Breast Cancer Patients In Taiwan Research Articles

P-317 Risk of endometrial polyps and hyperplasia after tamoxifen treatment in women with breast cancer: a population-based study in Taiwan

Abstract Study question This study aimed to examine the association between tamoxifen treatment and incident risks of uterine disease among breast cancer patients in Taiwan. Summary answer We found tamoxifen treatment group may have greater risk of endometrial polyps and hyperplasia than unexposured group after adjusting for age and body mass index. What is known already In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) breast cancer treatment trail reported that the women continue tamoxifen up to 10 years, compared with 5 years may reduce breast cancer recurrence and mortality rate. However, tamoxifen use has been reported to be associated with the cumulative risk of subsequently endometrial cancer during 5–14 years was 3.1%. Specifically, several Western studies have showed that the high incidence of endometrial cancer in breast cancer survivors with tamoxifen treatment. Study design, size, duration We conducted a retrospective cohort study using population-based data from Taiwan Cancer Registry and the National Health Insurance Research Database (NHIRD), and the National Population Registry Data set from 2011 to 2020. Participants/materials, setting, methods A total 138,934 newly diagnosed breast cancer female patients with age greater than 18 years old were included. We further used a 1-to-1 propensity score matching to generate comparable exposure and un-exposure groups. Cox proportional hazard regression models were used to examine the research question. All statistical analysis was performed using SAS version 9.4, and p-values < 0.05 were considered statistically significant Main results and the role of chance Incidence rate ratio (IRR) to compare incidence rate of uterine disease between tamoxifen treatment groups and unexposed group, adjusting for age and BMI. Our results showed that IRR were 1.36, 0.33, 3.73, 0.63, endometrial polyps, endometrial carcinoma, endometrial hyperplasia and uterine carcinosarcoma, respectively. This study found possible correlations between tamoxifen exposure with endometrial polyps and hyperplasia among breast cancer. During the 10-year study period, tamoxifen group did not significantly increase the risk of endometrial cancer in breast cancer survivors at aged 40 and over. Limitations, reasons for caution Our cohort study with 10-year period is its short study period, Tamoxifen group did not significantly increase the risk of endometrial cancer. Wider implications of the findings This cohort study found higher endometrial polyps and hyperplasia incidence rates among women with breast cancer who received tamoxifen women than those not treated with tamoxifen. Results of this study suggest that clinicians should consider the risk of uterine disease among tamoxifen use and counsel patients accordingly. Trial registration number KMUHIRB-G(II)20200217

The Use of San-Huang-Xie-Xin-Tang Reduces the Mortality Rate among Breast Cancer Patients

Globally, breast cancer is the most common cause of cancer deaths. In Taiwan, it is the most prevalent cancer among females. Since San-Huang-Xie-Xin-Tang (SHXXT) exerts not only an anti-inflammatory but an immunomodulatory effect, it may act as a potent anti-tumor agent. Herein, the study aimed to explore the influence of SHXXT and its constituents on the mortality rate among breast cancer patients in Taiwan regarding the component effect and the dose-relationship effect. By using the Taiwan National Health Insurance (NHI) Research Database (NHIRD), the study analyzed 5387 breast cancer patients taking Chinese herbal medicine (CHM) and 5387 breast cancer patients not using CHM. CHM means SHXXT and its constituents in the study. The Kaplan-Meier method was utilized to determine the mortality probabilities among patients. Whether the CHM influences the mortality rate among patients was estimated by Cox proportional hazard regression analysis. The use of CHM could lower the cancer mortality rate by 59% in breast cancer patients. The protective effect was parallel to the cumulative days of CHM use and the annual average CHM dose. In addition, the mortality rate was lower in patients who used SHXXT compared to those who only used one of its constituents. SHXXT and its constituents were all promising therapeutic weapons against breast cancer.

Breast-conserving surgery with whole breast radiation therapy has a subsequent lower mood disorder incidence rate than total mastectomy in early-stage breast cancer patients: a nationwide population-based longitudinal study.

Breast-conserving surgery (BCS) followed by whole breast radiation therapy (BCS-WBRT) or total mastectomy without WBRT (TM-no-WBRT) is the primary treatment for early stage breast cancer patients. Our study aimed to identify which early stage breast cancer treatment strategies had a subsequent lower incidence rate of mood disorder over a period of 10years after the primary treatment. This retrospective cohort study consisted of newly diagnosed early stage breast cancer patients in Taiwan from 2000 to 2013 using the National Health Insurance Research Database in Taiwan. We used a 1:1 propensity score matching by age to enrol patients into the BCS-WBRT and TM-no-WBRT groups. Statistical analyses were performed to calculate the hazard ratio and cumulative incidence rate. Our study consisted of 876 BCS-WBRT patients and 1949 TM-no-WBRT patients. After propensity score matching, each study group included 876 patients. The results showed that the mood disorder incidence rate was lower in the BCS-WBRT group than in the TM-no-WBRT group. Multivariate Cox regression analysis revealed that the BCS-WBRT group had a decreased risk of developing mood disorder (adjusted hazard ratio 0.69, 95% CI 0.53-0.90, p < 0.01). Furthermore, the Kaplan-Meier analysis showed that the BCS-WBRT group had a lower cumulative incidence rate of mood disorder, especially depression, after undergoing 10years of primary treatment (p = 0.004). Our results indicated that BCS-WBRT was associated with a lower risk of development of mood disorder over a 10-year period compared to TM-no-WBRT in early stage breast cancer patients. Our findings may provide helpful information, along with other clinical data, for breast cancer patients as they choose the type of appropriate surgery for treatment.

Risks of trastuzumab-related cardiotoxicity in breast cancer patients in Taiwan

Abstract Aims Despite being an essential therapy for breast cancer, trastuzumab has potential risks of cardiotoxicity. The incidence of trastuzumab-related major adverse cardiac and cerebrovascular event (MACCE) and its predictors remain unknown in Taiwan. Methods and results Through a three-hospital retrospective cohort study, we analyzed the incidence of MACCE in 386 breast cancer patients exposure to trastuzumab from 2010 to 2018. To further reconfirm our findings, in a nationwide study using the Taiwanese National Health Insurance Research Database and National Cancer Registry, we identified 13502 women diagnosed with breast cancer who received chemotherapy from 2010 to 2015 and found 6751 women who received initial treatment with trastuzumab. After 1:1 propensity score matching with trastuzumab nonusers, the incidence of MACCE was measured with a median follow-up of 36 months. In the hospital-based study, among 386 patients receiving trastuzumab, the 5-year incidences of MACCE and heart failure (HF) were 5.4% and 2.8%, respectively. In the national cohort, the crude incidences of MACCEs and HF were 4.67% and 3.21%, respectively. After adjustment for age and comorbidities, the hazard ratio of MACCE was 1.485 (95% CI 1.246–1.769). Notably, among the endpoints, only the hazard ratio of HF was significantly higher in patients receiving trastuzumab than in nonusers. In the subgroup analysis, except for patients also using taxanes, those receiving trastuzumab had a higher risk of MACCE than nonusers. Conclusions From clinical observations in a nationwide cohort, we found an increased risk of MACCE, especially HF, in patients receiving trastuzumab. Given that its cardiotoxicity is independent of traditional cardiovascular risks, our findings highlight critical concerns regarding the cardiac safety of trastuzumab use. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): Chi-Mei Medical Center, National Cheng Kung University Hospital

Risks of trastuzumab-related cardiotoxicity in breast cancer patients in Taiwan.

AimsIn contrast to Western patients with breast cancer, Asian patients are relatively younger at diagnosis, and most are free from traditional cardiovascular risk factors. Despite trastuzumab‐related major adverse cardiac and cerebrovascular event (MACCE) being reported, its incidence and predictors remain unknown in Taiwan.Methods and resultsThrough a three‐hospital retrospective cohort study, we analysed the incidence of MACCE in 386 breast cancer patients' exposure to trastuzumab from 2010 to 2018. To further reconfirm our findings, in a nationwide study using the Taiwanese National Health Insurance Research Database and National Cancer Registry, we identified 13 502 women diagnosed with breast cancer who received chemotherapy from 2010 to 2015 and found 6751 women who received initial treatment with trastuzumab. After 1:1 propensity score matching with trastuzumab non‐users, the incidence of MACCE was measured with a median follow‐up of 36 months. In the hospital‐based study, among 386 patients receiving trastuzumab, the 5‐year incidences of MACCE and heart failure (HF) were 5.4 and 2.8%, respectively. In the national cohort, the crude incidences of MACCEs and HF were 4.67 and 3.21%, respectively. After adjustment for age and comorbidities, the hazard ratio of MACCE was 1.485 (95% CI 1.246–1.769). Notably, among the endpoints, only the hazard ratio of HF was significantly higher in patients receiving trastuzumab than in nonusers. In the subgroup analysis, except for patients also using taxanes, those receiving trastuzumab had a higher risk of MACCE than non‐users.ConclusionsFrom clinical observations in a nationwide cohort, we found an increased risk of MACCE, especially HF, in patients receiving trastuzumab. Given that its cardiotoxicity is independent of traditional cardiovascular risks, our findings highlight critical concerns regarding the cardiac safety of trastuzumab use.

Comprehensive molecular profiling of Taiwanese breast cancers revealed potential therapeutic targets: prevalence of actionable mutations among 380 targeted sequencing analyses

BackgroundBreast cancer is one of the leading causes of cancer-related deaths in women, and there is a demand in developing an Asian-based genetic profiling database for breast cancer in improving the treatment response. This study aimed to determine molecular alternations and identify potential therapeutic targets by analyzing the genetic profiling from a cohort of Taiwanese breast cancers using a commercialized next-generation sequencing (NGS) targeted panel.MethodsThe study population comprised a broad spectrum of breast cancer patients in Taiwan, including Group 1: planned to receive first-line surgery and followed by adjuvant therapy, or early relapse within three years, Group 2: planned to receive first-line neoadjuvant therapy and followed by surgery, and Group 3: de novo stage IV, or stage IV with recurrence beyond three years. Molecular profiles were determined using Thermo Fisher™ Oncomine™ Comprehensive Assay version 3 (TMO comprehensive assay) from Formalin-Fixed Paraffin-Embedded (FFPE) tissues. Level of actionability was evaluated with the ESMO Scale of clinical actionability of molecular targets (ESCAT).ResultsA total of 380 TMO comprehensive assays were conducted on 372 patients, and we presented targeted sequencing analyses of Tier I: alteration-drug match associated with improved outcome in clinical trials including ERBB2 amplification, BRCA1/2 germline mutation, PIK3CA mutation, and NTRK translocation, and Tier II: antitumor activity associated with the matched alteration-drug but lack of prospective outcome data including PTEN loss, ESR1 mutation, AKT1 mutation, and ERBB2 mutation, and Tier III: matched drug-alteration that led to clinical benefit in another tumor type including MDM2 amplification, and ERBB3 mutation. Among them, 249 (66%) showed at least one actionable alternation based on the ESCAT criteria. The most frequent impacted genes (all variants combined within each sample) were PIK3CA (38%), followed by ERBB2 (23%), ESR1 (10%), AKT1 (6%), and BRCA2 (5%), and the remaining rare variants (less than 5% of assayed cohort) were BRCA1 (3%), MDM2 (2.2%), and ERBB3 (1.1%).ConclusionTargeted sequencing of actionable genes is believed to provide clinical applicability and substantial benefits for Taiwanese breast cancer patients. A valid scale of clinical actionability should be adopted for precision medicine practice under multidisciplinary molecular tumor board.

Effectiveness and healthcare costs of eribulin versus capecitabine among metastatic breast cancer patients in Taiwan

ObjectiveTo compare the real-world effectiveness and costs of eribulin to those of capecitabine in patients with metastatic breast cancer (MBC) pretreated with anthracyclines and taxanes. MethodsThis study extracted data from the Health and Welfare Database in Taiwan to identify MBC patients, and then eribulin and capecitabine users were matched at a 1:1 ratio by age, residential region, Charlson Comorbidity Index score, and molecular subtype of BC cell. The overall survival (OS) and time-to-treatment discontinuation (TTD) curves were plotted using the Kaplan–Meier method. Healthcare utilization and costs between the two groups were compared. ResultsA total of 24,550 MBC patients were identified, and 298 patients were enrolled in each group after matching. The median OS was 11.8 months for eribulin (95%CI: 11.5–13.5 months) and 15.2 months for capecitabine (95%CI: 15.3–17.9 months; HR = 1.7, p < 0.0001). The median TTD was 4.0 months for eribulin and 6.6 months for capecitabine (HR = 1.6; p < 0.0001). No significant difference was found between the two groups in patients with >4 prior chemotherapy agents (OS: HR 1.1, 95%CI 0.8–1.5; TTD: HR 1.2, 95%CI 0.9–1.7). The total healthcare costs per patient during the treatment period were NT$580,523.8 for eribulin versus NT$497,223.8 for capecitabine (p < 0.0001), and total medication costs were NT$438,335.8 and NT$348,438.4 (p < 0.0001), respectively. ConclusionAlthough eribulin showed an attenuated effect in the real-world setting in Taiwan, it may serve as an alternative for capecitabine in a heavy pretreated population. The total healthcare and medication costs were found to be higher with eribulin treatment.

Abstract PS2-28: The gut microbial signatures of premenopausal breast cancer in Taiwan

Abstract Background Unlike western countries, breast cancer tends to occur in older and postmenopausal female; in Taiwan, 40% of patients are younger than 50 years old and are mainly diagnosed in premenopausal women. Increasing evidence has demonstrated that microbiome-host interactions may contribute to breast cancer development and treatment in addition to genetic variations. Interestingly, current studies suggest the gut microbial community likely affects the risk for estrogen-related diseases in older adults. We aimed to explore the gut microbial profiles in regarding with menopausal status and elucidate whether the gut microbiomes and related function pathways were different in premenopausal and postmenopausal breast cancer patients in Taiwan. Methods A total of 70 healthy female controls (premenopausal/Pre-C, n=20; postmenopausal/Post-C, n=50) and 146 stage I/II breast cancer patients (premenopausal/Pre-BC, n=70; postmenopausal/Post-BC, n=76) were enrolled in our study. The microbial composition in fecal samples was analyzed using 16S rRNA amplicon sequencing (V3-V4 region) on the Illumina Miseq platform. The obtained data was analyzed using CLC Microbial Genomics Module (Qiagen, Germantown, MD, USA). Linear discriminant analysis effect size (LEfSe) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) were analyzed with Galaxy/HutLab and Metagenomic Profiles (STAMP) software. Results Alpha diversity of the Shannon index was unexpectedly higher in Pre-BC when compared with that of Pre-C. Weighted beta-diversity with the principal coordinate analysis (PCoA) demonstrated that total microbial compositions were significantly different between Pre-C versus Pre-BC (p=0.001) and Post-C versus Post-BC (p=0.054). The Operational Taxonomic Units (OTUs) and Krona analysis showed that the abundance of Proteobacteria was significantly increased in both Pre-BC and Post-BC (p=0.011 and 0.017), whereas Bifidobacterium was significantly reduced in both Pre-BC and Post-BC1 (p&amp;lt;0.001 and 0.009) when compared with the matched controls, Pre-C and Post-BC. We further clarified the microbial markers based on the linear discriminant analysis effect size (LEfSe). As compared with Pre-C, Pre-BC had a much higher abundance of pathogens including Shigella, Clostridium, Haemophilus and others. The total microbial composition was also significantly different between Pre-BC and Post-BC (p=0.001). Intriguingly, the abundance of the microbiomes in alpha-Linolenic acid metabolism was reduced in Pre-BC when compared with Post-BC, whereas alpha-Linolenic acid metabolism were increased in both Pre-BC and Post-BC as compared with their matched controls. Conclusion Our results provide hints that, dysbiosis might be one of triggers or niches in contributing to Taiwan Pre-BC and might modulate multiple signaling pathways in relation to lipid metabolism and pathogen infections. The mechanisms underlying the link of specific gut microbiomes to Taiwan breast cancer require further investigations. Citation Format: Ming-Feng Hou, Chih-Po Chiang, Yao-Tsung Yeh. The gut microbial signatures of premenopausal breast cancer in Taiwan [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-28.

Influence of Traditional Chinese Medicine on Medical Adherence and Outcome in Estrogen Receptor (+) Breast Cancer Patients in Taiwan: A Real-World Population-Based Cohort Study

BackgroundMedical adherence is often higher in clinical trials than in real world practice. The aim of this study was to investigate the effects of traditional Chinese medicine (TCM) on medical adherence to hormonal therapy (HT) and survival outcome in ER (+) breast cancer patients in Taiwan. Subjects and methodsUsing a nationwide longitudinal population-based database, we enrolled patients with newly diagnosed ER-positive breast cancer who had received HT, and followed for up to 5 years (N = 872). Medication adherence in terms of medication possession ratios (MPR) and patient outcome were evaluated with or without TCM exposure. We applied logistic regression and Cox proportional hazards (PH) analysis to identify factors, including TCM exposure, associated with adherence to HT and mortality. ResultsMPR to HT in general decreased over the 5-year period post breast cancer diagnosis. Both TCM and MPR to HT ≥ 80% were significantly associated with reduced risk of breast cancer-associated mortality. Subgroup analysis revealed that TCM annual visits ≥ 3 times with CHP prescription 1~90 days per year affected mortality reduction most significantly (HR: 0.26; 95% CI = 0.08–0.83; p < 0.05) compared to other TCM use. In contrast, using TCM (either short-term or long-term) was not associated with MPR in HT. ConclusionsOur results supported the potential advantage of TCM on breast cancer-associated mortality, whereas TCM use does not compromise medical adherence to HT. This study offers important insights in integrative therapy for HT in patients with estrogen receptor (+) breast cancer.

Recurrence risk stratification by Dutch clinical risk criteria for early-stage luminal breast cancer patients in Taiwan: A population-based analysis.

e12509 Background: Dutch clinical risk criteria (low-risk definition: age &gt; 35 years and (grade 1 with tumor ≤3cm, grade 2 with tumor ≤2cm, or grade 3 with tumor ≤1cm) have been used to stratify the benefit of MammaPrint and Oncotype DX for the decision-making regarding adjuvant chemotherapy for early-stage luminal breast cancer. We propose that the criteria could help to identify low-risk patients who could barely benefit from multi-gene testing. Methods: Breast cancer patients from Taiwan Cancer Database initially treated with primary surgeries between 2008 and 2012 who met the following criteria: (1) pathologic node-negative, (2) hormone receptor-positive, (3) HER2-negative, (4) undergone hormonal therapy, and (5) a minimum follow-up time of 5-year if free from any event, were enrolled in this study. Out of the total 2679 eligible patients, 1074 (40.1%) patients received adjuvant chemotherapy in addition to endocrine therapy. The study endpoints included breast cancer-specific survival (BCSS) and overall survival (OS). Kaplan-Meier statistics estimated the difference between clinical outcomes in low- and high-risk groups. Results: The median follow-up time of BSCC and OS was 5.9 years (range, 0-7 years) and 5.8 years (range, 0-7 years), respectively. There were statistical significances of 5-year BCSS (n = 2679) and 5-year OS (n = 2636) between low-risk and high-risk groups (in both endpoints, P &lt; 0.0001). According to the Dutch criteria, low-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 99.0% vs. 99.2% and a 5-year OS of 98.4% vs. 97.4%, respectively. High-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 97.7% vs. 98.1% and a 5-year OS of 96.4% vs. 95.3%, respectively. Conclusions: The benefit of chemotherapy in low-risk patients classified by Dutch criteria might be very small since the breast cancer mortality was less than 1% with a minimum of 5-year follow-up. Dutch criteria cannot identify high-risk patients who would benefit from chemotherapy. We assumed that multi-gene testing in low-risk patients would not be cost-effective.

A cost-effectiveness analysis of trastuzumab-containing treatment sequences for HER-2 positive metastatic breast cancer patients in Taiwan

ObjectiveTreatment options for HER-2-positive metastatic breast cancer (mBC) patients have expanded markedly since trastuzumab approval in 1998. Several other regimens are now available, including pertuzumab plus trastuzumab plus docetaxel, T-DM1, capecitabine plus lapatinib, and trastuzumab plus lapatinib. This study assesses the cost-effectiveness of four treatment sequences for HER-2-positive mBC according to the Taiwanese National Health Insurance Administration (TNHIA). MethodsCosts (U.S. Dollars) and effectiveness (quality-adjusted life years) of four treatment sequences for HER-2-positive mBC patients were examined using a Markov model over a lifetime horizon. Transition probabilities, disease progression, and probability of adverse events and survival were derived from clinical trial data. Costs and health utilities were estimated from TNHIA, Taipei Medical University Hospital, and the literature. Deterministic, probabilistic sensitivity analyses and a scenario analysis examined parameter uncertainty and accounted for drug wastage in dosage and cost calculations. ResultsSequence 3 (1st line: trastuzumab plus docetaxel; 2nd line: T-DM1; 3rd line: trastuzumab plus lapatinib) was the most cost-effective sequence followed by sequence 1 (1st line: pertuzumab plus trastuzumab plus docetaxel; 2nd line: T-DM1; 3rd line: capecitabine plus lapatinib), and sequence 4 (1st line: trastuzumab plus docetaxel; 2nd line: trastuzumab plus lapatinib; 3rd line: trastuzumab plus capecitabine), respectively. The model was sensitive to costs and transition probabilities, but not particularly sensitive to the wastage assumption. ConclusionsFrom the perspective of the TNHIA, trastuzumab plus docetaxel as 1st line followed by T-DM1 and trastuzumab plus lapatinib as 2nd and 3rd line represents the most cost-effective strategy among the four sequences considered for treating HER-2-positive mBC patients.

401P - Survey of diet and physical activity in new cases of young breast cancer patients in Taiwan

401P - Survey of diet and physical activity in new cases of young breast cancer patients in Taiwan

Abstract 3439: GATA3 mutation of luminal-type breast cancer patients in Taiwan

Abstract To investigate the mutation landscape of luminal-type breast cancer in Taiwan, we have conducted whole-genome sequencing on 20 cases of breast cancer, including 15 cases of those positive for estrogen receptor and 5 cases negative for estrogen receptor. Specifically, we searched for mutations in TP53, GATA3, and ESR1 genes. Additionally, we designed an amplificon sequencing scheme to interrogate the GATA3 coding sequences. GATA3 mutation has been previously reported to be correlated with suppression of proliferation upon aromatase inhibitor treatment. Also, the prevalence and clinical significance of GATA3 mutation-positive breast cancer differed between the TCGA cohort and the Fudan cohort. In our current series that focuses on breast cancer patients of Han Chinese living in Taiwan, we have identified 21 GATA3 mutations among 72 breast cancer tumor specimens screened by the amplicon sequence, and another 3 samples with GATA3 mutation by whole-genome sequencing. Notably, Pro409Alafs mutation occurred in six cases and this truncation mutation showed an average VAF of 0.155. A specific antibody was raised against the additional c-terminal amino acid sequence for the detection of the abnormally expressed proteins in these cases. As GATA3 is required for epithelial cell differentiation and as both normal breast luminal epithelium and estrogen-receptor-positive tumors showed high GATA3 expression, we are conducting further studies to demonstrate the clinical relevance of GATA3 mutation and the potential value of the Pro409Alafs as an outcome predictor for luminal-type breast cancer. Citation Format: Shih Feng Tsai. GATA3 mutation of luminal-type breast cancer patients in Taiwan [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3439.

The impact of the effectiveness of GATA3 as a prognostic factor in breast cancer

The transcription factor GATA3 plays a significant role in mammary gland development and differentiation. We analyzed expression of GATA3 in breast cancer (BC) cell lines and clinical specimens from BC patients in Taiwan. Semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), quantitative real-time PCR were carried out to determine the mRNA level of GATA3 from 241 pairs of matched tumor and adjacent normal tissues from anonymous female donors. GATA3 immunohistochemistry (IHC) staining and H-score were performed (n = 25). Inducing and silencing of GATA3 were done by exposure MCF-7 cell line to nicotine or curcumin, respectively. GATA3 expression was detected in most of the estrogen receptor-positive (ER+) tumor specimens (176/241, 73%) compared with paired normal tissues (65/241, 27%) (P < .001). The GATA3 level was highest in Luminal A, and independent t-tests revealed higher GATA3 was associated with ER+ (P = .018) and BC stages (stage II, and stage IV). Nuclear protein expression of GATA3 was detected in tumor tissues (P < .001) with higher H-score in Luminal A patients (P = .012). Kaplan-Meier survival analyses showed that ER+/progesterone receptor (PgR)+ and lower grade BC patients with relatively high GATA3 had better clinical overall survival (OS). GATA3 regulates ERα and BCL-2 as BC luminal subtype markers. Cox univariate and multivariate analyses demonstrated that the expression of GATA3 was an effective predictor of the risk of death. We demonstrated a correlation between GATA3 expression and only ER+ and suggest that a higher GATA3 expression is a good prognostic factor for OS for ER+ BC patients.

The Herb-Drug Pharmacokinetic Interaction of 5-Fluorouracil and Its Metabolite 5-Fluoro-5,6-Dihydrouracil with a Traditional Chinese Medicine in Rats.

Background: Xiang-Sha-Liu-Jun-Zi-Tang (XSLJZT) is the most common traditional formula given to colorectal and breast cancer patients in Taiwan, according to a statistical study of the National Health Insurance Research Database. 5-Fluorouracil (5-FU) is widely used as the first line of treatment for colorectal cancer. Thus, the aim of study is to investigate the pharmacokinetic interaction of XSLJZT and 5-FU. Methods: To investigate the herb–drug interaction of XSLJZT with 5-FU as well as its metabolite 5-fluoro-5,6-dihydrouracil (5-FDHU) using pharmacokinetics, a high-performance liquid chromatography (HPLC) system coupled with a photodiode array detector was developed to monitor 5-FU and 5-FDHU levels in rat blood. Rats were divided into three cohorts, one of which was administered 5-FU (100 mg/kg, iv—intravenous) alone, while the other two groups were pretreated with low and high doses of XSLJZT (600 mg/kg/day or 2400 mg/kg/day for 5 consecutive days) in combination with 5-FU. Results: The results demonstrated that 5-FU level was not significantly different between the group treated with only 5-FU and the group pretreated with a normal dose of XSLJZT (600 mg/kg/day). However, pharmacokinetic analysis revealed that pretreatment with a high dose of XSLJZT (2400 mg/kg/day) extended the residence time and increased the volume of distribution of 5-FU. No significant distinctions were found in 5-FDHU pharmacokinetic parameters at three doses of XSLJZT. Conclusions: Overall, the pharmacokinetic results confirm the safety of coadministering 5-FU with XSLJZT, and provide practical dosage information for clinical practice.

Abstract P5-08-29: Trends in age shifting and decreasing mortality of female breast cancer in Taiwan with emerging molecular subset of unmet medical need: A 30-year cohort observation from Taipei Veterans General Hospital

Abstract Background: Over the past thirty years, Taiwan has become a modern Asian country with an increasing incidence of breast cancer. We hypothesized that the epidemiological and demographic features of breast cancer patients in Taiwan have changed by using cohort study based on data collected from past three decades. However, despite improvement in prognosis of most breast cancer subtypes, we found that one subtype of luminal B type her-2 negative did not show significant improvement in overall survival and disease free survival from our cohort comparison. Methods:Patients with primary breast cancer diagnosed between 1979 and 2010 were identified from the cancer registry database at Taipei Veterans General Hospital, Taiwan. Three periods of time were divided (1979 to 1988, 1989 to 1998, and 1999 to 2010) and compared to determine the epidemiological changes in female breast cancer in Taiwan. Results:From 1979 to 2010, data from a total of 8417 breast cancer patients were collected. The ratio of breast cancer patients aged ≤ 35 years decreased from 13.3% in 1979 to 1988, to 10.6% in 1989 to 1998, and to 5.2% during 1999 to 2010.In the period of 1979 to 1988, 55.7% of patients were aged ≤ 50 years, and in the period of 1999-2010, only 45.7% of breast cancer patients were aged ≤ 50 yrs.From 1979-1988, ductal carcinoma in situ (DCIS) was rarely diagnosed (0.2%), and the ratio of patients who initially presented with DCIS increased to 2.9% in 1989 to 1998, and to 11.8% in 1999 to 2010. Patients diagnosed with stage I breast cancer also increased from 16.7% in 1979-1988 to 28.4% in 1999-2010.Patients diagnosed and treated in 1999-2010 (5-year overall survival: 81.7%) had a much better outcome than patients treated in 1979-1988 (5-year overall survival: 66.3%). Cohort comparison of survival outcome for breast cancer subtypes in luminal A type, luminal B type Her-2 positive, luminal B type Her-2 negative, Her-2 type, and triple negative type disclosed no improvement in both 5-year survival and 5-year disease free survival outcomes in the subtype of luminal B type Her-2 negative. Conclusions: The epidemiological features of female breast cancer in Taiwan have changed over the past thirty years. A molecular subtype of luminal B type Her-2 negative was characterized as an emerging group with unmet medical need. Citation Format: Lin Y-S, Tseng L-M, Liu C-Y. Trends in age shifting and decreasing mortality of female breast cancer in Taiwan with emerging molecular subset of unmet medical need: A 30-year cohort observation from Taipei Veterans General Hospital [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-08-29.

Validity and Reliability of the Taiwanese Version of the General Fatigue Scale in Cancer Patients.

Fatigue has been described as the most frequent and distressing problem of cancer patients undergoing chemotherapy. The aim of this study is to evaluate the validity and reliability of the Taiwanese version of the General Fatigue Scale (GFS-T) and to evaluate the severity of the fatigue among breast cancer patients in Taiwan. A cross-sectional research design was used, recruiting breast cancer patients from 2 medical centers in Taiwan. Patients completed the scale exploring their GFS-T, the Brief Fatigue Inventory-Taiwan Form, and the Eastern Cooperative Oncology Group Performance Status. The data were collected between the day before the first chemotherapy (T1) and 1 week after the first chemotherapy (T2). A total of 171 patients participated in this study. Cronbach's α for the GFS-T at both time points both were .94. Factor analysis generated 1 factor that accounted for 73.7% of variance in participants' fatigue. The receiver operating characteristic curve analyses suggested that the GFS-T cut-point of 24 had an adequate combination of sensitivity and specificity to distinguish high and low performance status. The receiver operating characteristic curve is 0.67 (95% confidence interval, 0.59-0.75). The GFS-T is a reliable and valid instrument for assessing fatigue among cancer patients. Further research is needed to better understand predictors of cancer-related fatigue. The GFS-T can provide clinical nurses with a useful measure to assess fatigue in cancer patients.

Building an Integrative Outpatient Care Program for Breast Cancer Patients in Taiwan.

Background. Breast cancer patients may experience various symptoms that affect the quality of life significantly and they seek complementary and alternative medicine (CAM). To meet the needs of patients, we developed an integrative outpatient care program. Methods. This program provided CAM consultation and acupuncture for breast cancer patients at Taipei Veterans General Hospital. The outcome measures included Medical Outcomes Study 12-Item Short-Form Health Survey (SF-12) and patient satisfaction questionnaires on the first visit (baseline) and at 6 months. Results. Forty-five breast cancer patients were enrolled. All patients completed the study. The median age was 53.3 (±8.3). The symptoms most often experienced during previous cancer treatments were fatigue (35.6%), arthralgia (20%), nausea (6.7%), and insomnia (6.7%). The symptoms most wished to be diminished by the patients were arthralgia (22.2%), insomnia (17.8%), and fatigue (15.6%). Thirty-four patients (75.6%) had sought CAM therapy to reduce these symptoms. Fifteen patients (33.3%) received CAM consultation only and 30 (66.7%) received acupuncture in addition. Sixteen patients completed at least 6 sessions of acupuncture. No serious adverse effect was reported. In the SF-12 Questionnaire on all the patients, physical component summary (PCS) was 49.6 (±5.6) at baseline and 44.9 (±7.6) at 6 months (P = .001); the mental component summary (MCS) was 44.7 (±6.1) at baseline and 52.3 (±9.3) at 6 months (P < .001). For patients who had completed acupuncture, PCS was 49.2 (±4.9) at baseline and 41.4 (±7.6) at 6 months (P = .148); the MCS was 45.6 (±6.2) at baseline and 49.7 (±11) at 6 months (P = .07). Thirty-eight (84.4%) patients were satisfied with this program. Conclusions. Our results demonstrated that an integrative outpatient care program of conventional and Chinese medicine is feasible. Most patients were satisfied with this program and the quality of life was improved. It is important to conduct more research to build a model that integrates CAM with conventional medicine in Taiwan.

Atrial Fibrillation is Associated With Morphine Treatment in Female Breast Cancer Patients: A Retrospective Population-Based Time-Dependent Cohort Study.

We investigated the relationship between morphine treatment and the risk of atrial fibrillation (AF) in female patients with breast cancer.We identified a malignancy cohort of 73,917 female breast cancer patients without an AF history before the date of breast cancer diagnosis between 2000 and 2010 by using the Longitudinal Health Insurance Database for Catastrophic Illness Patients in Taiwan. This malignancy cohort was divided into morphine and comparison cohorts comprising 18,671 and 55,246 patients, respectively, and the incidences of newly diagnosed AF were calculated. We used the Cox proportional hazard model with time-dependent exposure covariates to estimate the risk of AF. The effect of morphine was assessed through multivariable Cox proportional hazard regression controlling for age, the Charlson comorbidity index (CCI) score, and the use of bisphosphonates and paclitaxel.Compared with nonmorphine users, patients who received morphine exhibited a 4.37-fold (95% CI = 3.56–5.36) increase in the risk of developing AF. The risk of AF increased as the CCI score increased, but decreased in patients with tamoxifen treatment. This risk is especially significant in current morphine users of all ages and with low CCI score. AF risk increased as the duration of morphine use lengthened (P for trend <0.0001).The incidence of AF in female breast cancer patients in Taiwan is associated with morphine, but prevented by tamoxifen treatment.

31P - Multigene sequencing for the genetic diagnostics of patients with early-onset or familial breast cancer

Purpose: Epidemiologic studies show that the median age of breast cancer patients is younger in Taiwan than in western populations, and breast cancer patients in Taiwan carry a greater risk and a shorter interval to develop contralateral breast cancer. These two characteristics indicate genetic predisposing factors. In this study, we used a customized multigene sequencing panel to investigate the genetic impact for patients with early-onset or a significant family history in Taiwan.