Status Of Breast Cancer Patients Research Articles

Differences in the Survival Outcomes of Breast Cancer Patients after Mastectomy Based on the Medical Insurance Status

Purpose: In Korea, the national health insurance system covers the entire population. Patients with a lower socioeconomic status are supported by the medical aid system. In this study, we examined the association of the medical insurance status of breast cancer patients with their survival outcomes after mastectomy. Methods: We retrospectively reviewed 117 patients who underwent surgical treatment for breast cancer at the Seoul Medical Center between 1999 and 2012. Patients were stratified into two groups based on their insurance status: the national health insurance registered group (n=85). And the medical aid covered group (n=32). The survival rate was calculated by using the KaplanMeier method. Results: The overall 5-year survival rate was 80.0% in the national health insurance group and 73.8% in the medical aid covered group (p=0.039). Multivariate analysis determined that age (p=0.038) and the TNM stage (p=0.035) were independent prognostic factors. The medical insurance status was not a statistically significant prognostic factor for breast cancer patients (p=0.079). Conclusion: The medical insurance status reflects the socioeconomic status of a patient, and thus, it can influence the overall survival of breast cancer patients.

MiRNome of inflammatory breast cancer.

BackgroundInflammatory breast cancer (IBC) is an extremely malignant form of breast cancer which can be easily misdiagnosed. Conclusive prognostic IBC molecular biomarkers which are also providing the perspectives for targeted therapy are lacking so far. The aim of this study was to reveal the IBC-specific miRNA expression profile and to evaluate its association with clinicopathological parameters.MethodsmiRNA expression profiles of 13 IBC and 17 non-IBC patients were characterized using comprehensive Affymetrix GeneChip miRNA 3.0 microarray platform. Bioinformatic analysis was used to reveal IBC-specific miRNAs, deregulated pathways and potential miRNA targets.Results31 differentially expressed miRNAs characterize IBC and mRNAs regulated by them and their associated pathways can functionally be attributed to IBC progression. In addition, a minimal predictive set of 4 miRNAs characteristic for the IBC phenotype and associated with the TP53 mutational status in breast cancer patients was identified.ConclusionsWe have characterized the complete miRNome of inflammatory breast cancer and found differentially expressed miRNAs which reliably classify the patients to IBC and non-IBC groups. We found that the mRNAs and pathways likely regulated by these miRNAs are highly relevant to cancer progression. Furthermore a minimal IBC-related predictive set of 4 miRNAs associated with the TP53 mutational status and survival for breast cancer patients was identified.Electronic supplementary materialThe online version of this article (doi:10.1186/1756-0500-7-871) contains supplementary material, which is available to authorized users.

Immunohistochemical analysis of aldehyde dehydrogenase isoforms and their association with estrogen-receptor status and disease progression in breast cancer.

In many types of tumors, especially breast tumors, aldehyde dehydrogenase (ALDH) activity has been used to identify cancer stem-like cells within the tumor. The presence and quantity of these cells are believed to predict the response of tumors to chemotherapy. Therefore, identification and eradication of these cells would be necessary to cure the patient. However, there are 19 different ALDH isoforms that could contribute to the enzyme activity. ALDH1A1 and ALDH1A3 are among the isoforms mostly responsible for the increased ALDH activity observed in these stem-like cells, although the main isoforms vary in different tissues and tumor types. In the study reported here, we attempted to determine if ALDH1A1 or ALDH1A3, specifically, correlate with tumor stage, grade, and hormone-receptor status in breast-cancer patients. While there was no significant correlation between ALDH1A1 and any of the parameters tested, we were able to identify a positive correlation between ALDH1A3 and tumor stage in triple-negative cancers. In addition, ALDH1A3 was negatively correlated with estrogen-receptor status. Our data suggest that ALDH1A3 could be utilized as a marker to identify stem-like cells within triple-negative tumors.

Clinico-morphological profile and receptor status in breast cancer patients in a South Indian institution.

Breast cancer is the most common malignancy in women worldwide and the second most common cancer in females in India. Receptor status may be important for survival. To analyse and correlate the clinical and morphological parameters with receptor status in breast carcinoma patients in a tertiary care institution in Southern India. This retrospective study involved 320 patients of breast cancer diagnosed in an oncology hospital over a period of 31/2 years. Data was analysed using SPSS Version 21. Some 60.6% patients with breast carcinomas belonged to the age group of 40 to 60 years. The most common histological type was infiltrating ductal carcinoma, not otherwise specified, accounting for 84.4% of patients. On immunohistochemistry, estrogen receptor (ER) and progesterone receptor (PR) were expressed in 56.3% and 53.1% of cases, respectively. Breast cancers in India, a developing country, occur in younger women and tend to be more aggressive with lower rates of ER and PR expression and higher histological tumor grades. Both ER and PR status of the tumors had significant associations with the patient age, pathological TNM stage and histological tumor grade.

349P - Risk of Locoregional Recurrence After Mastectomy By Hormone Receptor Status and Her2 Status in Breast Cancer Patients with 1-3 Positive Nodes

ABSTRACT Aim: The postmastectomy irradiation therapy (PMRT) was standard treatment for patients with more than four involved axillar lymph nodes. But patient with 1-3 positive axillar lymph nodes is controversial. To identify subgroups of patients with 1-3 positive axillar lymph nodes at significant risk of locoregional recurrence (LRR) who might furthermore benefit from the addition of PMRT. Methods: We retrospectively analyzed the outcomes of 181 patients who had 1-3 positive nodes and treated with mastectomy without adjuvant irradiation between 2003 and 2008 in our hospital. Median follow-up time was 83.2 months. 156 (86.2%) patients received adjuvant chemotherapy (anthracycline alone: 29, anthracycline followed by taxane: 95, taxan alone: 10, CMF: 22 ). 76.9% (30/39) of the patients with HER2 positive cancer received trastuzumab and 92.3%(144/156) of the patients with hormone receptor positive cancer received hormone therapy. The median number of lymph nodes removed was 20. The rate of LRR and cause-specific survival were calculated by the Kaplan-Meier method, with comparisons among groups performed using log-rank tests. Results: 13 patients developed LRR as first events (local: 9, regional: 4). The 5-years and 10-years rates of LRR were 7.3 % and 8.6%, respectively. And the 5-years and 10-years rates of cause-specific survival were 95.1% and 91.7%, respectively. Furthermore, we analyzed the rates of LRR regard to subtype of tumor (ER+ group : ER+ and HER2-, HER2+ group: HER2+ and ER any, TN group: ER-and HER2-). The 5-year rates of LRR were 5.1%, 7.5%, and 24.5 % for patients with ER+ group, HER2+ group, TN group, respectively ( ER+ group vs TN group: p = 0.008, ER+ group vs HER2 group: p = 0.574 ). The 10-years rates of LRR were nearly identical among ER+ group and HER2+ group (7.0% vs 7.5%). The 5-years and 10-years rates of LRR were less than 10% for patients with any pathological tumor size. Conclusions: Patients who had 1-3 positive axillar lymph node and TN subtype tumor experience the 5-year rate of LRR in excess of 20% and should be offered PMRT. Disclosure: H. Iwata: Honoraria (Chugai Pharma, Hiroji Iwata). All other authors have declared no conflicts of interest.

Loss of expression and aberrant methylation of the CDH1 (E-cadherin) gene in breast cancer patients from Kashmir.

Aberrant promoter hypermethylation has been recognized in human breast carcinogenesis as a frequent molecular alteration associated with the loss of expression of a number of key regulatory genes and may serve as a biomarker. The E-cadherin gene (CDH1), mapping at chromosome 16q22, is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. The aim of our study was to assess the methylation pattern of CDH1 and to correlate it with the expression of E-cadherin, clinicopathological parameters and hormone receptor status in breast cancer patients of Kashmir. Methylation specific PCR (MSP) was used to determine the methylation status of CDH1 in 128 invasive ductal carcinomas (IDCs) paired with the corresponding normal tissue samples. Immunohistochemistry was used to study the expression of E-cadherin, ER and PR. CDH1 hypermethylation was detected in 57.8% of cases and 14.8% of normal adjacent controls. Reduced levels of E-cadherin protein were observed in 71.9% of our samples. Loss of E-cadherin expression was significantly associated with the CDH1 promoter region methylation (p<0.05, OR=3.48, CI: 1.55-7.79). Hypermethylation of CDH1 was significantly associated with age at diagnosis (p=0.030), tumor size (p=0.008), tumor grade (p=0.024) and rate of node positivity or metastasis (p=0.043). Our preliminary findings suggest that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast cancers associated with a decrease in E-cadherin expression. We found significant differences in tumor-related CDH1 gene methylation patterns relevant to tumor grade, tumor size, nodal involvement and age at diagnosis of breast tumors, which could be extended in future to provide diagnostic and prognostic information.

Comparison of Dako fluorescence in situ hybridization assays (FISH and IQFISH) in the assessment of HER2 amplification in breast cancer

Determining human epidermal growth factor receptor 2 (HER2) status in breast cancer patients can be attained by fluorescent in situ hybridization (FISH) analysis, which prompts targeted treatment options. This study was performed to compare the staining results of Dako’s manual overnight HER2 FISH pharmDx™ assay with the manual (4 hours) HER2 IQFISH pharmDx™ assay and the Dako Omnis automated (4 hours) HER2 IQFISH assay, for assessment of HER2 amplification.Thirty-four formalin-fixed paraffin-embedded (FFPE) tissue blocks from patients diagnosed with invasive breast cancer were used to compare three FISH assays in three experiments. All assays included Texas Red-labeled HER2 and fluorescein-labeled centromere 17 (CEN-17) probes. First, 20 blocks with known HER2 immunohistochemistry (IHC) and FISH results from a reference laboratory were used in the validation of HER2 FISH pharmDx™ assay. Secondly, 19 of the same blocks were used in a comparison of HER2 FISH pharmDx™ assay and HER2 Instant Quality FISH pharmDx (IQFISH pharmDx™) assays. The third experiment, which included 23 blocks, compared the HER2 FISH pharmDx™ assay with the Dako Omnis IQFISH assay (stained on a Beta version of Dako’s new Omnis platform). Stained slides were counted following American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines (2007 version), with three categories of labeling: <1·8 (negative), 1·8–2·2 (equivocal), and >2·2 (positive) calculated HER2/CEN-17 ratio. The results showed high agreement between all assays employed. Initial validation of HER2 FISH pharmDx™ assay to the results provided by a reference laboratory had a concordance of 95%. The concordance between HER2 FISH pharmDx™ assay and HER2 IQFISH pharmDx™ assay was 100%. There was also 100% concordance between manual and Omnis IQFISH staining. A high level of concordance was obtained in all three experiments, indicating that manual and automated IQFISH are comparable to HER2 FISH pharmDx™. IQFISH has a faster turn-around-time (TAT) and showed comparable results in quality and quantitation.

Accuracy of ultrasound imaging and ultrasound guided biopsy in the detecting axillary lymph node disease in patients with primary breast cancer

Introduction: Pre-operative ultrasound (US) examination of the axilla and, when indicated, US guided fine needle aspiration (FNA) or core biopsy can be used to assess lymph node status in breast cancer patients. A retrospective audit was performed to compare our results to published data.

Correlates of 25-Hydroxyvitamin D among Chinese Breast Cancer Patients

BackgroundFew studies have investigated vitamin D status in association with modifiable lifestyle factors and clinical characteristics among breast cancer patients, with no studies among Chinese women, who may be at higher risk of vitamin D deficiency. We aimed to evaluate circulating 25-hydroxyvitamin D (25(OH)D) levels in association with clinical and lifestyle factors among 1,940 Chinese breast cancer patients.MethodsParticipants included breast cancer cases aged 22–77 from a population-based case-control study conducted in Shanghai, China during 1996–1998 (n = 1,044) and 2002–2005 (n = 896). Circulating 25(OH)D levels were measured in plasma samples (95% collected ≤6 months post-diagnosis). Prevalence ORs and 95% CIs were derived from multinomial logistic regression models, adjusting for age, season, and other factors.ResultsAbout 23% and 48% of women were vitamin D deficient (<30 nmol/L) or insufficient (30–50 nmol/L), respectively. Tumor characteristics were not associated with vitamin D status. Higher BMI was associated with increased odds of vitamin D deficiency (ORs (95% CIs): 1 (reference), 1.12 (0.85,1.47), and 1.57 (1.02,2.42), for <23, 23–<27.5, and ≥27.5 kg/m2, respectively, Ptrend <0.06). Total physical activity was associated with reduced odds of vitamin D deficiency (ORs (95% CIs):1 (reference), 0.84 (0.59,1.20), 0.65 (0.45,0.93), and 0.69 (0.48,1.00), for <7.65, 7.65–<10.6, 10.6–<13.5, ≥13.5 MET-hours/day, respectively, Ptrend <0.02). Smoking was associated with vitamin D insufficiency and deficiency (ORs (95% CIs): 2.50 (1.07,5.84) and 2.78 (1.11,6.95), respectively).ConclusionsIn the largest study to date, the prevalence of low vitamin D status was high among Chinese breast cancer patients and associated with higher BMI, smoking, and lower physical activity. Our findings support careful monitoring of vitamin D status and recommendations for supplementation and other lifestyle modifications that may improve vitamin D status in breast cancer patients.

Assessment of Risk Factors and Nutritional Status of Breast Cancer Patients Attending a Tertiary Care Hospital

Background: Breast Cancer is the most common diagnosed malignancy in women worldwide and in India. The peak occurrence of breast cancer in developed countries is above the age of 50 years, where as in India it is above the age of 40 years. Factors like overweight and obesity, nulliparity, H/O abortions, family H/O breast cancer, H/O use of OCPs, non feeding of breast milk have been associated with breast cancer risk. Objectives:1: To assess the risk factors of breast cancer 2:To assess the nutritional status of study population. Materials and methods: A hospital based cross sectional study was conducted among 50 histopathologically confirmed female breast cancer patients. A pretested questionnaire was administered and the study variables include age, age at menarche, menopausal status, history of abortions, family history of breast cancer, BMI etc. Results: The age of the study population ranged from 30-80yrs. Nearly 60% of the study population were overweight and obese. Nulliparity and history of abortions were reported by 14% of study population and family history of breast cancer was seen among 8% of study participants .Regarding food intake in past one month, 50% had less than usual intake;6% had greater than usual and rest 44% stated that there was no change in the food intake. Conclusion: Majority of the risk factors for breast cancer are modifiable, prevention of these risk factors will have significant impact on the occurrence of the breast cancer.

The role of neopterin in patients with primary and metastatic breast cancer: correlation with clinicopathological data

Breast cancer is the commonest malignancy of women in many parts of the world and comprises 18% of all female cancers. There is one million new cases in the world each year. Neopterin which is a pteridine produced by activation of monocytes by IFN-γ may be used as a marker of immune system activation. The biological function of neopterin is still largely unknown and certain patho-physiologic roles have only recently been elucidated. Therefore, the aim of this work was to investigate the role of neopterin in females with primary and metastatic breast cancer. The obtained results were correlated with different clinicopathological data of those patients. The study population included females with primary and metastatic breast cancer as well as healthy age matched females were taken as a control group. Peripheral blood mononuclear cells were separated from each subject under study by Ficoll-Hypaque density gradient centrifugation technique. The isolated cells were cultured with and without PHA and neopterin levels were measured in serum and culture supernatants by ELISA technique. The results showed that neopterin levels were lowest in serum, followed by culture supernatants without PHA and highest in culture supernatants with PHA in each studied group. The mean neopterin values in serum and culture supernatants with PHA of metastatic breast cancer patients were significantly higher than in the primary breast cancer patients and the control group. Our results also indicated that neopterin levels positively correlated with the tumor grade, tumor stage and the presence of metastasis. From all mentioned data it is clear that, measurement of neopterin either in serum or in culture supernatants with or without PHA can give an indication about immunological status of breast cancer patients' response to therapy and early detection of metastasis. It gives an important and valuable prognostic information before surgical intervention is performed.

Comparison of HER2 status in breast cancer patients using CISH and immunohistochemical protocols

The evaluation of human epidermal growth factor receptor-2 (HER2) status in invasive breast carcinoma has been proven to be of prognostic value for the patients. HER2 overexpression is found in about 20% of the breast cancer cases and is thought to be associated with a poor clinical outcome. The test can be performed by different molecular methods, including in situ hybridization or immunohistochemistry. We evaluated the accuracy of our immu-nohistochemical protocol for HER2 breast cancer testing in comparison to the chromogenic in situ hybridization method (CISH). A total of 19 cases were analyzed. Using the HercepTest from Dako, three cases were initially evaluated as 3+ strong positive (with concomitant hormone receptor positivity). Fifteen cases were evaluated as 2+ weak positive and one triple negative case as 1+ negative. The results from CISH confirmed HER2 gene amplification in all three 3+ positive cases, whereas 46.7% of the 2+ cases showed gene amplification. The triple negative 1+ case did not reveal HER2 gene amplification. These results indicate that our immunohistochemical protocol has satisfactory sensitivity for detecting HER2 3+ positive cases and can reliably be used to select the HER2 negative cases. Nevertheless, CISH protocol should be used to clarify all ambiguous cases.

The Influence of Chlorella and Its Hot Water Extract Supplementation on Quality of Life in Patients with Breast Cancer

A self-control, randomized, and open-label clinical trial was performed to test the effects of the unicellular green algae Chlorella and hot water extract supplementation on quality of life (QOL) in patients with breast cancer. Forty-five female patients with breast cancer who were living at home and not hospitalized were randomly assigned to 3 groups receiving vitamin mix tablet (control), Chlorella granules (test food-1), or Chlorella extract drink (test food-2) daily for one month. The Functional Assessment of Cancer Therapy-Breast (FACT-B), the Izumo scale for abdominal symptom-specific QOL, and a narrative-form questionnaire were used to determine outcomes. Data of thirty-six subjects were included for final analysis. FACT-B scores at presupplementation found no significant group differences in all subscales. Scores on the breast cancer subscale in the Chlorella granule group significantly increased during the supplementation period (P = 0.042). Fifty percent of the Chlorella extract group reported positive effects by the test food such as reduction of fatigue and improvements of dry skin (P < 0.01 versus control group). The findings suggested the beneficial effects of Chlorella on breast cancer-related QOL and of Chlorella extract on vitality status in breast cancer patients. These findings need to be confirmed in a larger study.

The Role of Oxidative Stress in Carcinogenesis Induced By Metals in Breast Cancer Egyptian Females Sample at Dakahlia Governorate

Trace metals and metals induced Oxidative stress have been implicated in breast carcinogenesis. Our study aimed to evaluate alteration of trace metals in breast tissue, oxidative stress and antioxidant status in breast cancer patients. This study included 120 female patients: 100 with breast cancer and 20 with benign breast diseases. Trace metals in breast tissue, lipid peroxidation and oxidative status were assessed. The present Results showed a significant increase in lead, cadmium, chromium, nickel and iron concentrations in malignant breast tissues compared to control group (P < 0.001). Also, a significant decline in Glutathione-S-transferase (GST), Glutathione Reductase (GR) and Total Antioxidant Capacity (TAC) levels; however a significant rise in Malondialdehyde (MDA) and Ferritin levels was detected in patients with breast cancer compared to controls. In conclusion, the alteration of the elemental content in cancerous breast tissues and the disruption of oxidant/antioxidant balance highlight the role of trace metals in cancer development.

Abstract P1-01-16: Prediction of non-sentinel lymph node status in breast cancer patients with sentinel lymph node metastases: Comparison of the MD Anderson, Cambridge and Helsinki nomograms in a cohort of 80 patients

Abstract Introduction: Up to 60% of patients with one or more positive sentinel lymph nodes (SLNs) have no additional nodal involvement and do not benefit from completion axillary lymph node dissection (ALND). Several predictive nomograms have been developed to predict non-SLN status in patients with breast cancer and SLN metastases. The purpose of our retrospective investigation was to compare some of these nomograms and we chose 3, all of which incorporate the size of the metastases in the SLNs among their variables. Methods: Three different predictive nomograms (MD Anderson, Helsinki and Cambridge) were tested on a cohort of 80 SLN-positive patients who subsequently underwent completion ALND. The nomograms utilise 3 (Cambridge), 7 (MD Anderson) and 9 (Helsinki) variables. The predictive accuracy of the nomograms for our cohort was evaluated by assessing receiver operating characteristic (ROC) curves and areas under curves (AUC) for each nomogram. Descriptive characteristics of the patient populationTotal number of patients80 Tumor size (T)T1: 36 (45%)T2: 40 (50%)T3: 4 (5%)Tumor typeDuctal: 58 (72.5%)Lobular:17 (21.25%)Mixed:2 (2.5%) Other:3 (3.75%)Lympovascular invasionPresent: 49 (61.25%)Absent:31 (38.75%) Histological GradeG1: 9 (11.25%)G2: 54 (67.5%)G3: 17 (21.25%)Multifocality:Present:48 (60%)Absent:32 (40%) Average SLNs removed (range)3.7 (1-11) Average SLNs positive (range)1.8 (1-7) Average non-SLNs positive (range)3.5 (1-16) Max. size of metastasesAverage:5.2mmMicrometastases: 13 (16.25%)Macrometastases: 67 (83.75%)Her-2 statusPositive:10 (12.5%)Negative:70 (87.5%) Prevalence of non-sentinel node metastasis in patient series31 patients (39%) Extranodal extensionPresent:26 (32.5%)Absent:54 (67.5%) Results: In our cohort, the average number of SLNs removed was 3.7 (1-11) and the average number of positive SLNs was 1.8 (1-7). 13 of the 80 patients had micrometastases within the SLNs (16.2%). 31 of the 80 patients had at least one positive non-SLN (39%) and the average number of additional positive nodes found in the ALND was 3.5 (1-16). For our cohort, all of the nomograms had a similar predictive accuracy (MD Anderson AUC = 0.69, Helsinki AUC = 0.69, Cambridge AUC = 0.63). All nomograms fell short of an acceptable AUC value (at least 0.8). Variables included in the different predictive models testedVariablesMD AndersonHelsinkiCambridgeTumor size++ Tumor type+ Nuclear grade +Lymphovascular invasion++ Number of positive SLNs++ Number of negative SLNs + Number of SLNs+ Proportion of positive SLNs +Extranodal extension++ Max. size of SLN metastases+++Her-2 status + Prevalence of non-sentinel node metastasis in patient series + Multifocality + Conclusions: Our study found that none of the chosen nomograms could reliably predict the presence of positive non-SLNs in our cohort. One reason for this may be the fact they utilize different methods of pathological assessment of nodes and different surgical techniques to those used in our centre. In view of this it may be desirable to produce a more accurate nomogram for our population based on specific variables. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-16.

Abstract P3-09-01: NEPA, a fixed-dose combination of netupitant and palonosetron, prevents chemotherapy-induced nausea and vomiting (CINV) more effectively and reduces the impact on daily living for breast cancer patients compared with palonosetron

Abstract Background: Breast cancer (BC) patients receiving anthracycline-cyclophosphamide (AC) chemotherapy (CT) are at risk for developing CINV due not only to the emetogenicity of the CT but also to young age and gender. As recommended by international antiemetic guidelines, targeting multiple molecular pathways involved in emesis related to AC is important for maximizing control of CINV and improving the functional status of BC patients during CT. NEPA is a fixed-dose combination of netupitant (NETU), a highly-selective NK1 receptor antagonist (RA), and palonosetron (PALO), a pharmacologically distinct 5-HT3 RA, that targets dual antiemetic pathways with a convenient single day dose. Methods: This was a multinational, randomized, double-blind, phase 3 study evaluating the efficacy and safety of a single oral dose of NEPA (NETU 300 mg + PALO 0.50 mg) versus a single oral 0.50 mg dose of PALO in chemotherapy-naïve patients receiving AC. All patients received oral dexamethasone (DEX) on day 1 (12 mg NEPA arm; 20 mg PALO arm). The primary efficacy endpoint was complete response (CR: no emesis, no rescue medication) in the delayed phase, 25-120h after CT. The Functional Living Index-Emesis (FLIE) questionnaire with a 5-day recall period was used to assess the impact of CINV on patients’ daily lives as a secondary endpoint. The FLIE consists of 9 nausea-specific (nausea domain) and 9 vomiting-specific (vomiting domain) items that address the effect of nausea and vomiting on daily life. Each item is scored on a 7-point 100 mm visual analog scale with anchors of “none/not at all” and “a great deal”. The proportion of patients with an average item score &amp;gt;6 reflecting “no impact on daily life” (NIDL) (ie, total FLIE score &amp;gt;108, nausea/vomiting domain score &amp;gt;54) was compared for NEPA vs PALO using a Cochran-Maentel-Haenszel test stratified by age class and region. Results: 1455 patients with a mean age of 54 were randomized to receive NEPA or PALO. Treatment groups were similar; 98% were females with BC (97%). As previously reported (ASCO 2013), NEPA showed superior CR rates compared to PALO for the acute 0-24h (88% vs 85%; p = 0.047), delayed (77% vs 70%; p = 0.001) and overall 0-120h (74% vs 67%; p = 0.001) phases. A greater proportion of NEPA-treated patients reported NIDL for nausea, vomiting and combined domains compared to PALO. % Patients with NIDL (Overall 0-120h)NEPA (N = 724)PALO (N = 725)p-valueNausea domain72%66%0.015Vomiting domain90%84%0.001Overall combined79%72%0.0056 patients excluded who did not receive AC or study drug The adverse event (AE) profile was comparable between groups. Most frequently reported treatment-related AEs for NEPA and PALO, respectively, were headache (3.3%, 3.0%) and constipation (2.1%, 2.1%). Conclusions: In this large Phase 3 study of predominantly females with BC receiving AC, NEPA was superior to PALO in preventing CINV and reducing the negative impact of CINV on patients’ daily lives. As a fixed-dose antiemetic drug combination including an NK1 RA and 5-HT3 RA, NEPA offers improved efficacy over PALO alone, with a convenient single-day dose, and oral DEX only on day 1. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-09-01.

Factors associated with receipt of adjuvant chemotherapy among married women with breast cancer

BackgroundAdjuvant chemotherapies are recommended for most women after breast cancer surgery, and can greatly affect the patients’ survival. We describe and evaluate possible factors influencing receipt of postoperative adjuvant chemotherapy among breast cancer patients in China.MethodsA total of 1,431 women diagnosed with breast cancer from 1997 to 2005 were enrolled. We reviewed medical records and abstracted information about these patients. Details on social-demographic factors and clinical-pathological characteristics of participants were collected and analyzed. To meet our objectives, the patient’s age at diagnosis, comorbidities, menstrual status, rural/urban status, tumor size, lymph node status, distant metastasis, tumor stage and hormone receptor status were estimated.ResultsOverall, 936 of these 1,431 patients (65.41%) received adjuvant chemotherapy. Receipt of chemotherapy was significantly associated with age at diagnosis, rural–urban disparities, and lymph node status of patients, though no significant difference was found between the age <50 and age 50 to 64 groups. Moderate association was also observed between hormone receptor status and receipt of adjuvant chemotherapy, though it was still not statistically significant.ConclusionsOur study suggests that age at diagnosis, rural–urban disparities and lymph node status of breast cancer patients are independent predictors for receipt of adjuvant chemotherapy among married Chinese women. Further investigations are warranted, and related public health education needs to be expanded in China.

High chondroitin sulfate proteoglycan 4 expression correlates with poor outcome in patients with breast cancer

Chondroitin sulfate proteoglycan 4 (CSPG4), a transmembrane proteoglycan originally identified in melanoma cells, has been reported to be expressed in breast cancer cells. This study was performed to examine the expression and significance of CSPG4 in a cohort of breast cancer patients. Immunohistochemical analysis of CSPG4 was performed on tissue microarrays constructed from tissue specimens from 240 breast cancer patients. CSPG4 staining was correlated with clinical and pathological characteristics, overall survival (OS), and disease recurrence. Contradicting to a previous report, our results showed that high CSPG4 expression was not related to triple-negative status of breast cancer patients. The Kaplan–Meier method showed that high CSPG4 expression was significantly associated with shorter time to recurrence (TTR). Patients with high CSPG4 expression had poorer OS and shorter TTR in a multivariate survival analysis after adjustment for stage, tumor grade, expression of estrogen receptor and progesterone receptor, and HER2 overexpression. This study showed that high CSPG4 expression correlates with disease recurrence and OS in breast cancers.

Tumor histological subtyping determined by hormone receptors and HER2 status defines different pathological complete response and outcome to dose-dense neoadjuvant chemotherapy in breast cancer patients

To assess the impact in pathological complete response (pCR) and outcome of two dose-dense neoadjuvant chemotherapy (DDNC) regimens among different histological subtypes determined by hormonal receptor (HR) and HER2 status in breast cancer patients. A total of 127 breast cancer patients were treated with DDNC in two prospective studies. A: adriamycin 40 mg/m(2) on day (d) 1 plus paclitaxel 150 mg/m(2) and gemcitabine 2,000 mg/m(2) on d2 for six cycles (n = 54). B: epirubicin 90 mg/m(2), cyclophosphamide 600 mg/m(2) on d1 for three cycles, followed by paclitaxel 150 mg/m(2) and gemcitabine 2,500 mg/m(2) on d1 ± trastuzumab according to HER2 status (n = 73). Histological subtypes of breast cancer were 49 % HR+/HER2-, 17.5 % HR+/HER2+, 13.5 % HR-/HER2+ and 20 % HR-/HER2-. pCR (absence of invasive cells in breast and lymph node) was achieved in 35 patients (28 %). The pCR rate was significantly different between histological subtypes: HR+/HER2- (9 %), HR+/HER2+ (23 %), HR-/HER2+ (50 %), HR-/HER2- (56 %) (p < 0.001). The median follow-up was 81 months (r: 15-150 months). HR-/HER2- tumor subtype had a significantly worse DFS compared to HR+/HER2- (p = 0.02), RH+/HER2+ (p = 0.04) and HR-/HER2+ tumor subtypes (p = 0.02). HR-/HER2- tumor subtype had a significantly shorter OS compared to HR+/HER2- (p = 0.007), RH+/HER2+ (p = 0.05), and HR-/HER2+ (p = 0.03) tumor subtypes. However, no significant difference was observed in DFS and OS among HR-/HER2- tumors that achieved a pCR. HR-/HER2- and HR-/HER2+ subtypes had a high pCR rate to DDNC. HR-/HER2- tumors had a worse outcome compared to other tumor subtypes but no significant difference was observed among HR-/HER2- tumors that achieved a pCR.

Methylation ESR1 as a potential factor of resistence to HER2/neu therapy in patients with breast cancer.

24 Background: Estrogen receptor (ER)-positive breast cancers are considered prognostically more favorable than ER-negative tumors and are often responsive to anti-estrogen therapy. Whereas tumors overexpressing HER2 are endocrine resistant and they require the blockage of the HER2 pathway in addition to estrogen deprivation. To evaluate epigenetics differences in tumor-related genes to ESR1 and HER2/neu status in primary breast cancer is the objective of this study. Methods: We quantified methylation levels of promoter of ERS1 which are to confer growth adventage to cells in 107 women with breast cancer. Real Time QMS-PCR SYBR green (methylation-specific PCR) was used to analyze the hypermethylation. Tumours were classified as phenotype basal, luminal A, Luminal B, and phenotype HER2+. Results: Presence of methylated ESR1 in serum of breast cancer patients was associated with ER-negative phenotype (p=0.0179). Of the available cases, 60 pts (56%) were Luminal A, 10 pts (9.3%) Luminal B, 13 pts (12%) Basal like, and 9 pts (8.4%) HER2+. We observed that methylated ERS1 was preferably associated with phenotype Basal Like and worse interval progression free and survival global though p &gt; 0.05 and the amplification HER2+ was correlation with significant more frequent methylation gene (p&lt;0.05). Thet hypermethylation of normal ERS1 and 14-3-3σ combined differentiated between breast cancer patients and healthy controls (p = 0.0001) with a sensitivity of 81% (95% CI: 72–88%) and specificity of 88% (95% CI: 78–94%). Conclusions: This study identifies the presence of variations in global levels of methylation promoters genes in healthy controls and breast cancer with different phenotype classes and shows that these differences have clinical significance. These showed that frequent methylation had a strong association with molecular phenotype of breast cancer and perhaps in the future can explain therapy resistance related to RE and HER2/neu status and this may be of significance in the assessment of targeted therapy resistance related to ER and HER2/neu status in breast cancer patients.