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Barbara Dull, Andrew Linkugel, Julie A. Margenthaler, and Amy E. Cyr

Background: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) recommend that patients with clinical stage I/II breast cancer undergo advanced imaging for staging only when symptomatic. Regardless, many asymptomatic patients undergo chest CT. The goal of this study was to assess the use and results of chest CT in these patients at an NCCN Member Institution. Methods: Patients with breast cancer diagnosed between 1998 and 2012 were identified in a prospectively maintained database. All patients with clinical stage I/II disease who did not receive neoadjuvant chemotherapy were included. Data collected included demographics, tumor size, node status, chest CT within 6 months of diagnosis, imaging findings, need for additional workup, and identification of metastatic disease. Appropriate statistical tests were used for analysis. Results: From 1998 to 2012, 3,321 patients were diagnosed with early-stage breast cancer. Of these, 2,062 (62.1%) had clinical stage I breast cancer at diagnosis and 1,259 (37.9%) had stage II; 227 patients (11%) with stage I and 456 (36.2%) with stage II breast cancer received staging chest CT. Of patients undergoing CT, 184 (26.9%) were found to have pulmonary nodules, which measured ≤5 mm for 128 patients (69.6%), 5 to 10 mm for 46 patients (25.0%), 11 to 20 mm for 6 patients (3.2%), and ≥20 mm for 4 patients (2.2%). Patients undergoing chest CT for staging subsequently underwent a mean of 2.34 (range, 0–16) additional CTs in follow-up. Of all patients undergoing chest CT for staging, only 9 (1.3%) were ultimately diagnosed with pulmonary metastases at an average of 25 months (range, 0–97) after initial staging chest CT. Conclusions: A significant percentage of patients with stage I/II breast cancer underwent unnecessary chest CT as part of their initial workup. Nearly one-third of these patients were found to have pulmonary nodules, but only 1.3% were ever diagnosed with pulmonary metastases. Adherence to NCCN Guidelines will reduce the excessive use of CT chest imaging.

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Prashant Gabani, Emily Merfeld, Amar J. Srivastava, Ashley A. Weiner, Laura L. Ochoa, Dan Mullen, Maria A. Thomas, Julie A. Margenthaler, Amy E. Cyr, Lindsay L. Peterson, Michael J. Naughton, Cynthia Ma, and Imran Zoberi

Background: This study evaluated factors predictive of locoregional recurrence (LRR) in women with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy who do not experience pathologic complete response (pCR). Methods: This is a single-institution retrospective review of women with TNBC treated with neoadjuvant chemotherapy, surgery, and radiation therapy in 2000 through 2013. LRR was estimated between patients with and without pCR using the Kaplan-Meier method. Patient-, tumor-, and treatment-specific factors in patients without pCR were analyzed using the Cox proportional hazards method to evaluate factors predictive of LRR. Log-rank statistics were then used to compare LRR among these risk factors. Results: A total of 153 patients with a median follow-up of 48.6 months were included. The 4-year overall survival and LRR were 70% and 15%, respectively, and the 4-year LRR in patients with pCR was 0% versus 22.0% in those without (P<.001). In patients without pCR, lymphovascular space invasion (LVSI; hazard ratio, 3.92; 95% CI, 1.64–9.38; P=.002) and extranodal extension (ENE; hazard ratio, 3.32; 95% CI, 1.35–8.15; P=.009) were significant predictors of LRR in multivariable analysis. In these patients, the 4-year LRR with LVSI was 39.8% versus 15.0% without (P<.001). Similarly, the 4-year LRR was 48.1% with ENE versus 16.1% without (P=.002). In patients without pCR, the presence of both LVSI and ENE were associated with an even further increased risk of LRR compared with patients with either LVSI or ENE alone and those with neither LVSI nor ENE in the residual tumor (P<.001). Conclusions: In patients without pCR, the presence of LVSI and ENE increases the risk of LRR in TNBC. The risk of LRR is compounded when both LVSI and ENE are present in the same patient. Future clinical trials are warranted to lower the risk of LRR in these high-risk patients.

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William R. Kennedy, Christopher Tricarico, Prashant Gabani, Ashley A. Weiner, Michael B. Altman, Laura L. Ochoa, Maria A. Thomas, Julie A. Margenthaler, Souzan Sanati, Lindsay L. Peterson, Cynthia X. Ma, Foluso O. Ademuyiwa, and Imran Zoberi

Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) predicts decreased distant metastasis. However, most patients do not experience pCR, and other risk factors for distant metastasis after NAC are poorly characterized. This study investigated factors predictive of distant metastasis in TNBC without pCR after NAC. Methods: Women with TNBC treated with NAC, surgery, and radiation therapy in 2000 through 2013 were reviewed. Freedom from distant metastasis (FFDM) was compared between patients with and without pCR using the Kaplan-Meier method. In patients without pCR, univariate and multivariable Cox analyses were used to determine factors predictive of distant metastasis. Results: We identified 153 patients with median follow-up of 4.0 years (range, 0.5–14.0 years). After NAC, 108 had residual disease (pCR, 29%). Five-year FFDM was 98% and 55% in patients with and without pCR, respectively (P<.001). Factors independently predicting FFDM in patients without pCR were pathologic nodal positivity (hazard ratio, 3.08; 95% CI, 1.54–6.14; P=.001) and lymphovascular space invasion (hazard ratio, 1.91; 95% CI, 1.07–3.43; P=.030). Patients with a greater number of factors had worse FFDM; 5-year FFDM was 76.5% for patients with no factors (n=38) versus 54.9% and 27.5% for patients with 1 (n=44) and 2 factors (n=26), respectively (P<.001). Conclusions: Lack of pCR after NAC resulted in worse overall survival and FFDM, despite trimodality therapy. In patients with residual disease after NAC, pathologic lymph node positivity and lymphovascular space invasion predicted worse FFDM.