Trends in the distribution of gestational age and contribution of planned births in New South Wales, Australia

§<p>Relative change was calculated by: [(2009 rate –1994 rate)/(1994 rate)].</p>*<p>100; Test-for-trend was significant for all factors except stillbirths and multiple births, P<0.001.</p>†<p>Low risk pregnancies defined as primiparae, aged 20–34 years, without pregnancy complications; and with a liveborn singleton infant, born in cephalic presentation and of normal fetal growth at the 10^th–90th birth weight percentile of the distribution for gestational age and infant sex. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056238#pone.0056238-Cheng1" target="_blank">[16]</a>.</p>*<p>Numbers may not add up to totals due to missing data or rounding.</p

Adjuvant dose-dense doxorubicin-cyclophosphamide versus docetaxel-doxorubicin-cyclophosphamide for high-risk breast cancer: First results of the randomised MATADOR trial (BOOG 2004-04)

Background: Dose-dense administration of chemotherapy and the addition of taxanes to anthracycline-based adjuvant chemotherapy have improved breast cancer survival substantially. However, clinical trials directly comparing the additive value of taxanes with dose-dense anthracycline-based chemotherapy are lacking. Patients and methods: In the multicentre, randomised, biomarker discovery Microarray Analysis in breast cancer to Tailor Adjuvant Drugs Or Regimens (MATADOR) trial, patients with pT1-3, pN0-3 breast cancer were randomised (1:1) between six adjuvant cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 2 weeks (ddAC) and six cycles of docetaxel 75 mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 3 weeks (TAC). The primary objective was to discover a predictive gene expression profile for ddAC and TAC benefit. Here we report the preplanned secondary end-point recurrence-free survival (RFS) and overall survival (OS). Results: Between 2004 and 2012, 664 patients were randomised. At 5 years, RFS was 87% (95% confidence interval [CI] 83%–91%) in the ddAC-treated patients and 88% (84–92%) in the TAC-treated subgroup (hazard ratio [HR] 0.89, 95% CI 0.62–1.28, P = 0.53). OS at 5 years was 93% (90%–96%) in the ddAC-treated and 94% (91%–97%) in the TAC-treated patients (HR 0.89, 95% CI 0.57–1.39, P = 0.61). Anaemia was more frequent in ddAC-treated patients (62/327 patients [18.9%] versus 15/319 patients [4.7%], P < 0.001) and diarrhoea (21 [6.4%] versus 53 [16.6%], P<0.001) and peripheral neuropathy (15 [4.6%] versus 46 [14.4%], P < 0.001) were observed more often in TAC-treated patients. Conclusions: With a median follow-up of 7 years, no significant differences in RFS and OS were observed between six adjuvant cycles of ddAC and TAC in high-risk breast cancer patients. Trial registration numbers: ISRCTN61893718 and BOOG 2004-04

Carboplatin-cyclophosphamide or paclitaxel without or with bevacizumab as first-line treatment for metastatic triple-negative breast cancer (BOOG 2013-01)

Background: The addition of bevacizumab to chemotherapy conferred a modest progression-free survival (PFS) benefit in metastatic triple-negative breast cancer (mTNBC). However, no overall survival (OS) benefit has been reported. Also, its combination with carboplatin-cyclophosphamide (CC) has never been investigated. Methods: The Triple-B study is a multicenter, randomized phase IIb trial that aims to prospectively validate predictive biomarkers, including baseline plasma vascular endothelial growth factor receptor-2 (pVEGFR-2), for bevacizumab benefit. mTNBC patients were randomized between CC and paclitaxel (P) without or with bevacizumab (CC +/- B or P +/- B). Here we report on a preplanned safety and preliminary efficacy analysis after the first 12 patients had been treated with CC+B and on the predictive value of pVEGFR-2. Results: In 58 patients, the median follow-up was 22.1 months. Toxicity was manageable and consistent with what was known for each agent separately. There was a trend toward a prolonged PFS with bevacizumab compared to chemotherapy only (7.0 vs. 5.2 months; adjusted HR = 0.60; 95% CI 0.33-1.08; p = 0.09), but there was no effect on OS. In this small study, pVEGFR-2 concentration did not predict a bevacizumab PFS benefit. Both the intention-to-treat analysis and the per-protocol analysis did not yield a significant treatment-by-biomarker test for interaction (p(interaction) = 0.69). Conclusions:CC and CC+B are safe first-line regimens for mTNBC and the side effects are consistent with those known for each individual agent. pVEGFR-2 concentration did not predict a bevacizumab PFS benefit.Experimentele farmacotherapi

Predictive gene expression profile for adjuvant taxane benefit in breast cancer in the MATADOR trial

The primary objective of the prospective, randomized, multicenter, phase 3 biomarker Microarray Analysis in breast cancer to Taylor Adjuvant Drugs Or Regimens trial (MATADOR: ISRCTN61893718) is to generate a gene expression profile that can predict benefit from either docetaxel, doxorubicin, and cyclophosphamide (TAC) or dose-dense scheduled doxorubicin and cyclophosphamide (ddAC). Patients with a pT1-3, pN0-3 tumor were randomized 1:1 between ddAC and TAC. The primary endpoint was a gene profile-treatment interaction for recurrence-free survival (RFS). We observed 117 RFS events in 664 patients with a median follow-up of 7 years. Hallmark gene set analyses showed significant association between enrichment in immune-related gene expression and favorable outcome after TAC in hormone receptor-negative, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) (triple-negative breast cancer [TNBC]). We validated this association in TNBC patients treated with TAC on H&E slides; stromal tumor-infiltrating lymphocytes (sTILs) ≥20% was associated with longer RFS (hazard ratio 0.18, p = 0.01), while in patients treated with ddAC no difference in RFS was seen (hazard ratio 0.92, p = 0.86, pinteraction = 0.02). Experimentele farmacotherapi

Accuracy of MRI for treatment response assessment after taxane- and anthracycline-based neoadjuvant chemotherapy in HER2-negative breast cancer

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseaseImmunology and molecular genetics of gynecological cancersTI9 - Endometriumpathologi

Accuracy of treatment response assessment modalities after neoadjuvant therapy: A Dutch Breast Cancer Trialists' Group (BOOG) substudy

Surgical oncolog

Slow accrual of elderly patients with metastatic breast cancer in the Dutch multicentre OMEGA study

In a Dutch multicentre study, elderly (65 + year) metastatic breast cancer patients, eligible for first-line chemotherapy, were randomised between two types of single-agent chemotherapy. As accrual was slow, with 78 randomised patients between April 2007 and September 2011, we explored potential barriers in the accrual process and their consequences for characteristics of included patients. We sent surveys on the reasons for non-inclusion to all coordinating investigators. We also examined inclusion in a concurrent, non-elderly breast cancer study of the trialists' group and analysed baseline geriatric characteristics of included patients. Investigators from fifteen participating centres returned the survey. Most commonly reported barriers to inclusion were: patient's refusal of chemotherapy (n = 8) or of randomisation (n = 9), impaired cognition (n = 3) and insufficient cardiac function (n = 2). Oncologists' preference for combination regimens over single-agent chemotherapy was reported twice. Twenty-eight potentially eligible patients, aged 65-71 years, were included in a concurrent, study investigating combination chemotherapy in fit non-elderly patients with metastatic breast cancer. However, baseline characteristics of the included patients showed that the OMEGA study succeeded in including frail and older patients, with a performance status of 2 in 22% of patients and 54% of patients aged 75 years or older. Accrual in this study was mainly hampered by patient's refusal or preference for a particular type of treatment, and an overall condition considered as too fit or too frail for inclusion. Future trials in elderly metastatic breast cancer patients should focus on non-restrictive inclusion criteria as well as on education of physicians and elderly patients on the advantages of trial participatio

Clinical and pathological response after neoadjuvant chemotherapy with or without zoledronic acid for patients with HER2-negative large resectable or stage II or III breast cancer

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Optimal duration of extended letrozole treatment after 5 years of adjuvant endocrine therapy; results of the randomized phase III IDEAL trial (BOOG 2006-05)

Surgical oncolog