IR5 was inversely associated with ER (P = .037) and PR (P = .022) status. No IR sign was associated with HER2 status. Triple-negative (ER-negative, PR-negative, and HER2-negative) cancers tended to show higher IR1 scores compared to other types of cancers (P = .029).
Breast IR findings were associated with ER and PR status of breast cancers. Triple-negative cancers more frequently featured higher IR1 scores than other types of cancers.
Academic radiology 02/2011; 18(2):212-9. · 2.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Both IκB kinase (IKK) complex and oncgenic protein Myc play important roles in cancer progression, including cancer cell invasiveness and metastasis. The levels of Myc is regulated by the phosphorylation of Myc at Thr58 and Ser62.
In this study, we show that the expression of Myc is associated with IKKα and IKKβ in breast cancers and that Myc is an IKKs substrate. Suppression of IKK activity by either chemical inhibitor or transfection of kinase-dead mutants decreases the phosphorylation of Myc at Ser62 and enhances the degradation of Myc. Consequently, these treatments decrease the tumorigenic and invasive ability of breast cancer cells. Furthermore, doxorubicin, a frequently used anticancer drug in breast cancer, activates IKKs and Myc, thereby increasing invasiveness and tumorigenesis of breast carcinoma MCF7 cells. Inhibition of IKKs prevents these doxorubicin-induced effects.
Our study indicates that IKKs tightly regulate Myc expression through prolonging protein stability, and suggests that IKKs are potentially therapeutic targets and that suppression of IKKs may be used following chemotherapy to reduce the risk of treatment-induced tumor progression.
Molecular Cancer 01/2011; 10:53. · 3.99 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Single-agent mammalian target of rapamycin complex 1 (mTORC1) inhibitors have recently been reported as effective salvage treatment in non-Hodgkin lymphoma (NHL). The combined effect of mTORC1 inhibitor, RAD001, with chemotherapeutic agents used for relapsed or refractory NHL was examined. Synergistic interactions were observed for RAD001 plus gemcitabine or paclitaxel in six NHL cell lines; enhanced gemcitabine- and paclitaxel-induced caspase-dependent apoptosis associated with down-regulation of mTOR signaling was detected. Synergistic interactions were also observed with RAD001 plus gemcitabine and paclitaxel. In conclusion, synergistic cytotoxicity was observed with RAD001 plus gemcitabine and paclitaxel in NHL cells. Combination therapy with these three drugs should be examined in patients with refractory or relapsed NHL.
Cancer letters 12/2010; 298(2):195-203. · 4.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cancer-related acute disseminated intravascular coagulation (DIC) is uncommon, but it is a severe complication resulting in a very dismal prognosis. Choosing the appropriate chemotherapy agents to treat the underlying cancer and stop the acute DIC process effectively, while avoiding chemotherapy-induced myelosuppression which may contribute to bleeding-related mortality, is difficult. Acute DIC in breast cancer is a rare condition and is not well studied. Therefore, we designed this study to determine the clinical characteristics and effective treatment for breast cancer patients with acute DIC.
From March 1996 to November 2008, patients with histologically proven breast cancer who presented with acute DIC at National Taiwan University Hospital were retrospectively analyzed.
Sixteen patients were included in the study. Thirteen patients with breast cancer-related acute DIC were treated with various kinds of chemotherapy, one with tamoxifen, and two with supportive care only. Four patients responded to treatment; three of the responders received vinorelbine with high-dose 5-fluorouracil and leucovorin (HDFL), the other received vinorelbine with cisplatin. The median survival of the responders and non-responders was 13 months and 0.5 month (p<0.001). There were no grade 3 or 4 hematologic or non-hematologic toxicities in the patients receiving vinorelbine-HDFL.
Vinorelbine plus HDFL is considered a safe and effective palliative treatment of choice for breast cancer patients with acute DIC. Further prospective study is warranted.
Anticancer research 07/2010; 30(7):3087-91. · 1.73 Impact Factor
-
Yu-Yun Shao,
Kuan-Ting Kuo,
Fu-Chang Hu, Yen-Shen Lu,
Chiun-Sheng Huang,
Jau-Yu Liau,
Wei-Chung Lee,
Chiun Hsu,
Wun-Hon Kuo,
King-Jeng Chang,
Ching-Hung Lin,
Ann-Lii Cheng
[show abstract]
[hide abstract]
ABSTRACT: We studied tau and excision repair cross-complementing 1 expression to evaluate their predictive values in advanced breast carcinoma patients.
Patients treated with paclitaxel and cisplatin as the first-line chemotherapy for locally advanced or metastatic breast cancer were enrolled. The expression levels of tau and excision repair cross-complementing 1 were assessed by immunohistochemistry and examined for their associations with treatment response and survival.
Fifty-four patients were included in this study. Despite the strong association between tau expression and lower histological grade and estrogen receptor expression, tau expression remained an independent predictor for a lower response rate in multivariate analysis (odd ratio = 0.24, P = 0.02). However, tau expression was a predictor for longer overall survival in both univariate analysis (median, 57.5 vs. 30.4 months, P = 0.02) and multivariate analysis (hazard ratio = 0.36, P = 0.008). Excision repair cross-complementing 1 was not associated with treatment response or overall survival.
Tau expression but not excision repair cross-complementing 1 in advanced breast cancer predicts poor response to combination chemotherapy of paclitaxel and cisplatin. However, tau expression is significantly associated with longer overall survival.
Japanese Journal of Clinical Oncology 04/2010; 40(4):286-93. · 1.78 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Breast carcinoma is one of the most common cancers in women and is known to arise from a multifactorial process, the effect of reproductive risk factors strongly supporting a hormonal role in its etiology. Breast cancer in Asia is characterized by a lower incidence than in Western populations, but is still the leading type of cancer in Asian women, and a significant increasing tread indicates that it is an issue of particular public health importance. Asian breast cancer is characterized by early tumor onset, showing a relatively younger median age at diagnosis. Recently, scientists began to explore the tumorigenic mechanisms underlying breast cancer formation at the molecular level. Both a candidate-gene approach and genome-wide association studies have yielded crucial insights into breast cancer susceptibility genes initiating breast tumorigenesis. As expected, ethnic/racial variation in the genotypic frequency of these genes results in differences in breast cancer incidence in different populations. Furthermore, the question of how important these genes are in Asian breast cancer remains to be explored. It has been demonstrated that gene expression profiles and gene sets are prognostic and predictive for patients with breast cancer. Originally, due to its early onset, it was speculated that Asian breast cancer would have a higher frequency of the basal-like subtype of breast cancer, a molecular subtype characterized by poor differentiation, resulting in a relatively poor progression; however, recent findings do not support this speculation. The frequency of the luminal-A subtype of breast cancer, characterized by estrogen receptor expression, is similar to that in breast cancer in Caucasian, supporting the usefulness of hormone-based therapy in Asian breast cancer.
The Journal of steroid biochemistry and molecular biology 02/2010; 118(4-5):300-3. · 2.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To compare the prognostic prediction between dichotomized and fractionated evaluations of hormone receptor expressions.
Patients with stages I-III breast cancers, who received adjuvant tamoxifen, were enrolled. The expression of estrogen receptor (ER) and progesterone receptor (PR) was evaluated by immunohistochemistry (IHC). A fractionated score (F score), the percentage of positive-staining nuclei (0=none, 1=1%-10%, 2=11%-30%, 3=31%-50%, 4=51%-70%, and 5=71%-100%), was assigned to each case. The dichotomized scoring method defines an F score >1 as positive. The prognostic values of both scores were compared by multiple Cox's proportional hazard models of disease-free survival (DFS) and overall survival (OS).
Four hundred and sixteen patients with a median follow-up of 78.0 months were included. F scores for ER and PR correlated directly with DFS and OS. Although both the dichotomized and fractionated ER and PR scores were significantly associated with DFS and OS in univariate analyses, only fractionated ER and PR scores remained as independent prognostic factors of DFS and OS in the final multiple Cox's proportional hazard models.
Fractionated IHC hormone receptor expression evaluation enhances the prognostic prediction compared with a dichotomized assessment.
Journal of Zhejiang University SCIENCE B 01/2010; 11(1):1-9. · 1.10 Impact Factor
