Carla S. Fisher

Neoadjuvant Chemotherapy Is Associated with Improved Survival Compared with Adjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer Only after Complete Pathologic Response

IntroductionTriple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is known to be chemosensitive. In patients with TNBC, we sought to compare survival outcomes between patients receiving neoadjuvant chemotherapy, with and without complete pathologic response (pCR), and those receiving adjuvant chemotherapy.MethodsWe performed a retrospective chart review and identified 385 patients with stage I–III TNBC who were treated with neoadjuvant or adjuvant chemotherapy between 2000 and 2008. Patients were divided according to receipt of neoadjuvant chemotherapy with pCR, neoadjuvant chemotherapy without pCR, and adjuvant chemotherapy. Data were compared using Fisher’s exact test and analysis of variance (ANOVA). Kaplan–Meier curves were generated.ResultsOf 385 patients, 151 (39%) received neoadjuvant chemotherapy and 234 (61%) received adjuvant chemotherapy. Twenty-six (17%) of those patients receiving neoadjuvant chemotherapy had pCR. After controlling for covariates associated with survival in unadjusted tests, patients undergoing neoadjuvant chemotherapy with residual tumor had significantly worse survival compared with patients receiving adjuvant therapy [hazard ratio (HR) = 0.51, P = 0.007] and a trend towards worse survival compared with patients receiving neoadjuvant therapy with pCR (HR = 0.19, P = 0.10).ConclusionsAlthough previous clinical trials have not demonstrated a survival difference between patients receiving neoadjuvant versus adjuvant chemotherapy for breast cancer, our study suggests an overall survival benefit in patients with pCR following neoadjuvant chemotherapy compared with patients receiving adjuvant therapy. It is clear that a prospective study needs to be carried out to better elucidate the timing of chemotherapy in patients with TNBC.

Early postoperative outcomes in lumpectomy versus simple mastectomy.

BACKGROUND Relatively scarce outcomes research exists that compares early postoperative complications between breast conservation surgery (BCS) and simple mastectomy (SM). Such information would improve a surgeons ability to provide informed consent when considering treatment options, especially for women with early stage breast cancer who have the option to receive either BCS or SM. MATERIALS AND METHODS The National Surgical Quality Improvement Program database from years 2009-2012 was analyzed. For each treatment group, we used Current Procedural Terminology codes specific to the treatment modality with sentinel lymph node biopsy as an inclusion criteria. We excluded patients who received axillary lymphadenectomies, bilateral disease or symmetry procedures, and additional breast reconstructive surgery. We compared each group with chi square and two-sample t-tests to look for preoperative comorbidity differences, then used unadjusted odds ratios to compare postoperative complication rates. RESULTS Inclusion and exclusion criteria provided 6682 patients in the BCS group and 3339 patients in the SM group. Baseline comorbid condition characteristics showed no clinical differences between groups except for diabetes (8.5% in SM versus 6.5% in BCS). Statistical analysis between each treatment modality revealed that the SM group had significantly higher wound complications, bleeding, infections, and overall complications than the BCS group. CONCLUSIONS Although both BCS and SM options have low early postoperative complication rates when treating early stage breast cancer, BCS has fewer complications with regard to bleeding, wound complications and infections.

Anti-HER2 CD4+ T-helper type 1 response is a novel immune correlate to pathologic response following neoadjuvant therapy in HER2-positive breast cancer

IntroductionA progressive loss of circulating anti-human epidermal growth factor receptor-2/neu (HER2) CD4+ T-helper type 1 (Th1) immune responses is observed in HER2pos-invasive breast cancer (IBC) patients relative to healthy controls. Pathologic complete response (pCR) following neoadjuvant trastuzumab and chemotherapy (T + C) is associated with decreased recurrence and improved prognosis. We examined differences in anti-HER2 Th1 responses between pCR and non-pCR patients to identify modifiable immune correlates to pathologic response following neoadjuvant T + C.MethodsAnti-HER2 Th1 responses in 87 HER2pos-IBC patients were examined using peripheral blood mononuclear cells pulsed with 6 HER2-derived class II peptides via IFN-γ ELISPOT. Th1 response metrics were anti-HER2 responsivity, repertoire (number of reactive peptides), and cumulative response across 6 peptides (spot-forming cells [SFC]/106 cells). Anti-HER2 Th1 responses of non-pCR patients (n = 4) receiving adjuvant HER2-pulsed type 1-polarized dendritic cell (DC1) vaccination were analyzed pre- and post-immunization.ResultsDepressed anti-HER2 Th1 responses observed in treatment-naïve HER2pos-IBC patients (n = 22) did not improve globally in T + C-treated HER2pos-IBC patients (n = 65). Compared with adjuvant T + C receipt, neoadjuvant T + C — utilized in 61.5 % — was associated with higher anti-HER2 Th1 repertoire (p = 0.048). While pCR (n = 16) and non-pCR (n = 24) patients did not differ substantially in demographic/clinical characteristics, pCR patients demonstrated dramatically higher anti-HER2 Th1 responsivity (94 % vs. 33 %, p = 0.0002), repertoire (3.3 vs. 0.3 peptides, p < 0.0001), and cumulative response (148.2 vs. 22.4 SFC/106, p < 0.0001) versus non-pCR patients. After controlling for potential confounders, anti-HER2 Th1 responsivity remained independently associated with pathologic response (odds ratio 8.82, p = 0.016). This IFN-γ+ immune disparity was mediated by anti-HER2 CD4+T-bet+IFN-γ+ (i.e., Th1) — not CD4+GATA-3+IFN-γ+ (i.e., Th2) — phenotypes, and not attributable to non-pCR patients’ immune incompetence, host-level T-cell anergy, or increased immunosuppressive populations. In recruited non-pCR patients, anti-HER2 Th1 repertoire (3.7 vs. 0.5, p = 0.014) and cumulative response (192.3 vs. 33.9 SFC/106, p = 0.014) improved significantly following HER2-pulsed DC1 vaccination.ConclusionsAnti-HER2 CD4+ Th1 response is a novel immune correlate to pathologic response following neoadjuvant T + C. In non-pCR patients, depressed Th1 responses are not immunologically “fixed” and can be restored with HER2-directed Th1 immune interventions. In such high-risk patients, combining HER2-targeted therapies with strategies to boost anti-HER2 Th1 immunity may improve outcomes and mitigate recurrence.

Identification of breast cancer margins using intraoperative near-infrared imaging

Current methods of intraoperative breast cancer margin assessment are labor intensive, not fully reliable, and time consuming; therefore novel strategies are necessary. We hypothesized that near infrared (NIR) intraoperative molecular imaging using systemic indocyanine green (ICG) would be helpful in discerning tumor margins.

Dendritic Cell Vaccination Enhances Immune Responses and Induces Regression of HER2pos DCIS Independent of Route: Results of Randomized Selection Design Trial.

Purpose: Vaccination with HER2 peptide-pulsed DC1s stimulates a HER2-specific T-cell response. This randomized trial aimed to establish safety and evaluate immune and clinical responses to vaccination via intralesional (IL), intranodal (IN), or both intralesional and intranodal (ILN) injection. Experimental Design: Fifty-four HER2pos patients [42 pure ductal carcinoma in situ (DCIS), 12 early invasive breast cancer (IBC)] were enrolled in a neoadjuvant HER2 peptide-pulsed DC1 vaccine trial. Patients were randomized to IL (n = 19), IN (n = 19), or ILN (n = 16) injection. Immune responses were measured in peripheral blood and sentinel lymph nodes by ELISPOT or in vitro sensitization assay. Pathologic response was assessed in resected surgical specimens. Results: Vaccination by all injection routes was well tolerated. There was no significant difference in immune response rates by vaccination route (IL 84.2% vs. IN 89.5% vs. ILN 66.7%; P = 0.30). The pathologic complete response (pCR) rate was higher in DCIS patients compared with IBC patients (28.6% vs. 8.3%). DCIS patients who achieved pCR (n = 12) and who did not achieve pCR (n = 30) had similar peripheral blood anti-HER2 immune responses. All patients who achieved pCR had an anti-HER2 CD4 immune response in the sentinel lymph node, and the quantified response was higher by response repertoire (P = 0.03) and cumulative response (P = 0.04). Conclusions: Anti-HER2 DC1 vaccination is a safe and immunogenic treatment to induce tumor-specific T-cell responses in HER2pos patients; immune and clinical responses were similar independent of vaccination route. The immune response in the sentinel lymph nodes, rather than in the peripheral blood, may serve as an endpoint more reflective of antitumor activity. Clin Cancer Res; 23(12); 2961–71. ©2016 AACR.

A cost-utility analysis of the use of preoperative computed tomographic angiography in abdomen-based perforator flap breast reconstruction.

Background: Computed tomographic angiography is a diagnostic tool increasingly used for preoperative vascular mapping in abdomen-based perforator flap breast reconstruction. This study compared the use of computed tomographic angiography and the conventional practice of Doppler ultrasonography only in postmastectomy reconstruction using a cost-utility model. Methods: Following a comprehensive literature review, a decision analytic model was created using the three most clinically relevant health outcomes in free autologous breast reconstruction with computed tomographic angiography versus Doppler ultrasonography only. Cost and utility estimates for each health outcome were used to derive the quality-adjusted life-years and incremental cost-utility ratio. One-way sensitivity analysis was performed to scrutinize the robustness of the authors’ results. Results: Six studies and 782 patients were identified. Cost-utility analysis revealed a baseline cost savings of

Which Imaging Modality Is Superior for Prediction of Response to Neoadjuvant Chemotherapy in Patients with Triple Negative Breast Cancer

3179, a gain in quality-adjusted life-years of 0.25. This yielded an incremental cost-utility ratio of −

Medical School Surgical Boot Camps: A Systematic Review

12,716, implying a dominant choice favoring preoperative computed tomographic angiography. Sensitivity analysis revealed that computed tomographic angiography was costlier when the operative time difference between the two techniques was less than 21.3 minutes. However, the clinical advantage of computed tomographic angiography over Doppler ultrasonography only showed that computed tomographic angiography would still remain the cost-effective option even if it offered no additional operating time advantage. Conclusions: The authors’ results show that computed tomographic angiography is a cost-effective technology for identifying lower abdominal perforators for autologous breast reconstruction. Although the perfect study would be a randomized controlled trial of the two approaches with true cost accrual, the authors’ results represent the best available evidence.

A Cost-Utility Analysis Comparing the Sartorius versus the Rectus Femoris Flap in the Treatment of the Infected Vascular Groin Graft Wound.

Background and Objectives. Triple negative breast cancer (TNBC) has been shown to be generally chemosensitive. We sought to investigate the utility of mammography (MMG), ultrasonography (US), and breast magnetic resonance imaging (MRI) in predicting residual disease following neoadjuvant chemotherapy for TNBC. Methods. We identified 148 patients with 151 Stage I–III TNBC treated with neoadjuvant chemotherapy. Residual tumor size was estimated by MMG, US, and/or MRI prior to surgical intervention and compared to the subsequent pathologic residual tumor size. Data were compared using chi-squared test. Results. Of 151 tumors, 44 (29%) did not have imaging performed prior to surgical treatment. Thirty-eight (25%) tumors underwent a pathologic complete response (pCR), while 113 (75%) had residual invasive disease. The imaging modality was accurate to within 1 cm of the final pathologic residual disease in 74 (69%) cases and within 2 cm in 94 (88%) cases. Groups were similar with regards to patient age, race, tumor size and grade, and clinical stage (P > 0.05). Accuracy to within 1 cm was the highest for US (83%) and the lowest for MMG (56%) (P < 0.05). Conclusions. Breast US and MRI were more accurate than MMG in predicting residual tumor size following neoadjuvant chemotherapy in patients with TNBC. None of the imaging modalities were predictive of a pCR.

Addition of anti-estrogen therapy to anti-HER2 dendritic cell vaccination improves regional nodal immune response and pathologic complete response rate in patients with ERpos/HER2pos early breast cancer

PURPOSE Many medical schools have begun to offer surgical boot camps to senior medical students. The aim of the present study is to systematically review the literature and evidence surrounding medical school surgical boot camps to direct future research into the effectiveness of boot camps. METHODS A systematic review was conducted, searching MEDLINE, EMBASE, PsycINFO, CINAHL, and ERIC. The review was conducted according to the PICOTS structure, with an intervention of a surgical boot camp for senior medical students entering surgical residencies. RESULTS The search resulted in 5351 database hits, from which we identified 10 published studies that met the inclusion criteria. Two reviews were identified that met the PICOTS criteria but were excluded from data synthesis. Boot camps increase the confidence and competence of medical students entering their surgical internships. There is no objective assessment of the effect of boot camps on the clinical performance of interns. CONCLUSIONS Despite the success of medical school surgical boot camps, no objective data exist to show that boot camps translate into improved performance during internship.