Nutrient intakes from supplement and factors associated with supplement use among breast cancer survivors: A cross-sectional study.

OBJECTIVE: We investigated the contribution of supplement use to total nutrient intake, the prevalence of inadequate nutrient intake and the factors associated with supplement use among breast cancer survivors. METHODS: A total of 701 Korean breast cancer survivors were included. We calculated the contribution of dietary supplements to total nutrient intake and the proportion of the population below the estimated average requirements (EARs) or exceeding the tolerable upper intake levels (ULs). Stepwise logistic regression was used to identify factors associated with dietary supplement use. RESULTS: A total of 66.5% of the survivors used dietary supplements, with multivitamins and minerals being the most commonly consumed ones. The per cent contribution of supplement to the total intake was the highest for vitamin C. 28.2%-55.4% of the non-users consumed below the EAR of riboflavin, folate and calcium; 6.1%, 4.9% and 6.5% of the supplement users consumed above the UL of vitamins A and C, and iron, respectively. Supplement users had higher education levels or longer survival time. CONCLUSION: 66.5% of Korean breast cancer survivors used dietary supplements. A higher education level or prolonged survival time was associated with higher use of dietary supplements.

Effects of tamoxifen and aromatase inhibitors on the risk of acute coronary syndrome in elderly breast cancer patients: An analysis of nationwide data.

BACKGROUND: Aromatase inhibitors (AIs) are the preferred endocrine treatment for postmenopausal hormonal receptor-positive breast cancer. However, there is controversy on the long-term cardiovascular and cerebrovascular safety of AIs over that of tamoxifen. METHODS: We analyzed the National Health Information Database (NHID) of 281,255 women over a 20-year-old diagnosed with breast cancer between 2009 and 2016. Cardiovascular events (CVEs) were defined as the development of the following, acute coronary syndrome (ACS), ischemic and hemorrhagic stroke, defined by using insurance claim records. The model was constructed by Cox proportional hazard regression and this model was used to analyze the effects of AI and tamoxifen on CVE. RESULTS: We included 47,569 women for the final analysis. Patients were classified into 'No hormonal treatment (n = 18,807), 'Switch (n = 2097)', 'Tamoxifen (n = 7081)' and 'AI (n = 19,584)'. There were 2147 CVEs in 2032 patients (4.1%). Univariate analysis showed that women with tamoxifen had significantly lower risk for CVEs compared to no-treatment (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.74-0.97) while AI showed no such effect (HR 0.93, 95% CI 0.84-1.02). After adjusting for other risk factors (hypertension, dyslipidemia, family history), the use of tamoxifen was associated with significant protective effect against ACS (HR 0.63, 95% CI 0.47-0.84). CONCLUSIONS: Our results, based on the NHID, supports the protective effect of tamoxifen against CVE in Korean breast cancer patients aged 55 and older that is not seen with AIs. Our results can guide the selection of adjuvant hormonal treatment agents for Korean breast cancer patients based on their risk of developing CVE.

Prognostic Influence of BCL2 on Molecular Subtypes of Breast Cancer.

PURPOSE: We aimed to reveal the prognostic influence of B-cell CLL/lymphoma 2 (BCL2) on molecular subtypes of breast cancer. METHODS: We analyzed 9,468 patients with primary breast cancer. We classified molecular subtypes according to the National Comprehensive Cancer Network (NCCN) and St. Gallen guidelines, mainly on the basis of the expression of hormonal receptor (HR), human epidermal growth factor receptor 2 (HER2), and Ki-67. RESULTS: Regarding NCCN classification, BCL2 was a strong favorable prognostic factor in the HR(+)/HER2(-) subtype (p<0.001) and a marginally significant favorable prognosticator in the HR(+)/HER2(+) subtype (p=0.046). BCL2 had no prognostic impact on HR(-)/HER2(+) and HR(-)/HER2(-) subtypes. In relation to St. Gallen classification, BCL2 was a strong favorable prognosticator in luminal A and luminal B/HER2(-) subtypes (both p<0.001). BCL2 was a marginally significant prognosticator in the luminal B/HER2(+) subtype (p=0.046), and it was not a significant prognosticator in HER2 or triple negative (TN) subtypes. The prognostic effect of BCL2 was proportional to the stage of breast cancer in HR(+)/HER2(-), HR(+)/HER2(+), and HR(-)/HER2(-) subtypes, but not in HR(-)/HER2(+) subtype. BCL2 was not a prognostic factor in TN breast cancer regardless of epidermal growth factor receptor expression. CONCLUSION: The prognostic influence of BCL2 was different across molecular subtypes of breast cancer, and it was largely dependent on HR, HER2, Ki-67, and the stage of cancer. BCL2 had a strong favorable prognostic impact only in HR(+)/HER2(-) or luminal A and luminal B/HER2(-) subtypes, particularly in advanced stages. Further investigations are needed to verify the prognostic influence of BCL2 on molecular subtypes of breast cancer and to develop clinical applications for prognostication using BCL2.

Who are happy survivors? Physical, psychosocial, and spiritual factors associated with happiness of breast cancer survivors during the transition from cancer patient to survivor.

OBJECTIVE: This study aims to evaluate physical, psychosocial, and spiritual factors associated with happiness in breast cancer survivors during the reentry period. METHODS: It is a cross-sectional study with 283 nonmetastatic breast cancer survivors who completed treatment within 1 year. We included survivors who completed questionnaires on happiness and health-related quality of life (QoL) 2 years after cancer diagnosis. Happiness and QoL was measured using the Subjective Happiness Scale and EORTC QLQ-C30, respectively. Multivariable logistic regression was used to find factors associated with happiness. RESULTS: The mean age of the study participants was 48.5 ± 7.8 years. Among the 283 survivors, 14.5%, 43.8%, 32.5%, and 2.1% reported being "very happy," "happy," "neutral," and "not happy at all," respectively. Happy survivors reported a better general health status and QoL (67.6 vs 49.6; P < .01), and fewer symptoms compared to unhappy survivors. Happy survivors were more likely to feel certain about the future (27.2% vs 11.9%, P < .01), have a strong purpose in life (22.4% vs 9.3%, P < .01), and feel hopeful (36.4% vs 8.5%, P < .01) compared to unhappy survivors. In a multivariate model, having purpose (OR = 2.50, 95% CI 1.42-4.40) and hope (OR = 4.07, 95% CI 2.23-7.45) in life were found to be associated with happiness. CONCLUSIONS: During the reentry period, breast cancer survivors who are hopeful and have a clear purpose in life are more likely to be happy than those who are not. Setting proper life goals might be beneficial to help breast cancer survivors who experience persistent QoL issues.

Radioactive Iodine Therapy Did Not Significantly Increase the Incidence and Recurrence of Subsequent Breast Cancer.

CONTEXT: Previous studies on the extent to which radioactive iodine (RAI) therapy for thyroid cancer increases the risk of subsequently developing breast cancer have given conflicting results. OBJECTIVE: This study aimed to evaluate the effect of RAI treatment on breast cancer development and recurrence among female patients with primary thyroid cancer. DESIGN: This was a retrospective cohort study. The risk of subsequent breast cancer associated with RAI and its dose in hazard ratios (HRs) with 95% confidential intervals (CIs) were calculated using time-dependent Cox proportional hazard models. PATIENTS: A total of 6150 patients with thyroid cancer enrolled between 1973 and 2009 were followed until December 2012. Of these, 3631 (59.0%) received RAI therapy. During the follow-up period, 99 primary breast cancers were diagnosed. MAIN OUTCOME MEASURE: Risk of breast cancer development according to RAI therapy and RAI dose during treatment for primary thyroid cancer. RESULTS: RAI therapy did not significantly increase the incidence of subsequent breast cancer among female patients (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.22-1.06) when a 2-year latency period was accounted for. High-dose RAI (≥120 mCi) was associated with a reduced incidence of subsequent breast cancer (HR, 0.17; 95% CI, 0.05-0.62) in the cohort with a 2-year latency period. CONCLUSIONS: The long-term follow-up results of this study suggest that RAI treatment for patients with thyroid cancer may not increase the risk or recurrence of breast cancer.

Low adherence to upfront and extended adjuvant letrozole therapy among early breast cancer patients in a clinical practice setting.

OBJECTIVE: The aim of this study was to investigate the prevalence and causes of early discontinuation and non-adherence to upfront and extended adjuvant letrozole therapy in breast cancer patients. METHODS: Adherence was assessed using medical charts and longitudinal pharmacy records of 609 patients who initiated adjuvant letrozole between January 2002 and April 2011. A Cox proportional hazards regression model was adopted to identify potential predictors of non-adherence. RESULTS: The overall adherence rate after 1 year of therapy was 79.5%, with cumulative rates declining to 63.7% after 3 years and 57.1% after 5 years. A significantly lower rate of adherence in the extended adjuvant group was observed compared with the upfront adjuvant group (49.0 vs. 72.5%, p < 0.001). Adverse events (50.4%) were the major cause of early discontinuation, with musculoskeletal pain (73.2%) being the single most cited reason. Additional factors correlating with non-adherence in the upfront adjuvant group included a delay in initiation of adjuvant hormone therapy, breast-conserving surgery, calcium supplements, bisphosphonate therapy and concomitant medication for co-morbidity. CONCLUSIONS: We observed that approximately 57% of patients fully adhered to letrozole therapy over a 5-year treatment period, and that the adherence to extended letrozole was meaningfully lower than the upfront adjuvant letrozole in a clinical practice setting.

Breast-conserving surgery after tumor downstaging by neoadjuvant chemotherapy is oncologically safe for stage III breast cancer patients.

BACKGROUND: We conducted a retrospective study to evaluate the local recurrence (LR) rate depending on the use of neoadjuvant chemotherapy (NCT) and to determine the oncologic safety of breast-conserving surgery (BCS) after NCT by comparing LR between patients treated with BCS and mastectomy in clinical stage III breast cancer patients. PATIENTS AND METHODS: Between 2004 and 2007, 166 patients underwent BCS or mastectomy after NCT (NCT group) and 193 patients underwent surgery first (surgery group) in clinical stage III breast cancer patients. Patients whose tumor size became ≤4 cm after NCT, 57 patients underwent mastectomy (mastectomy group) 39 patients underwent preplanned BCS (preplanned BCS group), and 33 patients underwent downstaged BCS (downstaged BCS group). The recurrence rates between the groups and risk factors for LR were analyzed. RESULTS: The 5-year LR-free survival rates were 93.6 % in the NCT group and 95.9 % in the surgery group (P = 0.108). In the NCT group, the 5-year LR-free survival rates were 96.3 % in the mastectomy group, 94.7 % in the preplanned BCS group and 90.9 % in the downstaged BCS group (P = 0.669). High expression of Ki-67 was a predictor of LR in patients in three groups (Hazard ratio 8.300, P = 0.049). CONCLUSIONS: Our findings suggest that BCS after NCT in clinical stage III patients is oncologically safe in terms of LR if breast tumor size is ≤4 cm after NCT and Ki-67 is a predictor of LR after NCT.

Noninvasive identification of viable cell populations in docetaxel-treated breast tumors using ferritin-based magnetic resonance imaging.

BACKGROUND: Cancer stem cells (CSCs) are highly tumorigenic and are responsible for tumor progression and chemoresistance. Noninvasive imaging methods for the visualization of CSC populations within tumors in vivo will have a considerable impact on the development of new CSC-targeting therapeutics. METHODOLOGY/PRINCIPAL FINDINGS: In this study, human breast cancer stem cells (BCSCs) transduced with dual reporter genes (human ferritin heavy chain [FTH] and enhanced green fluorescence protein [EGFP]) were transplanted into NOD/SCID mice to allow noninvasive tracking of BCSC-derived populations. No changes in the properties of the BCSCs were observed due to ferritin overexpression. Magnetic resonance imaging (MRI) revealed significantly different signal intensities (R(2)* values) between BCSCs and FTH-BCSCs in vitro and in vivo. In addition, distinct populations of pixels with high R(2)* values were detected in docetaxel-treated FTH-BCSC tumors compared with control tumors, even before the tumor sizes changed. Histological analysis revealed that areas showing high R(2)* values in docetaxel-treated FTH-BCSC tumors by MRI contained EGFP+/FTH+ viable cell populations with high percentages of CD44+/CD24- cells. CONCLUSIONS/SIGNIFICANCE: These findings suggest that ferritin-based MRI, which provides high spatial resolution and tissue contrast, can be used as a reliable method to identify viable cell populations derived from BCSCs after chemotherapy and may serve as a new tool to monitor the efficacy of CSC-targeting therapies in vivo.

Web-based tailored education program for disease-free cancer survivors with cancer-related fatigue: a randomized controlled trial.

PURPOSE: To determine whether an Internet-based tailored education program is effective for disease-free cancer survivors with cancer-related fatigue (CRF). PATIENTS AND METHODS: We randomly assigned patients who had completed primary cancer treatment within the past 24 months in any of four Korean hospitals and had reported moderate to severe fatigue for at least 1 week to participate in a 12-week, Internet-based, individually tailored CRF education program or to receive routine care. We based the program on the CRF guidelines of the National Comprehensive Cancer Network (NCCN) and incorporated the transtheoretic model (TTM). At baseline and 12 weeks, we used the Brief Fatigue Inventory (BFI) and Fatigue Severity Scale (FSS) as primary outcomes and the Hospital Anxiety and Depression Scale (HADS) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) for secondary outcomes. RESULTS: We recruited 273 participants and randomly assigned 136 to the intervention group. Compared with the control group, the intervention group had an improvement in fatigue as shown by a significantly greater decrease in BFI global score (-0.66 points; 95% CI -1.04 to -0.27) and FSS total score (-0.49; 95% CI, -0.78 to -0.21). In secondary outcomes, the intervention group experienced a significantly greater decrease in HADS anxiety score (-0.90; 95% CI, -1.51 to -0.29) as well as global quality of life (5.22; 95% CI, 0.93 to 9.50) and several functioning scores of the EORTC QLQ-C30. CONCLUSION: An Internet-based education program based on NCCN guidelines and TTM may help patients manage CRF.

Proteomic approach reveals FKBP4 and S100A9 as potential prediction markers of therapeutic response to neoadjuvant chemotherapy in patients with breast cancer.

Although doxorubicin (Doxo) and docetaxel (Docet) in combination are widely used in treatment regimens for a broad spectrum of breast cancer patients, a major obstacle has emerged in that some patients are intrinsically resistant to these chemotherapeutics. Our study aimed to discover potential prediction markers of drug resistance in needle-biopsied tissues of breast cancer patients prior to neoadjuvant chemotherapy. Tissues collected before chemotherapy were analyzed by mass spectrometry. A total of 2,331 proteins were identified and comparatively quantified between drug sensitive (DS) and drug resistant (DR) patient groups by spectral count. Of them, 298 proteins were differentially expressed by more than 1.5-fold. Some of the differentially expressed proteins (DEPs) were further confirmed by Western blotting. Bioinformatic analysis revealed that the DEPs were largely associated with drug metabolism, acute phase response signaling, and fatty acid elongation in mitochondria. Clinical validation of two selected proteins by immunohistochemistry found that FKBP4 and S100A9 might be putative prediction markers in discriminating the DR group from the DS group of breast cancer patients. The results demonstrate that a quantitative proteomics/bioinformatics approach is useful for discovering prediction markers of drug resistance, and possibly for the development of a new therapeutic strategy.

Concurrent versus sequential administration of CMF chemotherapy and radiotherapy after breast-conserving surgery in early breast cancer.

AIMS AND BACKGROUND: To compare the outcome of concurrent versus sequential administration of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy and radiotherapy after breast-conserving surgery in early breast cancer. METHODS: From February 1992 to January 2002, 156 patients underwent CMF chemotherapy and radiotherapy, either concurrently (CCRT group, 88 patients) or sequentially (SCRT group, 68 patients). There was a predilection of patients with a larger tumor (P = 0.0035), with more frequent nodal involvement (P = 0.0686), and younger age (P = 0.0776) in the CCRT group. RESULTS: The planned radiotherapy was completed in every patient. No grade 3 or 4 late treatment-related toxicity was observed in the CCRT or SCRT group. Compliance to the treatment as well as cosmetic outcome of the two groups were comparable. Despite more adverse factors for local-regional recurrence in the CCRT group, the 5-year local-regional control rate of the CCRT group was similar to that of the SCRT group (97.7% vs 93.8%, respectively, P = 0.1688). On multivariate analysis, concomitant administration of chemotherapy and radiotherapy was associated with improved local-regional control (P = 0.0463). CONCLUSIONS: Concurrent administration of CMF chemotherapy and radiotherapy resulted in improved local-regional control over sequential administration without an increase in significant toxicity. Concurrent CMF chemoradiotherapy may serve as a viable option for patients at high-risk of local-regional relapse not suitable for anthracycline or taxane-based chemotherapy.

Fibrin glue reduces the duration of lymphatic drainage after lumpectomy and level II or III axillary lymph node dissection for breast cancer: a prospective randomized trial.

This randomized prospective study investigated the effect of fibrin glue use on drainage duration and overall drain output after lumpectomy and axillary dissection in breast cancer patients. A total of 100 patients undergoing breast lumpectomy and axillary dissection were randomized to a fibrin glue group (N=50; glue sprayed onto the axillary dissection site) or a control group (N=50). Outcome measures were drainage duration, overall drain output, and incidence of seroma. Overall, the fibrin glue and control groups were similar in terms of drainage duration, overall drain output, and incidence of seroma. However, subgroup analysis showed that fibrin glue use resulted in a shorter drainage duration (3.5 vs. 4.7 days; p=0.0006) and overall drain output (196 vs. 278 mL; p=0.0255) in patients undergoing level II or III axillary dissection. Fibrin glue use reduced drainage duration and overall drain output in breast cancer patients undergoing a lumpectomy and level II or III axillary dissection.

Berberine diminishes the side population and ABCG2 transporter expression in MCF-7 breast cancer cells.

The plant alkaloid berberine has many biological activities including the ability to induce cell cycle arrest and apoptosis, making it a potentially useful agent for targeting cancer cells. We have analyzed the effects of berberine on MCF-7 breast cancer cells. Berberine was added to MCF-7 cells in culture, and proliferation, side population (SP) cells and expression of ABCG2 were examined. Berberine caused a dose-dependent reduction in proliferation. Hoechst 33,342 dye staining and FACS analysis revealed that berberine treatment caused a decrease in SP cells relative to untreated controls. In addition, berberine treatment was associated with a decrease in expression of ABCG2 relative to untreated controls. These results indicate that the growth inhibitory effects of berberine treatment on MCF-7 cells may be partly via effects on SP and ABCG2 expression. Further work is warranted to explore whether berberine may be a novel therapeutic drug useful for targeting breast cancer stem cells.

Berberine inhibits growth of the breast cancer cell lines MCF-7 and MDA-MB-231.

The effects of berberine on the behavior of breast tumors have not yet been established. To determine whether this compound is useful in the treatment of breast cancer, we analyzed the impact of berberine on the human breast cancer cell lines MCF-7 and MDA-MB-231 cells. Berberine was added to proliferating MCF-7 and MDA-MB-231 cells in culture. Following treatment, changes in cell growth characteristics such as proliferation, cell cycle duration, and the degree of apoptosis were assayed. Following berberine treatment, a time-dependent reduction in proliferation was observed in both cell lines at differing concentrations: 20 microM for MCF-7 and 10 microM for MDA-MB-231 cells. Annexin V staining showed an increase in apoptosis in both cell lines of 31 % in MCF-7 and 12 % in MDA-MB-231 cells compared to their respective controls. In addition, 12 % of the MCF-7 cells were arrested at G0/G1, compared to 62 % of control cells. These results demonstrate that treatment with berberine inhibits growth in both MDA-MB-231 and MCF-7 cells. In addition, they show that this partly occurs through the induction of apoptosis in MDA-MB-231 cells, and through both cell cycle arrest and induction of apoptosis in MCF-7 cells. Thus, berberine may be a novel therapeutic drug for breast cancer.

Genomic alterations identified by array comparative genomic hybridization as prognostic markers in tamoxifen-treated estrogen receptor-positive breast cancer.

BACKGROUND: A considerable proportion of estrogen receptor (ER)-positive breast cancer recurs despite tamoxifen treatment, which is a serious problem commonly encountered in clinical practice. We tried to find novel prognostic markers in this subtype of breast cancer. METHODS: We performed array comparative genomic hybridization (CGH) with 1,440 human bacterial artificial chromosome (BAC) clones to assess copy number changes in 28 fresh-frozen ER-positive breast cancer tissues. All of the patients included had received at least 1 year of tamoxifen treatment. Nine patients had distant recurrence within 5 years (Recurrence group) of diagnosis and 19 patients were alive without disease at least 5 years after diagnosis (Non-recurrence group). RESULTS: Potential prognostic variables were comparable between the two groups. In an unsupervised clustering analysis, samples from each group were well separated. The most common regions of gain in all samples were 1q32.1, 17q23.3, 8q24.11, 17q12-q21.1, and 8p11.21, and the most common regions of loss were 6q14.1-q16.3, 11q21-q24.3, and 13q13.2-q14.3, as called by CGH-Explorer software. The average frequency of copy number changes was similar between the two groups. The most significant chromosomal alterations found more often in the Recurrence group using two different statistical methods were loss of 11p15.5-p15.4, 1p36.33, 11q13.1, and 11p11.2 (adjusted p values < 0.001). In subgroup analysis according to lymph node status, loss of 11p15 and 1p36 were found more often in Recurrence group with borderline significance within the lymph node positive patients (adjusted p = 0.052). CONCLUSION: Our array CGH analysis with BAC clones could detect various genomic alterations in ER-positive breast cancers, and Recurrence group samples showed a significantly different pattern of DNA copy number changes than did Non-recurrence group samples.

The effects of antioxidants and nitric oxide modulators on hepatic ischemic-reperfusion injury in rats.

Ischemic-reperfusion injury (IRI) is thought to be caused by oxygen radicals. Nitric oxide (NO) also has been thought to play a key role in IRI. This experiment was designed to evaluate the effects of antioxidants and NO supplement on hepatic IRI. Male Sprague-Dawley rats were divided into five groups: a sham operation group, a group with IRI, and three groups with vitamin C combined with vitamin E (VC&VE), L-arginine and N(G)-nitro-L-arginine (NNLA) injected after IRI. IRI was induced by clamping of the porta hepatis for 30 minutes and then by declamping. To prevent mesenteric blood congestion, a porto-systemic shunt had been made four weeks before the portal clamping. Biochemical assays of TNF-alpha level and NO2- level in the blood, malondialdehyde level, catalase activity and NO synthase activity in the liver tissue were performed. The results were as follows: IRI increased the malondialdehyde level and exhausted the catalase activity remarkably. VC&VE lowered the malondialdehyde levels and protected against catalase exhaustion, but had no significant effect on the NO production. L-arginine had a definite antioxidant effect, which was much weaker than that of VC&VE. In conclusion, antioxidants and a supplement of NO protected the liver tissue against IRI.