Benlong Yang

PPAR signaling pathway may be an important predictor of breast cancer response to neoadjuvant chemotherapy

PurposeNeoadjuvant chemotherapy for advanced breast cancer may improve the radicality for a subset of patients, but others may suffer from severe adverse drug reactions without any benefit. To predict the responses to chemotherapy, we performed a phase II trial of neoadjuvant chemotherapy using a weekly PCb [paclitaxel (Taxol) plus carboplatin] regimen for stage II/III breast cancer and assessed the correlation between baseline gene expression and the tumor response to treatment.MethodsA total of 61 patients with stage II-III breast cancer were included and administered four cycles of preoperative PCb. We performed a gene expression analysis using Affymetrix HG-U133 Plus 2.0 GeneChip arrays in 31 breast cancer tissues. Differentially expressed genes (DEGs) were identified by the significance analysis of microarrays (SAM) program using a false discovery rate of 0.05. The Functional Annotation Tool in the DAVID Bioinformatics Resources was used to perform the gene functional enrichment analysis. The other 30 patients (15 pCR and 15 non-pCR patients) were available as an independent validation set to test the selected DEGs by quantitative real-time PCR analysis (qRT-PCR).ResultsBy analyzing six pathological complete response (pCR) patients and 25 patients with non-pCR, 300 probes (231 genes) were identified as differentially expressed between pCR and residual disease by the SAM program when the fold change was >2. The gene functional enrichment analysis revealed 15 prominent gene categories that were different between pCR and non-pCR patients, most notably the genes involved in the peroxisome proliferator-activated receptor (PPAR), DNA repair and ER signal pathways and in the immune-related gene cluster. The qRT-PCR analysis results for the genes in the PPAR pathway (LPL, SORBS1, PLTP, SCD5, MMP1 and CSTA) in independent validation set were consistent with the results from the microarray data analysis.ConclusionIn the present study, we identified a number of gene categories pertinent to the therapeutic response. We believe that the PPAR pathway may be an important predictor of genes that are involved in the chemotherapy response.

Adjuvant chemotherapy increases the prevalence of fat necrosis in immediate free abdominal flap breast reconstruction

BACKGROUND Fat necrosis is one of the most common complications following free flap breast reconstruction. Although a minor complication, fat necrosis can compromise esthetic results and confuse with cancer recurrence. Perfusion-related factors and post-operative radiotherapy are the known risks. However, the influence of adjuvant chemotherapy on fat necrosis prevalence remains unknown. METHODS Our initial experience of 88 consecutive breast reconstructions with free abdominal flaps was reviewed. The prevalence of fat necrosis was recorded and the risk factors were analyzed using univariate and multivariate logistic regression models. RESULTS The overall prevalence of fat necrosis was 36.4% in this series. In a multivariate logistic regression model, adjuvant chemotherapy significantly increased the risk of fat necrosis. The relative risk was 4.762 (95% confidence interval (CI), 1.767-12.831; p = 0.002). There was no evidence of a specific chemotherapeutic agent causing fat necrosis. The first cycle of adjuvant chemotherapy was frequently delivered earlier in patients with fat necrosis than those without fat necrosis, although this tendency was not statistically significant. CONCLUSIONS Our initial experience with free flap breast reconstruction seems to suggest that chemotherapy may increase the risk of fat necrosis following immediate breast reconstruction. Patients should be fully informed, and the initiation of post-operative chemotherapy may be adjusted accordingly.

Localization and evaluation of sentinel lymph node in breast cancer from computed tomographic lymphography

Objective: This study aimed to determine the accuracy of computed tomographic (CT) localization and CT-based diagnosis of sentinel lymph nodes (SLNs) metastasis. Methods: Thirty-four patients with confirmed breast cancer underwent 40-row CT scanning, and the first one or several lymph node(s) in the lymphatic drainage pathway was/were defined as the SLN(s). Dye and &ggr; probe-guided SLN biopsy was performed on all patients. To accurately localize the SLN, 19 patients (55.9%) underwent the percutaneous lymph node puncture procedure. The morphologic features of all the SLNs on CT scans were analyzed and compared with the SLN biopsy pathologic diagnosis. Results: Sentinel lymph nodes were successfully identified for all patients without any significant adverse effects. All localized SLNs corresponded well with SLNs identified on SLN biopsy, with an accuracy of 89.5%. Accuracy increased to 100% when the CT scan technique was combined with the blue dye method. The size criteria for metastatic diagnosis had a sensitivity of 85%, which increased to 94.7% when long-to-short-axis ratio and margin characteristics were also considered. Conclusions: The CT lymphography combined with the blue dye method accurately localized the SLNs. The CT-based diagnostic criteria improved the diagnostic accuracy of SLN metastases and were useful for evaluating the axillary status in early stage breast cancer patients.

Using peripheral blood mRNA signature to distinguish between breast cancer and benign breast disease in non-conclusive mammography patients

Due to the small volume and high density of breast tissue in Asian women, particularly younger women, mammographic diagnosis is sometimes non-conclusive, with a Breast Imaging Reporting and Data System (BI-RADS) result of 0. No alternative based on blood biomarkers has yet succeeded in discriminating between patients with breast cancer (BC) and those with benign breast disease (BBD) among BI-RADS 0 patients. In our study, 84 BC and 94 BBD patients with mammographic results and confirmed pathologic information were enrolled and categorized into two groups, namely, 79 BC and 73 BBD patients with BI-RADS 1-5 and 5 BC and 21 BBD patients with BI-RADS 0. RNA extracted from peripheral blood samples collected in PAXgeneTM tubes was analyzed after NuGEN WT-OvationTM RNA amplification using Affymetrix GeneChip

The Type of Breast Reconstruction May Not Influence Patient Satisfaction in the Chinese Population: A Single Institutional Experience

Background The goal of this study was to evaluate patient satisfaction with four common types of breast reconstruction performed at our institution: latissimus dorsi myocutaneous (LDM) flap reconstruction with or without implants, pedicled transverse rectus abdominis musculocutaneous (TRAM) flap reconstruction, and free deep inferior epigastric perforator (DIEP) flap reconstruction. Methods A custom survey consisting of questions that assessed general and aesthetic satisfaction was sent to patients who had undergone breast reconstruction in the last 5 years. The clinical data and details of the surgery were also collected from the patients who returned the surveys. We compared satisfaction rates across the four breast reconstruction types and analyzed the effects of various factors on overall general and aesthetic satisfaction rates using a binary logistic regression model. Result A total of 207 (72%) patients completed the questionnaires. Overall, significant differences in general and aesthetic satisfaction among the four procedures were not observed. A multivariate analysis revealed that the factor “complications” (p = 0.001) played a significant role in general satisfaction and that the factors “> 2 years since reconstruction” (p = 0.043) and “age > 35 years” (p = 0.05) played significant roles in overall aesthetic satisfaction. Conclusion The present study demonstrated that the type of breast reconstruction might not influence satisfaction in Chinese patients.

Trends and clinicopathological predictors of axillary evaluation in ductal carcinoma in situ patients treated with breast-conserving therapy

The aim of this study was to investigate the trends of axillary lymph node evaluation in ductal carcinoma in situ (DCIS) patients treated with breast‐conserving therapy (BCT) and to identify the clinicopathological predictors of axillary evaluation. DCIS patients treated with BCT in 2006–2015 at our institute were retrospectively included in the analysis. Patients were categorized into three groups: sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND), and non‐evaluation. Univariate and multivariate logistic regression analyses were performed to identify factors that predicted axillary evaluation. A total of 315 patients were identified, among whom 135 underwent SLNB, and 15 underwent ALND. The proportion of patients who underwent axillary evaluation increased from 33.0% in 2006–2010 to 53.8% in 2011–2015 (P < 0.001), however, no patients had lymph node metastasis based on final pathology. In multivariate analysis, high‐grade tumor favored axillary evaluation (OR = 4.376, 95% CI:1.410–13.586, P = 0.011); while excision biopsy favored no axillary evaluation compared with other biopsy methods (OR = 0.418, 95% CI: 0.192–0.909, P = 0.028). Subgroup analysis of patients treated in 2011–2015 revealed that high‐grade tumor (OR = 5.898, 95% CI: 1.626–21.390, P = 0.007) and palpable breast lump (OR = 2.497, 95% CI: 1.037–6.011, P = 0.041) were independent predictors of axillary lymph node evaluation. Despite the significant decrease in ALND and a concerning overuse of SLNB, we identified no axillary lymph node metastasis, which justified omitting axillary evaluation in these patients. High‐grade tumor, palpable lump, and biopsy method were independent predictors of axillary evaluations. Excision biopsy of suspicious DCIS lesions may potentially preclude the invasive component of the disease and help to avoid axillary surgery

A prospective study of breast anthropomorphic measurements, volume and ptosis in 605 Asian patients with breast cancer or benign breast disease

Objectives The current study aims to summarize breast anthropomorphic measurement features in Chinese patients with breast diseases and to investigate their potential correlations with demographic factors. Materials and methods Fifteen breast anthropomorphic parameters of 605 Chinese female patients were collected prospectively. Breast ptosis status was scaled by two methods and breast volume was calculated according to a modified formula of BREAST-V. Results Among 1210 breasts, the average breast volume was 340.0±109.1 ml (91.8–919.2 ml). The distance from the nipple to the inframammary fold was 7.5±1.6 cm in the standing position. The width of the breast base was 14.3±1.4 cm (8.5–23.5 cm). The incidence of breast ptosis was 22.8% (274/1204), of which 37 (23.5%) and 79 (31.7%) women had severe ptosis assessed by different criteria. Increased height (OR[odds ratio] = 1.500, P<0.001), post-menopausal status (OR = 1.463, P = 0.02), increased BMI, breastfeeding for 7–12 months (OR = 1.882, P = 0.008) and more than one year (OR = 2.367, P = 0.001) were risk factors for an increased breast volume. Post-menopausal status (OR = 2.390, P<0.001 and OR = 2.621, P<0.001 for different scales), BMI≥24.7 kg/m2 (OR = 3.149, P<0.001 and OR = 2.495, P = 0.002), breastfeeding for 7–12 months (OR = 4.136, P = 0.004 and OR = 4.010, P = 0.002), and breastfeeding for more than one year (OR = 6.934, P<0.001 and OR = 6.707, P<0.001) were independent risk factors for breast ptosis. Conclusions The current study provides anthropomorphic measurements data of Chinese women with breast diseases, which are useful for cosmetic and reconstructive breast surgery decisions. Post-menopausal status, increased BMI, and breastfeeding for more than six months were independent risk factors for both increased breast volume and breast ptosis.

P3-07-36: Predicting Sentinel Lymph Node Metastasis of a Chinese Breast Cancer Population: Assessment of an Existing Nomogram and a New Predictive Nomogram.

Background: The Memorial Sloan-Kettering Cancer Center (MSKCC) developed a nomogram to predict the presence of sentinel lymph node (SLN) metastasis in breast cancer patients. In our study, The MSKCC nomogram performance for prediction of SLN metastases was assessed in Chinese breast cancer population. A new model (Shanghai Cancer Center Nomogram, SCC nomogram ) was developed with clinically relevant variables and possible advantages. Methods: Data were collected from 771 patients with successful SLN biopsy who were treated during March 2005 to June 2010. Touch imprint cytology (TIC) and serial section with HE71(24 Suppl):Abstract nr P3-07-36.

A Novel Technique for Localization of Sentinel Lymph Node in Breast Cancer Patients Based on Computed Tomographic Lymphography

To the Editor: Sentinel lymph node biopsy (SLNB) has world-wide acceptance by most surgeons as a standard surgical procedure for patients with early-stage breast cancer (1), which can reduce unnecessary surgical invasion and postoperative complications of axillary lymph node dissection (ALND). Isotope and ⁄ or blue dye are applied as the routine methods for localizing SLNs preoperatively in most of institutes (2). However, SLNB has not been extensively accepted in mainland of China. The main reason is that the radioisotope tracer is not available in many hospitals here. Recently, several previous studies using interstitial multidetector-row computed tomographic lymphography (MDCT-LG) with a non-ionic contrast medium iopamidol demonstrated a high concordance in the identification of SLN in breast cancer patients with the dye-guided and ⁄ or isotope method (3). However, the use of skin marker was not so persuasive and cannot provide enough information about the accurate position of SLNs (4). Therefore, within the present study, the Breast Lesion Localization Needle (interv Medical, Canada) was introduced to locate the SLNs with the guidance of the MDCT-LG, and the aim of the present study was to evaluate the clinical value of this novel mapping method compared with the traditional methods. From January-2009 to July-2009, 21 patients treated for primary early breast cancer at our department were enrolled in the study. The computed tomographic lymphography (CT-LG) technique was described by Suga et al. (3), which was performed in the early morning of operation day. In brief, the patient was placed in the supine position, with both arms upward and bent at the elbows. Two milliliters iopamidol (Iopamiron 370; BRACCO, Shanghai, China) was injected subcutaneously into the periareolar and ⁄ or peritumoral areas after induction of local anesthesia (0.2 mL of 2% lidocaine hydrochloride). The initial dynamic scan was obtained 1 minute after a gentle massage of the injection site. During CT image acquisition, each patient was placed in the same position if possible, the transverse CT images were reconstructed with a 1.4 mm pitch and section thickness of 1 mm. 3D CT image was then reconstructed from the postcontrast CT images in InSpace 3D software (the Siemens LEONARDO Workstation). The SLN was identified as the most inferiorly visible nodule in the axilla connected to the lymphatic vessel on the CT-imaging monitor. The CT scanning was performed using a multidetector-row CT scanner (SOMATOM SENSATION-40; Siemens, Erlangen, Germany) at 120 kV and 140–270 mA. The localization of the SLN was guided by a laser light navigator system (Fig. 1). The SLN spot was indicated precisely by the cross-point of horizontal and vertical lines of the thin beam of red laser light, which was navigated according to the defined SLN spot on the CT image. The distance between the nodal and skin was also measured in the system. The CT table was then automatically moved to the suitable location. After local anesthesia, the defined lymph node would be punctured by a professional intervention doctor guided by the CT monitor using the Breast Lesion Localization Needles (interv Medical, Canada). Once optimal placement of the needle tip was confirmed by CT scanning, the stylet was removed, and the hook wire was inserted and advanced to the tip of the needle. The needle insert was then withdrawn, and the wire was maintained in a stable position. The needle would be fixed by rubberized fabric and then stay in the patient’s axilla until the surgery. The patients were Address correspondence and reprint requests to: Jiong Wu, MD, Department of Breast Surgery, Cancer Hospital ⁄ Cancer Institute, Breast Cancer Institute, Fudan University, 399 Ling-Ling Road, Shanghai 200032, China, or e-mail: wujiong1122@vip.sina.com. Benlong Yang and Hongna Tan contribute equally to this paper.