Objectives Women with atypical ductal hyperplasia (ADH), unlike those with ductal carcinoma in situ (DCIS), are denied eligibility for active surveillance clinical trials. Methods We applied the inclusion criteria of the Comparison of Operative to Monitoring and Endocrine Therapy (COMET) trial to the cases of women (n = 165) at the Roswell Park Cancer Institute who had a diagnosis of ADH, ADH bordering on DCIS, or low- to intermediate-grade DCIS on core biopsy taken during screening mammography. Upgrade of lesions to high risk was based on invasive carcinoma, high-grade DCIS, or DCIS with comedo necrosis. Results In total, nine (5.5%) lesions were upgraded: two (1.7%) reported ADH, one (5.9%) reported ADH bordering on DCIS, and six (19.4%) reported DCIS (P = .002); and two (1.6%) reclassified ADH vs seven (17.1%) reclassified DCIS (P < .001). In multivariate analysis, only increased number of foci had the potential to predict high risk (odds ratio: 1.39; P = .06). Conclusions We conclude that ADH and ADH bordering on DCIS have lower upgrade rates than DCIS. We recommend opening an active surveillance clinical trial for women with these diagnoses.
Background. Gastrointestinal acute graft-versus-host disease (GVHD) occurring after allogeneic hematopoietic cell transplant is an allo-reactive T cell and inflammatory cytokine driven organ injury with epithelial apoptosis as 1 of its hallmark findings and is associated with significant mortality. Tumor necrosis factor (TNF)-alpha-induced protein 8 (TNFAIP8 or TIPE) acts as a negative mediator of apoptosis via inhibition of caspase-3 activation, promotes cell proliferation and Tipe −/− deficiency is associated with increased inflammation. Methods. To evaluate the role of TIPE in acute GVHD, naive C57BL/6 and Tipe −/− C57BL/6 mice were conditioned with 1000 cGy single dose total body irradiation, followed by transplantation of 10 million bone marrow cells and 20 million splenocytes from either syngeneic C57BL/6 or allogeneic BALB/c donors. Results. Allo TIPE-deficient mice developed exacerbated gut GVHD compared with allo controls and had significantly decreased survival (6 wk overall survival: 85% versus 37%; P < 0.05), higher clinical GVHD scores, more profound weight loss, increased serum proinflammatory cytokines (interleukin-17A, TNF, interleukin-6, and interferon-γ). T-cell infiltration into the ileum was increased; epithelial proliferation was decreased along with significantly higher levels of chemokines KC and monokine induced by gamma interferon. Using bone marrow chimeric experiments, TIPE was found to have a role in both hematopoietic and nonhematopoietic cells. Conclusions. Absence of TIPE results in excessive inflammation and tissue injury after allo-HCT, supporting that TIPE confers immune homeostasis and has tissue-protective function during the development of gut GVHD and may be a potential future target to prevent or treat this complication after allogeneic HCT.
The incidence of involved intramammary lymph node (intra‐MLN) with breast carcinoma (BC) is rare. Its clinical significance and impact on the clinical decision making is unclear. A total of 113 BC cases with at least one positive intra‐MLN were collected from 11 academic institutions. The inclusion criteria were subsequent axillary lymph node dissection, and the availability of information on T‐stage, size of node metastasis, extranodal extension status, biomarkers status, and clinical follow‐up. Stage 4 cases and/or neo‐adjuvant treated patients were excluded. AJCC TN‐stage was calculated twice, with and without intra‐MLN. Five‐year overall survival (OS) and relapse (local and/or distant)‐free survival (RFS) were calculated and correlated with the clinicopathologic variables. Excluding intra‐MLN, TN‐stage correlated with OS (P = .016) but not with RFS (P = .19). However, when intra‐MLN was included, TN‐stage correlated with both OS (P < .001) and RFS (P = .016). In the multivariate analysis, when intra‐MLN was excluded, only radiation therapy (RT) correlated with RFS (HR = 0.19, 95% CI: 0.054‐0.66, P = .009). However, when intra‐MLN was included in the TN‐stage both RT (HR = 0.13, 95% CI: 0.04‐0.45, P = .001) and TN‐stage 3 (HR = 8.92, 95% CI: 1.47‐54, P = .017) correlated with RFS. Tumor multifocality was the only variable correlated with OS when the intra‐MLN involvement was excluded. When intra‐MLN was included, multifocality became insignificant but TN‐stage 3 correlated with OS (HR = 8.59, 95% CI: 1.06‐69.71, P = .044). Positive intra‐MLN is an independent factor in predicting both RFS and OS.
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