https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53327 Wed 28 Feb 2024 16:29:04 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53837 Wed 28 Feb 2024 15:17:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50456 2 cm (4.5%) or grade 3 tumors (5.5%). These sustained reductions of the risk of recurrence with adjuvant exemestane + OFS, compared with tamoxifen + OFS, provide guidance for selecting patients for whom exemestane should be preferred over tamoxifen in the setting of OFS.]]> Wed 28 Feb 2024 15:10:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50457 Wed 28 Feb 2024 15:09:41 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45235 Wed 26 Oct 2022 19:59:05 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45244 Wed 26 Oct 2022 15:43:06 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44973 n = 257), obtained by using the same DNA chip, were used for validation. Fuzzy clustering was followed by functional annotation of the clusters. Immunohistochemistry was used to confirm transcriptomics results: CD138 and CD20 were used to test for plasma cell and B lymphocyte infiltrations, respectively; MECA79 and CD31 for tertiary lymphoid structures; and UCHL1/PGP9.5 and S100 for neurogenesis. Results: We identified three molecular clusters within TNBC: one molecular apocrine (C1) and two basal-likeenriched (C2 and C3). C2 presented pro-tumorigenic immune response (immune suppressive), high neurogenesis (nerve infiltration), and high biological aggressiveness. In contrast, C3 exhibited adaptive immune response associated with complete B cell differentiation that occurs in tertiary lymphoid structures, and immune checkpoint upregulation. External cohort subtyping by means of the same approach proved the robustness of these results. Furthermore, plasma cell and B lymphocyte infiltrates, tertiary lymphoid structures, and neurogenesis were validated at the protein levels by means of histological evaluation and immunohistochemistry. Conclusion: Our work showed that TNBC can be subcategorized in three different subtypes characterized by marked biological features, some of which could be targeted by specific therapies.]]> Wed 26 Oct 2022 15:01:31 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44999 Wed 26 Oct 2022 10:12:59 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55723 Wed 19 Jun 2024 09:40:41 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38724 Wed 19 Jan 2022 10:18:02 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36903 Wed 17 Nov 2021 16:30:02 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38849 P = 0.65). Conclusion: BCS seromas contoured by RTs compared well with those contoured by an RO. This research has provided further evidence to support RTs in assuming additional contouring responsibilities in radiation therapy planning for patients with early-stage breast cancer.]]> Wed 16 Feb 2022 12:07:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47165 2) was categorized as follows: 18.5 to < 25, lean; 25 to < 30, overweight; and ≥ 30, obese. Disease-free survival (DFS) was the primary endpoint, and overall survival (OS) was the secondary endpoint. A second-order interaction was assessed among treatment, BMI, and estrogen receptor (ER) status. Results: There was no difference in DFS or OS according to BMI in the non-docetaxel group, while reduced DFS and OS were observed with increasing BMI category in the docetaxel group. Adjusted hazard ratios for DFS and OS were, respectively, 1.12 (95% CI, 0.98 to 1.50; P = .21) and 1.27 (95% CI, 1.01 to 1.60; P = .04) for overweight versus lean groups and were 1.32 (95% CI, 1.08 to 1.62; P = .007) and 1.63 (95% CI, 1.27 to 2.09; P < .001), respectively, for obese versus lean groups. Similar results were obtained when considering ER-negative and ER-positive tumors separately and when considering only patients who received a relative dose intensity ≥ 85% for docetaxel. A joint modifying role of BMI and ER status on treatment effect was evident for DFS (adjusted P = .06) and OS (adjusted P = .04). Conclusion: This retrospective analysis of a large adjuvant trial highlights a differential response to docetaxel according to BMI, which calls for a body composition–based re-evaluation of the risk-benefit ratio of the use of taxanes in breast cancer. These results now must be confirmed in additional series.]]> Wed 14 Dec 2022 15:49:14 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54801 Wed 13 Mar 2024 11:41:50 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52417 Wed 11 Oct 2023 11:58:33 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41071 20% in TC and TCH inroutine clinical practice should guide primary GCSF use in accordance with international guidelines.]]> Wed 10 Jan 2024 11:15:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36827 Wed 08 Jul 2020 15:05:48 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53186 Wed 07 Feb 2024 15:28:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37129 via the integration of genomics and proteomics data. In the Breast Cancer Association Consortium (BCAC), with 122,977 cases and 105,974 controls of European descendants, we evaluated the associations of the genetically predicted concentrations of >1,400 circulating proteins with breast cancer risk. We used data from a large-scale protein quantitative trait loci (pQTL) analysis as our study instrument. Summary statistics for these pQTL variants related to breast cancer risk were obtained from the BCAC and used to estimate odds ratios (OR) for each protein using the inverse-variance weighted method. We identified 56 proteins significantly associated with breast cancer risk by instrumental analysis (false discovery rate <0.05). Of these, the concentrations of 32 were influenced by variants close to a breast cancer susceptibility locus (ABO, 9q34.2). Many of these proteins, such as insulin receptor, insulin-like growth factor receptor 1 and other membrane receptors (OR: 0.82-1.18, p values: 6.96 × 10^-43.28 × 10^-8), are linked to insulin resistance and estrogen receptor signaling pathways. Proteins identified at other loci include those involved in biological processes such as alcohol and lipid metabolism, proteolysis, apoptosis, immune regulation and cell motility and proliferation. Consistent associations were observed for 22 proteins in the UK Biobank data (p < 0.05). The study identifies potential novel biomarkers for breast cancer, but further investigation is needed to replicate our findings.]]> Wed 07 Apr 2021 20:21:39 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50015 Wed 06 Mar 2024 14:17:28 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54307 Wed 06 Mar 2024 14:07:32 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44015 4.5 minutes before bedtime had a significantly increased 5.27-fold risk of breast cancer compared to those who used a smartphone for ≤ 4.5 minutes before bedtime. Additionally, a closer distance between the smartphone and the breasts when using the smartphone exhibited a significantly increased 1.59-fold risk. Participants who carried their smartphone near their chest or waist-abdomen area had significantly increased 5.03-fold and 4.06-fold risks of breast cancer, respectively, compared to those who carried the smartphone below the waist. Moreover, there was a synergistic effect of smartphone addiction and smartphone use of > 4.5 minutes before bedtime which increased the breast cancer risk. Conclusion: Excessive smartphone use significantly increased the risk of breast cancer, particularly for participants with smartphone addiction, a close distance between the breasts and smartphone, and the habit of smartphone use before bedtime.]]> Wed 05 Oct 2022 15:28:25 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51107 20% in TC and TCH in routine clinical practice should guide primary GCSF use in accordance with international guidelines.]]> Wed 04 Oct 2023 11:54:27 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49034 Wed 03 May 2023 13:48:14 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49022 Wed 03 May 2023 12:38:07 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45673 Wed 02 Nov 2022 16:06:12 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47795 Tue 31 Jan 2023 15:32:49 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46746 Tue 29 Nov 2022 15:18:50 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43522 10) (OR = 2.83, 95% CI: 0.94–8.11, p = 0.047), being overweight (≥25 kg/m2) (OR = 2.57, 95% CI: 1.04 – 6.38, p = 0.036), received fewer post-surgery rehabilitation treatment (OR = 2.37, 95% CI: 1.05–5.39, p = 0.036) and hypertension (OR = 2.38, 95% CI: 1.01–5.62, p = 0.043 ) were associated with an increased risk of BCRL. Meanwhile, multivariate analysis showed that multiple surgeries remained significant and elevated the likelihood of BCRL (OR = 5.83, 95% CI: 1.14–29.78, p = 0.034). Arm swelling was more prominent in the forearm area demonstrated by the highest difference of arm circumference measurement when compared to the upper arm ( 2.07 ± 2.48 vs. 1.34 ± 1.91 cm, p < 0.001). The total of skinfold thickness of the affected forearm was also significantly higher than the unaffected arms (p < 0.05) as evidenced by the ultrasound examination. The continuous search for risk factors in specific populations may facilitate the development of a standardized method to reduce the occurrence of BCRL and provide better management for breast cancer patients.]]> Tue 27 Jun 2023 09:47:57 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54539 Tue 27 Feb 2024 20:41:38 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54475 Tue 27 Feb 2024 14:56:31 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54474 Tue 27 Feb 2024 14:35:23 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37400 n = 214,536) to national cancer and death registries, and estimated the strength of the associations between behaviours causally related to cancer incidence and death using adjusted proportional hazards models. We estimated exposure prevalence from representative health surveys. We combined these estimates to calculate Population Attributable Fractions (PAFs) with 95% confidence intervals (CIs), and compared PAFs for population subgroups. During the first 10 years follow‐up, there were 640 incident breast cancers for premenopausal women, 2,632 for postmenopausal women, and 8,761 deaths from any cause. Of future breast cancers for premenopausal women, any regular alcohol consumption explains 12.6% (CI = 4.3–20.2%), current use of oral contraceptives for ≥5 years 7.1% (CI = 0.3–13.5%), and these factors combined 18.8% (CI = 9.1–27.4%). Of future breast cancers for postmenopausal women, overweight or obesity (BMI ≥25 kg/m2) explains 12.8% (CI = 7.8–17.5%), current use of menopausal hormone therapy (MHT) 6.9% (CI = 4.8–8.9%), any regular alcohol consumption 6.6% (CI = 1.5–11.4%), and these factors combined 24.2% (CI = 17.6–30.3%). The MHT‐related postmenopausal breast cancer burden varied by body fatness, alcohol consumption and socio‐economic status, the body fatness‐related postmenopausal breast cancer burden by alcohol consumption and educational attainment, and the alcohol‐related postmenopausal breast cancer burden by breast feeding history. Our results provide evidence to support targeted and population‐level cancer control activities.]]> Tue 25 Oct 2022 09:19:19 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32265 Tue 25 Jul 2023 12:50:05 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47747 Tue 21 Mar 2023 19:00:49 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52761 Tue 14 Nov 2023 15:30:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48335 Tue 14 Mar 2023 17:16:01 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36613 Tue 14 Mar 2023 16:05:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48284 0.5 (OR 3.95, 95% CI 1.40–12.01, p = 0.006). Sequencing of 21 tumours from 20 heterozygous and 1 homozygous carriers of nine candidate MS variants identified four cases with biallelic inactivation through loss of the wild-type allele, while six lost the variant allele and ten that remained heterozygous. Biallelic loss of the wild-type alleles corresponded strongly with ER- and TN breast tumours, high homologous recombination deficiency scores and mutational signature 3. Using this approach, the p.Gly264Ser variant, which was previously suspected to be pathogenic based on small case–control analyses and loss of activity in in vitro functional assays, was shown to be benign with similar prevalence in cases and controls and seven out of eight tumours showing no biallelic inactivation or characteristic mutational signature. Conversely, evaluation of case–control findings and tumour sequencing data identified p.Ile144Thr, p.Arg212His, p.Gln143Arg and p.Gly114Arg as variants warranting further investigation.]]> Tue 14 Mar 2023 11:29:22 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47983 60 years (12·7, 11·6 months). Interpretation: Population-level improvements in OS for dnMBC have not been consistently observed in rMBC cohorts nor older women. These findings have implications for counselling patients about prognosis, planning cancer services and trial stratification. Funding: SL was funded in part by a National Health and Medical Research Council (NHMRC) Project Grant ID: 1125433. NH was funded by the NBCF Chair in Breast Cancer Prevention grant (EC-21–001) and a NHMRC Investigator (Leader) grant (194410). BD and SAP were funded in part by the NHMRC Centre of Research Excellence in Medicines Intelligence (1196900).]]> Tue 14 Feb 2023 14:22:54 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43134 Tue 13 Sep 2022 15:14:31 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48826 Tue 09 May 2023 10:38:07 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42894 Tue 06 Sep 2022 14:32:21 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49858 Tue 06 Jun 2023 20:32:36 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33639 Tue 03 Sep 2019 17:57:36 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50644 Tue 01 Aug 2023 10:11:43 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34779 Thu 31 Oct 2019 16:13:17 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45361 BRCA1 and BRCA2, including the identification of new predisposing genes. A total of 11,511 non-BRCA familial BC cases and population-matched cancer-free female controls in the BEACCON study were investigated in two sequencing phases: 1303 candidate genes in up to 3892 cases and controls, followed by validation of 145 shortlisted genes in an additional 7619 subjects. The coding regions and exon–intron boundaries of all candidate genes and 14 previously proposed BC genes were sequenced using custom designed sequencing panels. Pedigree and pathology data were analysed to identify genotype-specific associations. The contribution of ATM, PALB2 and CHEK2 to BC predisposition was confirmed, but not RAD50 and NBN. An overall excess of loss-of-function (LoF) (OR 1.27, p = 9.05 × 10⁻⁹) and missense (OR 1.27, p = 3.96 × 10⁻⁷³) variants was observed in the cases for the 145 candidate genes. Leading candidates harbored LoF variants with observed ORs of 2–4 and individually accounted for no more than 0.79% of the cases. New genes proposed by this study include NTHL1, WRN, PARP2, CTH and CDK9. The new candidate BC predisposition genes identified in BEACCON indicate that much of the remaining genetic causes of high-risk BC families are due to genes in which pathogenic variants are both very rare and convey only low to moderate risk.]]> Thu 27 Oct 2022 15:32:46 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45124 Thu 27 Oct 2022 10:53:06 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42105 PIK3CA-mutant cancer cells. The LORELEI trial tested whether taselisib in combination with letrozole would result in an increased proportion of objective responses and pathological complete responses. Methods: In this multicentre, randomised, double-blind, parallel-cohort, placebo-controlled phase 2, study, we enrolled postmenopausal women (aged ≥18 years) with histologically confirmed, oestrogen receptor (ER)-positive, HER2-negative, stage I–III, operable breast cancer, from 85 hospitals in 22 countries worldwide. To be eligible, patients had have an Eastern Cooperative Oncology Group (ECOG) performance status 0–1, adequate organ function, and had to have evaluable tumour tissue for PIK3CA genotyping. Patients were randomly assigned (1:1) by means of a permuted block algorithm (block size of four) via an interactive voice or web-based response system, to receive letrozole (2·5 mg/day orally, continuously) with either 4 mg of oral taselisib or placebo (on a 5 days-on, 2 days-off schedule) for 16 weeks, followed by surgery. Randomisation was stratified by tumour size and nodal status. Site staff, patients, and the sponsor were masked to treatment assignment. Coprimary endpoints were the proportion of patients who achieved an objective response by centrally assessed breast MRI and a locally assessed pathological complete response in the breast and axilla (ypT0/Tis, ypN0) at surgery in all randomly assigned patients and in patients with PIK3CA-mutant tumours. Analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02273973, and is closed to accrual. Findings: Between Nov 12, 2014, and Aug 12, 2016, 334 participants were enrolled and randomly assigned to receive letrozole and placebo (n=168) or letrozole and taselisib (n=166). Median follow-up was 4·9 months (IQR 4·7–5·1). The study met one of its primary endpoints: the addition of taselisib to letrozole was associated with a higher proportion of patients achieving an objective response in all randomly assigned patients (66 [39%] of 168 patients in the placebo group vs 83 [50%] of 166 in the taselisib group; odds ratio [OR] 1·55, 95% CI 1·00–2·38; p=0·049) and in the PIK3CA-mutant subset (30 [38%] of 79 vs 41 [56%] of 73; OR 2·03, 95% CI 1·06–3·88; p=0·033). No significant differences were observed in pathological complete response between the two groups, either in the overall population (three [2%] of 166 in the taselisib group vs one [1%] of 168 in the placebo group; OR 3·07 [95% CI 0·32–29·85], p=0·37) or in the PIK3CA-mutant cohort (one patient [1%) vs none [0%]; OR not estimable, p=0·48). The most common grade 3–4 adverse events in the taselisib group were gastrointestinal (13 [8%] of 167 patients), infections (eight [5%]), and skin–subcutaneous tissue disorders (eight [5%]). In the placebo group, four (2%) of 167 patients had grade 3 or worse vascular disorders, two (1%) had gastrointestinal disorders, and two (1%) patients had grade 3 or worse infections and infestations. There was no grade 4 hyperglycaemia and grade 3 cases were asymptomatic. Serious adverse events were more common in the taselisib group (eight [5%] patients with infections and seven [4%] with gastrointestinal effects) than in the placebo group (one [1%] patient each with grade 3 postoperative wound and haematoma infection, grade 4 hypertensive encephalopathy, grade 3 acute cardiac failure, and grade 3 breast pain). One death occurred in the taselisib group, which was not considered to be treatment-related. Interpretation: The increase in the proportion of patients who achieved an objective response from the addition of taselisib to endocrine therapy in a neoadjuvant setting is consistent with the clinical benefit observed in hormone receptor-positive, HER2-negative, metastatic breast cancer.]]> Thu 25 Aug 2022 10:26:11 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37693 Thu 24 Mar 2022 11:33:04 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51863 Thu 21 Sep 2023 10:16:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48421 Thu 16 Mar 2023 14:10:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43269 Thu 15 Sep 2022 12:11:44 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35186 Thu 14 Apr 2022 11:00:10 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:40147 in situ (DCIS) of the breast. Materials and methods: Baseline and 3-year cosmesis were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Cosmetic Rating System and digital images in a randomised trial of non-low risk DCIS treated with postoperative WBI +/− TBB. Baseline cosmesis was assessed for four geographic clusters of treating centres. Cosmetic failure was a global score of fair or poor. Cosmetic deterioration was a score change from excellent or good at baseline to fair or poor at three years. Odds ratios for cosmetic deterioration by WBI dose-fractionation and TBB use were calculated for both scoring systems. Results: 1608 women were enrolled from 11 countries between 2007 and 2014. 85–90% had excellent or good baseline cosmesis independent of geography or assessment method. TBB (16 Gy in 8 fractions) was associated with a >2-fold risk of cosmetic deterioration (p < 0.001). Hypofractionated WBI (42.5 Gy in 16 fractions) achieved statistically similar 3-year cosmesis compared to conventional WBI (50 Gy in 25 fractions) (p ≥ 0.18). The adverse impact of a TBB was not significantly associated with WBI fractionation (interaction p ≥ 0.30). Conclusions: Cosmetic failure from BCS was similar across international jurisdictions. A TBB of 16 Gy increased the rate of cosmetic deterioration. Hypofractionated WBI achieved similar 3-year cosmesis as conventional WBI in women treated with BCS for DCIS.]]> Thu 11 Aug 2022 14:56:25 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34901 Thu 09 Dec 2021 11:04:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33626 Thu 03 Feb 2022 12:22:13 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41461 TP53 vary depending on the subtype, such that ER-negative tumours have a high rate, and in ER-positive tumours they are less common. Previous studies have implicated the intronic polymorphism in TP53 (rs17878362; or PIN3) with an increased risk of developing breast cancer, although little has been discerned on its prevalence in different subtypes. In this study, we investigated the prevalence of the PIN3 genotype in the blood of cohorts with ER-positive and the ER-negative subtype TNBC, and assessed its association with outcome. Methods: We genotyped 656 TNBC and 648 ER-positive breast cancer patients, along with 436 controls, and compared the prevalence of polymorphism rs17878362 in these cohorts. Results: We found there to be no differences in the prevalence of the PIN3 genotype between the ER-positive and TNBC cohorts. Furthermore, no statistically significant difference was observed in the outcome of patients in either cohort with respect to their PIN3 genotype. Conclusions: Taken together, our results do not support an association of the PIN3 genotype with increased breast cancer risk, either in ER-positive or ER-negative patients.]]> Thu 01 Sep 2022 11:19:24 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32260 Thu 01 Jun 2023 10:46:47 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55805 Sat 22 Jun 2024 12:53:26 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48186 Sat 11 Mar 2023 12:23:00 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46604 400 g and/or >20-weeks' gestation, to women diagnosed with breast cancer in the first or second trimesters. Eighteen babies were exposed in utero to chemotherapy. Chemotherapy commenced at a median of 20 weeks gestation, for a mean duration of 10 weeks. Twelve exposed infants were born preterm with 11 by induced labour or pre-labour caesarean section. There were no perinatal deaths or congenital malformations. Our findings show that breast cancer diagnosed during mid-pregnancy is often treated with chemotherapy. Other than induced preterm births, there were no serious adverse perinatal outcomes.]]> Mon 28 Nov 2022 08:30:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36157 Mon 26 Oct 2020 12:11:15 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36694 Mon 26 Jul 2021 11:07:06 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32038 Mon 23 Sep 2019 13:42:04 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32258 Mon 23 Sep 2019 13:24:38 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33127 Mon 23 Sep 2019 12:39:30 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32034 Mon 23 Sep 2019 12:04:09 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:31979 Mon 23 Sep 2019 11:59:37 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32394 Mon 23 Sep 2019 11:45:21 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47564 Mon 23 Jan 2023 13:18:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48509 2 with filgrastim support every 3 weeks for 3 cycles (HDEC) or standard dose epirubicin 75 mg/m² and cyclophosphamide 750 mg/m² every 3 weeks for 6 cycles (SDEC). Primary outcomes were time to progression, overall survival and quality of life. Results: In 118 patients allocated HDEC 90% of the planned dose was delivered, compared to 96% in the 117 participants allocated SDEC. There were no significant differences in the time to disease progression (5.7 vs. 5.8 months, P = 0.19) or overall survival (14.5 vs. 16.5 months, P = 0.29) between HDEC and SDEC, respectively. Patients on HDEC reported worse quality of life during therapy, but scores improved after completion to approximate those reported by patients allocated SDEC. Objective tumour response was recorded in 33 (28%) on HDEC and 42 patients (36%) on SDEC. HDEC produced more haematologic toxicity. Conclusion: For women with metastatic breast cancer, disease progression, survival or quality of life were no better with high-dose intensity compared to standard dose EC chemotherapy. Australian Clinical Trials Registry registration number ACTRN12605000478617.]]> Mon 20 Mar 2023 16:24:14 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43439 Mon 19 Sep 2022 13:06:45 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44579 Mon 17 Oct 2022 14:17:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50311 Mon 17 Jul 2023 15:51:54 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50108 Mon 17 Jul 2023 11:54:03 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41881 Mon 15 Aug 2022 14:09:04 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50933 Mon 14 Aug 2023 12:30:10 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44187 Mon 10 Oct 2022 10:55:28 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44184 Mon 10 Oct 2022 10:48:32 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44148 Mon 10 Oct 2022 09:17:25 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41065 50 values of 0.098, 0.97, 0.13 and 0.21 μM, respectively). Indeed, 6 is 55 times more potent in MDA-MB-468 cells than normal MCF10A breast cells (GI₅₀ of 0.098 vs 5.4 μM) and more than 130 times more potent than in cell lines derived from pancreas, brain and prostate (GI₅₀ of 0.098 vs 10–13 μM). Molecular docking poses of 5 and 6 together with analogue synthesis and phenotypic screening show the importance of the naphthalene moiety, and an ortho-disposed substituent on the N-phenyl moiety for biological activity.]]> Mon 08 Aug 2022 15:04:26 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:40209 Mon 08 Aug 2022 13:40:19 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39586 in silico using the Kaplan-Meier Plotter (n=3,935), the TCGA invasive breast carcinoma (n=960) and GOBO (n=821) data sets. Functional effects of BAALC expression on breast cancer proliferation, migration and invasion were determined in vitro. We demonstrate herein that BAALC expression is progressively increased in primary and breast cancer metastases when compared to normal breast tissue. Increased BAALC mRNA is associated with a reduction in DMFS and disease-free survival, but not OS, in breast cancer patients, even when corrected for tumor grade. We show that overexpression of BAALC in MCF-7 breast cancer cells increases the proliferation, anchorage-independent growth, invasion, and migration capacity of these cells. Conversely, siRNA knockdown of BAALC expression in Hs578T breast cancer cells decreases proliferation, invasion and migration. We identify that this BAALC associated migration and invasion is mediated by focal adhesion kinase (FAK)-dependent signaling and is accompanied by an increase in matrix metalloproteinase (MMP)-9 but not MMP-2 activity in vitro. Our data demonstrate a novel function for BAALC in the control of breast cancer metastasis, offering a potential target for the generation of anti-cancer drugs to prevent breast cancer metastasis.]]> Mon 08 Aug 2022 11:48:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45818 Mon 07 Nov 2022 12:18:03 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42808 Mon 05 Sep 2022 09:57:19 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34339 Mon 03 Feb 2020 11:52:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45355 loss-of-function (LoF) variants in the base excision repair (BER) gene NTHL1 cause a high-risk hereditary multi-tumor syndrome that includes breast cancer, but the contribution of heterozygous variants to hereditary breast cancer is unknown. An analysis of 4985 women with breast cancer, enriched for familial features, and 4786 cancer-free women revealed significant enrichment for NTHL1 LoF variants. Immunohistochemistry confirmed reduced NTHL1 expression in tumors from heterozygous carriers but the NTHL1 bi-allelic loss characteristic mutational signature (SBS 30) was not present. The analysis was extended to 27,421 breast cancer cases and 19,759 controls from 10 international studies revealing 138 cases and 93 controls with a heterozygous LoF variant (OR 1.06, 95% CI: 0.82-1.39) and 316 cases and 179 controls with a missense variant (OR 1.31, 95% CI: 1.09-1.57). Missense variants selected for deleterious features by a number of in silico bioinformatic prediction tools or located within the endonuclease III functional domain showed a stronger association with breast cancer. Somatic sequencing of breast cancers from carriers indicated that the risk associated with NTHL1 appears to operate through haploinsufficiency, consistent with other described low-penetrance breast cancer genes. Data from this very large international multicenter study suggests that heterozygous pathogenic germline coding variants in NTHL1 may be associated with low- to moderate- increased risk of breast cancer.]]> Mon 01 May 2023 14:42:02 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41279 Mon 01 Aug 2022 10:24:24 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51940 Fri 22 Sep 2023 16:08:08 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:40171 F_1,45=10.09, P=.003, B=115.34, 95% CI 42.22-188.47) and education level (F_1,45=7.22, P=.01, B=1949.63, 95% CI 487.76-3411.50) were positively associated with the usage duration of the entire BCS program. Family monthly income was positively associated with the usage duration of the Learning Forum (F_1,45=11.85, P=.001, B=1488.55, 95% CI 617.58-2359.51) and the login frequency of the entire BCS program (F_1,45=4.47, P=.04, B=113.68, 95% CI 5.33-222.03). Employment was negatively associated with the usage duration of the Ask-the-expert Forum (F_1,45=4.50, P=.04, B=–971.87, 95% CI –1894.66 to –49.07) and the Your Story Forum (F_1,45=5.36, P=.03, B=–640.71, 95% CI –1198.30 to –83.11) and positively associated with the login frequency of the entire BCS program (F_1,45=10.86, P=.002, B=192.88, 95% CI 75.01-310.74). No statistical differences were found between BCS usage data and cancer stage, BMI, comorbidity, types of surgery, or cycles of chemotherapy. Conclusions: Overall, this study found considerable variability in the usage of app-based interventions. When health care professionals incorporate app-based interventions into their routine care for women with breast cancer, the learning and discussion functions of apps should be strengthened to promote engagement. Additionally, characteristics of women with breast cancer, such as age, level of education, income, and employment status, should be taken in consideration to develop tailored apps that address their particular needs and therefore improve their engagement with the app. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12616000639426; http://www.ANZCTR.org.au/ACTRN12616000639426.aspx]]> Fri 22 Jul 2022 13:55:22 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49499 Fri 19 May 2023 12:01:55 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46399 313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS₃₁₃ odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS₃₁₃ and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS₃₁₃ and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.]]> Fri 18 Nov 2022 14:15:23 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55358 Fri 17 May 2024 16:04:55 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55676 Fri 14 Jun 2024 13:50:00 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48913 Fri 14 Apr 2023 18:21:40 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30002 Fri 10 Mar 2023 19:02:11 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36560 Fri 05 Jun 2020 20:10:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38322 50 value of 100 nM is greater than 500-fold more sensitive to NAP-6 compared with other tumour derived cell models. Within 1 h exposure of these cells to NAP-6, CYP1A1 expression increases 25-fold, rising to 250-fold by 24 h. A smaller concurrent increase in CYP1A2 and CYP1B1 is also observed. Within 24 h these cells present with DNA damage as evident by enhanced H2AXγ expression, cell cycle checkpoint activation via increased CHK2 expression, S-phase cell cycle arrest and cell death. Specific small molecule inhibitors of the AHR and CYP1 family ameliorate these events. A positive luciferase reporter assay for NAP-6 induced XRE binding further confirms the role of the AHR in this phenomenon. Non-sensitive cell lines fail to show these biological effects. For the first time we identify 2-(2-aminophenyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione as a new AHR ligand that selectively targets breast cancer.]]> Fri 03 Sep 2021 14:57:31 AEST ]]>