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Background: The introduction of pertuzumab has greatly improved pathological complete response (pCR) rates in HER2-positive breast cancer, yet effects on long-term survival have been limited and it is uncertain which patients derive most benefit. In this study, we determine the prognostic value of BluePrint subtyping in HER2-positive breast cancer. Additionally, we evaluate its use as a biomarker for predicting response to trastuzumab-containing neoadjuvant chemotherapy with or without pertuzumab., Methods: From a cohort of patients with stage II-III HER2-positive breast cancer who were treated with neoadjuvant chemotherapy and trastuzumab with or without pertuzumab, 836 patients were selected for microarray gene expression analysis, followed by readout of BluePrint standard (HER2, Basal and Luminal) and dual subtypes (HER2-single, Basal-single, Luminal-single, HER2-Basal, Luminal-HER2, Luminal-HER2-Basal). The associations between subtypes and pathological complete response (pCR), overall survival (OS) and breast cancer-specific survival (BCSS) were assessed, and pertuzumab benefit was evaluated within the BluePrint subgroups., Results: BluePrint results were available for 719 patients. In patients with HER2-type tumors, the pCR rate was 71.9% in patients who received pertuzumab versus 43.5% in patients who did not (adjusted Odds Ratio 3.43, 95% CI 2.36-4.96). Additionally, a significantly decreased hazard was observed for both OS (adjusted hazard ratio [aHR] 0.45, 95% CI 0.25-0.80) and BCSS (aHR 0.46, 95% CI 0.24-0.86) with pertuzumab treatment. Findings were similar in the HER2-single subgroup. No significant benefit of pertuzumab was seen in other subtypes., Conclusions: In patients with HER2-type or HER2-single-type tumors, pertuzumab significantly improved the pCR rate and decreased the risk of breast cancer mortality, which was not observed in other subtypes. BluePrint subtyping may be valuable in future studies to identify patients that are likely to be highly sensitive to HER2-targeting agents., (© 2023. The Author(s).)

Background: Primary chemotherapy in breast cancer poses a dilemma with regard to adjuvant locoregional radiotherapy, as guidelines for locoregional radiotherapy were originally based on pathology results of primary surgery. We aimed to evaluate the oncological safety of de-escalated locoregional radiotherapy in patients with cT1-2N1 breast cancer treated with primary chemotherapy, according to a predefined, consensus-based study guideline., Methods: In this prospective registry study (RAPCHEM, BOOG 2010-03), patients referred to one of 17 participating radiation oncology centres in the Netherlands between Jan 1, 2011, and Jan 1, 2015, with cT1-2N1 breast cancer (one to three suspicious nodes on imaging before primary chemotherapy, of which at least one had been pathologically confirmed), and who were treated with primary chemotherapy and surgery of the breast and axilla were included in the study. The study guideline comprised three risk groups for locoregional recurrence, with corresponding locoregional radiotherapy recommendations: no chest wall radiotherapy and no regional radiotherapy in the low-risk group, only local radiotherapy in the intermediate-risk group, and locoregional radiotherapy in the high-risk group. Radiotherapy consisted of a biologically equivalent dose of 25 fractions of 2 Gy, with or without a boost. During the study period, the generally applied radiotherapy technique in the Netherlands was forward-planned or inverse-planned intensity modulated radiotherapy. 5-year follow-up was assessed, taking into account adherence to the study guideline, with locoregional recurrence rate as primary endpoint. We hypothesised that 5-year locoregional recurrence rate would be less than 4% (upper-limit 95% CI 7·8%). This study was registered at ClinicalTrials.gov, NCT01279304, and is completed., Findings: 838 patients were eligible for 5-year follow-up analyses: 291 in the low-risk group, 370 in the intermediate-risk group, and 177 in the high-risk group. The 5-year locoregional recurrence rate in all patients was 2·2% (95% CI 1·4-3·4). The 5-year locoregional recurrence rate was 2·1% (0·9-4·3) in the low-risk group, 2·2% (1·0-4·1) in the intermediate-risk group, and 2·3% (0·8-5·5) in the high-risk group. If the study guideline was followed, the locoregional recurrence rate was 2·3% (0·8-5·3) for the low-risk group, 1·0% (0·2-3·4) for the intermediate-risk group, and 1·4% (0·3-4·5) for the high-risk group., Interpretation: In this study, the 5-year locoregional recurrence rate was less than 4%, which supports our hypothesis that it is oncologically safe to de-escalate locoregional radiotherapy based on locoregional recurrence risk, in selected patients with cT1-2N1 breast cancer treated with primary chemotherapy, according to this predefined, consensus-based study guideline., Funding: Dutch Cancer Society., Translation: For the Dutch translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests For data management of the RAPCHEM study, LJB received a grant from Dutch Cancer Society (grant number 2010-4679). SCL reports grants from AstraZeneca, Eurocept Plaza, Roche, Genentech, Gilead Sciences, Tesaro, Novartis, Dutch Cancer Society, ZonMw, and A Sister's Hope; consulting fees from AstraZeneca, European Research Council (ERC), and NWO (Dutch Research Council); other financial support (eg, for attending meetings or travel) from Daiichi Sankyo, ESMO, ERC, and NWO; and non-financial support (ie, drugs, and gene expression tests) from Genentech, Roche, Gilead Sciences, Novartis, Agendia, and AstraZeneca, outside the submitted work. SCL has a patent (UN23A01/P-EP) pending. SCL is Chair of the Trial Steering Committee of the PIONEER trial (NCT03306472), and member of the Health Council of the Netherlands. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: We conducted a prospective cohort study in the Netherlands (RAPCHEM: NCT01279304, BOOG 2010-03) in breast cancer (BC) patients treated with primary systemic therapy (PST), followed by surgery and post-operative radiation therapy (RT) according to a predefined consensus-based study-guideline (SG). The aim of the current analysis is to evaluate adherence to the SG., Methods: From January 2011 to January 2015, patients with cT1-2N1 BC treated in 17 Dutch RT Centres were included. Patients with four or more suspicious nodes at imaging were excluded. SG recommended whole breast RT for patients treated with breast conserving therapy. SG on loco(-regional) RT were defined for three risk groups based on the ypN status: (1) ypN0 (low-risk): RT breast and no RT after mastectomy; (2) ypN1 (intermediate-risk): RT breast or chest wall; (3) ypN2 (high-risk): RT breast or chest wall, including regional lymph nodes., Results: We included 848 patients: 292 in the low-risk group; 374 in the intermediate-risk group; 182 in the high-risk group. Overall, 64% of the patients was treated according to the SG; 11% received less RT than the predefined target volumes and 25% received more extensive RT than according to the SG. The largest variation was seen in the intermediate risk group, where only 54% was treated according to the SG., Conclusion: Substantial deviation from the SG for post-operative RT was observed after PST, especially in patients with an intermediate-risk. Future analyses will evaluate outcome of these patients in relation to risk factors and the actual RT given., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: For the majority of sporadic Legionnaires' disease cases the source of infection remains unknown. Infection may possible result from exposure to Legionella bacteria in sources that are not yet considered in outbreak investigations. Therefore, potential sources of pathogenic Legionella bacteria--natural soil and rainwater puddles on roads--were studied in 2012., Methods and Results: Legionella bacteria were detected in 30% (6/20) of soils and 3·9% (3/77) of rainwater puddles by amoebal coculture. Legionella pneumophila was isolated from two out of six Legionella positive soil samples and two out of three Legionella positive rainwater samples. Several other species were found including the pathogenic Leg. gormanii and Leg. longbeachae. Sequence types (ST) could be assigned to two Leg. pneumophila strains isolated from soil, ST710 and ST477, and one strain isolated from rainwater, ST1064. These sequence types were previously associated with Legionnaires' disease patients., Conclusions: Rainwater and soil may be alternative sources for Legionella., Significance and Impact of the Study: The detection of clinically relevant strains indicates that rainwater and soil are potential sources of Legionella bacteria and future research should assess the public health implication of the presence of Leg. pneumophila in rainwater puddles and natural soil., (© 2014 The Authors. Journal of Applied Microbiology published by John Wiley & Sons Ltd on behalf of the Society for Applied Microbiology.)

The attribution of fresh produce to the overall community-associated exposure of humans to ESBL- or AmpC-producing bacteria is currently unknown. To address this issue, the prevalence of ESBL- and AmpC-producing Enterobacteriaceae on fresh produce produced in the Netherlands was determined. Seven vegetable types that are consumed raw were selected: blanched celery, bunched carrots, chicory, endive, iceberg lettuce, mushrooms, and radish. The vegetables were mostly obtained from supermarkets. To determine whether the agricultural environment is the source of ESBL-producing Enterobacteriaceae on fresh produce, iceberg lettuce was also obtained directly from three farms, in conjunction with soil and irrigation water. ESBL-producing Enterobacteriaceae isolated from vegetables and environment were all environmental species: Rahnella aquatilis (n = 119), Serratia fonticola (n = 45) and Pantoea agglomerans (n = 1). ESBL genes of R. aquatilis and S. fonticola were identified as blaRAHN-1 and blaRAHN-2 and blaFONA-1, blaFONA-2, blaFONA-3/6 and blaFONA-5, respectively. For R. aquatilis and S. fonticola, different prevalence numbers were observed using different isolation methods, which could at least partially be explained by an inverse correlation between the level of cefotaxime resistance of these species and incubation temperature. R. aquatilis was isolated from 0 to 46% of soil samples and 11 to 83% of vegetable samples, and S. fonticola from 2 to 60% of soil samples and 0 to 1.3% of vegetable samples. Third generation cephalosporin-resistant faecal Enterobacteriaceae were isolated from 2.7%, 1.3% and 1.1% of supermarket vegetables, iceberg lettuce from farms, and agricultural soil respectively. Faecal Enterobacteriaceae were all identified as Citrobacter and Enterobacter species and, with the exception of one Citrobacter koseri strain, all had phenotypes indicative of constitutive AmpC production. Comparison of fresh produce and its agricultural environment indicates that the Enterobacteriaceae population on fresh produce reflects that of the soil it is grown in. Public health risks associated with exposure to ESBL- and AmpC-producing bacteria through consumption of uncooked fresh produce are diverse. They range from occasional ingestion of 3GC-resistant opportunistic pathogens which may result in difficult-to-treat infections, to frequent ingestion of relatively harmless ESBL-producing environmental bacteria that may therewith constitute a continuously replenished intestinal reservoir facilitating dissemination of ESBL genes to (opportunistic) pathogens., (© 2013.)

Viable Legionella pneumophila bacteria were isolated by amoebal coculture from pluvial floods after intense rainfall and from water collected at sewage treatment plants. Several isolated L. pneumophila strains belonged to sequence types that have been previously identified in patients.