Immune Markers and Tumor-Related Processes Predict Neoadjuvant Therapy Response in the WSG-ADAPT HER2-Positive/Hormone Receptor-Positive Trial in Early Breast Cancer

Prognostic or predictive biomarkers in HER2-positive early breast cancer (EBC) may inform treatment optimization. The ADAPT HER2-positive/hormone receptor-positive phase II trial (NCT01779206) demonstrated pathological complete response (pCR) rates of ~40% following de-escalated treatment with 12 weeks neoadjuvant ado-trastuzumab emtansine (T-DM1) ± endocrine therapy. In this exploratory analysis, we evaluated potential early predictors of response to neoadjuvant therapy. The effects of PIK3CA mutations and immune (CD8 and PD-L1) and apoptotic markers (BCL2 and MCL1) on pCR rates were assessed, along with intrinsic BC subtypes. Immune response and pCR were lower in PIK3CA-mutated tumors compared with wildtype. Increased BCL2 at baseline in all patients and at Cycle 2 in the T-DM1 arms was associated with lower pCR. In the T-DM1 arms only, the HER2-enriched subtype was associated with increased pCR rate (54% vs. 28%). These findings support further prospective pCR-driven de-escalation studies in patients with HER2-positive EBC

Oncoplastic breast reconstruction after IORT

Prospective randomized clinical trials have shown that breast-conserving surgery followed by radiotherapy gives equivalent survival rates compared with mastectomy. The indications for breast-conserving therapy in breast cancer are expanding. The integration of oncoplastic surgery techniques with breast-conserving segmentectomy is a new approach that allows more extensive resections and results in more cosmetic favourable outcomes. During the last years we have defined five reconstruction principles in oncoplastic breast-conserving surgery. With these five principles we were able to perform more than 95% of all immediate reconstructions of partial mastectomy defects during breast-conserving surgery, resulting in optimized local and aesthetic outcomes. The oncoplastic reconstruction principles of partial mastectomy defects during breast-conserving surgery are as follows: glandular rotation, dermoglandular rotation, tumoradapted reduction mammoplasty, thoracoepigastric flap, Latissimus dorsi flap. Usually the whole breast is percutaneously irradiated after breast-conserving surgery. Depending on different risk factors, a local boost dose is applied to the tumor bed, which leads to a further reduction of local recurrences. Recently, the concept of intraoperative radiotherapy (IORT) as boost during breast-conserving surgery has been introduced internationally. From a surgical point of view intraoperative boost radiotherapy with a mobile device generating low-energy X-rays (Intrabeam (R)) can be combined with all oncoplastic principles for reconstructing partial mastectomy defects. The advantage of an oncoplastic reconstruction after breast-onserving surgery and IORT boost irradiation should be recommended to improve local outcome, to avoid seroma formation and to improve the cosmetic outcome after treatment

First Reported Use of Radiofrequency Identification (RFID) Technique for Targeted Excision of Suspicious Axillary Lymph Nodes in Early Stage Breast Cancer - Evaluation of Feasibility and Review of Current Recommendations

Background/Aim: The purpose of this study was to evaluate, whether radio frequency identification (RFID) labeling of axillary lymph nodes (LNs) for the use of targeted resection is feasible in primary breast cancer patients with suspicious LNs. Patients and Methods: We analyzed 10 consecutive patients where RFID technique was used for intraoperative detection of suspicious LNs without preceding neoadjuvant chemotherapy (NACT). We compared the specifics of these procedures to 10 consecutive sentinel lymph node biopsies (SLNB) in the cN0 situation. Results: Intraoperative detection rate (DR) for the RFID-labeled target lymph node (TLN) was 100%. Perioperative complications were infrequent and comparable to SLNB. Average time for location of the RFID labeled TLN was quicker than for the SLN. In 71.4% the chip bearing TLN equaled a SLN. Conclusion: The use of the RFID technique for intraoperative localization of axillary LNs for targeted excision seems feasible. RFID technique for targeted axillary dissection (TAD) following NACT should be investigated in a prospective manner

Factors Predictive of Sentinel Lymph Node Involvement in Primary Breast Cancer

Background/Aim: Sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) for axillary staging in patients with early-stage breast cancer. The need for therapeutic ALND is the subject of ongoing debate especially after the publication of the ACOSOG Z0011 trial. In a retrospective trial with univariate and multivariate analyses, factors predictive of sentinel lymph node involvement should be analyzed in order to define tumor characteristics of breast cancer patients, where SLNB should not be spared to receive important indicators for adjuvant treatment decisions (e.g. thoracic wall irradiation after mastectomy with or without reconstruction). Patients and Methods: Between 2006 and 2010, 1,360 patients with primary breast cancer underwent SLNB withlwithout ALND with evaluation of tumor localization, multicentricity and multifocality, histological subtype, tumor size, grading, lymphovascular invasion (LVI), and estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status. These characteristics were retrospectively analyzed in univariate and multivariate logistic regression models to define significant predictive factors for sentinel lymph node involvement. The multivariate analysis demonstrated that tumor size and LVI (p<0.001) were independent predictive factors for metastatic sentinel lymph node involvement in patients with early-stage breast cancer. Conclusion: Because of the increased risk for metastatic involvement of axillary sentinel nodes in cases with larger breast cancer or diagnosis of LVI, patients with these breast cancer characteristics should not be spared from SLNB in a clinically node-negative situation in order to avoid falsenegative results with a high potential for wrong indication of primary breast reconstruction or wrong non-indication of necessary post-mastectomy radiation therapy. The prognostic impact of avoidance of axillary staging with SLNB is analyzed in the ongoing prospective INSEMA trial

Clinical Significance of Urokinase-type Plasminogen Activator (uPA) and its Type-1 Inhibitor (PAI-1) for Metastatic Sentinel Lymph Node Involvement in Breast Cancer

Urokinase-type plasminogen activator (uPA) and its type-1 inhibitor (PAI-1) are key factors for tumor invasion and development of metastases in breast cancer. Prospective studies confirmed the prognostic significance of these factors for development of distant metastases. The predictive impact of uPA and PAI-1 for metastatic sentinel lymph node involvement is unclear. Patients and Methods: Between 2006 and 2008 uPA and PAI-1 were measured in 184 out of 1,035 patients for primary breast cancer. uPA and PAI-1 were analyzed with an ELISA assay. Measured concentrations were considered as negative for uPA <3 ng/ml and for PAI-1 <14 ng/ml. Results: In a retrospective analysis, 1731184 women had a negative sentinel lymph node and 11/184 women had a metastatic sentinel lymph node. From the 11 women with a positive sentinel lymph node 7 had elevated values for uPA and 4 had elevated values for PAI-1. Four and 7 women were uPA- and PAI-1-negative, respectively. Sensitivity, specificity, positive and negative predictive values for uPA were 63.3%, 50.9%, 7.6%, 95.6% and for PAI-1 36%, 52.6%, 4.7%, 92.9%. Even the combination of both uPA and PAI-1 values did not detect 3/11 women with metastatic lymph node involvement. Conclusion: uPA and PAI-1 alone or in combination did not identify all patients with metastatic lymph node involvement. Thus, uPA and PAI-1 cannot be considered as predictive selection parameters to avoid sentinel lymph node biopsy in case of negative values for uPA or PAI-1

A Retrospective Head-to-head Comparison Between TiLoop Bra/TiMesh (R) and Seragyn (R) in 320 Cases of Reconstructive Breast Surgery

Background/Aim: Clinical data concerning synthetic meshes in comparison to acellular dermal matrices (ADMs) in breast reconstruction are limited. Also, direct comparisons between titanium-coated polypropylene mesh and partially absorbable polypropylene mesh have not yet been reported. Materials and Methods: This analysis represents a retrospective, single-surgeon, multi-center study of 320 cases using either TiLoop Bra/TiMesh (R) (n=192) or Seragyn (R) (n=128) in breast reconstruction. Results were compared with ADM-based reconstructions (Epiflex (R) and SurgiMend (R)). Results: Major complication rates (i.e. revision surgery) occurred in 3.9% (Seragyn (R)) and 8.3% (TiLoop Bra/TiMesh (R)) of all cases. Minor complications occurred in 18% (Seragyn (R)) and 8.9% (TiLoop Bra/TiMesh (R)). Subgroup analysis showed red breast syndrome to occur more often in the Seragyn group (3.9% Seragyn (R) vs. 0.5% TiLoop Bra/TiMesh (R), p<0.05). Conclusion: TiLoop Bra/TiMesh (R) and Seragyn (R) do not differ significantly in complication rates. There was no difference in performance when compared to ADMs