Determination of Factors Associated with Upstage in Atypical Ductal Hyperplasia to Identify Low-Risk Patients Where Active Surveillance May be an Alternative.

BACKGROUND: Excision is routinely recommended for atypical ductal hyperplasia (ADH) found on core biopsy given cancer upstage rates of near 20%. Identifying a cohort at low-risk for upstage may avoid low-value surgery. Objectives were to elucidate factors predictive of upstage in ADH, specifically near-complete core sampling, to potentially define a group at low upstage risk. PATIENTS AND METHODS: This retrospective, cross-sectional, multi-institutional study from 2015 to 2019 of 221 ADH lesions in 216 patients who underwent excision or active observation (≥ 12 months imaging surveillance, mean follow-up 32.6 months) evaluated clinical, radiologic, pathologic, and procedural factors for association with upstage. Radiologists prospectively examined imaging for lesional size and sampling proportion. RESULTS: Upstage occurred in 37 (16.7%) lesions, 25 (67.6%) to ductal carcinoma in situ (DCIS) and 12 (32.4%) to invasive cancer. Factors independently predictive of upstage were lesion size ≥ 10 mm (OR 5.47, 95% CI 2.03-14.77, p < 0.001), pathologic suspicion for DCIS (OR 12.29, 95% CI 3.24-46.56, p < 0.001), and calcification distribution pattern (OR 8.08, 95% CI 2.04-32.00, p = 0.003, "regional"; OR 19.28, 95% CI 3.47-106.97, p < 0.001, "linear"). Near-complete sampling was not correlated with upstage (p = 0.64). All three significant predictors were absent in 65 (29.4%) cases, with a 1.5% upstage rate. CONCLUSIONS: The upstage rate among 221 ADH lesions was 16.7%, highest in lesions ≥ 10 mm, with pathologic suspicion of DCIS, and linear/regional calcifications on mammography. Conversely, 30% of the cohort exhibited all low-risk factors, with an upstage rate < 2%, suggesting that active surveillance may be permissible in lieu of surgery.

Factors associated with relapse-free survival after neoadjuvant chemotherapy for breast cancer at a safety net medical center.

BACKGROUND: This study was designed to assess prognostic factors associated with relapse-free survival (RFS) after neoadjuvant chemotherapy (NAC) for breast cancer. METHODS: A single-institution retrospective analysis was performed including clinical, radiographic, and pathologic parameters for all breast cancer patients treated with NAC from 2015 to 2018. All patients had pre-and post-NAC MRI. RESULTS: For 102 patients, median follow-up was 47.4 months, and the five-year RFS was 74%. The 41 (40%) patients who achieved pathologic complete response (pCR) after NAC had a significantly higher five-year RFS than the 61 not achieving pCR. For 31 patients with triple-negative cancers, the five-year RFS was significantly higher in those achieving pCR vs. no pCR. The 44 (43%) patients who achieved radiographic complete response (rCR) after NAC had similar five-year RFS to the 58 (57%) not achieving rCR. CONCLUSION: pCR, node-negativity after NAC, and triple-negative subtype were prognostic factors associated with relapse-free survival after NAC.

MRI does not predict pathologic complete response after neoadjuvant chemotherapy for breast cancer.

BACKGROUND: This study assessed whether magnetic resonance imaging (MRI) could accurately predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for patients receiving standardized treatment, pre- and post-NAC MRI on the same instrumentation using a consistent imaging protocol, interpreted by a single breast fellowship-trained radiologist. METHODS: A single-institution retrospective analysis was performed including clinical, radiographic, and pathologic parameters for all patients with breast cancer treated with NAC from 2015 to 2018. Radiographic complete response (rCR) was defined as absence of suspicious MRI findings in the ipsilateral breast or lymph nodes. pCR was defined as the absence of invasive cancer or ductal carcinoma in-situ in breast or lymph nodes after operation (ypT0N0M0). RESULTS: Data for 102 consecutive patients demonstrated that 44 (43.1%) had rCR and 41 (40.1%) had pCR. pCR occurred in 12 (25.0%) of 48 estrogen receptor positive (ER+) patients, 29 (53.7%) of 54 ER- patients, and 25 (52.1%) of 48 human epidermal growth factor receptor 2 positive patients. The positive predictive value for MRI after NAC was 84.5% and the negative predictive value was 72.7%. The accuracy rate for MRI was 78.6%. Of the 44 patients with rCR, 12 (27.3%) had residual cancer on the pathologic specimen after surgical excision. CONCLUSION: rCR is not accurate enough to serve as a surrogate marker for pCR on MRI after NAC.

De novo arteriovenous malformations: case report and review of the literature.

Intracerebral arteriovenous malformations (AVMs) are traditionally recognized as congenital lesions. However, with the advent of frequent, noninvasive imaging of the brain, that notion has been challenged. We describe another patient with a de novo cerebral arteriovenous malformation and evaluate the reported literature for trends in the development of these lesions. Cases were selected from the English literature using the PUBMED database using the search term "acquired or de novo cerebrovascular arteriovenous malformations". A total of seven patients (including the one reported in this study) with de novo arteriovenous malformations are reported. Majority of patients were female, and mostly diagnosed as children. Their mean age at diagnosis was 18 years (6-32), and the mean time from the initial intracranial study to the diagnosis of an AVM was 8 years (3-17). De novo formation of AVMs is being increasingly reported, especially in young females. We present only the seventh such case reported in the literature and challenge the traditional view that all arteriovenous malformations are congenital in nature.

Adaphostin cytoxicity in glioblastoma cells is ROS-dependent and is accompanied by upregulation of heme oxygenase-1.

PURPOSE: To delineate a role for reactive oxygen species (ROS) induction in adaphostin-induced apoptosis in glioblastoma cells. METHODS: Three glioblastoma cell lines with different sensitivities to adaphostin were characterized for sensitivity to an oxidant, tert-butyl hydroperoxide. The degree and duration of the ROS levels was assessed in the three cell lines after adaphostin exposure. Antioxidant protein levels were evaluated by Western blotting. RESULTS: Of the three glioblastoma cell lines, the U87 cells were least sensitive to adaphostin. These cells were also least sensitive to tert-butyl hydroperoxide, indicating that sensitivity to a direct oxidant stress mirrors the cells' adaphostin sensitivities. In addition, the antioxidant N-acetylcysteine, (NAC) was protective against adaphostin-induced apoptosis. Direct measurement of intracellular peroxides showed a transient increase in the two less sensitive cell lines (U87 and LN18) which diminishes by 24 h. In contrast, U251 cells, which are most sensitive to adaphostin, display a sustained increase in the ROS levels. After the initial increase in intracellular peroxides, the heat shock protein and antioxidant heme oxygenase-1 (HO-1) was upregulated. Levels of other antioxidant proteins, such as catalase and thioredoxin, however, were not altered by adaphostin in glioblastoma cell lines. NAC attenuated HO-1 upregulation, confirming the time course analysis. CONCLUSIONS: These results suggest a primary role for ROS in adaphostin-induced apoptosis in glioblastoma. Our data indicate that the duration of intracellular ROS levels is a key factor in mediating sensitivity to adaphostin. Furthermore, upregulation of HO-1 is a novel molecular marker of adaphostin's action. The kinetics with which adaphostin upregulates HO-1 correlates with sensitivity to the drug. Taken together, our data indicate that a cell's ability to cope with ROS dictates sensitivity to adaphostin and conceivably other chemotherapies that cause redox perturbations.