In this study the detection of HER2 gene amplification was evaluated using Fluorescence In Situ Hybridization (FISH; PathVysion) in comparison with Multiplex Ligation-dependent Probe Amplification ...(MLPA), a PCR based technique. These two methods were evaluated on a series of 46 formalin fixed paraffin embedded breast carcinomas, previously tested for protein overexpression by HercepTest (grouped into Hercep 1+, 2+ and 3+). HER2 gene amplification (ratio > or =2.0) by FISH was found in 9/10, 10/30 and 0/6 in IHC 3+, 2+ and 1+/0 cases, respectively. Digitalized automated spot counting performed with recently developed CW4000 CytoFISH software was 100% concordant with manual FISH scoring. Using MLPA 18/46 samples showed a clear HER2 amplification. Comparing MLPA and IHC showed the same results as for FISH and IHC. All but one FISH positive cases (18/19) were confirmed by MLPA for the presence of the gene amplification. The overall concordance of detection of Her2 gene amplification by FISH and MLPA was 98% (45/46). Furthermore, both the level of amplification and equivocal results correlated well between both methods. In conclusion, MLPA is a reliable and reproducible technique and can be used as an either alternative or additional test to determine HER2 status in breast carcinomas.
A population-based study was performed to assess the likelihood of axillary lymph node metastases in patients with clinically negative lymph nodes, according to patient age, tumor size and site, ...estrogen receptor status, histologic type and mode of detection. Data were obtained from the population-based Eindhoven Cancer Registry. During the period 1984-1997, 7680 patients with invasive breast cancer were documented, 6663 of whom underwent axillary dissection. Of the 5125 patients who were known to have clinically negative lymph nodes and underwent axillary dissection, 1748 (34%) had positive lymph nodes at pathological examination. After multivariate analysis, histologic type, tumor size, tumor site and the number of lymph nodes in the axillary specimen remained as independent predictors of the risk of nodal involvement (P < 0.001). Lower risks were found for patients with medullary or tubular carcinoma, smaller tumors, a tumor in the medial part of the breast and patients with less than 16 nodes examined. This study gives reliable estimates of the risk of finding positive lymph nodes in patients with a clinically negative axilla. Such information is useful when considering the need for axillary dissection and to predict the risk of a false-negative result when performing sentinel lymph node biopsy.
Predictors consistently associated with psychosis liability and course of illness in schizophrenia (SCZ) spectrum disorders (SSD), including the need for clozapine treatment, are lacking. ...Longitudinally ascertained medication use may empower studies examining associations between polygenic risk scores (PRSs) and pharmacotherapy choices.
To examine associations between PRS-SCZ loading and groups with different liabilities to SSD (individuals with SSD taking clozapine, individuals with SSD taking other antipsychotics, their parents and siblings, and unrelated healthy controls) and between PRS-SCZ and the likelihood of receiving a prescription of clozapine relative to other antipsychotics.
This genetic association study was a multicenter, observational cohort study with 6 years of follow-up. Included were individuals diagnosed with SSD who were taking clozapine or other antipsychotics, their parents and siblings, and unrelated healthy controls. Data were collected from 2004 until 2021 and analyzed between October 2021 and September 2022.
Polygenic risk scores for SCZ.
Multinomial logistic regression was used to examine possible differences between groups by computing risk ratios (RRs), ie, ratios of the probability of pertaining to a particular group divided by the probability of healthy control status. We also computed PRS-informed odd ratios (ORs) for clozapine use relative to other antipsychotics.
Polygenic risk scores for SCZ were generated for 2344 participants (mean SD age, 36.95 years 14.38; 994 female individuals 42.4%) who remained after quality control screening (557 individuals with SSD taking clozapine, 350 individuals with SSD taking other antipsychotics during the 6-year follow-up, 542 parents and 574 siblings of individuals with SSD, and 321 unrelated healthy controls). All RRs were significantly different from 1; RRs were highest for individuals with SSD taking clozapine (RR, 3.24; 95% CI, 2.76-3.81; P = 2.47 × 10-46), followed by individuals with SSD taking other antipsychotics (RR, 2.30; 95% CI, 1.95-2.72; P = 3.77 × 10-22), parents (RR, 1.44; 95% CI, 1.25-1.68; P = 1.76 × 10-6), and siblings (RR, 1.40; 95% CI, 1.21-1.63; P = 8.22 × 10-6). Polygenic risk scores for SCZ were positively associated with clozapine vs other antipsychotic use (OR, 1.41; 95% CI, 1.22-1.63; P = 2.98 × 10-6), suggesting a higher likelihood of clozapine prescriptions among individuals with higher PRS-SCZ.
In this study, PRS-SCZ loading differed between groups of individuals with SSD, their relatives, and unrelated healthy controls, with patients taking clozapine at the far end of PRS-SCZ loading. Additionally, PRS-SCZ was associated with a higher likelihood of clozapine prescribing. Our findings may inform early intervention and prognostic studies of the value of using PRS-SCZ to personalize antipsychotic treatment.
Abstract Introduction To investigate the effect of adjuvant chemotherapy on long term survival in addition to hormonal therapy in the systemic treatment of hormonal receptor positive breast cancer ...patients. Methods All patients with primary non-metastatic hormonal receptor positive invasive lobular (mixed) (=ILC) and invasive ductal (=IDC) breast cancer operated on between 1986 and 2007 were identified from a population based cohort. Four hundred ninety-eight patients with lobular (mixed) and sixteen hundred seventeen with ductal cancer were eligible. Both groups were divided in patients receiving adjuvant hormonal treatment with or without systemic chemotherapy. Results Overall survival was not statistically different in patients with ILC treated with adjuvant hormonal and chemotherapy compared to hormonal treatment alone (5-year survival 85.2% vs 82.8%, P = .68). In contrast, patients with IDC receiving adjuvant hormonal and chemotherapy had a significantly better overall survival compared to hormonal therapy alone (5-year survival rate 87.6% vs 80.8%, P < .001). In the multivariate analysis however, this significance disappeared suggesting that the data are possibly too small, too unbalanced, or influenced by other confounding factors to come to definitive conclusions. Conclusions There are good reasons to consider ductal and lobular breast cancers as different entities in future studies. Patients with hormone receptor positive ILC seem to benefit differently from additional adjuvant chemotherapy to hormonal therapy as compared with patients with IDC.
Abstract Purpose The aim of this population-based study was to examine the impact of postmastectomy radiotherapy on the risk of local recurrence in patients with invasive lobular breast cancer (ILC). ...Methods The population-based Eindhoven Cancer Registry was used to select all patients with ILC, who underwent mastectomy in five general hospitals in the southern part of the Netherlands between 1995 and 2002. Of the 499 patients 383 patients fulfilled the eligibility criteria. Of these patients, 170 (44.4%) had received postmastectomy radiotherapy. The median follow-up was 7.2 years. Fourteen patients (3.7%) were lost to follow-up. Results During follow-up 22 patients developed a local recurrence, of whom 4 had received postmastectomy radiotherapy. The 5-year actuarial risk of local recurrence was 2.1% for the patients with and 8.7% for the patients without postmastectomy radiotherapy. After adjustment for age at diagnosis, tumour stage and adjuvant systemic treatment, the patients who underwent postmastectomy radiotherapy were found to have a more than 3 times lower risk of local recurrence compared to the patients without (Hazard Ratio 0.30; 95% Confidence Interval: 0.10–0.89). Conclusion Local control is excellent for patients with ILC who undergo postmastectomy radiotherapy and significantly better than for patients not receiving radiotherapy.
A population-based study was performed to compare the characteristics of clinically detected breast cancers and cancers detected by the Dutch screening program. To determine whether differences are ...most likely to be explained by earlier diagnosis or by the detection of biologically different cancers in the screening program, comparisons were stratified according to tumor size. Data were obtained from the population-based Eindhoven Cancer Registry. During the period 1996-1999, 568 screen-detected and 630 clinically detected invasive breast cancers were available for analysis. Compared with patients with clinically detected breast cancer, women with screen-detected breast cancer had smaller tumors (P < 0.0001), were more likely to have negative lymph nodes (P < 0.0001), tumors with a positive estrogen (P = 0.007) or progesterone (P = 0.019) receptor status and a lower mitotic activity index (P = 0.009). In the group with cancers < or = 1.0 cm the screen-detected were more likely to have negative estrogen receptors (P = 0.027). The group with screen-detected tumors 1.1-2.0 cm across were more likely to have positive estrogen and progesterone receptors (P = 0.005 and P = 0.044, respectively) and tended to have a lower mitotic activity index (P = 0.078). No significant differences were found between screen-detected and clinically detected breast cancers of 2.1-3.0 cm across. After adjustments for tumor size, most of the differences between clinically detected and screen-detected breast cancers disappeared, suggesting that screen-detected breast cancers represent tumors in an earlier phase of their development, not a biologically different class.
: Determinants of prognosis were studied in patients with breast cancer with histologically proven tumor extension to the skin without clinical evidence of distant metastases (i.e., pT4b N0–3 M0). ...Data were collected retrospectively on 77 consecutive patients diagnosed in one community teaching hospital over the period from 1980 to 1995. The prognostic factor of tumor size showed a 5‐year survival rate for patients with a tumor ≤3 cm of 81% compared to 45% for patients with tumors larger than 3 cm (p = 0.002). Achievement of complete remission resulted in a 5‐year survival rate of 66%, compared to 27% when complete remission was not achieved (p = 0.005). Another important prognostic factor was the development of local‐regional recurrence: the 5‐year survival rates for patients with and without local‐regional recurrence were 39% and 87%, respectively (p < 0.001). Development of local‐regional recurrence was also significantly related to tumor size (p = 0.02). Pathologic tumor size and the achievement of complete remission and local‐regional control appear to be the most important prognostic factors for survival in patients with pT4b breast cancer without distant metastases. We conclude that the finding of a pT4b breast cancer does not always imply a dismal prognosis, especially for those patients with a tumor ≤3 cm. A favorable prognosis can be expected when treatment is effective in achieving complete remission and in preventing the development of local‐regional recurrence.
Perseverance’s Mastcam-Z instrument provides high-resolution stereo and multispectral images with a unique combination of spatial resolution, spatial coverage, and wavelength coverage along the ...rover’s traverse in Jezero crater, Mars. Images reveal rocks consistent with an igneous (including volcanic and/or volcaniclastic) and/or impactite origin and limited aqueous alteration, including polygonally fractured rocks with weathered coatings; massive boulder-forming bedrock consisting of mafic silicates, ferric oxides, and/or iron-bearing alteration minerals; and coarsely layered outcrops dominated by olivine. Pyroxene dominates the iron-bearing mineralogy in the fine-grained regolith, while olivine dominates the coarse-grained regolith. Solar and atmospheric imaging observations show significant intra- and intersol variations in dust optical depth and water ice clouds, as well as unique examples of boundary layer vortex action from both natural (dust devil) and Ingenuity helicopter–induced dust lifting. High-resolution stereo imaging also provides geologic context for rover operations, other instrument observations, and sample selection, characterization, and confirmation.
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