NSQIP Analysis of Axillary Lymph Node Dissection Rates for Breast Cancer: Implications for Resident and Fellow Participation.

INTRODUCTION: Management of the axilla in invasive breast cancer (IBC) has shifted away from more radical surgery such as axillary lymph node dissection (ALND), towards less invasive procedures, such as sentinel lymph node biopsy. Because of this shift, we hypothesize that there has been a national downward trend in ALND procedures, subsequently impacting surgical trainee exposure to this procedure using the ACS-NSQIP database to evaluate this. METHODS: Women with IBC were identified in the ACS-NSQIP database from 2007 to 2014. Procedures including ALND were identified using CPT codes. This number was divided by total cases, given a varying number of participating institutions each year. Next, cases involving resident participation were identified and divided by training level: junior (post graduate year-[PGY] 1-2), senior (PGY 3-5) and fellow (PGY ≥ 6). Two tailed z tests were used to compare proportions, with significance determined when p < 0.05. RESULTS: A total of 128,372 women were identified with IBC with 36,844 ALND. ALND rates decreased by an average of 2.43% yearly from 2007 to 2014. Resident participation significantly drops in 2011, from 49.3% before to 29.4% after (p < 0.01). Junior residents experienced a significant decrease in participation rate (43.3%-32.2%, p < 0.05). Senior residents and fellows experienced an upward trend in their participation, although not significant (51.2%-56.3%, p = 0.35, and 5.6%-11.6%, p = 0.056, respectively). CONCLUSIONS: Using the ACS-NSQIP database, we demonstrate the downward trend in rate of ALND for IBC with subsequent decrease in resident participation. Junior residents experienced a significant decrease in their participation with no significant change for senior or fellow-level trainees. Awareness of this trend is important when creating future surgical curriculum changes for general surgery and fellowship training programs.

Anti-HER2 CD4+ T-Helper Type 1 Immune Response is Superior to Breast MRI for Assessing Response to Neoadjuvant Therapy in Patients with HER2-Positive Breast Cancer.

BACKGROUND: In human epidermal growth factor 2-positive breast cancer (HER2+BC), neoadjuvant chemotherapy and anti-HER2-targeted therapy (nCT) achieves a complete pathologic response (pCR) in 40-67% of patients. Posttreatment magnetic resonance imaging (pMRI) is considered the gold standard, with high specificity but lower sensitivity for assessing response. The authors previously determined that anti-HER2Th1 immune response is associated with pathologic response after nCT in HER2+BC patients. This study contrasted pMRI with anti-HER2Th1 response for assessing pCR in HER2+BC. METHODS: A retrospective review of HER2+BC patients at the authors' institution was performed. Original pMRI reports were collected, and images were reviewed by a breast radiologist blinded to pCR and immune response. The post-nCT imaging-based tumor response was assessed by Response Evaluation Criteria in Solid Tumors. The anti-HER2Th1 response was determined by ex vivo stimulation of peripheral blood mononuclear cells with six major histocompatibility complex (MHC) class 2-derived HER2 peptides via enzyme-linked immunospot (ELISPOT). Posttreatment MRI and anti-HER2Th1 responses were cross-tabulated with pCR. Standard diagnostic metrics were computed. RESULTS: For 30 patients, pMRI and anti-HER2Th1 immune response were measured, with 13 patients (43.3%) achieving pCR. The mean anti-HER2Th1 response in pCR was 167 (range 53-418), and

Restoring Lost Anti-HER-2 Th1 Immunity in Breast Cancer: A Crucial Role for Th1 Cytokines in Therapy and Prevention.

The ErbB/B2 (HER-2/neu) oncogene family plays a critical role in the development and metastatic spread of several tumor types including breast, ovarian and gastric cancer. In breast cancer, HER-2/neu is expressed in early disease development in a large percentage of DCIS lesions and its expression is associated with an increased risk of invasion and recurrence. Targeting HER-2 with antibodies such as trastuzumab or pertuzumab has improved survival, but patients with more extensive disease may develop resistance to therapy. Interestingly, response to HER-2 targeted therapies correlates with presence of immune response genes in the breast. Th1 cell production of the cytokines interferon gamma (IFNγ) and TNFα can enhance MHC class I expression, PD-L1 expression, augment apoptosis and tumor senescence, and enhances growth inhibition of many anti-breast cancer agents, including anti-estrogens and HER-2 targeted therapies. Recently, we have identified that a loss of anti-HER-2 CD4 Th1 in peripheral blood occurs during breast tumorigenesis and is dramatically diminished, even in Stage I breast cancers. The loss of anti-HER-2 Th1 response is specific and not readily reversed by standard therapies. In fact, this loss of anti-HER-2 Th1 response in peripheral blood correlates with lack of complete response to neoadjuvant therapy and diminished disease-free survival. This defect can be restored with HER-2 vaccinations in both DCIS and IBC. Correcting the anti-HER-2 Th1 response may have significant impact in improving response to HER-2 targeted therapies. Development of immune monitoring systems for anti-HER-2 Th1 to identify patients at risk for recurrence could be critical to improving outcomes, since the anti-HER-2 Th1 response can be restored by vaccination. Correction of the cellular immune response against HER-2 may prevent recurrence in high-risk patients with DCIS and IBC at risk of developing new or recurrent breast cancer.

Restoring anti-oncodriver Th1 responses with dendritic cell vaccines in HER2/neu-positive breast cancer: progress and potential.

HER2/neu is expressed in the majority of in situ breast cancers, but maintained in 20-30% of invasive breast cancer (IBC). During breast tumorigenesis, there is a progressive loss of anti-HER2 CD4(pos) Th1 (anti-HER2Th1) from benign to ductal carcinoma in situ, with almost complete loss in IBC. This anti-HER2Th1 response can predict response to neoadjuvant therapy, risk of recurrence and disease-free survival. Vaccines consisting of HER2-pulsed type I polarized dendritic cells (DC1) administered during ductal carcinoma in situ and early IBC can efficiently correct anti-HER2Th1 response and have clinical impact on the disease. In this review, we will discuss the role of anti-HER2Th1 response in the three phases of immunoediting during HER2 breast cancer development and opportunities for reversing these processes using DC1 vaccines alone or in combination with standard therapies. Correcting the anti-HER2Th1 response may represent an opportunity for improving outcomes and providing a path to eliminate escape variants.

Outcomes After Oncoplastic Breast-Conserving Surgery in Breast Cancer Patients: A Systematic Literature Review.

BACKGROUND: Surgeons have increasingly performed breast-conserving surgery (BCS) utilizing oncoplastic techniques in place of standard lumpectomy for early-stage breast cancer. We assess oncologic outcomes after oncoplastic BCS for T1-T2 breast cancer. METHODS: A systematic literature review identified peer-reviewed articles in PubMed evaluating BCS with oncoplastic reconstruction. Selected studies reported on positive margin rate (PMR), re-excision rate (RR), conversion to mastectomy rate (CMR), overall survival (OS), disease-free survival (DFS), local recurrence (LR), distant recurrence (DR), complication rate, and/or cosmetic outcomes. RESULTS: The search yielded 474 articles; 55 met the inclusion criteria and collectively evaluated 6011 patients with a mean age 54.6 years over a mean follow-up 50.5 months. T1 (43.8 %) and T2 (39.3 %) invasive ductal carcinoma were the most common tumor histopathologies. PMR, RR, and CMR were 10.8, 6.0, and 6.2 %, respectively, while OS, DFS, LR and DR were 95.0, 90.0, 3.2, and 8.7 %, respectively. Margin widths were heterogeneously defined in studies that included margin assessment. The PMR was not significantly different when positive margins were defined as tumor <10, <5, < 2, and <1 mm from ink margin, or tumor on ink (p = 0.162). Eleven studies reported specific margins for 1455 patients, of whom 143 (9.8 %) had positive margins, including 113 (7.8 %) with tumor on ink. CONCLUSIONS: This study is the largest comprehensive literature review to date on oncoplastic BCS. Our systematic review reveals high rates of OS and DFS with low LR, DR, PMR, RR, CMR and complication rates, thereby confirming the oncologic safety of this procedure in patients with T1-T2 invasive breast cancer.

Immediate breast reconstruction using porcine acellular dermal matrix (Strattice™): long-term outcomes and complications.

BACKGROUND: There has been limited reported experience with the use of Strattice™ (LifeCell Corp., Branchburg, NJ), a porcine-derived acellular dermal matrix, in implant-based breast reconstruction. The purpose of this study is to evaluate our experience with this matrix. METHODS: Patients who underwent immediate single-stage or two-stage implant-based breast reconstruction with the assistance of Strattice were included in this study. Patient charts were reviewed for indications for mastectomy, adjunctive radiotherapy use, implant or expander volume, length of follow-up period, and type and incidence of complications during the follow-up period. Biopsies of Strattice were taken for histological analyses. RESULTS: A total of 105 reconstructions were performed in 54 patients: 77% were prophylactic and 23% were oncologic. All, but 4, reconstructions were single stage. Mean implant volume of single-stage reconstructions were 444.1 (range: 150-700 cc) and mean expander volume after completion of expansion was 400 (range: 350-450). Mean follow-up period was 41.3 months (range: 35.5-48.4 months). Total complication rate was 8.6%. Complications occurred in 9 breasts: implant loss or explantation (3.8%), infection (3.8%), skin breakdown or necrosis (2.9%), seroma (1.9%), implant exposure (1.0%), and delayed skin healing (1.0%). Histological analyses of implanted Strattice revealed a viable matrix with fibroblast infiltration and revascularization. CONCLUSIONS: Over a mean 3.5-year follow-up period, low complication rates and good outcomes were observed with the use of Strattice that are comparable to those reported with human acellular dermal matrices.

Reduction of time to definitive care in trauma patients: effectiveness of a new checklist system.

This study evaluated the feasibility of establishing a new trauma transfer checklist and assessed its impact on trauma-related interhospital transfers. A standard envelope with a printed checklist (N.E.W.S.) incorporating four key concepts in the care and transfer of trauma patients was used. A prospective comparison of consecutive interhospital trauma transfers to the major trauma service between July 1999-May 2000 (pre-N.E.W.S.) and August 2000-November 2000 (post-N.E.W.S.) was made. Changes in management satisfaction were assessed by a Likert scale (1=poor to 5=excellent). Pre-N.E.W.S., 88 trauma patients were transferred and 20 trauma transfers were recorded post-N.E.W.S. The time to definitive care pre-N.E.W.S. was 443+/-322 min, and 339+/-108 min (P=0.014) post-N.E.W.S. The time in the referring hospital was also reduced from 343+/-310 min pre-N.E.W.S. to 197+/-90 min post-N.E.W.S (P=0.0002). The checklist system prompted changes in the management of the trauma patient in 20% of the cases and there was a high level of satisfaction expressed by users of the checklist (4.6+/-0.7). The N.E.W.S. checklist is effective in facilitating the interhospital transfer of trauma patients by shortening the time to definitive care.