Everolimus Plus Exemestane Versus Everolimus or Capecitabine Monotherapy in Breast Cancer : BOLERO-6

The data from this trial will provide insight into the safety and efficacy of the combination of EVE and EXE versus EVE or capecitabine monotherapy in women with ER+, HER2- ABC progressing on/after prior LET or ANA.Peer reviewe

A randomized cross-over trial to detect differences in arm volume after low- and heavy-load resistance exercise among patients receiving adjuvant chemotherapy for breast cancer at risk for arm lymphedema:study protocol

BACKGROUND: In an effort to reduce the risk of breast cancer-related arm lymphedema, patients are commonly advised to avoid heavy lifting, impacting activities of daily living and resistance exercise prescription. This advice lacks evidence, with no prospective studies investigating arm volume changes after resistance exercise with heavy loads in this population. The purpose of this study is to determine acute changes in arm volume after a session of low- and heavy-load resistance exercise among women undergoing adjuvant chemotherapy for breast cancer at risk for arm lymphedema. METHODS/DESIGN: This is a randomized cross-over trial. Participants: Women receiving adjuvant chemotherapy for breast cancer who have undergone axillary lymph node dissection will be recruited from rehabilitation centers in the Copenhagen area. Intervention: Participants will be randomly assigned to engage in a low- (two sets of 15–20 repetition maximum) and heavy-load (three sets of 5–8 repetition maximum) upper-extremity resistance exercise session with a one week wash-out period between sessions. Outcome: Changes in extracellular fluid (L-Dex score) and arm volume (ml) will be assessed using bioimpedance spectroscopy and dual-energy x-ray absorptiometry, respectively. Symptom severity related to arm lymphedema will be determined using a visual analogue scale (heaviness, swelling, pain, tightness). Measurements will be taken immediately pre- and post-exercise, and 24- and 72-hours post-exercise. Sample size: A sample size of 20 participants was calculated based on changes in L-Dex scores between baseline and 72-hours post exercise sessions. DISCUSSION: Findings from this study are relevant for exercise prescription guidelines, as well as recommendations regarding participating in activities of daily living for women following surgery for breast cancer and who may be at risk of developing arm lymphedema. TRIAL REGISTRATION: Current Controlled Trials ISRCTN97332727. Registered 12 February 2015. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2548-y) contains supplementary material, which is available to authorized users

Novel de novo BRCA2 mutation in a patient with a family history of breast cancer

<p>Abstract</p> <p>Background</p> <p><it>BRCA2 </it>germ-line mutations predispose to breast and ovarian cancer. Mutations are widespread and unclassified splice variants are frequently encountered. We describe the parental origin and functional characterization of a novel <it>de novo BRCA2 </it>splice site mutation found in a patient exhibiting a ductal carcinoma at the age of 40.</p> <p>Methods</p> <p>Variations were identified by denaturing high performance liquid chromatography (dHPLC) and sequencing of the <it>BRCA1 </it>and <it>BRCA2 </it>genes. The effect of the mutation on splicing was examined by exon trapping in COS-7 cells and by RT-PCR on RNA isolated from whole blood. The paternity was determined by single nucleotide polymorphism (SNP) microarray analysis. Parental origin of the <it>de novo </it>mutation was determined by establishing mutation-SNP haplotypes by variant specific PCR, while <it>de novo </it>and mosaic status was investigated by sequencing of DNA from leucocytes and carcinoma tissue.</p> <p>Results</p> <p>A novel <it>BRCA2 </it>variant in the splice donor site of exon 21 (nucleotide 8982+1 G→A/c.8754+1 G→A) was identified. Exon trapping showed that the mutation activates a cryptic splice site 46 base pairs 3' of exon 21, resulting in the inclusion of a premature stop codon and synthesis of a truncated BRCA2 protein. The aberrant splicing was verified by RT-PCR analysis on RNA isolated from whole blood of the affected patient. The mutation was not found in any of the patient's parents or in the mother's carcinoma, showing it is a <it>de novo </it>mutation. Variant specific PCR indicates that the mutation arose in the male germ-line.</p> <p>Conclusion</p> <p>We conclude that the novel <it>BRCA2 </it>splice variant is a <it>de novo </it>mutation introduced in the male spermatozoa that can be classified as a disease causing mutation.</p

TIMP-1 and responsiveness to gemcitabine in advanced breast cancer:results from a randomized phase III trial from the Danish breast cancer cooperative group

BACKGROUND: Tissue inhibitor of metalloproteinases-1 (TIMP-1) has anti-apoptotic functions, which may protect TIMP-1 positive cancer cells from the effects of chemotherapy such as docetaxel and gemcitabine. The purpose of the present study was to evaluate TIMP-1 immunoreactivity as a prognostic and predictive marker in advanced breast cancer patients receiving docetaxel (D) or gemcitabine plus docetaxel (GD). METHODS: Patients with locally advanced or metastatic breast cancer who were assigned to D or GD by participation in a randomized phase III trial were included in the study. Assessment of TIMP-1 status was performed retrospectively on primary tumor whole-tissue sections by immunohistochemistry and tumor samples were considered positive if epithelial breast cancer cells were stained by the anti-TIMP-1 monoclonal antibody VT7. Time to progression (TTP) was the primary endpoint. Overall survival (OS) and response rate (RR) were secondary endpoints. Associations between TIMP-1 status and outcome after chemotherapy were analyzed by Kaplan-Meier estimates and Cox proportional hazards regression models. RESULTS: TIMP-1 status was available from 264 of 337 patients and 210 (80%) of the tumors were classified as cancer cell TIMP-1 positive. No significant difference for TTP between TIMP-1 positive versus TIMP-1 negative patients was observed in multivariate analysis, and RR did not differ according to TIMP-1 status. However, patients with TIMP-1 positive tumors had a significant reduction in OS events (hazard ratio = 0.71, 95% confidence interval (CI) = 0.52-0.98, P = 0.03). Additionally, a borderline significant interaction for OS was observed between TIMP-1 status and benefit from GD compared to D (P(interaction) = 0.06) such that median OS increased by nine months for TIMP-1 negative patients receiving GD. CONCLUSIONS: TIMP-1 status was an independent prognostic factor for OS but not TTP in patients with advanced breast cancer receiving either D or GD. There was no statistically significant interaction between TIMP-1 status and treatment, but a trend towards an incremental OS from the addition of gemcitabine to docetaxel in patients with TIMP-1 negative tumors suggests further investigation