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- Balmativola, D., et al.
(författare)
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Pathological non-response to chemotherapy in a neoadjuvant setting of breast cancer: an inter-institutional study
- 2014
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 148:3, s. 511-523
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Tidskriftsartikel (refereegranskat)abstract
- To identify markers of non-response to neoadjuvant chemotherapy (NAC) that could be used in the adjuvant setting. Sixteen pathologists of the European Working Group for Breast Screening Pathology reviewed the core biopsies of breast cancers treated with NAC and recorded the clinico-pathological findings (histological type and grade; estrogen, progesterone receptors, and HER2 status; Ki67; mitotic count; tumor-infiltrating lymphocytes; necrosis) and data regarding the pathological response in corresponding surgical resection specimens. Analyses were carried out in a cohort of 490 cases by comparing the groups of patients showing pathological complete response (pCR) and partial response (pPR) with the group of non-responders (pathological non-response: pNR). Among other parameters, the lobular histotype and the absence of inflammation were significantly more common in pNR (p < 0.001). By ROC curve analyses, cut-off values of 9 mitosis/2 mm(2) and 18 % of Ki67-positive cells best discriminated the pNR and pCR + pPR categories (p = 0.018 and < 0.001, respectively). By multivariable analysis, only the cut-off value of 9 mitosis discriminated the different response categories (p = 0.036) in the entire cohort. In the Luminal B/HER2- subgroup, a mitotic count < 9, although not statistically significant, showed an OR of 2.7 of pNR. A lobular histotype and the absence of inflammation were independent predictors of pNR (p = 0.024 and < 0.001, respectively). Classical morphological parameters, such as lobular histotype and inflammation, confirmed their predictive value in response to NAC, particularly in the Luminal B/HER2- subgroup, which is a challenging breast cancer subtype from a therapeutic point of view. Mitotic count could represent an additional marker but has a poor positive predictive value.
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- van Wendel de Joode, Berna, et al.
(författare)
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Aerial Application of Mancozeb and Urinary Ethylene Thiourea (ETU) Concentrations among Pregnant Women in Costa Rica: The Infants' Environmental Health Study (ISA).
- 2014
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 122:12, s. 1321-1328
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mancozeb and its main metabolite ethylene thiourea (ETU) may alter thyroid function; thyroid hormones are essential for fetal brain development. In Costa Rica, mancozeb is aerially sprayed at large-scale banana plantations on a weekly basis. Objectives: (1) evaluate urinary ETU concentrations in pregnant women living nearby large-scale banana plantations; (2) compare their estimated daily intake (EDI) with established Reference Doses (RfDs); and (3) identify factors that predict their urinary ETU concentrations. Methods: We enrolled 451 pregnant women from Matina County, Costa Rica, with large-scale banana production. We visited 445 women up to three times during pregnancy to obtain urine samples (n = 872) and information on factors that possibly influence exposure. We determined urinary ETU concentrations using liquid chromatography mass spectrometry (LCMS). Results: Pregnant women's median urinary ETU concentrations were more than five times higher than reported for other general populations. Seventy-two percent of the women had EDIs above the RfD. Women who lived closest (1st quartile, < 48 meters) to banana plantations on average had a 45% (95% CI: 23, 72%) higher urinary ETU compared with women who lived farthest away (4th quartile, ≥ 565 meter). Compared with the other women, ETU was also higher in women who washed agricultural work clothes on day before sampling (11%; 95% CI; 4.9, 17%), worked in agriculture during pregnancy (19%; 95% CI: 9.3, 29), and immigrant women (6.2%; 95% CI: 1.0, 13%). Conclusions: The pregnant women's urinary ETU concentrations are of concern, and the principal source of exposure is likely to be aerial spraying of mancozeb. The factors predicting ETU provide insight into possibilities for exposure reduction.
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