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Individual, provider, clinic, and societal level barriers have been shown to undermine the potential impact of genetic testing. The current approach in the primary care setting places an exorbitant burden on both providers and patients. Current literature provides insight into how to address barriers across multiple levels (patient, provider, clinic, system) and at multiple stages in the testing process (identification, referral, counseling, and testing) but interventions have had limited success. After outlining the current approach to genetic testing in the primary care setting, including the barriers that prevent genetic testing uptake and the methods proposed to address these issues, we recommend integrating genetic testing into routine medical care through population-based testing. Success in efforts to increase the uptake of genetic testing will not occur without significant changes to the way genetic services are delivered. These changes will not be instantaneous but are critical in moving this field forward to realize the potential for cancer risk genetic assessment to reduce cancer burden.

There is evidence that epigenetic changes occur early in breast carcinogenesis. We hypothesized that early-life exposures associated with breast cancer would be associated with epigenetic alterations in breast tumors. In particular, we examined DNA methylation patterns in breast tumors in association with several early-life exposures in a population-based case–control study. Promoter methylation of E-cadherin, p16 and RAR-β2 genes was assessed in archived tumor blocks from 803 cases with real-time methylation-specific PCR. Unconditional logistic regression was used for case–case comparisons of those with and without promoter methylation. We found no differences in the prevalence of DNA methylation of the individual genes by age at menarche, age at first live birth and weight at age 20. In case–case comparisons of premenopausal breast cancer, lower birth weight was associated with increased likelihood of E-cadherin promoter methylation (OR = 2.79, 95% CI, 1.15–6.82, for ⩽2.5 v. 2.6–2.9 kg); higher adult height with RAR-β2 methylation (OR = 3.34, 95% CI, 1.19–9.39, for ⩾1.65 v. <1.60 m); and not having been breastfed with p16 methylation (OR = 2.75, 95% CI, 1.14–6.62). Among postmenopausal breast cancers, birth order was associated with increased likelihood of p16 promoter methylation. Being other than first in the birth order was inversely associated with likelihood of ⩾1 of the three genes being methylated for premenopausal breast cancers, but positively associated with methylation in postmenopausal women. These results suggest that there may be alterations in methylation associated with early-life exposures that persist into adulthood and affect breast cancer risk. [ABSTRACT FROM PUBLISHER]

Residential care facilities are an enduring feature of Ontario's community mental health system. While these facilities offer affordable housing, they are also custodial environments that are poorly suited to goals of recovery and rehabilitation. This paper examines the extent to which facilities can be 'reengineered' to improve tenants' daily lives using a case study of facilities in Hamilton, Ontario. Data from a 2005 survey of 50 people with psychiatric disabilities living in residential care facilities were used to assess quality of life and the extent to which operators have implemented newly revised municipal regulations. The findings are compared with those of earlier researchers (Taylor, Elliott, & Kearns, 1989) who conducted a similar survey in 1986 in Hamilton. While the two surveys differ with regard to specific items, broad comparison suggests little has changed, raising questions about the extent to which such facilities should continue to play a central role in housing for people with psychiatric disabilities. [ABSTRACT FROM AUTHOR]

The practice of partial depopulation or thinning (early removal of a portion of birds from a commercial broiler flock) is a reported risk factor for Campylobacter colonization of residual birds because of the difficulty in maintaining biosecurity during the thinning process. The effect of this practice was studied in detail for 51 target flocks, each at a different growing farm belonging to one of seven major poultry companies throughout the United Kingdom. On 21 of these farms, the target flock was already colonized by Campylobacter, and at slaughter all cecal samples examined were positive, with a mean of 8 log CFU/g. An additional 27 flocks became positive within 2 to 6 days of the start of thinning and had similarly high levels of cecal carriage at slaughter. Just before the thinning process, Campylobacter was isolated frequently from the farm driveways, transport vehicles, equipment, and personnel. Strains from seven farms on which flocks became colonized after thinning were examined by pulsed-field gel electrophoresis typing. An association was found between strains occurring at specific sampling sites and those isolated subsequently from the thinned flocks. The results indicated that particular strains had spread from one farm to another when the farms were jointly owned by the same company and employed the same bird-catching teams and/ or vehicles. These results highlight the need for better hygiene control in relation to catching equipment and personnel and more effective cleaning and disinfection of vehicles and bird-transport crates. [ABSTRACT FROM AUTHOR]

This article presents comments on various studies related to breast cancer. It includes "Applicability of the Nipple-Areola Complex-Sparing Mastectomy: A Prediction Model Using Mammography to Estimate Risk of Nipple-Areola Complex Involvement in Breast Cancer Patients," "A Pathologic Assessment of Adequate Margin Status in Breast-Conserving Therapy" and "Breast-Conserving Therapy After Neoadjuvant Chemotherapy: Long-Term Results."

The compaction behavior of three “as supplied” commercially available grades of sodium starch glycolate (SSG), Explotab, Primojel, and Vivastar P, was investigated at compression speeds of 0.17 and 30 mm/sec. The results suggested that the three “as supplied” materials exhibit different compression and compaction behavior. Primojel and Explotab exhibited similar compactibility, whereas Vivastar P produced compacts of poor integrity. This behavior was not mirrored in the compressibility of the powders, where Vivastar P and Explotab exhibited similar performance. The materials were studied using x-ray diffraction, scanning electron microscopy, Carr's compressibility index, and swelling volume. In terms of material characteristics, all the products exhibited similar swelling in water. Primojel and Explotab retained most of the crystallographic order from the parent potato starch and exhibited comparable particle surface topographies. Vivastar P contained the lowest moisture level. However, it is not clear if the poor compactibility of Vivastar P is due to differences in moisture content, the reduced surface topography, or subtle differences in the SSG polymer structures (substitution, cross-linking, and crystallinity). Overall, even though the three commercial grades of sodium starch glycolate are successfully used as disintegrants, they do exhibit differences in their “as supplied” powder mechanical properties: Primojel and Explotab exhibit similar compactibility, whereas Vivastar P is poorly compactable but exhibits similar compressibility to Explotab. These observations may have implications when formulating poorly compactable or moisture-sensitive drugs. [ABSTRACT FROM AUTHOR]

The internal and surface chemical compositions of three sodium starch glycolate (SSG) products, Explotab, Primojel and Vivastar P were studied using scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), time of flight secondary ion mass spectrometry (TOF-SIMS) and 23Na nuclear magnetic resonance spectroscopy (NMR). The surfaces of Explotab and Primojel contained very distinct features containing Na and Cl, however, Primojel also contained features which contained Na which may reflect the presence of Na glycolate and/or Na citrates. Vivastar P contained relatively few surface Cl containing features. Analysis of cross-sections of the particles showed that Na appeared to be uniformly distributed throughout the particles of all the products. Additionally, there was a significant concentration of Cl in the periphery of Explotab and Primojel. In the case of Vivastar P, significant levels of Na and Cl were detected in the internal regions of the particles which, together with 23Na NMR, suggests that NaCl is uniformly distributed within Vivastar P. 23Na NMR also suggested that the ratio of organic Na to NaCl was considerably lower in Vivastar P than Primojel and Explotab. Overall, even though all these three products satisfy the pharmacopeial descriptions of SSG, these studies suggest that Primojel and Explotab exhibit different chemical compositions to Vivastar P. Since the three products studied are reported to be prepared from potato starch, the apparent differences in chemical composition probably reflect the different manufacturing processes used, however, batch to batch variations may account for some of the subtle differences. [Copyright &y& Elsevier]

The mechanical properties of compacts of microcrystalline cellulose (MCC) and silicified microcrystalline cellulose (SMCC) were evaluated by tensile testing, diametric compression testing, and compression testing. For tensile and compression testing, cubic specimens were carefully machined from MCC and SMCC compacts, and the tensile and compression strengths were evaluated both normal and parallel to the compaction direction. The cubic tensile strengths were compared to values obtained from the diametric compression test. The results obtained using the diametric compression test suggested compacts of SMCC exhibit greater strength than those of MCC. In addition, the cubes machined from compacts of MCC and SMCC exhibited directional strength; the direction normal to the compaction direction displayed the greater tensile strength; and the parallel direction had greater compression strength. The diametric compression test afforded strength values with reduced spread compared to the values collected from the cubic tensile test, suggesting that the errors involved in collecting diametric compression test data of compacts are less than those for the cubic tensile test. Analysis of the cubes using X-ray diffraction (XRD) suggested that they display directional structural anisotropy, with the direction normal to the compaction direction being more crystalline than the parallel direction. However, it is not clear whether the difference in the directional strength is solely a consequence of the increased crystallinity or a culmination of crystallographic and mechanical keying effects. [ABSTRACT FROM AUTHOR]

Purpose.--In the current pTNM classification system, nodal status of breast cancer is based on the number of involved lymph nodes and does not account for the total number of lymph nodes removed. In this study, we assessed the prognostic value of the lymph node ratio (LNR; ie, ratio of positive over excised lymph nodes) as compared with pN staging and determined its optimal cutoff points. Patients and Methods.--From the Geneva Cancer Registry, we identified all women diagnosed with node-positive breast cancer between 1980 and 2004 (n = 1,829). The prognostic value of LNRs was calculated for values ranging from 0.05 to 0.95 by Cox regression analysis and validated by bootstrapping. Based on maximum likelihood, we identified cutoff points classifying women into low-, intermediate-, and high-risk LNR groups. Results.--Optimal cutoff points classified patients into low- (≤ 0.20), intermediate- (> 0.20 and ≤ 0.65), and high-risk (> 0.65) LNR groups, corresponding to 10-year disease-specific survival rates of 75%, 63%, and 40%, and adjusted mortality risks of 1 (reference), 1.78 (95% CI, 1.46 to 2.18), and 3.21 (95% CI, 2.54 to 4.06), respectively. In contrast to LNR risk categories, survival curves of pN2 and pN3 crossed after 15 years, and their adjusted mortality risks showed overlapping CIs: 2.07 (95% CI, 1.69 to 2.53) and 2.84 (95% CI, 2.23 to 3.61), respectively. Conclusion.--LNR predicts survival after breast cancer more accurately than pN classification and should be considered as an alternative to pN staging. [ABSTRACT FROM AUTHOR]

Abstract Background Inter-individual variation in DNA repair capacity is thought to modulate breast cancer risk. The phenotypic mutagen sensitivity assay (MSA) measures DNA strand breaks in lymphocytes; women with familial and sporadic breast cancers have a higher mean number of breaks per cell (MBPC) then women without breast cancer. Here, we explore the relationships between the MSA and the Rad51 gene, which encodes a DNA repair enzyme that interacts with BRCA1 and BRCA2, in BRCA1 mutation carriers and women with sporadic breast cancer. Methods Peripheral blood lymphoblasts from women with known BRCA1 mutations underwent the MSA (n = 138 among 20 families). BRCA1 and Rad51 genotyping and sequencing were performed to identify SNPs and haplotypes associated with the MSA. Positive associations from the study in high-risk families were subsequently examined in a population-based case-control study of breast cancer (n = 1170 cases and 2115 controls). Results Breast cancer diagnosis was significantly associated with the MSA among women from BRCA1 families (OR = 3.2 95%CI: 1.5-6.7; p = 0.004). The Rad51 5'UTR 135 C>G genotype (OR = 3.64; 95% CI: 1.38, 9.54; p = 0.02), one BRCA1 haplotype (p = 0.03) and in a polygenic model, the E1038G and Q356R BRCA1 SNPs were significantly associated with MBPC (p = 0.009 and 0.002, respectively). The Rad51 5'UTR 135C genotype was not associated with breast cancer risk in the population-based study. Conclusions Mutagen sensitivity might be a useful biomarker of penetrance among women with BRCA1 mutations because the MSA phenotype is partially explained by genetic variants in BRCA1 and Rad51.

The article focuses on research on the significance of intramammary lymph nodes (intraMLNs) in the staging of breast cancer and its correlation with tumor characteristics and outcome. It references a study by A. Nassar et al. published in the 2008 issue of "Breast Journal." According to the study, the presence of intraMLN metastases does not appear to influence the survival of patients with stage II breast cancer.

An atomic force microscope (AFM) colloid probe technique has been used to investigate the effect of relative humidity (RH) on the adhesion properties of pharmaceutical powder surfaces. The adhesion between a model substrate, α-lactose monohydrate, and model particulate drugs, salbutamol sulphate and budesonide, was investigated between RHs of 15 and 75%. The surface topography of the model α-lactose monohydrate was produced by controlling the supersaturation conditions during crystal growth to produce sub-nanometre scale roughness. The adhesion interactions between lactose and drug probes of salbutamol sulphate and budesonide were shown to be significantly increased with each incremental rise in humidity. Capillary forces were significantly more dominant for the adhesion in the budesonide–lactose system up to 60% RH but were more dominant for salbutamol sulphate–lactose above 60% RH. These studies suggested that non-surface-specific capillary forces play a dominant role in the adhesion between drug and carrier, which may significantly reduce the deaggregation and dispersion properties of a dry powder formulation. [Copyright &y& Elsevier]

Introduction: Population based studies (eg, Hershman et al. BCRT 2006 and Lohrisch et al. JCO 2006) showed poorer survival associated with long delays in adjuvant chemotherapy (CTX) initiation following definitive surgery (DS) for women with breast cancer (BC). Delays in CTX following diagnosis (DX) have not been evaluated. The ASCO/NCCN quality measures (QMs) recommend CTX <=120 days after DX for patients with stage II/III ER/PR negative disease. We sought to examine the impact of delayed CTX on survival overall and stratified by disease-specific prognostic factors. Methods: 4,608 women with stage I-III HER2 negative breast cancer diagnosed between 2000 and 2006 at 8 NCCN centers were identified using the NCCN outcomes database. Patients with T3/4 disease or who received neoadjuvant therapy were excluded. The association between CTX timing and OS was evaluated using multivariate Cox models adjusted for CTX type, age, race, BMI, residential distance, insurance, SES, comorbidity, ER/PR, LVI, grade, T stage, and N stage. The impact of CTX timing was evaluated using a >90-day (d) DS-to-CTX threshold, based on poor outcomes observed in prior studies, and a >120d DX-to-CTX threshold, based on the ASCO/NCCN QMs. Results: Median follow-up was 7.2 years and OS at 7 years was 89%. Overall, 401 (8.7%) patients received CTX >120d after DX and 113 (2.4%) patients received CTX >90d after DS. The DX-to-CTX interval was more strongly correlated with the DX-to-DS (r = 0.74) interval than DS-to-CTX (r = 0.54) interval. A >90d DS-to-CTX interval was significantly associated with poorer survival (HR: 1.65, 95% CI 1.04-2.60, p = 0.03) in adjusted analyses. Shorter DS-to-CTX thresholds of >60d (n = 636, HR: 1.13, 95% CI: 0.89-1.43, p = 0.319) or >75d (n = 273, HR: 1.05, 95% CI 0.74-1.49, p = 0.76) were not associated with OS. The association between a >120d DX-to-CTX interval and OS was not statistically significant (HR: 1.32, 95% CI 0.99-1.76, p = 0.06). Patients who received CTX >135d(n = 231, HR1.25, 95% CI: 0.87-1.81, p = 0.22)or>150d(n = 128, HR1.15, 95% CI: 0.59-2.24, p = 0.69) after DX did not display an increased risk of death. Excluding pathological staging factors from the model had no effect on the results. In subgroup analyses stratified by ER/PR, LVI, grade, T stage or N stage, a >120d delay in CTX did not display significant associations with OS. Among ER/PR negative patients, the association between a >120d delay and OS was borderline non-significant after adjusting the p-value for multiple hypothesis testing using the false discovery rate method (HR: 1.80, 95% CI: 1.16-2.79, p = 0.09). Conclusion: Consistent with previous studies, CTX delays of >90 days following surgery were associated with poorer survival. OS was not significantly compromised in patients with DX-to-CTX intervals >120 days although this analysis may have limited power to detect small effects. More variation in the DX-to-CTX interval was attributed to pre-surgery time which may explain the differences observed between the DX-to-CTX and DS-to-CTX intervals. Among patients with ER/PR negative disease, a non-significant association between OS and a >120 day DX-to -CTX interval was observed that warrants further examination. [ABSTRACT FROM AUTHOR]

Background: The results of the ACOSOG- Z0011 trial have had potential practice changing implications for the management of patients with positive sentinel lymph node (SLN) undergoing lumpectomy and radiation for breast cancer. However, some evidence suggests a shift in axillary management even prior to the initial report of data supporting sentinel lymph node biopsy (SLNB) alone in mid-2010. We analyzed data in the National Comprehensive Cancer Network (NCCN) outcomes database from NCCN centers and the Michigan Breast Oncology Quality Initiative (MiBOQI) hospitals to examine institutional practice patterns with respect to use of completion axillary dissection (CALND) for SLN positive breast cancer in the years leading up to publication of these trial results. We hypothesized that CALND would be omitted more frequently in women treated at NCCN centers compared to those treated at MiBOQI programs. Methods: We identified 2,172 women with clinical T1/T2 N0 breast cancer who underwent breast surgery and SLNB and had a positive SLN from 2007 through 2010 at one of 12 participating NCCN centers or 12 MiBOQI sites. Patient and tumor characteristics, definitive breast procedure, year of diagnosis, and institutional affiliation were analyzed as predictors of use of SLNB alone in univariate Chi-Square and multivariable logistic regression models. Results: CALND was omitted in 314 (14.5%) of the 2,172 patients. Over time, there was a dramatic increase in the use of SLNB alone (12% in 2007 to 23% in 2010). In the univariate analyses, increased patient age, later year of diagnosis, lower T stage, and lower pathologic N stage were significant predictors of use of SLNB alone (all p < .0001). There was no association between definitive breast surgery type, hormone receptor status, Her-2 Neu status, or institutional affiliation and use of SLNB alone. In the multivariable model, older age at diagnosis, later year of diagnosis, and lower pathologic N stage remained significant independent predictors of SLNB alone. There were no significant differences in rates of omission of CALND between NCCN and MIBOQI sites. Conclusions: Omission of CALND occurred frequently in women with SLN positive breast cancer cared for in both NCCN and MiBOQI institutions in advance of reporting results of ACOSOG-Z0011. This shift was seen in management of patients undergoing lumpectomy as well as mastectomy. Further study is warranted to determine the extent of durable practice changes as well as any impact on survival and local-regional control. [ABSTRACT FROM AUTHOR]

Introduction: Alterations in homologous recombination repair (HRR) genes occur in 20%-30% of men with metastatic castration-resistant prostate cancer (mCRPC) which may increase sensitivity to platinum chemotherapy. Specifically, exceptional responses to platinum chemotherapy have been reported among patients with BRCA mutations. This study aimed to evaluate the efficacy of platinum chemotherapy in patients with mCRPC with and without HRR., Patient and Methods: In this retrospective, multi-institution series, we analyzed patients with mCRPC to assess response to platinum-containing chemotherapy based on HRR alteration status. Outcome measures were prostate specific antigen (PSA)50 response rate (percentage of patients achieving at least a 50% decline in PSA from baseline), overall survival (OS) and progression-free survival (PFS)., Results: From 1999 to 2020, 24 patients with mCRPC who received platinum chemotherapy were included with 7 patients analyzable for PSA outcomes. HRR alterations were found in 19 out of 24 patients (79.2%) with mutations recognized in 11 different HRR genes. Patients with a HRR alteration achieved a PSA50 response rate of 20% (1 out of 5) after platinum chemotherapy compared to 50% (1 out of 2) in patients without a HRR mutation. No difference in OS or PSA PFS was detected among patients with BRCA1/2 mutations compared to HRR alterations other than BRCA1/2 and patients without HRR alterations., Conclusion: In patients with mCRPC, we did not find a statistical difference in anti-tumor activity after receiving platinum chemotherapy among patients harboring a pathogenic HRR alterations compared to patients without a HRR alteration. Additionally, we were unable to detect an association between BRCA1/2 mutation status and response to platinum chemotherapy. Platinum chemotherapy, however, had clinically meaningful activity in a subset of patients regardless of HRR alteration status. Additional studies are warranted using genomic data to predict sensitivity to platinum chemotherapy., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Higher cytotoxic T lymphocyte (CTL) numbers in the tumor microenvironment (TME) predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) and positive long-term outcomes in triple-negative breast cancer (TNBC). pCR to NAC is achieved only in 30-40% of patients. The combination of NAC with pembrolizumab increases the pCR rate but at the cost of immune-related adverse events (irAEs). Based on these considerations, we tested if systemic infusion of the chemokine modulatory regimen (CKM; selective toll-like receptor 3 (TLR3) agonist rintatolimod, interferon (IFN)-α2b, and cyclooxygenase-2 (COX-2) inhibitor celecoxib) regimen can be safely combined with NAC to enhance intratumoral CTL numbers and NAC effectiveness., Methods: Phase I study NCT04081389 evaluated nine patients with early-stage TNBC who received 3 weeks of paclitaxel with CKM (dose-escalation of IFN-α2b), followed by 9 weeks of paclitaxel alone, dose-dense doxorubicin and cyclophosphamide, and surgery. Primary and secondary endpoints were safety and clinical efficacy, respectively., Results: The combination treatment was well-tolerated with no dose-limiting toxicities or irAEs. 5/9 patients achieved pCR and one patient had microinvasive disease (ypTmic). We observed elevated IFN signature and uniform decreases in CTL numbers (average 8.3-fold) in the blood of all treated patients. This was accompanied by reciprocal uniform increases in CD8β (overall 5.9-fold), CD8α/FoxP3 (2.11-fold), and CCL5 (4.73-fold) transcripts in TME, particularly pronounced in patients with pCR. Multiplex immunohistochemistry revealed selectively increased numbers of CTL (but not regulatory T cells) in both the epithelial and stromal tumor compartments and early decreases in the numbers of αSMA + vascular/stromal cells in the tumors of all pCR patients., Conclusions: Combined paclitaxel/CKM regimen was safe, with desirable TME changes and preliminary indications of promising pCR+ypTmic of 66%, comparable to the combination of NAC with pembrolizumab., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Experimental evidence in tumor-bearing mouse models shows that exposure to cool, that is, sub-thermoneutral environmental temperature is associated with a higher tumor growth rate and an immunosuppressive tumor immune microenvironment than seen at thermoneutral temperatures. However, the translational significance of these findings in humans is unclear. We hypothesized that breast cancer patients living in warmer climates will have better survival outcomes than patients living in colder climates., Methods: A retrospective population-based analysis was conducted on 270,496 stage I-III breast cancer patients, who were retrieved from the Surveillance, Epidemiology and End Results (SEER) over the period from 1996 to 2017. The average annual temperature (AAT) was calculated based on city level data from the National Centers for Environmental Information., Results: A total of 270, 496 patients were analyzed. Temperature as assessed in quartiles. After adjusting for potential confounders, patients who lived in the 3rd and 4th quartile temperature regions with AAT 56.7-62.5°F (3rd quartile) and > 62.5°F (4th quartile) had a 7% increase in the OS compared to patients living at AAT < 48.5°F (1st quartile) (HR 0.93, 95% CI 0.90-0.95 and HR 0.93, 95% CI 0.91-0.96, respectively). For DSS, When comparing AAT quartiles, patients living with AAT in the range of 56.7-62.5°F and > 62.5°F demonstrated a 7% increase each in DSS after adjustment (HR 0.93, 95% CI 0.90-0.96 and HR 0.93, 95% CI 0.90-0.96)., Conclusions: Higher environmental temperatures are associated with significantly better OS and DSS in breast cancer patients. Future research is warranted to confirm this observation using large datasets to elucidate the underlying mechanisms and investigate novel therapeutic strategies to minimize this geographic disparity in clinical outcomes., (© 2024. The Author(s).)