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Background: The objective of this study was to investigate the association between participation of sports activity (SA) and quality of life (QoL) among Chinese women with early stage breast cancer (BC) during the first five years post BC diagnosis. Methods: BC survivors underwent assessment of QoL and level of SA at 3 time-points: 18-, 36- and 60-months after diagnosis. SA was measured using a validated modified Chinese Baecke questionnaire in the prior 12 months; QoL was measured using EORTC-QLQC30. Results: In total, 1289, 1125 and 1116 BC survivors were included at 18-, 36- and 60-month follow-up, respectively. At 18-month, the percentages of patients belonged to no [0 metabolic equivalent of task (MET)-hours per week], low-level ( Citation Format: Winnie Yeo, Yuanyuan Lei, Kali Cheung, Roselle Lee, Carol Kwok, Ashely Cheng, Ashely Cheng, Frankie Mo, Suzanne Ho. Association of sports activity during the first five years of survival with quality of life among Chinese breast cancer survivors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-10.

Purpose: Although risk factors related to chemotherapy-induced nausea and vomiting (CINV) have been identified by prior studies, there are only few studies evaluating risk factors associated with the contemporary antiemetic prophylaxis, including that of olanzapine/aprepitant- or NEPA- containing regimens. The present study aimed to identify the risk factors related to CINV development in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide chemotherapy. Methods: Data from 304 patients who were enrolled to 3 previously reported prospective antiemetic studies were included. Multivariate logistic regression models were used to predict risk factors associated with the occurrence of CINV. Additionally, likelihood of treatment failure in relation to number of risk factors of individual patient was evaluated. Results: Multivariate analysis of the entire study group revealed that obese status (defined as body mass index >/= 25.0 kg/m2) and the use of olanzapine/aprepitant- or NEPA- containing antiemetic regimens were associated with high likelihood, while history of motion sickness was associated with lower likelihood, of complete response (CR) and ‘no nausea’ in the overall phase. History of vomiting in pregnancy was also associated with lower likelihood of overall CR. Patients with increasing number of risk factors had higher likelihood of treatment failure as well as shorter time to first vomiting. Those who did not achieve CR and ‘no nausea’ in the first cycle were less likely to achieve these parameters in the subsequent cycle of chemotherapy. Conclusions: This present study confirmed the previously reported risk factors to be important for CINV in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide. Further optimization of CINV control is required for patients with identifiable risk factors; olanzapine/aprepitant- or NEPA- containing prophylaxes are the preferred contemporary antiemetics regimens for Chinese breast cancer patients undergoing doxorubicin and cyclophosphamide chemotherapy. Citation Format: Winnie Yeo, Nicole Ngai, Christopher Yip, Victoria Yeo, Jonathan Ko, Claudia Yip, Frankie Mo. Risk factors associated with chemotherapy-induced nausea and vomiting among breast cancer patients receiving highly emetogenic chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-03.

Background: Lignans intake has been suggested to affect breast cancer outcomes based on a few studies from the West. However, to date, the relationship of lignan consumption and breast cancer outcomes has not been investigated in Chinese patient population. Since the habitual intake of lignan and food sources for lignan may vary between different geographical population and ethnicities, it is necessary to develop a population-specific Food Frequency Questionnaire (FFQ) to enable the conduct of dietary lignan studies in Chinese patient population. The objective of this study is to validate a modified FFQ that could be utilized for assessing lignan intake in a Chinese population. Methods: 133 Hong Kong Chinese women with early-stage breast cancer who were participating in an on-going prospective cohort study (The Hong Kong New Territories East Cluster (NTEC)-Kowloon West Cluster (KWC) Breast Cancer Survival Study) were being consented into the present study; the NTEC-KWC study investigates the associations of phytoestrogens and other factors with breast cancer outcomes. 103 of the 133 patients completed all the study assessments and were included in the analysis; they underwent two face-to-face interviews during which they responded to a modified 130-item FFQ at 1-year apart (FFQ1, FFQ2). In addition, 12 monthly 24-hour dietary recalls (24-h DRs) were conducted through telephone during the same 1-year period. Total lignans intake from the FFQs and 24-h DRs, correlation coefficients and cross classification between the two FFQs and between FFQ and 24-h DR were examined. Results: Median intakes of total lignans for FFQ1, FFQ2 and 24-h DRs were 2.39, 2.15 and 1.36 mg/day, respectively. Both the energy-adjusted correlation coefficients between FFQ1 and FFQ2, and that between FFQ2 and 24-h DR were 0.59 for log-transformed lignans intake (p Conclusion: The 130-item FFQ has acceptable validity and reproducibility, and is a reasonable and useful instrument to assess dietary lignans intake among Hong Kong Chinese women with early-stage breast cancer. Funding: World Cancer Research Fund International (Grant Number WCRF 2010/249 and WCRF 2014/1197) Citation Format: Yiqian He, Yuan-Yuan Lei, Carol Kwok, Ashley Cheng, Ka-Li Cheung, Iris Lee, Roselle Lee, Suzanne Ho, Winnie Yeo. Validation of a Chinese-specific food frequency questionnaire for assessing dietary lignans intake among breast cancer patients in Hong Kong [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-13-19.

Background: Adjuvant chemotherapy improves outcomes of pts with early breast cancer, but CINV have been regarded as two of the most disturbing side effects, affecting their quality of life (QoL). In this study, the primary objective was to compare the efficacy of olanzapine in addition to the standard aprepitant-based antiemetic regimen for CINV in pts receiving the 1st cycle of adjuvant AC chemotherapy (adriamycin 60mg/m2 and cyclophosphamide 600mg/m2). The secondary objective was to compare the tolerability and efficacy of such regimen in the 4 cycles of AC. Methods: This is a prospective single center, randomized study. Eligible pts had early stage breast cancer of Chinese ethnicity; they were chemotherapy- naive and treated with adjuvant AC chemotherapy. Antiemetic regimen for all studied population included aprepitant, ondansetron and dexamethasone; patients were randomly allocated to Olanzapine (with olanzapine) or Standard (without olanzapine) arms. Individual patient filled in self-reported diary and visual analogue scale for nausea from which information on nausea, vomiting and use of rescue medication were collected; outcomes were compared during acute phase (0-24 hrs), delay (24-120 hrs) and overall time-frame (0-120 hrs) from initiation of AC. QoL was assessed by Functional Living Index-Emesis (FLIE). Results: 120 pts were randomized. For CINV in Cycle 1 AC, outcomes of Olanzapine vs Standard arms were: complete response (acute phase 70.0 vs 51.7%, p=0.0397; delay phase 75.0 vs 45.0%, p=0.0008; overall time-frame 65.0 vs 38.3%, p=0.0035), complete protection (acute phase 70.0 vs 50.0%, p=0.0253; delay phase 71.7 vs 40.0%, p=0.0005; overall 61.7 vs 36.7%, p=0.0062), total control (acute phase 65.0 vs 41.7%, p=0.0104; delay phase 60.0 vs 31.7%, p=0.0018; overall 51.7 vs 26.7%, p=0.0050), ‘no vomiting’ (acute phase 73.3 vs 51.7%, p=0.0142; delay phase 76.7 vs 48.3%, p=0.0013; overall 68.3 vs 40.0%, p=0.0018), ‘no significant nausea’ (acute phase 95.0 vs 75.0%, p=0.0017; delay phase 91.7 vs 65.0%, p=0.0004; overall 91.7 vs 63.3%, p=0.0002),‘no nausea’ (acute phase 76.7 vs 53.3%, p=0.0074; delay phase 65.0 vs 35.0%, p=0.0010; overall 58.3 vs 33.3%, p=0.0060), and need of rescue medication (acute phase 3.3 vs 11.7%, p=0.0654; delay phase 6.7 vs 21.7%, p=0.0133; overall 8.3 vs 23.3%, p=0.0244). Assessment of FLIE on Day 6 after Cycle 1 AC between the Olanzapine vs Standard arms revealed better QOL mean scores for nausea domain (p Conclusions: In this prospective study of Chinese women with breast cancer, the addition of olanzapine to standard antiemetic regimen increases the control of CINV and improves the QoL of pts during AC chemotherapy. Funding: Madam Diana Hon Fun Kong Donation for Cancer Research. Citation Format: Winnie Yeo, Thomas KH Lau, Vicky TC Chan, Li Leung, Dong Lai, Elizabeth Pang, Maggie Cheung, Ashley Wong, Winnie MT Soo, Vanessa TY Yeung, Teresa Tse, Eva WM Yeung, Daisy CM Lam, Kenneth CW Wong, David R Johnson, Kim PK Ng, Herbert Loong, Joyce TY Ng, Florence Mok, Mimi KM Lee, Darren MC Poon, Yvonne SH Yau, Macy Tong, Joyce JS Suen, Frankie KF Mo. Randomized study to determine the efficacy of Olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV) in Chinese breast cancer patients (PTS) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-12-09.

Background:Anticancer treatment for breast cancer has been associated with weight gain but such observation has mainly been reported in western patients. More recent data in Asian patients have inconsistent findings. Factors including socio-demographic, clinical and lifestyle may be associated with post-diagnosis weight gain. In this prospective cohort study of women with breast cancer, the objectives were to determine the body mass index (BMI) and weight changes over 36 months after initial diagnosis and the factors associated with such changes. Methods: Chinese women with newly diagnosed early-stage breast cancer were recruited. Individual woman had her weight measured at breast cancer diagnosis (W0), at study entry (W1) and at 36-month follow-up (W2). Body height was measured at W0. We evaluated change in weight and body mass index (BMI) before and after breast cancer diagnosis.Socio-demographic, clinical and lifestyle factors were assessed to identify potential associated factors with weight changes. Results: A total of 1133 women with breast cancer had detailed weight measurements at the 3 time-points of assessment. The mean age at diagnosis was 52 years. Fifty-four percent were premenopausal at W1. The proportion of patients with stage 0-I, II and III diseases were 35%, 46% and 19%, respectively. The proportions of patients who were overweight and obese at the three assessment time-points were 21.2% and 28.5% at W0, 19.7% and 26.6% at W1, and 21.7% and 30.9% at W2 assessment, respectively. When compared to W0, the proportions of women who gained weight within 2-5kg at W1 and W2 were 2.4% and 20.6% respectively, that with weight gain of >5kg at W1 and W2 were 0.5% and 10.0% respectively; 6.1% and 19.6% of women had weight loss >2kg at W1 and W2 respectively. Compared to W0, the median value of weight change was -0.5 kg (range: -11.4, 18.3) at W1 and 0.6 kg (range: -19.6, 20.5) at W2. On multivariate analysis, only BMI at diagnosis were significantly associated with weight change betweenassessments at diagnosis and W2; the median (range) for weight changes for women who were underweight, normal, overweight and obese were respectively 0.9 (-4.8, 7.6), 0.6 (-13.2, 20.5), 0.5 (-11.5, 13.0) and 0.5 (-19.6, 12.6) kg, p Conclusions: In this prospective study of Chinese women with a history of breast cancer who were followed-up over a 36-months' period, the proportions of women with overweight and obese statuses were relatively stable; weight gain was uncommon among Hong Kong women with breast cancer during the same period. These findings are in contrast with studies conducted in the West, where weight gains were more commonly reported. Funding: World Cancer Research Fund International (Grant Number WCRF 2010/249 and WCRF 2014/1197) Citation Format: Yeo W, Lei YY, Cheng AC, Kwok CC, Cheung KL, Lee R, Lee IC, He YQ, Ho S. Prospective 36-month follow-up to determine changes in body mass index and weight among Chinese breast cancer survivors [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 P1-12-07.

Background: Epidemiologic studies in the West have found that lifestyle factors, including maintaining normal body weight, being physically active and eating a healthy diet are individually associated with better quality of life (QOL) among breast cancer survivors. Limited data is available on lifestyle modifications in association with quality of life of breast cancer survivors in Asian region. The objectives of this study were to [1] determine the lifestyle changes among Chinese breast cancer survivors at diagnosis and 18-month post diagnosis; and [2] to assess the association of lifestyle changes with QOL. Methods: In this prospective cohort study, 1300 Chinese breast cancer patients were assessed at breast cancer diagnosis (baseline; reflecting pre-diagnosis) and at 18-month post-diagnosis. During each assessment, individual patient's lifestyle within the previous 12 months were recorded and included exercise, diet, and body mass index (BMI) data; each patient also underwent self-administered QOL assessment. Assessment of lifestyle modifications were based on World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendation adherence scores (range: 0-6).QOL was evaluated by European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire C-30 (EORTC-QLQ-C30). Paired t-test was performed to compare the overall recommendation adherence score before and after diagnosis.To investigate the association between recommendation adherence score and HRQoL, generalized linear models were used to compare the least-square means by tertiles of adherence score (T1, T2, and T3) and continuous adherence score. In the multivariate models, adjustment were made for age, stage of cancer, education level, marital status, comorbidities, smoking status, current hormonal therapy and energy intake. Results: The mean recommendation adherence score significantly increased from baseline of 3.2 (SD=1.1) to 3.9 (SD=1.1, p Conclusions: Positive lifestyle changes were made among Chinese breast cancer survivors after cancer diagnosis. Increased adherence to WCRF/AICR recommendations after cancer diagnosis improves QOL, suggesting that Chinese breast cancer survivors should follow the WCRF/AICR guideline for cancer prevention. Acknowledgments: This study is funded by the World Cancer Research Fund International (Grant Number WCRF 2010/249and WCRF 2014/1197) and Madam Diana Hon Fun Kong Donation for Cancer Research. Citation Format: Lei Y-Y, Lee IC-K, Cheung KL, Lee R, He Y, Yeo W. Quality of life of Chinese breast cancer survivors in association with lifestyle changes before and after cancer diagnosis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-04.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers. Signaling pathways including AKT-mTOR axis is often dysregulated in HCC. RAD001 principally targets at the mTOR complex 1. mTOR inhibition is reportedly associated with activation of feedback loop and parallel pathways. TKI258 is a potent tyrosine kinase inhibitor targeting the FGFRs and VEGFRs, which blocks subsequent PI3K/AKT signaling pathways in cancer cells. In the current study, we aim to study the in-vitro and in-vivo effects of the drug combination with reference to the parallel and upstream pathway of AKT-mTOR axis. We have treated the HCC cell line Hep3B with TKI258 and RAD001. RAD001 could suppress the phosphorylation of down stream signal mediators of mTOR pathway including p70S6 kinase 1 (S6K) and eukaryotic initiation factor binding protein 1 (4E-BP1) and led to G1 phase arrest. The results demonstrated a significant increase in suppression of cell proliferation in vitro with the combination of TKI258 (300nM) and RAD001 (either 200nM or 200pM) compared with either drug alone. Although the addition of the TKI258 only slightly suppressed the AKT positive feedback loop induced by RAD001, the combination of drugs could significantly suppress the phosphorylation of mTOR (Ser2448), ERK1/2 (Ser217/221) and p38 (Thr180/Tyr182) as well as their endogenous protein expression levels. The expression levels of FGFR1 and FGFR2 were also suppressed. The overall protein reduction was due to the synergistic inhibition of p70S6 (Ser240/244) and 4E-BP1 (Ser65) phosphorylation, which indicated a strong suppression in translation and protein synthesis. Pro-caspases 3 and PARP cleavage were not observed at 24 hours and only slightly detected at 48 hours post-treatment, suggesting that the drug combination did not further increase cytotoxic effects but mainly increased in cytostatic arrest ability. In Hep3B derived xenograft model, TKI258 (15mg/ml) and RAD001 (2.5mg/kg) had shown a synergistic inhibition of tumor growth in volume and weight. In addition, there was a significant reduction in microvessel density (MVD) in the xenograft, which indicated an improved effect in angiogenesis inhibition. Our data showed that the combination of RAD001 and TKI258 were active in controlling HCC proliferation via double inhibition of both AKT-mTOR axis and its parallel pathway. Acknowledge: The works are supported by Novartis Oncology. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2811. doi:1538-7445.AM2012-2811

Hepatocellular carcinoma (HCC) shows low responses to most conventional chemotherapies. To facilitate target identifications for novel therapeutic developments, we deployed gene expression profiling on 43 paired HCC tumors and adjacent non-tumoral liver. Coupled with ontology analysis, the major functional process suggested in the malignant transformation of HCC was microtubule-related cellular assembly. We further examined the potential use of microtubule targeting Taxane drugs, including Paclitaxel and Docetaxel, and compared findings to the results obtained from Doxorubicin, a common chemotherapeutic agent used in the treatment of a number of neoplasms. Recent studies showed that drug delivery by nanoparticles have enhanced efficacy with reduced side effects. In this regard, the nanoparticle albumin-bound (nab)-Paclitaxel was also examined. In a panel of HCC cell lines studied, a high sensitivity towards Taxane drugs was generally found, although the effect from nab-Paclitaxel was most profound. The nab-Paclitaxel showed an effective IC50 dose at 15-fold lower than Paclitaxel alone or the derivative analogue Docetaxel, and approx.450-fold less compared to Doxorubicin. Flow cytometric analysis confirmed a cell cycle blockade at the G2/M phase and increased apoptosis following treatment with nab-Paclitaxel. In-vivo animal study also showed that nab-Paclitaxel readily inhibited xenograft growth with less toxicity compared to other anti-microtubule drugs and Doxorubicin. Silencing of a major microtubule regulatory gene STMN1 suggested a distinct synergistic effect in the combined treatment with nab-Paclitaxel. Our findings in this study would suggest the microtubule organizations to represent a promising target for treatment developments in HCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4423.