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Objective: Everolimus (EVE)+exemestane (EXE; n = 485) more than doubled median progression-free survival versus placebo (PBO) + EXE (n = 239), with a manageable safety profile and no deterioration in health-related quality-of-life (HRQOL) in patients with hormone-receptor-positive (HR(+)) advanced breast cancer (ABC) who recurred or progressed on/after nonsteroidal aromatase inhibitor (NSAI) therapy. To further evaluate EVE + EXE impact on disease burden, we conducted additional post-hoc analyses of patient-reported HRQOL.Research Design and Methods: HRQOL was assessed using EORTC QLQ-C30 and QLQ-BR23 questionnaires at baseline and every 6 weeks thereafter until treatment discontinuation because of disease progression, toxicity, or consent withdrawal. Endpoints included the QLQ-C30 Global Health Status (QL2) scale, the QLQ-BR23 breast symptom (BRBS), and arm symptom (BRAS) scales. Between-group differences in change from baseline were assessed using linear mixed models with selected covariates. Sensitivity analysis using pattern-mixture models determined the effect of study discontinuation on/before week 24. Treatment arms were compared using differences of least squares mean (LSM) changes from baseline and 95% confidence intervals (CIs) at each timepoint and overall.Clinical Trial Registration: Clinicaltrials.gov: NCT00863655.Main Outcome Measures: Progression-free survival, survival, response rate, safety, and HRQOL.Results: Linear mixed models (primary model) demonstrated no statistically significant overall difference between EVE + EXE and PBO + EXE for QL2 (LSM difference = -1.91; 95% CI = -4.61, 0.78), BRBS (LSM difference = -0.18; 95% CI = -1.98, 1.62), or BRAS (LSM difference = -0.42; 95% CI = -2.94, 2.10). Based on pattern-mixture models, patients who dropped out early had worse QL2 decline on both treatments. In the expanded pattern-mixture model, EVE + EXE-treated patients who did not drop out early had stable BRBS and BRAS relative to PBO + EXE.Key Limitations: HRQOL data were not collected after disease progression.Conclusions: These analyses confirm that EVE + EXE provides clinical benefit without adversely impacting HRQOL in patients with HR(+) ABC who recurred/progressed on prior NSAIs versus endocrine therapy alone. [ABSTRACT FROM AUTHOR]

Introduction: Effective treatments for hormone-receptor-positive (HR +) breast cancer (BC) following relapse/progression on nonsteroidal aromatase inhibitor (NSAI) therapy are needed. Initial Breast Cancer Trials of OraL EveROlimus-2 (BOLERO-2) trial data demonstrated that everolimus and exemestane significantly prolonged progression-free survival (PFS) versus placebo plus exemestane alone in this patient population. Methods: BOLERO-2 is a phase 3, double-blind, randomized, international trial comparing everolimus (10 mg/day) plus exemestane (25 mg/day) versus placebo plus exemestane in postmenopausal women with HR + advanced BC with recurrence/progression during or after NSAIs. The primary endpoint was PFS by local investigator review, and was confirmed by independent central radiology review. Overall survival, response rate, and clinical benefit rate were secondary endpoints. Results: Final study results with median 18-month follow-up show that median PFS remained significantly longer with everolimus plus exemestane versus placebo plus exemestane [investigator review: 7.8 versus 3.2 months, respectively; hazard ratio = 0.45 (95% confidence interval 0.38–0.54); log-rank P < 0.0001; central review: 11.0 versus 4.1 months, respectively; hazard ratio = 0.38 (95% confidence interval 0.31–0.48); log-rank P < 0.0001] in the overall population and in all prospectively defined subgroups, including patients with visceral metastases, patients with recurrence during or within 12 months of completion of adjuvant therapy, and irrespective of age. The incidence and severity of adverse events were consistent with those reported at the interim analysis and in other everolimus trials. Conclusion: The addition of everolimus to exemestane markedly prolonged PFS in patients with HR + advanced BC with disease recurrence/progression following prior NSAIs. These results further support the use of everolimus plus exemestane in this patient population. ClinicalTrials.gov #NCT00863655. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article on the association of CYP2D6 genotype with tamoxifen hormone therapy response in the 2012 issue.

Background: Paclitaxel is a microtubule-stabilizing drug that has been commonly used in treating cancer. Due to genetic heterogeneity within patient populations, therapeutic response rates often vary. Here we used the NCI60 panel to identify SNPs associated with paclitaxel sensitivity. Using the panel's GI50 response data available from Developmental Therapeutics Program, cell lines were categorized as either sensitive or resistant. PLINK software was used to perform a genome-wide association analysis of the cellular response to paclitaxel with the panel's SNP-genotype data on the Affymetrix 125 k SNP array. FastSNP software helped predict each SNP's potential impact on their gene product. mRNA expression differences between sensitive and resistant cell lines was examined using data from BioGPS. Using Haploview software, we investigated for haplotypes that were more strongly associated with the cellular response to paclitaxel. Ingenuity Pathway Analysis software helped us understand how our identified genes may alter the cellular response to paclitaxel. Results: 43 SNPs were found significantly associated (FDR < 0.005) with paclitaxel response, with 10 belonging to protein-coding genes (CFTR, ROBO1, PTPRD, BTBD12, DCT, SNTG1, SGCD, LPHN2, GRIK1, ZNF607). SNPs in GRIK1, DCT, SGCD and CFTR were predicted to be intronic enhancers, altering gene expression, while SNPs in ZNF607 and BTBD12 cause conservative missense mutations. mRNA expression analysis supported these findings as GRIK1, DCT, SNTG1, SGCD and CFTR showed significantly (p < 0.05) increased expression among sensitive cell lines. Haplotypes found in GRIK1, SGCD, ROBO1, LPHN2, and PTPRD were more strongly associated with response than their individual SNPs. Conclusions: Our study has taken advantage of available genotypic data and its integration with drug response data obtained from the NCI60 panel. We identified 10 SNPs located within protein-coding genes that were not previously shown to be associated with paclitaxel response. As only five genes showed differential mRNA expression, the remainder would not have been detected solely based on expression data. The identified haplotypes highlight the role of utilizing SNP combinations within genomic loci of interest to improve the risk determination associated with drug response. These genetic variants represent promising biomarkers for predicting paclitaxel response and may play a significant role in the cellular response to paclitaxel. [ABSTRACT FROM AUTHOR]

Summary: Background: A systematic review was undertaken to evaluate the evidence for the use of trastuzumab as (neo)adjuvant therapy for women with HER-2/neu-positive breast cancer and to develop and support recommendations pertaining to its use across five domains: as a single-agent therapy, in combination with chemotherapy, methods to identify women who will benefit from it, adverse events associated with it, and optimal dose, schedule, and duration. Methods: MEDLINE, EMBASE, the American Society of Clinical Oncology, the San Antonio Breast Cancer Symposia proceedings, and the Cochrane Library were searched through May 2007 for reports of randomized controlled trials that met the inclusion criteria. Results: Eight randomized trials, described across 23 citations, were identified. All six trials of adjuvant trastuzumab reported significantly improved disease-free survival (DFS) while 4 of 6 adjuvant trials showed significant improvement in overall survival (OS) for patients treated with trastuzumab over those that were not. Two trials of trastuzumab in the neoadjuvant setting reported significantly better pathological complete response (pCR) in patients treated with trastuzumab although both studies were limited by small sample size, and longer follow-up is needed. Conclusion: Although the optimal duration, schedule, and timing of adjuvant trastuzumab remains undefined, the bulk of the available evidence supports that adjuvant trastuzumab be offered for 1 year to all patients with HER-2-positive and node-positive or high-risk node-negative (tumour ⩾1cm in size) primary breast cancer who are receiving or have received (neo)adjuvant chemotherapy. [Copyright &y& Elsevier]

The article discusses whether adjuvant aromatase inhibitors (AIs) increase the cardiovascular risk in postmenopausal women with early breast cancer. In this review, Phase 3 randomized clinical trials (RCT) comparing AI with tamoxifen in early breast cancer were considered. The results of the meta-analysis showed that the risk of grade 3 and 4 cardiovascular events (CVAE) in patients who were receiving AI was higher compared with the risk in patients who were receiving tamoxifen and the difference reached statistical significance.

Presents correspondence between medical practitioners as of July 24, 2001. Condition of women treated for breast cancer at teaching hospitals; Handling raloxifene; Nonclinical factors in patient selection for surgery; Responses.

The article presents abstracts on drug side effects and quality of life topics which include the symptom burden and quality of life in patients with breast cancer, treatment of acute pain syndrome, and chemotherapy-related cognitive impairment (CRCI).

Presents information on internal medicine. Standards for controlled trials of surgical therapy; Advances in hormonal therapy of breast cancer; Hypercalcemia in advanced breast cancer caused by tamoxifen.

In identifying research priorities it is important to take the needs and prospective of patients with breast cancer into account. [ABSTRACT FROM AUTHOR]

The 13th St Gallen International Breast Cancer Conference (2013) Expert Panel reviewed and endorsed substantial new evidence on aspects of the local and regional therapies for early breast cancer, supporting less extensive surgery to the axilla and shorter durations of radiation therapy. It refined its earlier approach to the classification and management of luminal disease in the absence of amplification or overexpression of the Human Epidermal growth factor Receptor 2 (HER2) oncogene, while retaining essentially unchanged recommendations for the systemic adjuvant therapy of HER2-positive and ‘triple-negative’ disease. The Panel again accepted that conventional clinico-pathological factors provided a surrogate subtype classification, while noting that in those areas of the world where multi-gene molecular assays are readily available many clinicians prefer to base chemotherapy decisions for patients with luminal disease on these genomic results rather than the surrogate subtype definitions. Several multi-gene molecular assays were recognized as providing accurate and reproducible prognostic information, and in some cases prediction of response to chemotherapy. Cost and availability preclude their application in many environments at the present time. Broad treatment recommendations are presented. Such recommendations do not imply that each Panel member agrees: indeed, among more than 100 questions, only one (trastuzumab duration) commanded 100% agreement. The various recommendations in fact carried differing degrees of support, as reflected in the nuanced wording of the text below and in the votes recorded in supplementary Appendix S1, available at Annals of Oncology online. Detailed decisions on treatment will as always involve clinical consideration of disease extent, host factors, patient preferences and social and economic constraints.

The article discusses the response of Dr. Saira Nasim and clinical research fellow Kathleen I. Pritchard on Dr. Pritchard and Dr. Richard Love's paper about adjuvant hormonal therapy and ovarian ablation in premenopausal women with operable breast caner. It states that the authors differentiated the general differences of Love and Pritchard's paper. It notes that Love's paper raises a lot of important issues which include his view of breast cancer as a worldwide disease.

Purpose: A cross-sectional study was conducted to investigate the feasibility of implementing routine collection of the Euro-Qol 5 dimensions (EQ-5D) questionnaire, to inform drug and health technology reimbursement decision making. Methods: Women with breast cancer were recruited during scheduled clinic visits to an academic cancer centre. EQ-5D-5L was self-administered using electronic tablets. Diagnostic and treatment data were abstracted from patient charts. Feasibility was assessed primarily by the proportion of patients who fully completed EQ-5D-5L and by their willingness to complete the instrument at each clinic visit. Results: 588 women were approached for study participation, 341 were enrolled. Fully completed EQ-5D-5L questionnaires were obtained in 323 participants (95% of participants, 95% CI 92–97%). Median time for EQ-5D-5L completion was 1.5 minutes (range:0.35 to 14.7). Mean age of participants was 58 years old. Most women who completed EQ-5D were White, born outside Canada and presented a high education level; one-quarter had metastatic disease. Most participants reported "No problems" in all EQ-5D-5L dimensions. Mean EQ-5D-5L index and mean EQ-5D-5L VAS values for all participants were respectively 0.83 (SD 0.13) and 75.7 (SD 17.45), with patients with metastatic disease scoring the lowest values. Seventy-eight percent of participants were willing to complete EQ-5D-5L at each clinic visit; lower Charlson comorbidity index and higher education level were predictors of willingness to continue to answer EQ-5D-5L. Conclusions: Tablet-based collection of EQ-5D-5L in the context of routine clinical practice proved to be feasible. However, many patients declined study participation or reported being in full health, raising concerns about whether this method of collecting EQ-5D adequately represents the health status of all breast cancer patients. [ABSTRACT FROM AUTHOR]

Examines the effectiveness of screening for endometrial cancer. Introduction of periodic health examination in Great Britain and North America in the 20th century. Information on endometrial cancer; Incidence of endometrial cancer in Canada.

The authors comment on a novel approach that was developed and validated in selecting patients who benefit from anthracycline/cyclophosphamide chemotherapy. They cite multiple guidelines relating to the approach, including the Evaluation of Genomic Applications in Practice and Prevention (EGAPP), and Biospecimen Reporting for Improved Study Quality (BRISQ). They state that the approach assessed reproducibility using a less-rigorous criterion.