'I presumed the pain would eventually get better by itself'; challenges with access to rehabilitation for upper limb dysfunction after breast cancer treatment - Descriptive and qualitative findings from a cross-sectional survey.

Purpose: Sixty percent of breast cancer patients develop persistent upper limb pain and dysfunction, but only limited knowledge exists about how these symptoms relate to rehabilitation access.

Methods: A postal survey was sent to patients treated at a London University Teaching Hospital (2018-2020). Data were collected on pain (Pain Detect), shoulder function (Disability of Shoulder Arm and Hand (DASH)), quality-of-life (QoL) (EQ-5D-5L), and clinical characteristics, including treatment and access to rehabilitation.

Employing multiple synchronous outcome samples per subject to improve study efficiency.

Background: Accuracy can be improved by taking multiple synchronous samples from each subject in a study to estimate the endpoint of interest if sample values are not highly correlated. If feasible, it is useful to assess the value of this cluster approach when planning studies. Multiple assessments may be the only method to increase power to an acceptable level if the number of subjects is limited.

Cancer Biology and Survival Analysis in Cancer Trials: Restricted Mean Survival Time Analysis versus Hazard Ratios.

Hazard ratios are commonly used when comparing survival between two groups and make the assumption that the relative event rates do not change markedly during follow-up, i.e. that event rates are proportional.

Correlation between DNA damage responses of skin to a test dose of radiation and late adverse effects of earlier breast radiotherapy.

Aim: To correlate residual double strand breaks (DSB) 24h after 4Gy test doses to skin in vivo and to lymphocytes in vitro with adverse effects of earlier breast radiotherapy (RT).

Patients And Methods: Patients given whole breast RT ⩾5years earlier were identified on the basis of moderate/marked or minimal/no adverse effects despite the absence ('RT-Sensitive', RT-S) or presence ('RT-Resistant', RT-R) of variables predisposing to late adverse effects. Residual DSB were quantified in skin 24h after a 4Gy test dose in 20 RT-S and 15 RT-R patients.

DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer.

Background: Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.

Methods: We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day.

Extreme chromosomal instability forecasts improved outcome in ER-negative breast cancer: a prospective validation cohort study from the TACT trial.

Background: Chromosomal instability (CIN) has been shown to be associated with drug resistance and poor clinical outcome in several cancer types. However, in oestrogen receptor (ER)-negative breast cancer we have previously demonstrated that extreme CIN is associated with improved clinical outcome, consistent with a negative impact of CIN on tumour fitness and growth. The aim of this current study was to validate this finding using previously defined CIN thresholds in a much larger prospective cohort from a randomised, controlled, clinical trial.

A phase II trial to assess the activity of gemcitabine and docetaxel as first line chemotherapy treatment in patients with unresectable leiomyosarcoma.

Background: Gemcitabine and docetaxel have been shown to be active in pre-treated relapsed leiomyosarcoma. This study investigated the combination as first line treatment in patients with unresectable locally advanced/metastatic leiomyosarcoma.

Methods: Patients received gemcitabine 900 mg/m(2) days 1 and 8, and docetaxel 100 mg/m(2) day 8, administered 3-weekly for up to 8 cycles, with GCSF support on days 9-15.

Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

Background: Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points.

Antiproliferative Effect of Lapatinib in HER2-Positive and HER2-Negative/HER3-High Breast Cancer: Results of the Presurgical Randomized MAPLE Trial (CRUK E/06/039).

Purpose: Not all breast cancers respond to lapatinib. A change in Ki67 after short-term exposure may elucidate a biomarker profile for responsive versus nonresponsive tumors.

Experimental Design: Women with primary breast cancer were randomized (3:1) to 10 to 14 days of preoperative lapatinib or placebo in a multicenter phase II trial (ISRCTN68509377).

Residual proliferative cancer burden to predict long-term outcome following neoadjuvant chemotherapy.

Background: The purpose of this study was (i) to test the hypothesis that combining Ki67 with residual cancer burden (RCB) following neoadjuvant chemotherapy, as the residual proliferative cancer burden (RPCB), provides significantly more prognostic information than either alone; (ii) to determine whether also integrating information on ER and grade improves prognostic power.

Patients And Methods: A total of 220 patients treated with neoadjuvant chemotherapy for primary breast cancer were included in the study. Analyses employed a Cox proportional hazard model.

Differences in the transcriptional response to fulvestrant and estrogen deprivation in ER-positive breast cancer.

Purpose: Endocrine therapies include aromatase inhibitors and the selective estrogen receptor (ER) downregulator fulvestrant. This study aimed to determine whether the reported efficacy of fulvestrant over anastrozole, and high- over low-dose fulvestrant, reflect distinct transcriptional responses.

Experimental Design: Global gene expression profiles from ERα-positive breast carcinomas before and during presurgical treatment with fulvestrant (n = 22) or anastrozole (n = 81), and corresponding in vitro models, were compared.

Predictive performance of microarray gene signatures: impact of tumor heterogeneity and multiple mechanisms of drug resistance.

Gene signatures have failed to predict responses to breast cancer therapy in patients to date. In this study, we used bioinformatic methods to explore the hypothesis that the existence of multiple drug resistance mechanisms in different patients may limit the power of gene signatures to predict responses to therapy. In addition, we explored whether substratification of resistant cases could improve performance.

Biomarker changes associated with the development of resistance to aromatase inhibitors (AIs) in estrogen receptor-positive breast cancer.

Background: The purpose of this study was to identify any differences in key biomarkers associated with estrogen action between biopsies taken at diagnosis and at recurrence or progression during treatment with an aromatase inhibitor (AI).

Patients And Methods: Patients were retrospectively identified from a clinical database as having relapsed or progressed during AI treatment. Immunohistochemistry was carried out against estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), insulin-like growth factor type-1 receptor (IGF1R), insulin receptor substrate-1 (IRS-1), stathmin, phosphatase and tensin homolog and Ki67.

Assessment of microtubule-associated protein (MAP)-Tau expression as a predictive and prognostic marker in TACT; a trial assessing substitution of sequential docetaxel for FEC as adjuvant chemotherapy for early breast cancer.

The TACT trial is the largest study assessing the benefit of taxanes as part of adjuvant therapy for early breast cancer. The goal of this translational study was to clarify the predictive and prognostic value of Tau within the TACT trial. Tissue microarrays (TMA) were available from 3,610 patients.

Characterization of the genomic features and expressed fusion genes in micropapillary carcinomas of the breast.

Micropapillary carcinoma (MPC) is a rare histological special type of breast cancer, characterized by an aggressive clinical behaviour and a pattern of copy number aberrations (CNAs) distinct from that of grade- and oestrogen receptor (ER)-matched invasive carcinomas of no special type (IC-NSTs). The aims of this study were to determine whether MPCs are underpinned by a recurrent fusion gene(s) or mutations in 273 genes recurrently mutated in breast cancer. Sixteen MPCs were subjected to microarray-based comparative genomic hybridization (aCGH) analysis and Sequenom OncoCarta mutation analysis.

Taxane benefit in breast cancer--a role for grade and chromosomal stability.

Chromosomal instability, which is a characteristic of many human cancers, contributes to intratumour heterogeneity and has been functionally implicated in resistance to taxane therapy in tumour models. However, defining the status of tumour chromosomal instability in a given tumour to test this hypothesis remains challenging. Measurements of numerical and structural chromosomal heterogeneity demonstrate that histological grade correlates with chromosomal instability in oestrogen receptor (ER)-positive breast cancer.

Phosphorylation of AKT pathway proteins is not predictive of benefit of taxane therapy in early breast cancer.

Results from the NSABP B-28 trial suggest AKT activation may predict reduced benefit from taxanes following standard anthracycline therapy. Pre-clinical data support a link between PI3 K/AKT signalling and taxane resistance. Using the UK taxotere as adjuvant chemotherapy trial (TACT), we tested the hypothesis that activation of AKT or downstream markers, p70S6K or p90RSK, identifies patients with reduced benefit from taxane chemotherapy.

Mutation profiling of adenoid cystic carcinomas from multiple anatomical sites identifies mutations in the RAS pathway, but no KIT mutations.

Aims: The majority of adenoid cystic carcinomas (AdCCs), regardless of anatomical site, harbour the MYB-NFIB fusion gene. The aim of this study was to characterize the repertoire of somatic genetic events affecting known cancer genes in AdCCs.

Methods And Results: DNA was extracted from 13 microdissected breast AdCCs, and subjected to a mutation survey using the Sequenom OncoCarta Panel v1.