Status Of Breast Cancer Patients Research Articles

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.

Promoter methylation status of the FHIT gene and Fhit expression: Association with HER2/neu status in breast cancer patients

Aberrant DNA methylation has been recognized to contribute to breast carcinogenesis, and promoter hypermethylation of several tumor suppressor genes has been correlated with decreased gene expression. The fragile histidine triad (FHIT) gene is a putative tumor suppressor gene in breast and other types of cancer, and loss of Fhit expression has been observed in breast cancer. The aim of the present study was to evaluate the association between methylation of the FHIT gene and its expression in breast cancer, and to investigate whether methylation and expression of the FHIT gene correlates with clinicopathological characteristics in relation to human epidermal growth factor receptor 2 (HER2) status. Pyrosequencing of bisulfite-treated DNA was performed to study the methylation status of the FHIT gene in 60 breast cancer samples. We examined the expression of Fhit using tissue microarrays by immunohistochemical staining. FHIT methylation was detected in 96.7% and the positive expression rate of Fhit was 87.3% of the patients. The mean methylation level of the FHIT gene was associated with intratumoral inflammation. Methylation level of the FHIT gene had no significant differences according to molecular subtypes. Loss of Fhit expression was associated with large tumor size, basal-like subtype and positive expression of EGFR. In HER2-negative breast cancer, loss of Fhit expression was significantly associated with tumor size, estrogen receptor status and Ki-67 proliferation index. No significant correlation between methylation of the FHIT gene and its expression was observed in the present study. Our results suggest that loss of Fhit expression in breast cancer is associated with poor prognostic features, and it is also relevant to the results in HER2-negative breast cancer. Further studies with larger sample sizes and longer follow-up are required to clarify the predictive and prognostic value of Fhit expression and the FHIT gene methylation status in breast cancer.

Pattern of brain metastatic disease according to HER-2 and ER receptor status in breast cancer patients

To document the type, location, extent, and complications of brain metastases in patients with breast cancer and identify associations with oestrogen receptor (ER) negative and human epidermal growth factor receptor 2 (HER-2) receptor expression. Breast cancer patients with known brain metastases were included in this retrospective study, if cross-sectional imaging of the brain [computed tomography (CT)] was available to review and HER-2 and ER status was known. Two neuroradiologists, who were blinded to the receptor status, separately and for each patient, documented on a proforma the location, number, and dimensions of the deposits and the presence or absence of hydrocephalus. Adjudication was sought where there was discrepancy between the two reports. ER status, HER-2 receptor status, and patient age were also documented. The results were analysed using two-sided Fisher's exact tests with Lancaster's mid-P correction and associations were sought between the tumour characteristics and the pattern of brain disease. Sixty patients were included in the study. There was an association between young age (<40 years) and HER-2 positivity [10 of 24 (41.7%) versus three of 36 (8.3%); p = 0.002]. In ER-negative women, HER-2 positivity was found to be associated with a larger number (six or more) of metastases [11 of 18 (61%) versus nine of 25 (36%); p = 0.049], more brain stem metastases [11 of 18 (61%) versus three of 26 (11.5%); p = 0.035], more frequent occurrence of hydrocephalus [7 of 12 (36.8%) versus three of 26 (11.5%); p = 0.049], and a higher incidence of occipital metastases [12 of 18 (66.7%) versus eight of 26 (30.8%); p = 0.029]. ER-negative HER-2-positive women are more likely to present with a larger number of lesions, more brain stem/occipital metastases, and hydrocephalus, which may predispose them to unfavourable outcomes following treatment.

One-step nucleic acid amplification (OSNA) for intraoperative evaluation of sentinel lymph node status in breast cancer: a comparative study between CK19 protein expression and CK19 mRNA level in primary tumors and lymph node metastasis

The one-step nucleic acid amplification (OSNA) method is an increasingly used procedure for intraoperative analysis of sentinel lymph node (SLN) status in breast cancer patients. It measures cytokeratin19 (CK19) mRNA copy numbers in homogenized samples of SLN; CK19 has been chosen for identifying node metastasis because most breast cancers express this molecule. However, to avoid false-negative OSNA results, testing the preoperative needle core biopsy (NCB) of breast carcinomas for CK19 by immunohistochemistry (IHC) has been recommended. This procedure relies on the assumption that protein expression is strictly related to mRNA expression. We developed this study to evaluate if IHC gives similar result to the molecular assay. In a series of breast cancer patients with axillary metastasis, corresponding surgically resected tumor and metastatic lymph node specimens have been tested for CK19 protein by IHC and for CK19 mRNA by real-time PCR; furthermore, CK19 immunostaining has been performed in NCBs when available. Statistical analysis revealed that (1) the immunohistochemical evaluation of CK19 in NCB is a reliable test, reflecting protein expression in the whole tumor and in the metastatic lymph node; (2) there is no correlation between CK19 protein expression and CK19 RNA level neither within the primary breast cancer nor within the metastatic node; moreover, no correlation as well has been found between protein expression in NCB and mRNA level in metastatic lymph nodes. Thus, our results suggest that there is no evidence-based reason to stain every NCB for CK19 before performing OSNA in patients with breast cancer.

Comparative analysis of bone marrow micrometastases with sentinel lymph node status in early-stage breast cancer.

570 Background: A definitive relationship between bone marrow (BM) micrometastases (M) and sentinel lymph node (SLN) status has not been established in Breast Cancer (BRCa). Hence, a retrospective study was done to examine the relationship between BMM and SLN status in BRCa patients (pts). Methods: T1/T2 BRCa pts underwent SLN biopsy and definitive surgery for primary tumors. At the operation, BM aspiration from bilateral post-superior iliac spines was performed. BM samples were examined using a Cytokeratin Detection Kit using CAM 5.2 monoclonal antibody and visualization achieved with a Ventana iView V-Red detection system. An Automated Cellular Imaging System was applied to identify metastatic BRCa cells. Pts with +ve BM underwent repeat BM analysis 6 months after completing initial treatments. Data was collected for T-stages, SLN, BM, ER/PR receptor and Her-2/neu statuses and analyzed using Chi-Square Analysis or Fischer’s Exact Test. Results: We analyzed 458 consecutive pts, of which SLN metastasesv(mets) were detected in 22.9% and BMM were detected in 8.1%. BMM were found 23% bilaterally and 77% unilaterally. BMM were detected in 11.4% of SLN +ve pts versus 7.1% of SLN -ve ptsv(p=0.15) and 6.8% of T1 pts versus 12.3% of T2 ptsvv(p=0.07). BMM were found in 8.7% of ER/PR +ve pts versus 4.5% of ER/PR –ve ptsvv(p=0.1) and 9.5% of HER2/neu +ve pts versus 7.7% of HER2/neu –ve ptsv (p=0.5) (Table). Repeat BM analysis detected BMM only in 6.6% pts. Conclusions: Bilateral BM aspirate resulted in a significant increase in detection of micrometastases. BM metastases may occur independently of lymphatic metastasis. Therefore, evaluation for the presence of BMM may help identify high risk pts with node negative disease in early stage BRCa. [Table: see text]

Status of Oral Ulcerative Mucositis and Biomarkers to Monitor Posttraumatic Stress Disorder Effects in Breast Cancer Patients

This study was designed to assess oral ulcerative mucositis, C-reactive protein, blood pressure, heart rate and thyroid function in breast cancer patients in relation to the occurrence of posttraumatic stress disorder (PTSD). A total of 120 female breast cancer patients and women 100 healthy subjects were enrolled in this study. PTSD status was assessed by questionnaire. Before and after treatment (modified radical mastectomy and chemotherapy), serum samples were collected and measured for levels of triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH) and high-sensitivity C-reactive protein (hs-CRP) by ELISA. Oral ulcerative mucositis was evaluated by the number and duration of oral ulcers and the degree of pain. Breast cancer patients experienced long-term PTSD and had elevated serum T3 and T4 levels. Patients experienced more severe pain and longer duration of oral ulcers compared with the healthy group. Oral ulcers were significantly associated with PTSD score in terms of the number of ulcers (p=0.0025), the degree of pain (p<0.0001) and the duration of ulcers (p<0.0001). These findings support that thyroid function is altered in breast cancer patients with PTSD. Elevation of T3 and T4 and oral ulcerative mucositis might be indicative of the emotional status of breast cancer patients.

Quantitative ultrasound image analysis of axillary lymph node status in breast cancer patients

Ultrasonography has the potential to accurately stage breast cancer with automated analysis to detect axillary lymph node metastasis. The aim of this study was to develop and test automated quantitative ultrasound image analysis of axillary lymph nodes for breast cancer staging. Following an IRB-approved HIPAA compliant protocol, ultrasound images of 90 breast cancer patients presenting for lymph node assessment were retrospectively collected. There were 51 node-positive and 39 node-negative patients, yielding images of 223 lymph nodes (109 positive for metastasis and 114 negative for metastasis). The analysis was completely automated apart from the manual indication of the approximate center of each lymph node. Mathematical descriptors of the nodes, which served as image-based biomarkers, were computer-extracted and input to a classifier for the task of distinguishing between positive (i.e., metastatic) and negative lymph nodes. The performance of this task was assessed using receiver operating characteristic (ROC) analysis with evaluation by-node and by-patient using the area under the ROC curve (AUC) as the performance metric. The AUC was 0.85 (standard error 0.03) for by-node evaluation when distinguishing between positive and negative lymph nodes. The AUC was 0.87 (0.04) for patient-based prognosis, i.e., assessing whether patients were lymph node-positive or lymph node-negative. Based on these classification results, we conclude that mathematical descriptors of sonographically imaged lymph nodes may be useful as prognostic biomarkers in breast cancer staging and demonstrate potential for predicting patient lymph node status.

Mammographic Density and Prediction of Nodal Status in Breast Cancer Patients.

Aim: Nodal status remains one of the most important prognostic factors in breast cancer. The cellular and molecular reasons for the spread of tumor cells to the lymph nodes are not well understood and there are only few predictors in addition to tumor size and multifocality that give an insight into additional mechanisms of lymphatic spread. Aim of our study was therefore to investigate whether breast characteristics such as mammographic density (MD) add to the predictive value of the presence of lymph node metastases in patients with primary breast cancer. Methods: In this retrospective study we analyzed primary, metastasis-free breast cancer patients from one breast center for whom data on MD and staging information were available. A total of 1831 patients were included into this study. MD was assessed as percentage MD (PMD) using a semiautomated method and two readers for every patient. Multiple logistic regression analyses with nodal status as outcome were used to investigate the predictive value of PMD in addition to age, tumor size, Ki-67, estrogen receptor (ER), progesterone receptor (PR), grading, histology, and multi-focality. Results: Multifocality, tumor size, Ki-67 and grading were relevant predictors for nodal status. Adding PMD to a prediction model which included these factors did not significantly improve the prediction of nodal status (p = 0.24, likelihood ratio test). Conclusion: Nodal status could be predicted quite well with the factors multifocality, tumor size, Ki-67 and grading. PMD does not seem to play a role in the lymphatic spread of tumor cells. It could be concluded that the amount of extracellular matrix and stromal cell content of the breast which is reflected by MD does not influence the probability of malignant breast cells spreading from the primary tumor to the lymph nodes.

Methylation of BRCA1 Promoter Region Is Associated with Unfavorable Prognosis in Women with Early-Stage Breast Cancer

BRCA1-associated breast cancers are associated with particular features such as early onset, poor histological differentiation, and hormone receptor negativity. Previous studies conducted in Taiwanese population showed that the mutation of BRCA1 gene does not play a significant role in the occurrence of breast cancer. The present study explored methylation of BRCA1 promoter and its relationship to clinical features and outcome in Taiwanese breast cancer patients. Tumor specimens from a cohort of 139 early-stage breast cancer patients were obtained during surgery before adjuvant treatment for DNA extraction. Methylation of BRCA1 promoter region was determined by methylation-specific PCR and the results were related to clinical features and outcome of patients using statistical analysis. Methylation of the BRCA1 promoter was detected in 78 (56%) of the 139 tumors. Chi-square analysis indicated that BRCA1 promoter methylation correlated significantly with triple-negative (ER-/PR-/HER2-) status of breast cancer patients (p = 0.041). The Kaplan-Meier method showed that BRCA1 promoter methylation was significantly associated with poor overall survival (p = 0.026) and disease-free survival (p = 0.001). Multivariate analysis which incorporated variables of patients' age, tumor size, grade, and lymph node metastasis revealed that BRCA1 promoter methylation was associated with overall survival (p = 0.27; hazard ratio, 16.38) and disease-free survival (p = 0.003; hazard ratio, 12.19). Our findings underscore the clinical relevance of the methylation of BRCA1 promoter in Taiwanese patients with early-stage breast cancer.

SP3, a reliable alternative to HercepTest in determining HER-2/neu status in breast cancer patients

Accurate assessment of HER-2/neu gene status in breast cancer patients has important prognostic and therapeutic implications. Overexpression/gene amplification of HER-2 is associated with a more aggressive clinical course and eligibility...

Original article: Predictors to assess non-sentinel lymph node status in breast cancer patients with only one sentinel lymph node metastasis

Background The purpose of this study was to investigate the feasibility of avoiding axillary lymph node dissection (ALND) for patients with only one sentinel lymph node (SLN) metastasis. The characteristics and predictive factors for non-sentinel lymph node (NSLN) metastasis of patients with single positive SLN were also analyzed. Methods Patients with no and only one SLN metastasis (0/n and 1/n group, n ≥2) were selected from 1228 cases of invasive breast carcinoma, who underwent axillary dissection in Shandong Cancer Hospital between November 1999 and December 2011, to compare the characteristics of NSLN metastasis between them. For the 1/n group, the factors that influenced the NSLN metastasis were analyzed by univariate and multivariate analysis. Results Differences of the NSLN metastasis between the 0/n and the 1/n groups were significant (P &lt;0.001). There was no significant difference between the axillary lymph node metastasis on level III in 1/n group and 0/n group (P=0.570). When the total SLN number was ≥4 and with one positive case, the NSLN metastasis was not significantly different from that in the 0/n group (P=0.118). In the 1/n group, clinical tumor size (P = 0.012), over-expression of Her-2 (P=0.003), tumor grade (P=0.018) and the total number of SLN (P=0.047) significantly correlated with non-SLN metastasis. Clinical tumor size (P=0.015) and the expression of Her-2 (P=0.01) were independent predictive factors for non-SLN metastasis by the Logistic regression model. Conclusion Under certain conditions, breast cancer patients with single SLN metastasis could avoid ALND.

Non-Invasive Evaluation of Axillary Lymph Node Status in Breast Cancer Patients Using Shear Wave Elastography

Less invasive procedures are currently required to examine the axillary lymph node status. Shear wave elastography with acoustic radiation force impulse provides objective and reproducible quantification of the intrinsic property of the soft tissue. In this study, we measured shear wave velocity of the axillary lymph nodes of patients with breast cancer using Virtual Touch Tissue Quantification (VTTQ). The degree of lymph node metastasis was evaluated by measuring the expression level of cytokeratin 19 (CK19) mRNA, a specific marker for breast cancer cells. The one-step nucleic acid amplification (OSNA) was used to determine the copy number of CK19 mRNA in 149 lymph node specimens of 149 primary breast cancer patients. Axillary lymph node status according to OSNA (copy number/μl) were categorized as 0-249 copies (-), 250-5,000 copies (+), and copy number > 5,000 (++). A category (-) represents no metastasis in the axillary lymph node. There were 121 patients with OSNA-, 9 with OSNA+ and 19 with OSNA++. The average velocities according to OSNA categories were 1.64 ± 0.42 m/second for OSNA-, 2.25 ± 0.78 m/second for OSNA+, and 2.79 ± 0.98 m/second for OSNA++. There were significant differences in the shear wave velocity between OSNA- and OSNA+ (P = 0.040) or OSNA++ (P < 0.001). The most optimal cutoff velocity to distinguish benign from metastasis is 1.44 m/second, as determined using the receiver operating characteristic method. The shear wave velocity measured with VTTQ could provide clinically useful information about axillary lymph node metastasis in patients with primary breast cancer.

Evaluation of CA 15-3, Her-2/neu and estrogen/progesterone status in breast cancer patients treated by surgical removal and chemotherapy

Objective: This study was conducted to evaluate serum CA 15-3 in breast cancer patients after surgery and chemotherapy. The relationship between serum CA 15-3 and Her-2/neu, estrogen, or progesterone receptors were also studied in the breast cancer patients. Patients and methods: This study was conducted at Al-Jammhori Teaching Hospital, and Al-Zahrawi Private Hospital, Mosul, Iraq, during the period from January to Jun 2011. Fifty breast cancer women diagnosed by using triple assessments by a surgeon (history examination, ultrasound mammography, and fine needle aspiration cytology) were included in the study. Blood samples (5 mL) were taken from the patients and analyzed for serum CA 15-3 by monoclonal antibody technique. The blood samples were taken from the patients a week before and after one week of the operation and other blood samples were taken after two weeks of the first cycle of chemotherapy treatment. Combination therapy of 5-fluorouracil, epirubicin, cyclophosphamide, for three cycles every 21 days, was given to the patients, followed by three cycles docytaxil every 21 days. Samples from the tumor on paraffin sections taken from the patients were analyzed for Her-2/neu, estrogen and progesterone receptors by immunochemical methods. Results: Serum CA 15-3 was significantly decreased by 54% (p ≤ 0.001) after surgical removal of the cancer compared with results before surgery. Chemotherapy of the patients further decreased serum CA 15-3 significantly by 78% (p ≤ 0.001) compared with the results before surgery. CA 15-3 and tumor size in positive Her-2/neu patients were significantly higher than in negative Her-2/neu patients. However, serum CA 15-3 and tumor size in positive estrogen patients were significantly lower than in negative estrogen patients. In progesterone positive patient's serum CA 15-3 was only significantly (p ≤ 0.001) lower than in the negative progesterone patients. Mean ages was significantly (p ≤ 0.001) higher in positive Her-2/neu patients than in negative Her-2/neu patients. However, mean ages was significantly (p ≤ 0.001) higher in positive estrogen and progesterone patients than in negative receptors. Metastasis occurred in 39 patients (78 %) out of the studied patients. Negative significant correlation was noticed between Her 2/neu and estrogen receptors (r= - 0.745, p ≤ 0.001). Negative significant correlation was also noticed between Her 2/neu and progesterone receptors (r= - 0.786, p ≤ 0.001). Weak but significant correlation was found between serum CA 15-3 and tumor size (r= 0.281, p≤ 0.05). Conclusion: CA 15-3 and Her 2/neu are useful tumor markers for diagnosis of breast cancer in the treatment through surgery and chemotherapy. The co-expression between hormonal and Her-2/neu receptors is negative. The need for more sensitive tumor markers is still wanted.

Abstract P2-05-08: Determination of HER2 amplification by dual-color in situ hybridization before and after neoadjuvant chemotherapy

Abstract Background: HER2-targeted therapies such as trastuzumab neoadjuvant chemotherapy for patients with HER2-positive breast cancer can increase pathological complete response (pCR) better than non-HER2-targeted therapies. Previous studies have suggested that trastuzumab may convert HER2-positive (HER+) primary breast tumors to HER2 negative (HER−) after neoadjuvant chemotherapy. We compared the HER2 status in breast cancer patients before and after neoadjuvant treatment by using dual-color in situ hybridization (DISH). Methods: We retrospectively identified 46 patients from the Breast Cancer database at Tokai University Hospital, in whom HER2-positive primary breast cancer was diagnosed between 2000 and 2010, and who were treated with neoadjuvant chemotherapy or endocrine therapy with or without trastuzumab. Surgical specimens from patients achieving less than pCR were assessed to determine if there was enough residual tissue to evaluate the post-treatment HER2 status by DISH. HER2 status was defined as positive if DISH demonstrated a gene copy ratio of HER2:CEP17 &amp;gt;2.0. Paraffin tissue sections (4-μm thick) were mounted on glass slides (New Sliane III, Catalog No. 5126–25; MUTO PURE CHEMICALS, CO. LTD., Tokyo, Japan) and stained using the newly developed, fully automated HER2 Dual ISH assay on a BenchMark® XT slide stainer according to the recommended procedure (Ventana Medical Systems Inc., Tucson, AZ). Thereafter, the stained slides were rinsed with tap water containing neutral detergent and then rinsed again with distilled water. The slides were dried at room temperature for at least 60 min and cover-slipped with cover grass for SGC (MUTO PURE CHEMICALS). HER2 Dual ISH and H&amp;E images were obtained using an Olympus BX51 microscope. Results: A pCR was achieved in 9 of the 46 patients (19.6%). Specimens from core needle biopsy were not sufficient to assess the pretreatment HER2 status in 3 patients. In 9 patients, the post-treatment HER2 status could not be assessed because residual tumors were DCIS only in 4 patients and there were less than 20 invasive cells in 5 patients. Residual tumor was sufficient to assess the post-treatment HER2 status in 25 patients. In pretreatment specimens, of the 25 patients identified as HER2 + by immunohistochemical analysis, 3 patients were identified as HER2− by DISH. No post-treatment specimens were found to be HER2− by DISH among the tumors identified as HER2+ by DISH at pretreatment. Among the 3 pretreatment tumors identified as HER2− by DISH, 1 tumor was found to be HER2+ by DISH at post-treatment, and 2 showed a stable HER2 status. Conclusion: DISH revealed a stable HER2 status in pretreatment breast tumors and in residual tumors. However, we found a discrepancy in the HER2 status between the immunohistochemical analysis and DISH. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-08.

The level of circulating miRNA-10b and miRNA-373 in detecting lymph node metastasis of breast cancer: potential biomarkers

MicroRNAs (miRNAs) are a class of small noncoding RNAs whose expression changes are associated with cancer development and invasion. We hypothesized that miR-10b and miR-373, which are increased in lymphatic metastatic tissues, could be directly assayed in the plasma and used to detect the lymph node status of breast cancer patients. Between November 2009 and January 2012, 35 breast ductal carcinoma patients with lymph node metastasis (N patients), 25 ductal carcinoma patients without lymph node metastasis (N(0) patients), and ten healthy female donors were enrolled in the study. Circulating miR-10b and miR-373 were determined in preoperative plasma samples by reverse transcription quantitative real-time PCR assay. In preliminary tests, the plasma levels of circulating miR-10b and miR-373 were found to be significantly higher in ten breast cancer patients with lymph node metastasis compared to ten N(0) patients and ten normal donors (P < 0.01). On validation analysis, the median value level of miR-10b in the 35 N patients was 4.44-fold (P < 0.01) increased, and miR-373 was 4.38-fold (P < 0.01) increased in comparison to the 25 N(0) patients. MiR-10b was used for differentiation of N patients from N(0) patients; the odds ratio was 2.19, and the value of the area under the receiver-operating curve (AUC) was 0.80, with sensitivity of 71% and specificity of 72%. For miR-373, the odds ratio was 2.62, and the AUC was 0.84, with sensitivity of 68% and specificity of 89%. A combination of the two circulating miRNAs further enhanced the sensitivity to 72% and the specificity to 94.3%. Our data suggest that circulating miRNA-10b and miRNA-373 are potential biomarkers for detecting the lymph node status of breast cancer.

Validation of a proxy for estrogen receptor status in breast cancer patients using dispensing data

To assess the performance of a proxy for estrogen receptor (ER) status in breast cancer patients using dispensing data. We derived our proxy using 167 patients. ER+ patients had evidence of at least one dispensing record for hormone therapy during the lookback period, irrespective of diagnosis date and ER- had no dispensing records for hormone therapy during the period. We validated the proxy against our gold standard, ER status from pathology reports or medical records. We assessed the proxy's performance using three lookback periods: 4.5 years, 2 years, 1 year. More than half of our cohort (62%) were >50 years, 54% had stage III/IV breast cancer at recruitment, (46%) were diagnosed with breast cancer in 2009 and 23% were diagnosed before 2006. Sensitivity and specificity were high for the 4.5 year lookback period (93%, 95% CI: 86-96%; and 95%: 83-99%), respectively) and remained high for the 2-year lookback period (91%: 84-95%; and 95%: 83-99%). Sensitivity decreased (83%: 75.2-89%) but specificity remained high (95%: 83-99%) using the 1-year lookback period and the period is long enough to allow sufficient time for hormone therapy to be dispensed. Our proxy accurately infers ER status in studies of breast cancer treatment based on secondary health data. The proxy is most robust with a minimum lookback period of 2 years.

Influencia del estado nutricional, niveles hormonales séricos e historia familiar de cáncer en el desarrollo del cáncer de mama

Several studies have analyzed the relation between obesity and the hormonal imbalances generated by overweight and a family history of breast cancer. All of these factors are potentially implicated in the early development of breast cancer. To verify the existence of a significant relation between the nutritional status of breast cancer patients, their hormone serum levels (estrogens, prolactin, and progesterone), and the existence of a family history of breast cancer. Retrospective data was collected from clinical records of 524 women diagnosed with breast cancer in a Spanish hospital. There was a positive association between estrogen, progesterone and prolactin serum levels and body mass index. The elevations in hormone levels occurred earlier in life among women with a family history of breast cancer. A two way ANOVA found a significant association between progesterone and prolactin levels with the age at diagnosis of breast cancer. Extreme serum levels of these hormones appear to be related to the early development of breast cancer, which in turn is influenced by the existence of a family history of cancer among those women with normal or average hormone levels.

Assessment of the Memorial Sloan-Kettering Cancer Center nomogram to predict sentinel lymph node metastases in a Dutch breast cancer population

AimSentinel lymph node (SLN) biopsy is an accepted alternative to axillary lymph node dissection to assess the axillary tumour status in breast cancer patients. Memorial Sloan-Kettering Cancer Center (MSKCC) developed a nomogram to predict the likelihood of SLN metastases in breast cancer patients. Nomogram performance was tested on a Dutch population. MethodsData of 770 breast cancer patients who underwent successful SLN biopsy were collected. SLN metastases were present in 222 patients. A receiver operating characteristic (ROC) curve was drawn and the area under the curve was calculated to assess the discriminative ability of the MSKCC nomogram. A calibration plot was drawn to compare actual versus nomogram-predicted probabilities. ResultsThe area under the ROC curve for the predictive nomogram was 0.67 (95% confidence interval 0.63–0.72) as compared to 0.75 in the original population. The nomogram was well-calibrated in the Dutch population. ConclusionsIn a Dutch population, the MSKCC nomogram estimated risk of sentinel node metastases in breast cancer patients well (i.e. calibration) with reasonable discrimination (area under ROC curve). Nomogram performance on core needle biopsy data has to be evaluated prospectively.

Effect of Intake Black Seeds and Bee Honey on Health Status of Breast Cancer Patients

Effect of Intake Black Seeds and Bee Honey on Health Status of Breast Cancer Patients