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Background The purpose of this study was to determine the antitumor activity of the epidermal growth factor receptor (EGFR) inhibitor gefitinib in patients with recurrent/metastatic salivary gland cancer. Methods We conducted a phase II study in adenoid cystic carcinoma (ACC) and non-ACC. Gefitinib was administered 250 mg orally daily. The primary endpoint was tumor response. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and disease control rates. EGFR and human epidermal growth factor receptor 2 (HER2) expression were evaluated and correlated with outcomes. Results Thirty-seven patients were enrolled in this study, and 36 were evaluable (18 with ACC and 18 with non-ACC). No responses were observed. Median PFS was 4.3 months and 2.1 months, and median OS was 25.9 months and 16 months for patients with ACC and non-ACC, respectively. The disease control rate at 8 weeks was higher in patients with ACC. No unexpected toxicities occurred. EGFR and HER2 overexpression did not correlate with outcomes. Conclusion We did not observe significant clinical activity of gefitinib in advanced salivary gland cancer. NCT00509002. © 2015 Wiley Periodicals, Inc. Head Neck 37: 644-649, 2015 [ABSTRACT FROM AUTHOR]

To study gene function in neural progenitors and radial glia of the retina and hypothalamus, we developed a Rax-CreERT2 mouse line in which a tamoxifen-inducible Cre recombinase is inserted into the endogenous Rax locus. By crossing Rax-CreERT2 with the Cre-dependent Ai9 reporter line, we demonstrate that tamoxifen-induced Cre activity recapitulates the endogenous Rax mRNA expression pattern. During embryonic development, Cre recombinase activity in Rax-CreERT2 is confined to retinal and hypothalamic progenitor cells, as well as progenitor cells of the posterior pituitary. At postnatal time points, selective Cre recombinase activity is seen in radial glial-like cell types in these organs – specifically Müller glia and tanycytes – as well as pituicytes. We anticipate that this line will prove useful for cell lineage analysis and investigation of gene function in the developing and mature retina, hypothalamus and pituitary. [ABSTRACT FROM AUTHOR]

Breast cancer is a heterogeneous disease. For the past decades, new technical tools have been developed for biomarkers at the DNA, RNA, and protein levels to better understand the biology of breast cancer. This progress is essential to classify the disease into clinically relevant subtypes, which may lead to new therapeutic opportunities. Novel biomarker development is paramount to deliver personalized cancer therapies. Further, tumor evolution, being natural or under treatment pressure, should be monitored and “liquid biopsies” by detecting circulating tumor cells or circulating free tumor DNA in blood samples will become an important option. This article reviews the new generation of biomarkers and the current evidence to demonstrate their analytical validity, clinical validity and clinical utility. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Whether or not to biopsy the metastasis in recurrent breast cancer has become mired in controversy. Several studies have shown an important discordance of the immunohistochemical (IHC) determinations for ER, PR and HER2 between primary (PT) and recurrent tumors (RT). Yet it remains unknown within this what impact technical issues have. The aim of our study was to assess whether technical variability might have an impact on the concordance between PT and RT. Methods: IHC determinations in paired biopsies from PT and RT were compared under routine vs study conditions. In the former, pathological analysis reproduced the conditions used in the routine of a University Pathology Department. In the latter, in a technical bias-minimizing manner, samples were re-assessed at the same timing and by two independent observers. Results: 128 paired biopsies from 64 patients were analyzed under both conditions. Concordance under routine vs study conditions for ER was 66% vs 93.4% (p = 0.001), for PR 58.7% vs 80.3% (p = 0.064) and for HER2 86.8% vs 96.8% (p = 0.25). Kappa index under routine versus study conditions for ER was 0.27 vs 0.79 (p = 0.002), for PR 0.26 vs 0.39 (p = 0.47) and for HER2 0.67 vs 0.9 (p = 0.14). Conclusions: Although discordance rate between PT and RT decreased under conditions minimizing technical issues, some discordant cases appeared not to be subjected to this confounding factor. Either for clinical practice or for future studies reassessment of PT in recurrent breast cancer should be encouraged. [Copyright &y& Elsevier]

BACKGROUND: The current study was conducted to determine the frequency and association between recurrence-free survival (RFS) and MET and catalytic subunit of phosphoinositide-3-kinase ( PIK3CA) copy number elevations in patients with early stage breast cancer. METHODS: Tumor DNA was extracted from 971 formalin-fixed, paraffin-embedded early breast cancers for molecular inversion probes arrays. Data were segmented using the single-nucleotide polymorphism (SNP)-FASST2 segmentation algorithm. Copy number gains were called when the copy number of each segment was greater than 2.3 or 1.7, respectively. RFS was estimated by the Kaplan-Meier method. Cox proportional hazards models were fit to determine independent associations between copy number and RFS. RESULTS: Of the 971 tumors studied, 82 (8.44%) and 134 (13.8%) had an elevation of the MET or PIK3CA copy number, respectively, and 25.6% of tumors with a MET copy number elevation had a PIK3CA copy number elevation. Patients with either a MET or PI3KCA high copy number tended to have poorer prognostic features (larger tumor size, higher tumor grade, and hormone receptor negativity). Both MET and PIK3CA high copy numbers were more likely to occur in patients with triple receptor-negative disease ( P = .019 and P < .001, respectively). At a median follow-up of 7.4 years, there were 252 cases of disease recurrence. The 5-year RFS rates were 63.5% and 83.1% for MET high copy number and MET normal/low copy number, respectively ( P = .06) and 73.1%, and 82.3% for PIK3CA high copy number and PIK3CA normal/low copy number, respectively ( P = .15). A high copy number for either gene was not found to be an independent predictor of RFS. CONCLUSIONS: A high copy number of MET or PIK3CA was found to be associated with poorer prognostic features and triple receptor-negative disease. Coamplification was frequent. Patients with tumors with high MET copy numbers tended to have a worse RFS. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemotherapy (NAC) induces a pathological complete response (pCR) in ?30% of patients with breast cancer. However, many patients have residual cancer after chemotherapy, which correlates with a higher risk of metastatic recurrence and poorer outcome than those who achieve a pCR. We hypothesized that molecular profiling of tumors after NAC would identify genes associated with drug resistance. Digital transcript counting was used to profile surgically resected breast cancers after NAC. Low concentrations of dual specificity protein phosphatase 4 (DUSP4), an ERK phosphatase, correlated with high post-NAC tumor cell proliferation and with basal-like breast cancer (BLBC) status. BLBC had higher DUSP4 promoter methylation and gene expression patterns of Ras-ERK pathway activation relative to other breast cancer subtypes. DUSP4 overexpression increased chemotherapy-induced apoptosis, whereas DUSP4 depletion dampened the response to chemotherapy. Reduced DUSP4 expression in primary tumors after NAC was associated with treatment-refractory high Ki-67 scores and shorter recurrence-free survival. Finally, inhibition of mitogen-activated protein kinase kinase (MEK) synergized with docetaxel treatment in BLBC xenografts. Thus, DUSP4 downregulation activates the Ras-ERK pathway in BLBC, resulting in an attenuated response to anti-cancer chemotherapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: The US Food and Drug Administration's (FDA's) recent decision to remove the indication of bevacizumab for metastatic breast cancer (MBC) has fueled a debate in the breast cancer community. We conducted a survey to assess the perception of health care workers involved in the management of women with MBC on the FDA's decision to ascertain how it will affect practice and to determine how bevacizumab is commonly used in the community for MBC. METHODS: E-mails were sent out between September and November 2010 using a database of 3000 addresses maintained by the United Arab Emirates Cancer Congress. Individuals working for Roche or Genentech were excluded. The survey consisted of 22 questions that were divided into 3 parts addressing each participant's demographic profile, their opinion of the FDA's decision, and the typical use of bevacizumab in the community in the setting of MBC. RESULTS: A total of 564 participants were included in the final analysis, contributing to an 18.8% response rate. Of these participants, 14.6% were from the United States, 7.8% were from Canada, 31.1% were from Europe, 2.0% were from the United Arab Emirates, 11.1% were from Asia, and 33.3% were from other countries. The majority of participants believed progression-free survival to be a surrogate for overall survival, that cost played a role in the FDA's decision, and that the decision would adversely affect the future of newer drugs currently being investigated for MBC. The majority of participants indicated that they would use bevacizumab for triple receptor-negative MBC (46.5%), would use it in a first-line setting (44.7%), and would use it in combination with paclitaxel (51.9%). CONCLUSION: Our survey results highlight the discord between the opinion of community oncologists and the FDA's recent decision to withdraw the indication of bevacizumab for MBC. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The aim of this study was to evaluate the pathologic complete response (pCR) rates and relapse-free survival (RFS) and overall survival (OS) of patients receiving neoadjuvant systemic therapy (NST) with trastuzumab in combination with an anthracycline- or nonanthracycline-based regimen. METHODS: In this retrospective nonrandomized study, the authors reviewed records of 300 patients with HER2-positive breast cancer treated with either sequential paclitaxel and trastuzumab and FEC75 in combination with trastuzumab (PH-FECH) or docetaxel, carboplatin, and trastuzumab (TCH). The Kaplan-Meier product-limit method was used to estimate RFS and OS rates. Logistic regression models and Cox proportional hazards models were fit to determine the associations between NST, pCR, and survival. RESULTS: There was no significant difference in the decline in cardiac ejection fraction; however, patients who received PH-FECH had fewer cardiac comorbidities at baseline ( P = .002). pCR rates were 60.6% and 43.3% for patients who received PH-FECH (n = 235) and TCH (n = 65), respectively ( P = .016). Patients who received PH-FECH were 1.45 times more likely to have a pCR (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.06-1.98; P = .02). Three-year RFS rates were 93% and 71% ( P < .001), and 3-year OS rates were 96% and 86% ( P = .008) for patients who received PH-FECH and TCH, respectively. Patients who received PH-FECH had a lower risk of recurrence (hazard ratio [HR], 0.27; 95% CI, 0.12-0.60; P = .001) and death (HR, 0.37; 95% CI, 0.12-1.13; P = .08) than those treated with TCH. CONCLUSIONS: The type of NST in HER2-positive breast cancer is predictive of pCR rate independent of disease and patient characteristics. Although TCH is active, PH-FECH shows a higher pCR rate and RFS advantage. Cancer 2012. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

PURPOSE: To evaluate the impact of low estrogen/progesterone receptor (ER/PR) expression and effect of endocrine therapy on survival outcomes in human epidermal growth factor receptor 2 (HER2)-negative tumors with ER/PR <10%, previously labeled as triple negative. METHODS: In a retrospective review, 1257 patients were categorized according their ER/PR percentages into 3 groups, ER/PR <1% (group A), ER/PR 1% to 5% (group B), and ER/PR 6% to 10% (group C). Kaplan-Meier product limit method was used to estimate survival outcomes. Cox proportional hazards models was used to adjust for patient and tumor characteristics. RESULTS Groups A, B, and C had 897 (71.4%), 241 (19.2%), and 119 (9.4%) patients, respectively. After a median follow-up of 40 months there was no significant difference in 3-year recurrence-free survival (RFS): 64%, 67%, and 77% ( P = .34) or overall survival (OS): 79%, 81%, and 88% ( P = .33) for groups A, B, and C, respectively. ER/PR expression was not an independent predictor for RFS (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.86-1.39; P = .46 for group B, and HR, 0.96; 95% CI, 0.66-1.38; P = .81 for group C, compared with group A), or OS (HR, 1.11; 95% CI, 0.84-1.46; P = .46 for group B, and HR, 0.94; 95% CI, 0.63-1.42; P = .78 for group C, compared with group A). Endocrine therapy had no impact on survival outcomes (RFS: P = .10; OS: P = .45) among groups. CONCLUSIONS: In this cohort, a low ER/PR level (1%-5%) does not appear to have any significant impact on survival outcomes. There was a tendency for survival advantages in the ER/PR 6% to 10% is seen. Benefit of endocrine therapy in these patients is unclear. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Previous studies evaluating the effect of cytochrome P450 2D6 (CYP2D6) polymorphisms on outcomes of adjuvant tamoxifen therapy have been conflicting due to differences in study design, concomitant medications that alter CYP2D6 metabolism, and tamoxifen adherence. METHODS: The authors performed CYP2D6 genotyping from whole blood and fresh frozen tumor samples (n 106) in patients at The University of Texas MD Anderson Cancer Center who were receiving, or had received, tamoxifen as adjuvant therapy for early breast cancer (EBC), using the AmpliChip CYP450 Test. Each patient's medical history was assessed for drugs that affected CYP2D6. Fifty-five patients who had experienced breast cancer recurrence were matched (by date of diagnosis, menopausal status, clinical stage [TNM Staging System], and race) to patients without recurrence. RESULTS: Unadjusted for other patient characteristics, the odds ratio for disease recurrence associated with CYP2D6 functional status was 1.0 (95% confidence interval, 0.35-2.85). After adjustment for stage, CYP2D6 inhibitors (moderate or strong vs none), and follow-up time, no significant association was found between CYP2D6 genotype and breast cancer recurrence in patients who were treated with adjuvant tamoxifen for EBC. CONCLUSIONS: This case-control study demonstrated no significant effect of CYP2D6 genotype on risk of recurrence in breast cancer patients who received adjuvant tamoxifen therapy. Cancer 2012;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Recent observational studies have shown that metformin use in diabetic patients decreases both cancer incidence and mortality. Metformin use is also independently predictive of pathologic complete response. In the current study, the authors explored the association between metformin use and survival outcomes in patients with triple receptor-negative breast cancer (TNBC) who were receiving adjuvant chemotherapy. METHODS: The Breast Cancer Management System database of The University of Texas MD Anderson Cancer Center identified 1448 women who received adjuvant chemotherapy for TNBC between 1995 and 2007. Patients were categorized by diabetes status and metformin use. The Kaplan-Meier product-limit method was used to calculate distant metastasis-free survival (DMFS), recurrence-free survival (RFS), and overall survival (OS). Cox proportional hazards models were fit to determine the association between metformin use and survival outcomes. RESULTS: The study cohort was comprised of 63 diabetic patients receiving treatment with metformin, 67 diabetic patients not receiving metformin, and 1318 nondiabetic patients. Patients in the diabetic groups tended to be older ( P = .005); more diabetic patients were postmenopausal ( P = .0007), black ( P = .0001), and obese ( P < .0001). At a median follow-up of 62 months, there were no significant differences with regard to 5-year DMFS ( P = .23), RFS ( P = .38), and OS ( P = .58) between the 3 groups. Compared with the metformin group, patients who did not receive metformin (hazard ratio [HR], 1.63; 95% confidence interval [95% CI], 0.87-3.06 [ P = .13]) and nondiabetic patients (HR, 1.62; 95% CI, 0.97-2.71 [ P = .06]) tended to have a higher risk of distant metastases. CONCLUSIONS: The findings of the current study suggest that metformin use during adjuvant chemotherapy does not significantly impact survival outcomes in diabetic patients with TNBC. Cancer 2012;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Women who are diagnosed with a deleterious mutation in either breast cancer ( BRCA) gene have a high risk of developing breast and ovarian cancers at young ages. In this study, the authors assessed age at diagnosis in 2 generations of families with known mutations to investigate for earlier onset in subsequent generations. METHODS: Of the 132 BRCA-positive women with breast cancer who participated in a high-risk protocol at The University of Texas MD Anderson Cancer Center (Gen 2), 106 women could be paired with a family member in the previous generation (Gen 1) who was diagnosed with a BRCA-related cancer (either breast cancer or ovarian cancer). Age at diagnosis, location of the mutation, and year of birth were recorded. A previously published parametric anticipation model was applied in these genetically predisposed families. RESULTS: The median age of cancer diagnosis was 42 years (range, 28-55 years) in Gen 2 and 48 years (range, 30-72 years) in Gen 1 ( P < .001). In the parametric model, the estimated change in the expected age at onset for the entire cohort was 7.9 years ( P < .0001). Statistically significant earlier ages at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, maternal inheritance, paternal inheritance, breast cancer only, and breast cancer-identified and ovarian cancer-identified families. CONCLUSIONS: Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations. The authors concluded that patients who are younger at the onset of BRCA-related cancers should continue to be tracked to offer appropriate screening modalities at appropriate ages. Cancer 2011. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background. Numerous studies have demonstrated that expression of estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor (HER)-2 is important for predicting overall survival (OS), distant relapse (DR), and locoregional relapse (LRR) in early and advanced breast cancer patients. However, these findings have not been confirmed for inflammatory breast cancer (IBC), which has different biological features than non-IBC. Methods. We retrospectively analyzed the records of 316 women who presented to MD Anderson Cancer Center in 1989-2008 with newly diagnosed IBC without distant metastases. Most patients received neoadjuvant chemotherapy, mastectomy, and postmastectomy radiation. Patients were grouped according to receptor status: ER+ (ER+/ PR+ and HER-2--; n=105), ER+HER-2+ (ER+/PR+ and HER-2+; n = 37), HER-2+ (ER--/PR-- and HER-2+; n = 83), or triple-negative (TN) (ER--PR--HER-2--; n = 91). Kaplan--Meier and Cox proportional hazards methods were used to assess LRR, DR, and OS rates and their associations with prognostic factors. Results. The median age was 50 years (range, 24--83 years). The median follow-up time and median OS time for all patients were both 33 months. The 5-year actuarial OS rates were 58.7% for the entire cohort, 69.7% for ER+ patients, 73.5% for ER+HER-2+ patients, 54.0% for HER2+ patients, and 42.7% for TN patients (p < .0001); 5-year LRR rates were 20.3%, 8.0%, 12.6%, 22.6%, and 38.6%, respectively, for the four subgroups (p < .0001); and 5-year DR rates were 45.5%, 28.8%, 50.1%, 52.1%, and 56.7%, respectively (p<.001). OS andLRRrates were worse for TN patients than for any other subgroup (p < .0001-.03). Conclusions. TN disease is associated with worse OS, DR, and LRR outcomes in IBC patients, indicating the need for developing new locoregional and systemic treatment strategies for patients with this aggressive subtype. [ABSTRACT FROM AUTHOR]

Purpose. Tyrosine 1248 is one of the autophosphorylation sites of human epidermal growth factor receptor (HER)-2. We determined the prognostic value of the expression level of tyrosine 1248 -phosphorylated HER-2 (pHER-2) in patients with HER-2+ primary breast cancer using a reverse-phase protein array. Patients and Methods. The optimal cutoff value of pHER-2 for segregating disease-free survival (DFS) was determined by receiver operating characteristic (ROC) curve analysis. Five-year DFS for pHER-2 expression level was estimated with the Kaplan-Meier method using both derivation (n = 162) and validation (n = 227) cohorts. Results. Of the 162 patients in the derivation cohort, 26 had high HER-2 expression levels. The area under the ROC curve for pHER-2 level and DFS was 0.662. Nineteen of the 162 patients (11.7%) had high pHER-2 expression levels (pHER-2high); 143 patients (88.3%) had low pHER-2 expression levels (pHER-2low). Among the 26 patients with high HER-2 expression levels, the 17 pHER-2high patients had a significantly lower 5-year DFS rate than the nine pHER-2low patients (23.5% versus 77.8%). On multivariate analysis, only pHER-2high independently predicted DFS in the Cox proportional hazards model. In the validation cohort, among 61 patients with high HER-2 expression, the difference in 5-year DFS rates between pHER-2high (n = 7) and pHER-2low (n = 54) patients was marginal (57.1% versus 81.5%). Conclusion. In patients with HER-2+ primary breast cancer, pHER-2high patients had a lower 5-year DFS rate than pHER-2low patients. Quantification of pHER-2 expression level may provide prognostic information beyond the current standard HER-2 status. [ABSTRACT FROM AUTHOR]

The article discusses research on increased locoregional (LR) recurrence in patients with only one positive hormone receptor compared with patients with estrogen receptor (ER)-positive progesterone receptor (PR)-positive disease in very early stage breast cancer. Records of 635 patients with breast cancer who received definitive treatment at their institution between 1997 and 2002 and had archival tissue blocks for prospective assessment of ER/PR expression were reviewed. Results showed higher LR recurrence rates in patients with 1 receptor positive.

The article offers information on a study assessing various perceptions on medical strategies such as screening and surgical in women with high-risk for breast cancer. The methods used in the study were based on the responses of women who were positively and negatively tested for deleterious mutation. Results from the study show that majority of BRCA+ women attest the effectivity of prophylactic mastectomy (PM) in risk-reduction of breast cancer in women.

Simple Summary: In semi-arid regions, providing a roughage adapted to water deficient conditions, such as spineless cactus, associated with a source of physically effective fiber, could be a feed alternative for sheep. Five inclusion levels of spineless cactus plus urea and ammonium sulfate to replace Tifton-85 hay were tested in sheep diets with a roughage/concentrate ratio of 70:30. The dry matter and digestible organic matter intake, as well as ruminal fermentation, nitrogen balance, and microbial protein supply, were evaluated. The results suggested that spineless cactus inclusion affected quadratically the dry matter and digestible organic matter intake, as well as retained nitrogen and microbial protein supply. The spineless cactus plus urea and ammonium sulfate improved nitrogen utilization, reducing linearly urinary nitrogen excretion, serum urea, and ammonia plasma. On the other hand, spineless cactus inclusion increased the ruminal acetate and propionate concentrations, while ruminal pH and ruminal ammonia nitrogen were decreased. We recommend a roughage consisting of spineless cactus (plus urea and ammonium sulfate) and Tifton-85 hay in a 41:29 ratio, in order to maximize the digestible organic matter intake and N-utilization. This could lead to an improvement in the productive performance of animals in semi-arid regions. The aim of this study was to evaluate the effect of replacing Tifton-85 hay (Cynodon spp. cv. Tifton 85) with 0, 150, 300, 450 and 600 g/kg dry matter (DM) of spineless cactus (SC, Nopalea cochenilifera Salm-Dyck) plus urea and ammonium sulfate (UAS; 9:1) on DM, digestible organic matter (DOM) and indigestible neutral detergent fiber (iNDF) intakes, as well as ruminal fermentation, N-balance, and microbial protein supply (MPS). Five rumen-fistulated and cannulated crossbred weathers, weighing 43.8 ± 5.80 kg, were randomized in a 5 × 5 Latin square design. Isonitrogenous diets (14% crude protein) were supplied with a roughage/concentrate ratio of 70:30. The DOM intake, N-retained, and MPS showed quadratic responses (p < 0.05), with maximum values estimated at the levels of SC+UAS of 414, 438 and 418 g/kg DM, respectively. Rumen pH and ammonia nitrogen, iNDF intake, N-urinary excretion, and serum urea and plasma ammonia reduced linearly (p < 0.05) with increasing SC+UAS inclusion. Ruminal acetate and propionate concentrations increased linearly with increasing SC+UAS inclusion. In weathers fed diets with a roughage/concentrate ratio of 70:30, roughage constituted of a SC+UAS/hay (Tifton-85) ratio of 41:29 is recommended in order to maximize the DOM intake, N-retention, and MPS. [ABSTRACT FROM AUTHOR]

Background: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer with poorly understood prognostic variables. The purpose of this study was to define the prognostic impact of HER-2 status on survival outcomes of patients with IBC.Methods: In all, 179 patients with IBC, diagnosed between 1989 and 2005, with known HER-2 status, and treated with an anthracycline-based chemotherapy regimen without trastuzumab, were included in the analysis. Patients with HER-2-positive disease who received trastuzumab at the time of disease recurrence were included. Survival outcomes were estimated by the Kaplan-Meier product limit method and compared across groups using the log-rank statistic. A Cox proportional hazards model was fitted to determine the association of survival outcomes with HER-2 status after adjusting for patient and tumor characteristics.Results: A total of 111 patients (62%) had HER-2-negative disease and 68 (38%) had HER-2-positive disease. The median follow-up among all patients was 35 months. At the time of the analysis, 62 patients (55.9%) with HER-2-negative disease and 42 patients (61.8%) with HER-2-positive disease had a recurrence. Thirty-one patients (73.8%) with HER-2-positive disease who had a disease recurrence went on to receive trastuzumab. On univariate analysis, no statistically significant difference was observed for either recurrence-free survival (P = .75) or overall survival (P = .24) between patients who had HER-2-positive disease and those who had HER-2-negative disease. In a multivariate model, HER-2 status did not appear to significantly affect recurrence-free survival (hazards ratio [HR] of 0.75; 95% confidence interval [95% CI], 0.46-1.22 [P = .241]). In the multivariate model, patients with HER-2-positive disease had a decreased hazard of death (HR of 0.56; 95% CI, 0.34-0.93 [P = .024]) compared with patients with HER-2-negative disease.Conclusions: HER-2 status, in the absence of trastuzumab, did not appear to significantly affect recurrence-free survival. After adjusting for other characteristics, the addition of trastuzumab in the metastatic setting significantly improved survival in the HER-2-positive group above and beyond that of the HER-2-negative group. This gives us further insight into the biology of this aggressive disease and underlines the major effect of targeted intervention. [ABSTRACT FROM AUTHOR]

Purpose: We examined the correlation between HER2 expression and pathologic complete response (pCR) to paclitaxel/FAC (T/FAC) preoperative chemotherapy in breast cancer. Patients and Methods: Retrospective analysis of data including 534 patients treated with preoperative T/FAC was performed. Gene expression results were available from two datasets of 132 and 286 patients, and were used to examine the co-expression of HER2 and topoisomerase II α (TOP2A) and microtubule associated protein tau (MAP-Tau). Results: Of the 534 patients, 105 (20%) had HER2-overexpressing breast cancer. The pCR rates were 33% and 15% for patients with HER2+ and HER2- tumors ( P < 0.001). The 5-year relapse-free survival rates were 94% and 70% in HER2+ tumors with and without pCR ( P = 0.009). HER2 overexpression (odds ratio 2.3, 95%CI: 1.3-3.9, P = 0.004), estrogen receptor (ER) status, grade and weekly schedule of paclitaxel were each significantly and independently associated with pCR in multivariate analysis. When patients were stratified by ER status, the pCR rates were 50% for HER2+/ER−, 30% for HER2−/ER−, 19% for HER2+/ER+, and 6% for HER2−/ER+ tumors. HER2 overexpression was associated with lower expression of MAP-tau ( P = 0.001 and P < 0.001) and higher expression of TOP2A mRNAs ( P = 0.048 and P = 0.001) in patients with ER+ disease. ER− cancers had low MAP-tau expression regardless of HER-status. Conclusion: HER2 overexpression is associated with higher rate of pCR to preoperative T/FAC chemotherapy regardless of ER status. HER2 overexpression also correlates with increased TOP2A and decreased MAP-tau expression in ER-positive cancers. [ABSTRACT FROM AUTHOR]

This phase II trial was conducted to assess the efficacy and safety of 10-Ethyl-10-Deaza-Aminopterin (10-EDAM), a folate antagonist, in metastatic breast cancer patients who had received no more than one prior chemotherapy regimen. Fifty-five patients were treated on an initial weekly dose 80 mg/m2 of 10-EDAM. Patients who had received a prior chemotherapy regimen in the adjuvant setting (group 1) were considered separately from patients who had received a prior chemotherapy regimen in the metastatic setting (group 2). The response rate for both groups combined was 18%, and median time to progression was 3 months. Median overall survival was 12 months. Treatment was associated with common chemotherapy-related toxicities, such as 25% grade three or four neutropenia and 20% grade three or four stomatitis. In patients with metastatic breast cancer who had received one prior chemotherapy regimen, 10-EDAM was well tolerated. In general, while definite antitumor activity was documented, time to progression was brief. [ABSTRACT FROM AUTHOR]

The objective of this paper is to analyse consumers' attitudes and acceptability of GM food products in Spain. From the methodological point of view, a three-equation model of consumer behaviour is estimated assuming a kind of causal chain among the degree of knowledge, attitudes and buying intentions. Explanatory variables include socioeconomic characteristics of respondents as well as endogenous variables of the previous equations. The model provides a better knowledge of how attitudes and buying intentions towards GM food are formed. Higher educated consumers, more concerned about labelling information and less about price, and regular buyers of organic foods show a higher (not necessarily better) knowledge on GM technology and its consequences. However, those consumers with a lower level of knowledge, together with those who are not concerned about safety, are not used to recycle but to purchase fast food generate more positive attitudes towards GMs, which finally determine future purchasing intention. [ABSTRACT FROM AUTHOR]

This paper analyses whether the growing amount of information about the relationship between diet and health has had an impact on the demand for different types of meat and fish in Spain. To achieve this objective, a health information index, based on the number of papers published in the MEDLINE database, is introduced into a ‘CBS’system of demand equations. Given the time series properties of the variables, a cointegrated CBS model is estimated. Meat demand and health information elasticities are calculated. Results indicate that, in the case of Spain, health information elasticities are significant, having a positive effect on fish and poultry and a negative effect on beef and pork. [ABSTRACT FROM PUBLISHER]

The article focuses on a study which represents a positive step towards the goal of using microfluidics for personalized cancer therapy. It references a study by J. Komen et al published in the 2008 issue of the "Biomedical Microdevices" periodical. The study describes the use of microfluidic chips to culture a breast cancer cell line (MCF-7) for up to 7 days. It found that exposure of the MCF-7 cells cultured on the chip to a flow of staurosporine followed by a static incubation resulted in reduced viability than control cells exposed to medium alone.

Background: Controversy exists regarding the impact of CYP2D6 genotype on tamoxifen responsiveness. We examined loss of heterozygosity (LOH) at the CYP2D6 locus and determined its impact on genotyping error when tumor tissue is used as a DNA source.Methods: Genomic tumor data from the adjuvant and metastatic settings (The Cancer Genome Atlas [TCGA] and Foundation Medicine [FM]) were analyzed to characterize the impact of CYP2D6 copy number alterations (CNAs) and LOH on Hardy Weinberg equilibrium (HWE). Additionally, we analyzed CYP2D6 *4 genotype from formalin-fixed paraffin-embedded (FFPE) tumor blocks containing nonmalignant tissue and buccal (germline) samples from patients on the North Central Cancer Treatment Group (NCCTG) 89-30-52 tamoxifen trial. All statistical tests were two-sided.Results: In TCGA samples (n =627), the CYP2D6 LOH rate was similar in estrogen receptor (ER)-positive (41.2%) and ER-negative (35.2%) but lower in HER2-positive tumors (15.1%) (P < .001). In FM ER+ samples (n = 290), similar LOH rates were observed (40.8%). In 190 NCCTG samples, the agreement between CYP2D6 genotypes derived from FFPE tumors and FFPE tumors containing nonmalignant tissue was moderate (weighted Kappa = 0.74; 95% CI = 0.63 to 0.84). Comparing CYP2D6 genotypes derived from buccal cells to FFPE tumor DNA, CYP2D6*4 genotype was discordant in six of 31(19.4%). In contrast, there was no disagreement between CYP2D6 genotypes derived from buccal cells with FFPE tumors containing nonmalignant tissue.Conclusions: LOH at the CYP2D6 locus is common in breast cancer, resulting in potential misclassification of germline CYP2D6 genotypes. Tumor DNA should not be used to determine germline CYP2D6 genotype without sensitive techniques to detect low frequency alleles and quality control procedures appropriate for somatic DNA. [ABSTRACT FROM AUTHOR]

Abstract: Women with breast cancer involving the lymph nodes are typically treated with cytotoxic chemotherapy. Retrospective evaluations of prior studies suggest that the 21-gene test (OncotypeDX®), may allow identification of those who can safely avoid chemotherapy. To better understand the performance of the 21-gene test, the RxPONDER (Rx for Positive Node, Endocrine Responsive breast cancer) study was designed, a multicenter Phase III trial randomizing women with hormone receptor-positive and HER2-negative breast cancer involving 1–3 lymph nodes and a 21-gene assay recurrence score (RS) of 25 or less to endocrine therapy alone versus chemotherapy followed by endocrine therapy. As one of the first large-scale comparative-effectiveness studies in oncology, RxPONDER utilized an external stakeholder group to help inform the design of the trial. Stakeholders met with representatives of SWOG over several months through a structured discussion process. The stakeholder engagement process resulted in several changes being made to the trial design. In addition, stakeholder representatives from the health insurance industry provided guidance regarding a mechanism whereby the costs of OncotypeDX® would be paid by the majority of health insurers as part of the trial. The process may serve as a template for future studies evaluating the comparative effectiveness of genomic tests in oncology, particularly those that are conducted within cooperative clinical trials groups. [Copyright &y& Elsevier]

Background and purpose There is mounting evidence that histone deacetylase (HDAC) inhibitors, e.g. valproic acid (VPA), synergize with radiation to improve outcomes in several cancers. This study was conducted to ascertain whether VPA affected outcomes in breast cancer patients with brain metastases treated with whole brain radiotherapy (WBRT). Materials and methods Records from 253 breast cancer patients with brain metastases treated with WBRT were reviewed. Data regarding use of all antiepileptic drugs (AEDs) were extracted. Kaplan–Meier survival times were calculated using the date of brain involvement as time zero. Cox proportional hazard models were used to determine the association between patient and tumor characteristics and overall survival (OS). Results Median OS for the entire patient cohort was 6 months. Patients receiving VPA ( n = 20) had a median OS of 11 months versus 5 months for those not receiving VPA ( p = 0.028). Median OS was 9 months for patients taking any AED ( n = 101) versus 4 months for those not taking AEDs ( p = 0.0003). On multivariate analysis both VPA and AED use were associated with improved OS (HR 0.61, p = 0.0419; HR 0.59, p = 0.0002, respectively). Conclusions This study suggests the use of AEDs, including VPA, is associated with improved OS in breast cancer patients with brain metastases following WBRT. [ABSTRACT FROM AUTHOR]

Purpose: Triple-negative breast cancer (TNBC) is defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression. In this study, we compared response to neoadjuvant chemotherapy and survival between patients with TNBC and non-TNBC., Patients and Methods: Analysis of a prospectively collected clinical database was performed. We included 1,118 patients who received neoadjuvant chemotherapy at M.D. Anderson Cancer Center for stage I-III breast cancer from 1985 to 2004 and for whom complete receptor information were available. Clinical and pathologic parameters, pathologic complete response rates (pCR), survival measurements, and organ-specific relapse rates were compared between patients with TNBC and non-TNBC., Results: Two hundred fifty-five patients (23%) had TNBC. Patients with TNBC compared with non-TNBC had significantly higher pCR rates (22% v 11%; P = .034), but decreased 3-year progression-free survival rates ( P < .0001) and 3-year overall survival (OS) rates ( P < .0001). TNBC was associated with increased risk for visceral metastases ( P = .0005), lower risk for bone recurrence ( P = .027), and shorter postrecurrence survival ( P < .0001). Recurrence and death rates were higher for TNBC only in the first 3 years. If pCR was achieved, patients with TNBC and non-TNBC had similar survival ( P = .24). In contrast, patients with residual disease (RD) had worse OS if they had TNBC compared with non-TNBC ( P < .0001)., Conclusion: Patients with TNBC have increased pCR rates compared with non-TNBC, and those with pCR have excellent survival. However, patients with RD after neoadjuvant chemotherapy have significantly worse survival if they have TNBC compared with non-TNBC, particularly in the first 3 years.