Chinese Breast Research Articles

Abstract P4-01-13: Molecular characterization of circulating tumor DNA in Chinese metastatic breast cancer (mBC) patients

Abstract Background: Circulating tumor DNA (ctDNA) have been increasingly used as a minimal invasive test to detect genomic alterations of cancer patients. Methods: We performed a retrospective analysis of blood samples from mBC patients (pts) collected at baseline, on-treatment, and disease progression. A highly sensitive, plasma-derived ctDNA-based NGS assay (PredicinePLUS, a comprehensive 180 key cancer gene panel) was used to detect somatic mutations and copy number variations in ctDNA with an in-house propriety algorithm. Results: In this study, we evaluated 162 blood samples from 109 mBC pts who underwent systematic therapy at Beijing Cancer Hospital with approval from Research Ethics Committee. 129 samples from 92 pts passed NGS quality check, and were included in the analysis. Among these pts, the percent of HR+, HER2+ and Triple-Negative pts is 36.8%, 29.5% and 31.5%, respectively. About 86% samples contain somatic mutations and/or copy number variations. Collectively, 372 somatic mutations (SNV and Indels) were detected on 76 genes, among which TP53 (44.2%), PIK3CA (25.3%), BRCA2(10.5%) and ATM (10.5%) were frequently altered with frequency varying across different subtypes. ESR1 hotspot mutations ((D538G and Y537S/N/C) were also detected in a subset of HR+ patients. Copy number gain or loss was detected on 32 genes, including amplification of ERBB2, PIK3CA, FGFR1 and deletion of CDKN2A, ATM, RB1 etc. Importantly, ERBB2 copy number amplifications were only detected in HER2 IHC positive cases for base-line samples, leading to 68% sensitivity and 100% specificity. Interestingly, ctDNA yield increased as disease progressed, suggesting ctDNA yield may serve as a potential biomarker for predicting treatment response and monitoring disease progression. Additional genomic alterations that change dynamically along with the course of treatment or associate with drug response and/or resistance were also identified. Conclusions: This study demonstrated ctDNA-based genomic analysis was highly sensitive and specific in detecting various genomic alterations, consistent with other published studies. It also suggests that HER2 copy number amplification could be robustly assessed in a non-invasive manner. Citation Format: Yu J, Li H, Zhang S, Wang A, Zhao Z, Liu X-R. Molecular characterization of circulating tumor DNA in Chinese metastatic breast cancer (mBC) patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-01-13.

Abstract P5-09-12: Germline mutation in TP53 gene in a cohort of 2,561 Chinese high-risk breast cancer patients using multigene panel testing

Abstract Background: Li-Fraumeni syndrome (LFS) is a rare autosomal genetic disorder with germline TP53 mutations. Patients with TP53 mutations have a higher risk of developing breast cancer than those harboring BRCA mutations. Although limited studies have shown that TP53 mutation carriers are less responsive to low dose radiation and more susceptible to induce new malignancies from radiotherapy. Moreover screening strategies allows early detection of a spectrum of cancers related to TP53 mutations. From work of BRCA mutations where over 40% novel mutations were detected in Chinese cohort, it is important to evaluate the frequency of TP53 mutation in Chinese to better understand the spectrum to guide appropriate clinical management of these high risk individuals. Methods: TP53 gene mutation screening was performed on 2,561 high-risk breast cancer patients using multigene panel testing. The patients were accrued by Hong Kong Hereditary and High Risk Breast Cancer Program from March 2007 to May 2018. All detected pathogenic mutations were further validated by bi-directional DNA sequencing and analyzed by our in-house developed bioinformatics pipeline. Results: Sixteen distinct pathogenic or likely pathogenic variants were identified, and 3 of them were de novo TP53 mutations (18.75%). The mean age of patients who harbored TP53 mutation was 30.44 years (range 18-44), and 50% of the tumors were bilateral breast cancer. Of sixteen different pathogenic mutations, majority of them were missense mutation (87.5%), and 2 were nonsense mutation (12.5%). Four of the sixteen TP53 mutation carriers had family history of breast cancer, while others had a family history of lung cancer (43.75%). Conclusion: This study revealed that seven patients were found to habor TP53 mutation even when they did not meet the criteria of LFS of LFS-like phenotype, implicated the importance of using multigene panel test for probands and their relatives to offer a comprehensive surveillance programe for TP53 carriers. Citation Format: Kwong A, Shin V, Au CH, Ho C, Slavin T, Weitzel J, Chan TL, Ma E. Germline mutation in TP53 gene in a cohort of 2,561 Chinese high-risk breast cancer patients using multigene panel testing [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-09-12.

Detection, dynamic monitoring, and resistance mechanism exploration of genomic alterations in circulating cell free tumor DNA (ctDNA) in Chinese metastatic breast cancer (mBC).

1080Background: Circulating DNA fragments (ctDNA) are using to longitudinal non-invasive molecular monitoring and resistance mechanism interrogation of the disease by detecting genomic alteration c...

Radiomodifying effects of Centella asiatica and Withania somnifera

ABSTRACTAqueous extracts of Centella asiatica and Withania somnifera were evaluated for their radiomodifying effects in normal Chinese hamster lung fibroblasts (V79) and human breast epithelial cells (MCF-12A), using the colony-forming assay. The results showed that aqueous extracts of C. asiatica and W. somnifera may either sensitize or protect normal cells from the cytotoxic effects of ionizing radiation. The combined use of these extracts with radiotherapy may prove beneficial in treatment of cancer.

Abstract 5290: Racial variation in terminal duct lobular unit (TDLU) involution in Chinese and Polish breast cancer patients

Abstract Introduction: Terminal duct lobular unit (TDLU) involution, an age-related physiological process, is characterized by the reduction of size and numbers. Reduced involution is associated with higher mammographic density, a strong breast cancer risk factor. Both factors predict risk of developing breast cancer among women with benign disease. Given that prior studies have been conducted mainly in White women, we compared the extent of TDLU involution among Western and Asian breast cancer cases to describe potential racial heterogeneity in breast cancer etiology. Method: We obtained three TDLU involution metrics (count/100 mm2, mean span, and mean acini count/TDLU; all inversely correlated with TDLU involution) measured in benign breast tissue sections from 379 Chinese (254 luminal A and 125 core basal phenotype [CBP] cases) and 476 Polish (407 luminal A and 69 CBP) breast cancer cases. Polytomous logistic regression was performed using tertiles of TDLU measures as ordinal dependent variable and race as an independent variable. Covariates included age, body mass index, and parity. Analyses were performed separately by age group (<50, ≥50) and subtype (luminal A and CBP). Results: Among luminal A cases, Chinese had significantly greater TDLU count compared with Polish in both age groups (ORtrend= 11.0; 95% CI=2.80-43.2; Ptrend=0.001 for age<50; ORtrend= 12.1; 95% CI=5.12-28.7; Ptrend=1E-08 for age≥50). In addition, Chinese were more likely to have greater mean span and acini count among younger cases (ORtrend=2.5; 95% CI=1.44-4.28; Ptrend=0.001 for mean span and ORtrend=7.4; 95% CI=4.13-13.4; Ptrend=3E-11 for acini count) but not among older cases. Among CBP cases, Chinese were more likely to have greater acini count compared to Polish only among younger women (ORtrend=2.6; 95% CI=1.12-6.95; Ptrend=0.03 for age<50). Conclusion: We found Chinese were more likely to have reduced TDLU involution compared to Polish cases after accounting for potential confounders, with greater differences for luminal A and younger women. Studies of TDLU involution in diverse populations are needed to confirm and understand whether population difference in TDLU involution metrics are related to age at breast cancer onset and risks for specific tumor subtypes. Citation Format: Hyuna Sung, Changyuan Guo, Jennifer Guida, Shan Zheng, Erni Li, Jing Li, Nan Hu, Joseph Deng, Montserrat Garcia-Closas, Jonine Figueroa, Mark Sherman, Gretchen Gierach, Ning Lu, Xiaohong R. Yang. Racial variation in terminal duct lobular unit (TDLU) involution in Chinese and Polish breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5290. doi:10.1158/1538-7445.AM2017-5290

Association of circulating tumor cells (CTCs) with hyperglycemia in the follow-up of Chinese non-metastatic breast cancer patients.

e23020 Background: CTCs has been confirmed to associate with a poor outcome of breast cancer at primary diagnosis. To date, CTC has not been studied with sufficient details in the follow-up of non-MBC pts, especially in Chinese population. We investigated the associations of CTC with clinicopathological features and metabolic factors to gain insight into potential interactions between physiology and disease burden. Methods: We recruited 264 cases of postoperative pts with non-MBC in Guangdong General Hospital from Jan 2009 to Dec 2015. For each enrolled pts 7.5mL blood samples were drawn for CTC enumeration using the CellSearch system. CTC results were correlated with clinicopathological features, obesity related indicators and HBsAg. A multivariate logistic regression analysis was performed to further determine the independent predictors of CTC. The study defined CTC positive as CTC ≥1. Results: In 10.6 % of all pts (n = 28) a median of 1 (range, 1–108) CTC was detected. A pT1 tumor was present in 47% of pts, 11.4 % had G1 grading and 64.4 % were node-negative. The positive rate of CTCs in pts with IDC and ILC was lower than that in pts with other pathological types (9% and 11.1% vs 28.6% P=0.02). A similar trend that approached significance was noted for age (p=0.062), histological grade( p=0.087), invasion of the nipple areola (p=0.06). CTCs was positively correlated with blood glucose (p=0.015), and negatively correlated with high density lipoprotein (p=0.049). In addition, glycated hemoglobin was positively associated with CTC in correlations that neared significance (p=0.059). The result of multivariate logistic regression analysis is shown in the Table. No associations were observed in triglycerides, free fatty acid, total cholesterol, low-density lipoprotein and HBsAg. Conclusions: This study suggested pathological type and blood glucose were independent predictors of CTC, supporting the notion that high fasting glucose level in BC pts may have severe disease burden, leading to a higher frequency of CTC. [Table: see text]

Abstract 4683: Verapamil and tamoxifen modulate ABCB1 expression in multidrug-resistant cells and resensitize them to conventional chemotherapy

Abstract Multidrug-resistant (MDR) tumors are an increasingly important obstacle in cancer treatment, wherein many cases are associated with the overexpression of P-glycoprotein 1 (P-gp1, ABCB1). Previous efforts to sensitize ABCB1-expressing tumor cells to anti-cancer drugs were associated with severe side effects, so interest in clinical trials using these drugs has dwindled. Studies have shown P-glycoprotein-overexpressing cells to be hyper sensitive (or collaterally sensitive) to a diverse group of non-toxic compounds. Given earlier results demonstrating a significant increase in ABCB1 expression post-chemotherapeutic treatment of cancer patients (e.g., breast, ovarian, myeloma, and acute myeloid leukemia), and the role of ABCB1 in drug resistance, it was determined that targeting ABCB1-expressing tumor cells with effective collateral sensitivity drugs should increase the effectiveness of current chemotherapeutic treatments. In this report, it was of interest to determine the effect of the collateral sensitivity drugs verapamil and tamoxifen on P-glycoprotein 1 expression at the level of cells and individual cell clones. Clones from P-gp1-overexpressing Chinese hamster ovarian cell lines (CHRC5) or triple negative breast cancer cells (MDA-MB-231/400 nM doxo) were treated with varying levels of collateral sensitivity drugs and ABCB1 expression was determined by Western blots and ELISAs. The sensitivity of each cell clone to anti-cancer or collateral sensitivity drugs was determined using cytotoxicity assays. Our results demonstrate a drop in ABCB1 expression in each clone, together with decreased collateral sensitivity and overall increased sensitivity to anti-cancer drugs in cell lines selected with verapamil and tamoxifen. Work is in progress to study the various mechanisms responsible for this drop in ABCB1 expression and its impact on treatment outcome. Citation Format: Georgia Limniatis, Elias Georges. Verapamil and tamoxifen modulate ABCB1 expression in multidrug-resistant cells and resensitize them to conventional chemotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4683.

Prognostic impact of progesterone receptor status in 3030 Chinese estrogen receptor positive early breast cancer patients.

e12002Background: Estrogen receptor (ER) and progesterone receptor (PR) have been used as indicators of endocrine system since the mid-1970s in the breast cancer. The predictive role of ER in endocrine therapy is undisputed, but the prognostic value of PR is still debated.The objective of this study was to investigate the clinical characteristics and prognosis of ER+ early breast cancer in different PR expression. Methods: A population cohort of 3030 ER+ primary invasive breast cancer with curative intent patients presenting to a single Cancer Centre over 6 years (2004–2010) underwent surgery and received adjuvant endocrine therapy. Age, menopausal status, tumor size, histology, lymph node status, PR status, Her-2, and Ki-67 were collected. The follow-up data for disease-free survival (DFS) and overall survival (OS) was obtained and distribution of factors was compared using the standard Chi-Square test. Univariate Cox hazard models were used to assess the effects of treatment and predictive factors on cl...

Abstract IA30: Modeling of socioeconomic wellbeing, follow-up care communication, stress appraisal, coping, and physical functioning among Chinese and non-Hispanic white breast cancer survivors

Abstract IA30: Modeling of socioeconomic wellbeing, follow-up care communication, stress appraisal, coping, and physical functioning among Chinese and non-Hispanic white breast cancer survivors

Efficacy and safety of pirarubicin plus capecitabine versus pirarubicin plus cyclophosphamide in Chinese node-negative breast cancer patients: a 4-year open-label, randomized, controlled study

This study aimed to evaluate the efficacy and safety of adjuvant chemotherapy with pirarubicin plus capecitabine (AX regimen) in Chinese node-negative breast cancer (BCa) patients. Two hundred eighty Chinese pT1-2N0M0 BCa patients under 70years of age were equally and randomly assigned to receive four cycles of adjuvant therapy with the AX regimen or pirarubicin and cyclophosphamide (AC regimen) between January 2010 and May 2011. End points included overall survival (OS), disease-free survival (DFS), chemotherapy-induced toxicities, and quality of life (QoL). The 4-year DFS (AX vs. AC, 93.6 vs. 92.9%, P=0.761) and OS (97.1 vs. 96.4%, P=0.965) were similar between the two treatment arms. The AX group, compared to the AC group, experienced significantly less frequent grade III/IV vomiting (11.4 vs. 26.4%, P<0.001), whereas the incidence of other grade III/IV chemotherapy-associated toxicities was comparable between the two groups (all P values >0.05). Use of the AX regimen was associated with significantly higher QoL scores in the domains of physical, role, and social functions than the AC regimen (P values <0.05), although the two regimens were similar in the domains of emotional and cognitive functions (all P values >0.05). In comparison with the AC regimen, AX adjuvant chemotherapy is equally beneficial for node-negative BCa patients younger than 70years with respect to OS and DFS. The AX regimen is primarily advantageous over the AC regimen based on less frequent severe toxicities and better health-related QoL.

Lack of epidermal growth factor receptor (EGFR)-activating mutations in triple-negative breast cancer in China.

We read with interest the study by Teng and colleagues reporting a high frequency (11.4 %) of epidermal growth factor receptor (EGFR)-activating mutations in triplenegative breast cancer (TNBC) in a Singapore cohort [1]. In a separate study, EGFR-activating mutations were detected in 7.7 % (1 out of 13) of Chinese basal-like breast cancers [2]. Interestingly, this frequency ranged from 0 to 3 % of other Asian and Caucasian patients [3, 4]. These results indicate that the frequency of these mutations may vary according to geographic and ethnic differences, as reported in non-small cell lung cancer, and these mutations appear to be limited mostly to Chinese patients with TNBC. In this study, in-depth characterization of these mutations in Chinese TNBC was attempted on retrospective archival tissues. Fifty freshly frozen specimens of TNBC from patients without neoadjuvant chemotherapy were randomly selected from Zhejiang Cancer Hospital, China, from 2010 to 2011. The specimens were confirmed to be estrogen receptor- and progesterone receptor-negative, and less than 1 % of tumor cells showed positive nuclear staining by an immunohistochemistry (IHC) assay. HER-2 negativity was defined as a score of 0 or 1+ by IHC assay or a HER-2 /chromosome 17 ratio of less than 2a nd fewer than 4 HER-2 copies per nucleus by a fluorescence in situ hybridization assay. Written consent was obtained from all participants. This study was approved by the Research and Ethics Committee of Zhejiang Cancer Hospital. Twenty-five EGFR-activating mutations (G719S, G719A, G719C, S768I, L858R, and L861Q and 19 mutations of exon 19-Del) were analyzed by an Amplification Refractory Mutation System (ARMS) assay by using an ADx EGFR29 Mutation Kit (Amoy Diagnostics, Xiamen, China). The ARMS assay is able to detect mutations with allele frequencies as low as 1 % [5]. Exons 18, 19, 20, and 21 were amplified by polymerase chain reaction assay, and all fragments were bidirectionally sequenced to screen for other mutations. None of the EGFR-activating mutations was found by these two assays, but four single-nucleotide polymorphisms (SNPs) were identified by the sequencing assay (Table 1). In silico prediction was performed to investigate the effect of the SNPs on gene splicing by using two programs: NNSplice 0.9 version (http://www.fruitfly.org/ seq_tools/splice.html) and Human Splicing Finder (http://www.umd.be/HSF3/). All four SNPs, particularly the c.2457G > A SNP, were predicted to alter splicing by one or both programs. In summary, none of the well-known EGFR-activating mutations was identified in our cohort. This suggests that TNBCs form a group of cancers with marked heterogeneity. Targetable mutations may be present and clinically helpful in only a limited number of Chinese patients with TNBC.

Efficacy and safety of trastuzumab plus different chemotherapy regimens in treatment of the patients with HER-2-positive advanced breast cancer

To evaluate the efficacy and safety of trastuzumab plus different chemotherapy regimens in treatment of patients with HER-2-positive advanced breast cancer. 132 patients with advanced HER-2-positive breast cancer were treated with trastuzumab plus different regimens. The clinical characteristics, efficacy and toxicity of the 132 patients were retrospectively analyzed. Five patients had complete response (CR), 61 patients had partial response (PR), 39 patients had stable disease (SD), and 27 patients had progressive disease (PD). The objective response rate was 50.0% and the disease control rate was 79.5%. The median progression-free survival was 9.3 months. The median overall survival time was 46.2 months. The 1-, 2-, 5- year survival rates were 98.3%, 81.9% and 40.2%, respectively. Trastuzumab combined with chemotherapy is superior to trastuzumab monotherapy (51.2% vs. 33.3%). The number of metastatic sites, efficacy, different previous treatment lines were independent prognostic factors of PFS (P = 0.002, P < 0.0001 and P < 0.0001, respectively). Visceral metastases, pathological grade, and PFS were independent prognostic factors of OS (P = 0.041, P = 0.001, P = 0.025, P < 0.001, P < 0.0001 and P < 0.0001, respectively). Regarding the toxicities, one case discontinued treatment due to the decrease of left ventricular ejection fraction to 47%, two cases had heartbeat tachycardia, 6 cases had palpitation, 17 cases had a fever during first input trastuzumab. No other serious cardiac toxicity was observed. The most common toxicities were chemotherapy-related hematological and non-hematological toxicities. Trastuzumab combined with chemotherapy is superior to trastuzumab monotherapy. Patients may get benefits for early use of trastuzumab. Trastuzumab plus chemotherapy is effective and well tolerated in patients with advanced HER-2 positive breast cancer. No heart failure occurred in this series of patients, and cardiac safety seems better than that in Caucasians because of younger age at the onset in Chinese advanced breast cancer patients.

Clinical observation of accelerated partial-breast intensity-modulated radiotherapy in patients with early-stage breast cancer after breast-conserving surgery

To explore the clinical feasibility of accelerated partial breast irradiation (APBI) by intensity-modulated radiotherapy (IMRT). Twenty-six patients with T1N0M0 breast cancer were enrolled into a prospective accelerated partial-breast IMRT protocol between January 2008 and January 2010. Inverse planning of IMRT was employed at a prescribed dose of 34 Gy/10 f/5 d. Acute radiation skin responses and clinical effects were observed. All of them completed radiation. During the radiation, Grade 1 of acute radiation skin reaction (mild hyperpigmentation) was seen in 8 patients and there was not > grade 2 of skin reaction. At Month 1 post-radiation, Grade 1 of acute radiation skin reaction (mild hyperpigmentation) was seen in all patients and there was not > grade 2 of skin reaction. At Month 3 post-radiation, all instances of acute radiation skin reactions recovered. The median follow-up period was 51 months (range: 35 - 59). The follow-up period of 23 patients were over 3 years. No local recurrences developed. The 3-year disease-free survival was 100%. Cosmesis was good or excellent in all cases at Year 2. External beam-partial breast irradiation delivered by IMRT is feasible for selected Chinese early-stage breast cancer patients after breast-conserving surgery. The cosmetic effect, local control rate and long-term survival rate are satisfactory. And acute radiation toxicity is quite low.

Challenges and Needs of Chinese and Korean American Breast Cancer Survivors: In-Depth Interviews.

Breast cancer incidence and the number of breast cancer survivors have been rapidly increasing among Chinese and Korean women in the United States. However, few data are available regarding quality of life in Asian American breast cancer survivors. This qualitative study aims to describe Asian American women's perceptions of quality of life and their breast cancer experiences. In-depth interviews with four Chinese and five Korean American breast cancer survivors and three oncologists were conducted in Chinese, Korean, or English. Interviews were recorded and transcripts were translated into English. Qualitative analyses were performed by two independent coders and then discussed and agreed upon by the research team. The respondents reported that the breast cancer experience had affected various domains of quality of life, but women reported having limited resources with which to cope effectively. Depression, anxiety, and stress were commonly reported, but women rarely discussed these issues with family and friends or sought professional help. As immigrants, women's loneliness and a lack of social support and culturally relevant resources seemed to be major barriers to maintaining good quality of life. Women also expressed interest in learning more about alternative therapies and relaxation skills. These findings can be used to help inform the development of a culturally appropriate intervention for Asian American breast cancer survivors. Future programs may provide information in women's native languages to teach skills to cope with stress and anxiety, increase women's self-efficacy within the context of their cultural background, and enhance social support among women from the same ethnic group.

Feasibility, efficacy and cosmetic effect of three-dimensional conformal external beam partial breast irradiation for the selected early stage breast cancer patients after breast-conserving surgery

Objective To explore the feasibility,efficacy and cosmetic effect of three-dimensional conformal external beam partial breast irradiation (EB-PBI) after breast-conserving surgery for the selected Chinese early stage breast cancer patients.Methods From June 2003 to December 2010,Forty-four early stage breast cancer patients underwent EB-PBI after breast-conserving surgery.Twenty patients had CT simulation scan in moderate deep inspiration breathing hold,and twenty-four patients in free breathing.EB-PBI was planned and delivered by three-dimensional conformal radiotherapy (3DCRT) with four noncoplanar beams.The prescribed dose was 3.40 Gy per fraction in thirty-nine patients and 3.85 Gy per fraction in five patients,twice per day at an interval of at least six hours,in five consecutive days.Results The number of patients with follow up time of 2,3 and 5 years were 39,31 and 16.Grade 1 acute radiationinduced dermatitis was observed in 17 patients (39％) at three months.Cosmesis was good or excellent in all cases at six months after radiotherapy and in 95％ cases at two years after radiotherapy.The 2-,3-and 5-year local control rates were 100％,99％ and 94％,respectively.The 2-,3-,and 5-year survival rates were all 100％ and no metastases occurred.Conclusions EB-PBI delivered by 3DCRT is feasible for selected Chinese early stage breast cancer patients after breast-conserving surgery.The cosmetic effect,local control rate and long-term survival rate are satisfactory,and acute radiation toxicity is very low. Key words: Breast neoplasms/surgery; Surgery, breast-conserving treatment; Breast neoplasms/radiotherapy; Radiotherapy, three-dimensional conformal; Radiotherapy, partial breast; Prognosis

Cross-Ethnicity Measurement Equivalence of Family Coping for Breast Cancer Survivors

Objective: The current study examines the equivalence of a measure of family coping, the Family Crisis Oriented Personal Evaluation scales (F-COPES), in Chinese American and Korean American breast cancer survivors (BCS). Methods: Factor structure and cross-ethnicity equivalence of the F-COPES were tested using structural equation modeling with 157 Chinese American and Korean American BCS in California. Results: Of the original F-COPES subscales, acquiring social support, reframing, and passive appraisal did not adequately fit the data. Thus, a modified five-factor structure of the F-COPES was created. The modified F-COPES was validated with respect to quality of life, psychological distress, and family communication. Conclusions: The findings illustrate the importance of cross-ethnicity measurement testing and provide a rationale for developing culturally tailored measurements for ethnic minority populations.

Feasibility, efficacy, and cosmetic effect of three-dimensional conformal external beam partial breast irradiation for the selected early-stage breast cancer patients after breast-conserving surgery in China.

e11520 Background: To explore the feasibility, efficacy and cosmetic effect of three-dimensional conformal external beam partial breast irradiation after breast-conserving surgery for the selected Chinese early stage breast cancer patients Methods: Forty four early stage breast cancer patients undertaken EB-PBI after breast-conserving surgery. Twenty patients undertaken CT simulation scan in the state of moderate deep inspiration breathing hold (mDIBH), and twenty-four patients during free breathing (FB). The surgical cavity marked by silver clips was delineated and defined as gross tumor volume (GTV), and planning target volume (PTV) was defined as the area encompassed GTV with extended margin of 15 mm for the patients treated in the state of mDIBH or 20 mm for the patients treated in the state of FB. EB-PBI was planned and carried out by three-dimensional conformal radiotherapy (3DCRT) , the total prescribed dosage was 34 Gy delivered in 3.4 Gy per fractions in thirty nine patients and 38.5Gy delivered in 3.85 Gy per fractions in five patients, twice per day at intervals of at least six hours, in five consecutive days Results: Grade 1 of acute radiation-induced dermatitis was observed in 38.6% (17/44) of all the patients, no equal or more than grade 2 of radiation-induced dermatitis was observed, and no any grade of acute radiation-induced pneumonitis was observed. Cosmesis scored basing on Harris critieria was good or excellent in all cases at the time of six months after radiotherapy and in 94.9% cases at the time of two years after radiotherapy. The 2-, 3- and 5-year local control rates were 100% (39/39), 98.8% (30/31) and 93.8% (15/16), respectively. The 2-, 3-, and 5-year survival rates were all 100% and no metastases occurred Conclusions: EB-PBI delivered by 3DCRT is feasible for the selected Chinese early stage breast cancer patients after breast-conserving surgery, satisfactory cosmetic effect, local control rate and long-term survival rate are obtained, meanwhile, acute radiation response rate is lower.

P5-13-14: Drug-Metabolizing Enzyme Polymorphisms and Clinical Outcome of Anthracycline-Based Chemotherapy in Chinese Han Breast Cancer Patients.

Abstract Background Anthracycline is one of the most effective drugs in the treatment of breast cancer and many of our most effective treatment regimens include anthracycline. Its efficacy can be influenced by cellular detoxification mechanisms involving drug metabolism and transport pathways. This study aimed to assess whether the functional polymorphisms in drug-metabolizing enzymes (MnSOD, CAT and GSTs) and transporter MDR1 may predict anthracycline treatment-related outcomes in Chinese Han breast cancer patients. Material and methods: Genotyping was performed by allele-specific oligonucleotide ligation reaction (MnSOD T47C, CAT C-262T, GSTP1 A313G), multiplex PCR (GSTM1 null, GSTT1 null), and PCR-RFLP (MDR1 C3435T, G2677T/A and C1236T). Based on 153 evaluable patients received anthracycline-based neoadjuvant chemotherapy for breast cancer, the associations of these genotypes or their haplotypes with clinical response and recurrence-free survival (RFS) were analyzed. Results: Of the 153 cases, the patients with GSTP1 313AA genotype had inferior response rates relative to those with AG or GG genotype (58.4% vs 77.8% or 100.0%; χ2=4.922, P=0.027). Moreover, the response rate of the combination of GSTP1 AA with both GSTT1 present and GSTM1 present was 44%, which was also lower comparing with the other groups (70.3%; χ2=6.454, P=0.011). A similar result was noticed for MDR1 3435 TT genotype, which had a significantly worse chemotherapy response compared with wild-type C allele carrier (33.3% vs 71.2%; χ2=11.586, P=0.001). Further, the response rate of the patients with 3435T-2677T, 3435T-1236T or 3435T-2677T-1236T haplotypes was lower than that of the patients with the other corresponding haplotypes (P=0.018, 0.011 and 0.019, respectively), too. Of note, the patients with both the adverse genotypes of GSTP1 314AA and MDR 3435TT shown the worst treatment efficacy in all (14.3%;χ2=26.33, P=0.000). Mean follow-up time of the 149 patients (4 patients lost) was 51 months. The recurrence rate in the patients with GSTP1 313AA or/and MDR 3435TT in the first three years was 39.0% (41/105), higher significantly than those with no adverse genotype [15.9% (7/44); OR=0.725, 95%Cl: 0.594−0.885, P=0.006]. Kaplan-Meier survival analysis showed that the patients with no adverse genotype were associated with reduced hazard of relapse (long-rank test, P&amp;lt;0.01), compared to those with 1 or 2 adverse genotypes. Conclusion: Polymorphisms in GSTs and MDR1 genes may help to predict clinical response and RFS of anthracycline-based chemotherapy in breast cancer, but further validation is required. These results provide support for a polygenic pathway approach for assessing the predictive potential of polymorphisms in treatment outcomes. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-13-14.

Clinical implications of ERβ methylation on sporadic breast cancers in Chinese women

Estrogens play a key role in the genesis and progression of breast cancer, activating two estrogen receptors, alpha and beta (ERα and ERβ). We have previously observed that ERα methylation occurs in high frequency and may be one of the mechanisms of ERα expression silence in a subset of Chinese sporadic breast cancers. However, the ERβ promoter methylation status and the relationship between clinicopathological characteristics and ERβ methylation in sporadic breast cancer are still unknown, especially in Chinese women. This study acted to determine the methylation status of the ERβ promoter and its correlation with clinicopathological features of sporadic breast cancers in Chinese women, and lay a foundation for the management of breast cancer. In total, 178 cases with sporadic breast cancers were enrolled in the study. ERβ methylation was determined using a methylation-specific polymerase chain reaction (MSP). In general, ERβ promoter methylation was found in 44.9% (80/178) of breast tumor samples, significantly higher than the benign breast hyperplasia (44.9% vs. 14.3%, X(2) = 4.986, P = 0.026). A total of 58% (40/69) of ERβ-negative tumors got methylation compared with 36.7% (40/109) of ERβ-positive cases being methylated (X(2) = 7.728, P = 0.005). The levels of ERβ protein expression diminished with the frequency of ERβ methylation (r = -0.249, P < 0.0001). In addition, we observed a strong correlation between ERα promoter and ERβ promoter methylation (odds ratio 2.054, 95% confidence interval 1.086-3.886, P = 0.026), and the triple-negative tumors showed a significantly higher methylation rate of ERβ. This study presents, for what we believe to be the first time, that ERβ methylation is also a frequent event in breast cancer and maybe also one of the mechanisms of ERβ expression silence in a subset of Chinese sporadic breast cancers. Epigenetic alteration of the ERβ gene may play an important role in the pathogenesis of breast cancer.

5078 POSTER Polymorphisms in Genes Involved in Drug Detoxification and Response to Anthracyclines Chemotherapy in Chinese Han Breast Cancer Patients

Background: The combination of anthracyclines and taxanes is considered among the most effective treatments in MBC. The main limitation of these regimens is the cumulative cardiotoxicity of anthracyclines. The liposomal doxorubicins have been demonstrated to be less toxic for myocardial tissue, resulting in a better cardiac safety profile. Purpose: We report our experience regarding efficacy and safety of the combination of Myocet ® with Taxotere ® in first-line treatment of MBC patients (PTS). Patients and Methods: All 16 PTS with median age of 61 years (range 54−75), had histologically confirmed MBC. Anti-allergic premedication with steroids and H1/H2 receptor antagonists was administered to all PTS 12 hours before Taxotere . Treatment plan was: Myocet ® (60mg/m, i.v. on day 1) followed by Taxotere ® (35mg/m i.v. on days 2 and 9), every 3 weeks. A total of 92 cycles of CHT were delivered. Mean number was 5.75 (range 2−8). Seventy-six percent of PTS received at least 6 cycles of CHT. The primary endpoint was overall response rate (ORR), whilst time to progression (TTP) and safety were considered as secondary end points. Results: According to the WHO criteria, 3 PTS (18.5%) achieved a complete remission and 4 (25%) a partial remission for an ORR of 44%. We report a median TTP of 9.5 months. Two patients who achieved RC had lymph nodal disease, one patient had liver disease. None of the PTS experienced severe cardiac toxicity. The most common hematological toxicity was grade 3−4 neutropenia, according to WHO criteria, detected in 68% of PTS. Use of G-CSF, in 55% PTS, for treatment and prophylaxis of severe neutropenia allowed to maintain adequate dose-intensity. Stomatitis occurred in 25% of PTS, while grade 3 neurological toxicity in 12.5%. Conclusions: Our report confirms the effectiveness of the Myocet Taxotere ® combination administered in MBC according to the schedule described above. Moreover the substitution of conventional doxorubicin with Myocet ® probably reduced cardiotoxicity. Myelotoxicity rate is in line with other similar reports.