METHODS: One hundred and one formalin-fixed and paraffin-processed triple-negative breast cancer cases from the University of Malaya Medical Centre were tested immunohistochemically for cytokeratins 5/6 and 14, PTEN, and IGFBP2. The resulting slides were scored for proportion and intensity of staining.
RESULTS: Loss of tumor nuclear and cytoplasmic staining for PTEN occurred in 48.3% of cases and was significantly associated with younger age at diagnosis (47 years compared with 57 years in those without PTEN loss; P = .005). Independent predictors of PTEN loss were late stage at presentation (P = .026), cytokeratin 5/6 positivity (P = .028), and IGFBP2 expression (P = .042). High levels of IGFBP2 expression were seen in 32% of cases; an independent predictor of high levels was cytokeratin 14 negativity (P = .005). PTEN loss and high levels of IGFBP2 expression were associated with poorer survival, but neither of these trends was significant.
CONCLUSIONS: PTEN loss is a frequent event in triple-negative breast cancers and is significantly associated with younger age at onset of breast cancer, late stage, and IGFBP2 expression.
METHODS: We developed a decision analytic model to estimate the lifetime costs and quality-adjusted life-years (QALYs) accrued through BRCA mutation testing or routine clinical surveillance (RCS) for a hypothetical cohort of 1000 early-stage breast cancer patients aged 40 years. In the model, patients would decide whether to accept testing and to undertake risk-reducing mastectomy, oophorectomy, tamoxifen, combinations or neither. We calculated the incremental cost-effectiveness ratio (ICER) from the health system perspective. A series of sensitivity analyses were performed.
RESULTS: In the base case, testing generated 11.2 QALYs over the lifetime and cost US$4815 per patient whereas RCS generated 11.1 QALYs and cost US$4574 per patient. The ICER of US$2725/QALY was below the cost-effective thresholds. The ICER was sensitive to the discounting of cost, cost of BRCA mutation testing and utility of being risk-free, but the ICERs remained below the thresholds. Probabilistic sensitivity analysis showed that at a threshold of US$9500/QALY, 99.9% of simulations favoured BRCA mutation testing over RCS.
CONCLUSIONS: Offering BRCA mutation testing to early-stage breast cancer patients identified using a locally-validated risk-assessment tool may be cost effective compared to RCS in Malaysia.
MATERIALS AND METHODS: Results that are possible to be compared in more than two articles were presented as forest plots. A 95% confidence interval was calculated for each effect size, and we calculated the I 2 statistic, which presents the percentage of total variation attributable to the heterogeneity among studies. The random effects model was used to calculate the effect size.
RESULTS: Seven articles were included to the final analysis. Case groups were composed of HTO without concurrent procedures and control groups were composed of HTO with concurrent procedures such as marrow stimulation procedure, mesenchymal stem cell transplantation, and injection. The case group showed a higher hospital for special surgery score and mean difference was 4.10 [I 2 80.8%, 95% confidence interval (CI) - 9.02 to 4.82]. Mean difference of the mechanical femorotibial angle in five studies was 0.08° (I 2 0%, 95% CI - 0.26 to 0.43). However, improved arthroscopic, histologic, and MRI results were reported in the control group.
CONCLUSION: Our analysis support that concurrent procedures during HTO for medial compartment OA have little beneficial effect regarding clinical and radiological outcomes. However, they might have some beneficial effects in terms of arthroscopic, histologic, and MRI findings even though the quality of healed cartilage is not good as that of original cartilage. Therefore, until now, concurrent procedures for medial compartment OA have been considered optional. Nevertheless, no conclusions can be drawn for younger patients with focal cartilage defects and concomitant varus deformity. This question needs to be addressed separately.
METHODS: One hundred fifty-three orthopaedic residents were recruited and randomly assigned to either the LAC or CAC. They were allocated 2 practice sessions, with 20 minutes each, to practice 4 given arthroscopic tasks: task 1, transferring objects; task 2, stacking objects; task 3, probing numbers; and task 4, stretching rubber bands. The time taken for participants to complete the given tasks was recorded in 3 separate tests; before practice, immediately after practice, and after a period of 3 months. A comparison of the time taken between both groups to complete the given tasks in each test was measured as the primary outcome.
RESULTS: Significant improvements in time completion were seen in the post-practice test for both groups in all given arthroscopic tasks, each with P < .001. However, there was no significant difference between the groups for task 1 (P = .743), task 2 (P = .940), task 3 (P = .932), task 4 (P = .929), and total (P = .944). The outcomes of the tests (before practice, after practice, and at 3 months) according to repeated measures analysis of variance did not differ significantly between the groups in task 1 (P = .475), task 2 (P = .558), task 3 (P = .850), task 4 (P = .965), and total (P = .865).
CONCLUSIONS: The LAC is equally as effective as the CAC in basic arthroscopic skills training with the advantage of being cost-effective.
CLINICAL RELEVANCE: In view of the scarcity in commercial arthroscopic devices for trainees, this low-cost device, which trainees can personally own and use, may provide a less expensive and easily available way for trainees to improve their arthroscopic skills. This might also cultivate more interest in arthroscopic surgery among junior surgeons.
METHODS: Search was performed using a MEDLINE, EMBASE, and Cochrane database, and each of the selected studies was evaluated for methodological quality using a risk of bias (ROB) covering 7 criteria. Clinical and radiological outcomes with more than 5 years of follow-up were evaluated after surgical treatment of DLM. They were analyzed according to the age, follow-up period, kind of surgery, DLM type, and alignment.
RESULTS: Eleven articles (422 DLM cases) were included in the final analysis. Among 7 criteria, 3 criteria showed little ROB in all studies. However, 4 criteria showed some ROB ("Yes" in 63.6% to 81.8%). The minimal follow-up period was 5.5 years (weighted mean follow-up: 9.1 years). Surgical procedures were performed with open or arthroscopic partial central meniscectomy, subtotal meniscectomy, total meniscectomy, or partial meniscectomy with repair. The majority of the studies showed good clinical results. Mild joint space narrowing was reported in the lateral compartment, but none of the knees demonstrated moderate or advanced degenerative changes. Increased age at surgery, longer follow-up period, and subtotal or total meniscectomy could be related to degenerative change. The majority of the complications was osteochondritis dissecans at the lateral femoral condyle (13 cases) and reoperation was performed by osteochondritis dissecans (4 cases), recurrent swelling (2 cases), residual symptom (1 case), stiffness (1 case), and popliteal stenosis (1 case).
CONCLUSIONS: Good clinical results were obtained with surgical treatment of symptomatic DLM. The progression of degenerative change was minimal and none of the knees demonstrated moderate or advanced degenerative changes. Increased age at surgery, longer follow-up period, and subtotal or total meniscectomy were possible risk factors for degenerative changes.
LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies.
METHODS: The MassARRAY genotyping was conducted in 1,394 Chinese, 406 Malay and 310 Indian breast cancer cases and 1,071 Chinese, 167 Malay and 255 Indian healthy controls. The association of individual variant with breast cancer risk was analyzed using logistic regression model adjusted for ethnicity, age and family history.
RESULTS: Our study confirmed BRCA2 p.Ile3412Val is presented in >2% of unaffected women and is likely benign, and BRCA2 p.Ala1996Thr which is predicted to be likely pathogenic by in-silico models is presented in 2% of healthy Indian women suggesting that it may not be associated with breast cancer risk. Single-variant analysis suggests that BRCA1 p.Arg762Ser may be associated with breast cancer risk (OR = 7.4; 95% CI, 0.9-62.3; p = 0.06).
CONCLUSIONS: Our study shows that BRCA2 p.Ile3412Val and p.Ala1996Thr are likely benign and highlights the need for population-specific studies to determine the likely functional significance of population-specific variants. Our study also suggests that BRCA1 p.Arg762Ser may be associated with increased risk of breast cancer but other methods or larger studies are required to determine a more precise estimate of breast cancer risk.
METHODS: From October 2011 to June 2015, 1,778 asymptomatic women, aged 40-74 years, underwent subsidised mammographic screening. All patients had a clinical breast examination before mammographic screening, and women with mammographic abnormalities were referred to a surgeon. The cancer detection rate and variables associated with a recommendation for adjunct ultrasonography were determined.
RESULTS: The mean age for screening was 50.8 years and seven cancers (0.39%) were detected. The detection rate was 0.64% in women aged 50 years and above, and 0.12% in women below 50 years old. Adjunct ultrasonography was recommended in 30.7% of women, and was significantly associated with age, menopausal status, mammographic density and radiologist's experience. The main reasons cited for recommendation of an adjunct ultrasound was dense breasts and mammographic abnormalities.
DISCUSSION: The cancer detection rate is similar to population-based screening mammography programmes in high-income Asian countries. Unlike population-based screening programmes in Caucasian populations where the adjunct ultrasonography rate is 2-4%, we report that 3 out of 10 women attending screening mammography were recommended for adjunct ultrasonography. This could be because Asian women attending screening are likely premenopausal and hence have denser breasts. Radiologists who reported more than 360 mammograms were more confident in reporting a mammogram as normal without adjunct ultrasonography compared to those who reported less than 180 mammograms.
CONCLUSION: Our subsidised opportunistic mammographic screening programme is able to provide equivalent cancer detection rates but the high recall for adjunct ultrasonography would make screening less cost-effective.
METHODS AND ANALYSIS: The measurement challenge has been established as an international resource to offer a common set of anonymised mammogram images for measurement and analysis. To date, full field digital mammogram images and core data from 1650 cases and 1929 controls from five countries have been collated. The measurement challenge is an ongoing collaboration and we are continuing to expand the resource to include additional image sets across different populations (from contributors) and to compare additional measurement methods (by challengers). The intended use of the measurement challenge resource is for refinement and validation of new and existing mammographic measurement methods. The measurement challenge resource provides a standardised dataset of mammographic images and core data that enables investigators to directly compare methods of measuring mammographic density or other mammographic features in case/control sets of both raw and processed images, for the purposes of the comparing their predictions of breast cancer risk.
ETHICS AND DISSEMINATION: Challengers and contributors are required to enter a Research Collaboration Agreement with the University of Melbourne prior to participation in the measurement challenge. The Challenge database of collated data and images are stored in a secure data repository at the University of Melbourne. Ethics approval for the measurement challenge is held at University of Melbourne (HREC ID 0931343.3).
METHODS: PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV.
RESULTS: 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml-l, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers.
CONCLUSIONS: PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.
METHODS: We used pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer Association Consortium (BCAC). In a case-only analysis, we used logistic regression to assess associations between reproductive factors and BC subtype compared to luminal A tumors as a reference. The interaction between age and parity in BC subtype risk was also tested, across all ages and, because age was modeled non-linearly, specifically at ages 35, 55 and 75 years.
RESULTS: Parous women were more likely to be diagnosed with triple negative BC (TNBC) than with luminal A BC, irrespective of age (OR for parity = 1.38, 95% CI 1.16-1.65, p = 0.0004; p for interaction with age = 0.076). Parous women were also more likely to be diagnosed with luminal and non-luminal HER2-like BCs and this effect was slightly more pronounced at an early age (p for interaction with age = 0.037 and 0.030, respectively). For instance, women diagnosed at age 35 were 1.48 (CI 1.01-2.16) more likely to have luminal HER2-like BC than luminal A BC, while this association was not significant at age 75 (OR = 0.72, CI 0.45-1.14). While age at menarche was not significantly associated with BC subtype, increasing age at FFTP was non-linearly associated with TNBC relative to luminal A BC. An age at FFTP of 25 versus 20 years lowered the risk for TNBC (OR = 0.78, CI 0.70-0.88, p
METHODS: In this study, we determined the prevalence of germline APOBEC3B deletion and its association with breast cancer risk in a cross-sectional hospital-based Asian multi-ethnic cohort of 1451 cases and 1442 controls from Malaysia. We compared gene expression profiles of breast cancers arising from APOBEC3B deletion carriers and non-carriers using microarray analyses. Finally, we characterised the overall abundance of tumour-infiltrating immune cells in breast cancers from TCGA and METABRIC using ESTIMATE and relative frequency of 22 immune cell subsets in breast cancers from METABRIC using CIBERSORT.
RESULTS: The minor allelic frequency of APOBEC3B deletion was estimated to be 0.35, 0.42 and 0.16 in female populations of Chinese, Malay and Indian descent, respectively, and that germline APOBEC3B deletion was associated with breast cancer risk with odds ratios of 1.23 (95 % CI: [1.05, 1.44]) for one-copy deletion and 1.38 (95 % CI: [1.10, 1.74]) for two-copy deletion compared to women with no deletion. Germline APOBEC3B deletion was not associated with any clinicopathologic features or the expression of any APOBEC family members but was associated with immune response-related gene sets (FDR q values