bluuebunny/crossref_metadata_2025 huggingface dataset:
P2-15-01: Surgical Patterns of Care after Magnetic Resonance Imaging in the Academic Setting in Patients with Operable Breast Cancer Treated with Neoadjuvant Systemic Therapy: A Secondary Analysis of TBCRC 017.
Authors: De Los Santos J , Cantor A , Mcguire K , Golshan M , Meric-Bernstam F , Horton J , Nanda R , Amos K , Forero A , Hudis C , Meszoely I , Hwang S
Published: June 2012

Background: Neoadjuvant chemotherapy is increasingly used to downstage locally advanced tumors, test new regimens, and improve chances of breast conservation. In parallel, use of breast MRI for surgical planning and as a potential response biomarker has also increased along with an observed increase in mastectomy rates. This secondary analysis reports surgical patterns of care across 8 NCI comprehensive cancer centers in women receiving both neoadjuvant therapy and breast MRIs.

Methods: 770 women from 8 institutions were retrospectively identified as having received neoadjuvant systemic therapy with MRI done before and after systemic treatment. Univariate and multivariate analyses of covariates associated with surgical management were performed. Within MRI complete response or not, the Jonckheere-Terpstra Test (JTT) was used to test for a trend in mastectomy rate by T stage.

Results: Surgical data was available on 763/770 patients. Table 1 lists MRI response by pretreatment imaging size and final breast surgery. Distribution of pretreatment imaging-defined T stage was as follows: T1 66 (8%), T2 436 (57%), T3 230 (30%), and T4 36 (5%). 347/763 (45%) patients received breast conserving surgery and 416/763 (55%) had a mastectomy. 58% vs 43% (p=0.0003) of those with an incomplete vs complete MRI response had a mastectomy, respectively. Univariate logistic regression analysis of covariates significantly associated with use of mastectomy included ER- status (p=0.01), incomplete MRI response (p=0.0003), higher T stage (p<0.0001), chemotherapy regimen (p=0.006), younger age (p<0.0001), and institution (p=0.002); all except chemotherapy regimen and institution remained independent predictors of mastectomy on multivariate analysis. Patients with larger baseline T stage and an incomplete response on MRI (P<0.001) were more likely to undergo mastectomy. Overall, breast conservation was low (262/495, 53%) of all T1-T2 patients, especially in the T1 subset (26/65, 40%).

Conclusions: In a contemporary group of women treated with preoperative chemotherapy at NCI designated cancer centers and with available pre/post MRI, we observed a lower frequency of breast conservation as compared to historical data from prospective randomized trials. Larger tumor size at baseline was associated with higher mastectomy rates. However, even among those with a complete MRI response, 43% had a mastectomy. In addition to clinical response and MRI findings, factors not examined here (e.g., BRCA status, education level, and patient/provider preference) may influence the decision-making process and deserve further evaluation.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-01.
P2-15-09: Prospective Randomized Comparison of Conventional Instruments and the Harmonic Focus® Device in Breast-Conserving Therapy for Primary Breast Cancer.
Authors: Böhm D , Kubitza A , Lebrecht A , Schmidt M , Kölbl H
Published: June 2012

Background: In recent years, surgeons have utilized Harmonic instruments to perform breast cancer resection. Retrospective and prospective studies have demonstrated that the use of this surgical device for mastectomy and axillary dissection can reduce perioperative blood loss, seroma formation, and duration and total amount of drainage. No study has analyzed the feasibility of Harmonic instruments in breast-conserving surgery. We conducted a prospective, randomized clinical trial comparing Harmonic instrument and conventional surgery in the performance of breast conserving surgery and axillary procedures to determine differences in surgical procedures, postoperative outcome, and complications.

Methods: One hundred and forty seven patients with operable breast cancer who underwent breast-conserving surgery at a single institution between December 2009 and March 2011 were included in the analysis. Surgery was performed in 73 patients with the Harmonic Focus® device and in 74 with scissors and electrocautery. Charts were reviewed for patient demographics, histopathologic reports, surgical procedures, length of stay, volume and duration of postoperative drainage, complications such as seroma and hematoma formation, and postoperative pain.

Results: We found a statistically significant difference in size of resected breast tissue (p<0.001), postoperative serum hemoglobin (p=0.001), volume (p<0.001) and duration (p<0.001) of breast drainage, volume (p<0.001) and duration (p=0.001) of axillary drainage, intramammary (p=0.04) and axillary (p=0.006) seroma formation, subjective (p=0.012) and objective (p<0.001) postoperative pain, and length of hospital stay (p=0.002) in favor of the Harmonic surgical device.

Discussion: This is the only study comparing the Harmonic instrument with traditional surgery in both breast conserving surgery and axillary procedures. From this study, we conclude that despite higher costs, the Harmonic device is safe to use and provides key benefits in intraoperative technique, postoperative outcome, and rate of complications in breast cancer surgery.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-09.
P2-16-16: Nipple Sparing Mastectomy and Immediate Breast Reconstruction: Critical Appraisal of Five Year, Single Centre Outcomes.
Authors: Westbroek D , Karat I , Min-Hui H , Gukas I , Daoud R , Laidlaw IJ
Published: June 2012

Background

Approximately 5,000 patients undergo breast reconstruction annually in the United Kingdom ( 2:1 ratio of immediate versus delayed respectively). Whilst skin sparing mastectomy is an accepted modality for local control in appropriately selected patients, nipple preservation remains controversial. In over 1,800 peer reviewed nipple sparing mastectomy (NSM) cases, the local event rate attributable to NAC preservation following NSM (therapeutic and prophylactic) is 0.16% with no evidence of deleterious impact on disease free survival. This study aims to evaluate in a selected cohort of patients, the oncological safety and aesthetic outcome of nipple- sparing mastectomy and immediate breast reconstruction (IBR). We highlight the surgical technique used and propose in/exclusion criteria.

Material and Methods: Patients were identified retrospectively from our Institution's electronic patient records and WinPath™ database by searching clinical codes corresponding to NSM & IBR, performed by the senior authors (IJL and RD) between January 2004 and December 2008. Pre-operative selection criteria included: 100% pre-operative lesion characterisation; 5mm margin acceptance; submission of separate nipple core specimens for paraffin block histological assessment and re-excision of all involved/close margins. Follow-up data was verified from patients’ case notes, histo- pathological review and standardised photographic views. Endpoints include: local recurrence rate, disease free survival, peri-operative NAC subcutaneous tissue loss and validated aesthetic outcome measures.

Results*: 84 patients underwent NSM & IBR for invasive disease. The mean age was 52.1 years and a median follow-up of 38 months. IBR utilised autologous tissue (latissimus dorsi or transverse rectus abdominus musculocutaneous flaps) with/without implant prosthesis. There was one case of local recurrence (1.2%) in a patient who declined re-excision of close/involved margins and no recorded breast cancer related deaths. Peri-operative complication rates were within the national mastectomy breast reconstruction audit outcome guidelines.

Conclusion: In this cohort of patients, nipple sparing mastectomy and immediate breast reconstruction achieves comparable oncological outcomes with excellent aesthesis relative to traditional ablative procedures for local control. Nipple preservation although not evaluated independently does enhance cosmetic outcomes.

*(Preliminary analysis)

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-16-16.
P3-03-04: Targeted Modulation of HER Receptor Signaling in Breast Cancer Using miR-21.
Authors: Aubele M , Ludyga N , Braselmann H , Atkinson MJ , Auer G , Anastasov N
Published: June 2012

Introduction: MicroRNAs (miRNAs) are multifunctional nucleic acids that regulate the stability and translational efficiency of targeted messenger RNAs. Endogenously altered miRNA levels have been linked in breast cancer to acquired chemoresistance and changed radiosensitivity. Thus the modification of miRNA expression represents an attractive therapeutic strategy. We now show that the targeted inhibition of miR-21 can modify expression of the HER2 receptor in breast cancer.

Materials and Methods: Using TaqMan-based technology the expression of five selected miRNAs (miR-7b, miR-10a, miR-17-5p, miR-125a, and miR-21) was investigated in formalin-fixed, paraffin-embedded breast carcinoma tissues expressing different levels of HER2 (n=60). Possible regulation of HER2 was explored in cell lines using lentivirus to stably downregulate or upregulate HER2 and miR-21 expressions. The effects were analyzed using qRT-PCR, Western blots, proliferation and migration assays.

Results: In tumor tissues we identified overexpression of miR-10a and miR-21, and underexpression of miR-17-5p and miR-125a in most of the tumor tissue samples. Significant associations (p≤0.05) were found between HER receptor expression and the expression of miR-17-5p and miR-125a, and miR-21 showed correlation with expression of ER and PR. Furthermore, analysis of miR-21 downregulation in breast cancer cell lines showed inhibition of cellular proliferation and HER2 protein synthesis. Additionally, downregulation of HER2 expression decreased miR-21 expression and showed moderate change in cellular proliferation activity.

Conclusions: Based on these results we conclude that there is tight interplay between HER2 and miR-21 expression in breast cancer cells. Because miRNAs modulate gene expression we suggest that modulation of miR-21 has the potential to impact tumor therapy by interference with specific signaling pathways.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-03-04.
P3-04-02: Bevacizumab Treatment Alters Intrinsic Subtypes in a VEGF-Reinforced Xenograft Model of ER-Positive Breast Cancer.
Authors: Gökmen-Polar Y , Toroni RA , Goswami C , Sanders KL , Sirimalle U , Mehta R , Li L , Ivan M , Badve S , Sledge GW
Published: June 2012

Background: Anti-vascular endothelial growth factor (anti-VEGF) therapy improves disease-free but not overall survival in metastatic breast cancer. To seek further insight on resistance to anti-VEGF antibody bevacizumab (BEV) at the molecular level, we developed breast cancer xenograft models allowing comparison of tumor response at different time-points. Here we report the gene expression and miRNA analyses of response and non-response to BEV in these models.

Methods: MCF-7 cells transfected with control vector (ML20) or VEGF (MV165) were implanted into the mammary fat pads of athymic mice. Tumors from short-term treatment with BEV (3 weeks; Responders to BEV, R) or long-term treatment (8 weeks; Non-Responders, NR) or with vehicle control group (V) were subjected to whole-genome gene expression analysis (Human WG-6v2 Expression Beadchips, Illumina) and miRNA profiling (TaqMan ArrayHuman MicroRNA A+B Cards Set v3.0, Applied Biosystems).Validation of the chosen genes was performed using quantitative real-time RT-PCR (qRT-PCR) and Immunohistochemistry (IHC). Results: Short-term treatment to BEV (3 weeks; 5 mg/kg, i.p./twice weekly) inhibited primary tumor growth significantly in MV165 xenografts compared with vehicle control, whereas BEV treatment did not affect the tumor growth in the ML20 model. MV165 xenografts progressed after 8 weeks of BEV treatment. Gene set enrichment analysis (GSEA) revealed that luminal A-related gene sets were enriched in MV165-R compared to MV165-NR group including DESMEDT (ESR1), SMID_Breast_Cancer_Luminal_A_up, and MASSARWEH_ Tamoxifen_Resistance_ Down. Myoepithelial-specific gene sets were upregulated in both the R and NR groups compared with the vehicle group. qRT-PCR analysis showed that estrogen receptor alpha (ESR1) representative for luminal A decreased significantly in the MV-165-NR group (P=0.001) compared to vehicle. In contrast, Cytokeratin 5 (KRT5) levels increased significantly in both R (P=0.02) and NR (P=0.03) groups. In addition, KRT14 was upregulated in R (P= 0.04) and in NR (P=0.14) group in comparison with the vehicle group, suggesting the upregulation of myoepithelial phenotype specific to BEV treated MV165 model, but not ML20 model. Similar results were obtained by IHC. Consistent with mRNA changes, ESR1 regulated miRNA such as miR-107 (P=0.007) and miRNA important in tamoxifen resistance such as mir-451 (P= 0.0003) were also altered in MV165-NR group compared to vehicle. Conclusion: These results suggest that treatment with BEV may alter the intrinsic subtypes in the presence of VEGF expression. These data may help to explain the variable results to anti-VEGF therapy based on the duration of BEV treatment.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-04-02.
P3-05-04: Changes in Recurrence Risk of Breast Cancer Intrisic Subtypes over Time.
Authors: Ribelles N , Perez-Villa L , Pajares B , Jerez JM , Vicioso L , Jimenez B , de Luque V , Franco L , Alvarez M , Perez-Rivas LG , Sanchez-Muñoz A , Gallego E , Marquez A , Hierro I , Alba E
Published: June 2012

Background: Gene expression profiling and their immunohistochemistry-based surrogates have consistently revealed prognostically significant breast cancer (BC) subtypes: Luminal A (Lum A), Luminal B (Lum B), HER2, Basal-like (BL) and Triple negative phenotype-nonbasal (TNP-nb). In addition, there are clinical evidence that hazard of BC recurrence varies over time with two peaks of high risk at 18–24 and 60 months. This study compares the time-related patterns of recurrence within BC subtypes. Methods: Tissue microarrays were constructed from 937 early BC patients diagnosed and treated at our Hospital from 1982 to 2005 with available archival paraffin tissue blocks. BC subtypes were defined using an immunopanel of estrogen receptor, progesterone receptor, HER2, epidermal growth factor receptor, cytokeratin 5/6 and Ki67 by prespecified published methods. Univariate and multivariate analysis (Cox regression) were performed on progression-free survival. Smoothed curves for hazard rates (HR) were estimated by a Kernel-like smoothing procedure. The statistical analysis was done by using the R software environment.

Results: Cases were classified as follows: Lum A 46.8%, Lum B 25.2%, HER2 11.3%, BL 11.3%, TNP-nb 5.4%. None of the patients were treated with adjuvant trastuzumab. With a median follow up of 80 months age, tumor size, nodal status and intrinsic subtypes were independent prognostic factors. HER2 and BL show high and early peak in HR curves and decreasing sharply to 36 and 48 months respectively. HR in Lum A, Lum B and TNP-nb exhibit a smoother and nearly steady curve.

Conclusions: BC subtypes have distinct outcome but also displays different pattern of recurrence over time. These data might imply that pathways underlying early and late recurrences could be different. This additional information would suggest the convenience of considering different timings and duration of adjuvant treatments depending of BC subtypes, and also in the design of surveillance recommendations.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-05-04.
P3-05-09: Comparison of Clinical Features and Patterns of Recurrence in Triple Negative Breast Cancers in Relation to Other Breast Cancers.
Authors: Tosello de Oliveira C , Barbosa EM , Costa de Andrade J , Lyra EC , Felzener MC , Krutman Zveibil D , Grosso SHG , Sampaio Goes de Oliveira R , Sampaio Góes JC
Published: June 2012

Background : Breast cancer is an heterogeneous disease that have several and different biological characteristics and clinical behaviours. Of these, triple negative breast cancer represents 10–17%.This kind of tumor is characterized by estrogen, progesterone and HER2 receptor negativity and they are very aggressive, associated with poor prognosis, younger patients, high incidence of metastases and shorter relapse free survival. Triple negative breast tumours are more likely to experience local recurrence and distant relapse than other breast tumors, and require a more aggressive intervention.

PURPOSE : To compare the incidence of metastases, clinical features and outcome among patients with triple negative breast cancer and women with other types of breast cancer.

METHODS : This is a retrospective cohort analysis from 3893 patients with invasive breast cancer, diagnosed between January 2000 and April 2011 and attended at Brazilian Institute of Cancer Control (IBCC) in Sao Paulo, Brazil. Five hundred of these tumors were triple negative. We made a correlation of clinical variables such as age, tumor stage (TNM) and analysis of last follow-ups, such as metastases, disease free survival, death for tumor, death for other reasons, lost of follow-up, hygiene and diet regime (RHD) and local recurrence.

Results: The median follow-up for the cohort was 4,29 years. The mean age at diagnosis in triple negative group was 54,8 and for the others group was 57,1 years. Subgroup analysis of tumor grade showed that the triple negative breast tumors were diagnosed later (Stage II and III; p:<0,0001). There was no difference in the appearance of the two types of tumors, when considering diagnose age. The incidence of metastases, death for tumor and free survival in triple negative tumors, respectively; 25,6%, 13,8% and 57,2% (p:<0,0001) demonstrates the aggressiveness of this kind of tumor.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-05-09.
P3-06-05: Comparison of Oncotype DX® Recurrence Scores between Surgical and Core Biopsy Specimens in Breast Cancer Patients.
Authors: Stull TS , Goodwin MC , Anderson JM , Baehner FL , Sing AP , Yoshizawa CN , Barrio AV , Frazier TG
Published: June 2012

Introduction: The Oncotype DX® 21 gene assay is usually performed on surgical resection specimens (SRx) for patients (pts) with early stage, estrogen receptor positive (ER+) breast cancer to predict the risk of recurrence and likelihood of benefit from adjuvant chemotherapy (CT) and hormonal therapy (HT). Using the Recurrence Score (RS) to aid in making a decision to administer preoperative CT requires assaying the core biopsy specimen (CBx). The objective of this study is to compare the RS obtained from paired CBx and SRx specimens. Methods: 25 pts with invasive breast cancer diagnosed by CBx with a subsequent Oncotype DX® 21 gene assay performed on the SRx were identified. Fixed, paraffin embedded tissue from these paired CBx were sent to Genomic Health. The H&E slide from the paired SRx sample sent for the RS was used to compare the histology with the paired CBx. The RS from the CBx and SRx pairs were examined descriptively with scatterplots and Pearson correlation coefficients.

Results: Median age of diagnosis was 64 (range 39–78). Sufficient RNA was obtained from all but 1 of the CBx. H&E from CBx and SRx were histologically dissimilar for 3 of 24 pairs with RT-PCR data. The Pearson correlation for RS between CBx and SRx was 0.83 (95% CI 0.64, 0.92) for all 24 pairs. The distribution of RS groups from CBx was 19 low (RS<18), 3 intermediate (RS 18–30), 2 high (RS>31). The RS group from SRx was unchanged for 22 (92%) pts. Two pts switched RS groups, CBx RS 5 to SRx RS 18 and CBx RS 8 to SRx RS 24; only the latter is clinically meaningful because the former straddles the low-intermediate cutpoint. Correlations between CBx and SRx for individual single gene scores were 0.84 (95% CI 0.65, 0.93) for ER, 0.83 (95% CI 0.64, 0.92) for PR, and 0.82 (95% CI 0.61, 0.92) for HER2. Similar results were obtained excluding the 3 histologically dissimilar pairs.

Conclusion: The RS's obtained from CBx's were consistently similar to the RS's obtained from the paired SRx. Using an RS obtained from a CBx in pts with ER+ disease to make a decision regarding neoadjuvant CT or HT is clinically acceptable, thus, giving physicians an additional tool to improve pt care and outcomes.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-06-05.
P3-07-03: One-Step Nucleic Acid Amplification (OSNA) for the Diagnosis of Sentinel Lymph Nodes of Breast Cancer – Results of the China Multicenter Study CBCSG-001c.
Authors: Wang YS , Ouyang T , Wu J , Liu YH , Cao XC
Published: June 2012

Background

With the adoption of sentinel lymph node (SLN) biopsy as the standard of care, there is an increasing need for the rapid and accurate intra-operative diagnosis of SLNs. CBCSG-001c was a prospective multicenter trial to validate the One-step nucleic acid amplification (OSNA) assay in China. The primary endpoint was the concordance rates of intraoperative OSNA assay with the in-depth permanent histological analyses based both on cases and SLNs.

Methods: From Feb. to Dec. 2010, 1188 SLNs from 552 breast cancer patients were enrolled in the CBCSG-001c study at 5 centers. SLNs were cut into alternating ∼2mm sections. One half of the sections were sampled for H&E, with 4 sections at different intervals. The other half was fully tested with the OSNA assay. Predetermined cutoffs were calibrated so only metastases >0.2 mm were detected.

Results: The concordance rate was 89.1% (95% CI, 86.3−91.5%), sensitivity 87.7% (95% CI, 81.0−92.7%), and specificity 89.6% (95% CI, 86.3−92.4%) based on 552 cases, and the concordance rate was 91.4% (95% CI, 89.7−92.9%), sensitivity 83.7% (95% CI, 77.7−88.6%), and specificity 92.9% (95% CI, 91.1−94.4%) based on the 1188 SLNs. This quantitative molecular assessment allows the distinction of the size of the metastasis, and the PPV of OSNA [++] for macrometastases was 83.2% (95% CI, 75.0- 89.1%). Discordant results were thought to be partly due to the fact that different tissue sections were used for OSNA assay and histology, and SLNs with ITCs were not considered as histological positive nodes. After discordant case investigation, the senstivity of OSNA assay was significantly higher than that of intraoprative frozen section and touch imprint cyctology.

Discussion: As the largest OSNA study to date, our results, together with that of Japan, Germany, and France study, proved the OSNA assay based on CK19 mRNA expression to be a reliable and standardized tool for the intraoperative detection of SLN metastases of breast cancer patients as compared to in-depth permanent histology. The high sensitivity of OSNA assay means reducing the risk of second operation for ALND, medical care costs and patients anxiety.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-03.
P3-07-10: Sentinel Lymph Node Navigation Surgery Using Combination of Indocyanine Green Fluorescence and Blue Dye for Breast Cancer Patients.
Authors: Takahashi M , Hayashida T , Jinno H , Kitagawa Y
Published: June 2012

Background: Sentinel lymph node (SLN) biopsy is now widely accepted for staging the axilla in breast cancer patients. Several methods are presently used to detect SLNs. Combined use of blue dye and radiocolloid has previously been described as a superior method for detecting SLNs in breast cancer patients, but radiocolloid is not generally available in Japan. SLN detection guided by indocyanine green (ICG) fluorescence could emerge as a new and effective method for SLN biopsy. The aim of this study was to evaluate SLN biopsy using combination of ICG fluorescence and blue dye methods for breast cancer patients.

Material and Methods: We enrolled 75 patients with clinically node-negative breast cancer. An isosulfan blue dye solution (5ml) was injected subcutaneously just above the tumor and in the periareolar area after the induction of anesthesia. The injection site was massaged for five minutes and ICG (2ml) was then injected subcutaneously just above the tumor and in the periareolar area before starting the surgical procedure. Subcutaneous lymphatic channels draining from the areola to the axilla were visualized with a fluorescence imaging system (Photodynamic Eye: PDE, Hamamatsu Photonics Corporation, Japan) under fluorescence within several minutes. SLNs were dissected under direct visualization supported by fluorescence and dye navigation and diagnosed by intraoperative frozen section with hematoxylin and eosin staining. Any patient with a positive SLN underwent immediate axillary lymph node dissection (ALND).

Results: SLNs were detected in all 75 patients. The fluorescence imaging identified 2.6 SLNs in 74 (98.7%) of 75 patients. The blue dye identified 1.6 SLNs in 68 (90.1%) of 75 patients. Twelve of the 75 (16.0%) patients had metastatic SLNs and ALND was immediately performed. No metastasis revealed in any non-SLN in eight of these 12 patients. Metastatic SLNs were detected by the ICG fluorescence and not by blue dye in four of these 12 patients. Discussion: The combination of ICG fluorescence and blue dye method had two advantages: it could reveal lymph flow on the surface before we determined the skin incision line; and it had a high SLN detection rate. In hospitals where radioisotopes are unavailable, a combination of the two methods would be advantageous.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-10.
P3-07-16: The Efficacy of Arm Node Preserving Surgery Using Axillary Reverse Mapping for Preventing Lymphedema in Patients with Breast Cancer.
Authors: Seo YJ , Hwang MJ , Lee JH , Son GT , Choi JE , Bae YK , Kang SH , Lee SJ
Published: June 2012

Background

Lymphedema affects over 20% of breast cancer patients undergoing axillary dissection. Axillary reverse mapping (ARM) technique to identify and preserve arm node during sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) was developed to prevent lymphedema. The purpose of this study was to investigate the location and the metastatic rate of the arm node, and finally to evaluate the short term incidence of lymphedema after arm node preserving surgery.

Patients and Methods

From January 2009 to October 2010, 97 breast cancer patients who underwent ARM were enrolled. 2.5ml blue dye was injected in ipsilateral upper inner arm. After at least 20 minutes after injection, SLNB or ALND was performed in the usual manner and blue stained arm nodes and/or lymphatics were identified. We checked arm circumference at baseline and average of 8.8 months after operation in ALND cases and 13.7 months in SLNB cases. Patients were divided into two groups, arm node preserved group (70 patients in ALND, 10 patients in SLNB) and unpreserved group (13 patients in ALND, 4 patients in SLNB). The difference of arm circumference between preoperative and postoperative was checked in these groups.

Results: The mean number of identified blue stained arm nodes was 1.4±0.6. The arm nodes were found in the inferolateral side of axillary and thoracodorsal vessels in 57 patients (58.76%), the inferomedial side in 37 patients (38.14%), the superolateral side in 2 patients (2.06%), and the superomedial side in 1 patient (1.04%). In the majority of patients (92%), arm nodes were located between the lower level of the axillary vein and just below the second intercostal brachial nerve.

In arm node unpreserved group, 2 patients had metastasis in their arm node. The one had a common pathway between the arm node and the sentinel lymph node. Another did not have a common pathway, but had extranodal extension with N3 metastasis. Among ALND patients, in arm node preserved group, the difference of arm circumference between preoperative and postoperative in ipsilateral and contralateral arm was 0.27cm and 0.07cm, respectively, whereas 0.47cm and −0.03cm in unpreserved group, and one lymphedema was found after 6 months. No difference was found between arm node preserved and unpreserved group amoung SLNB patients (0.21cm and 0.39cm in in preserved group, 0.2cm and 0.02cm in unpreserved group).

Conclusion: Arm node preserving was possible in all breast cancer patients with identifiable arm node, during ALND or SLNB, except for those with high surgical N stage, and lymphedema did not developed in patient with arm node preserving surgery. Metastasis was not found in arm node preserving group in current results, but need to be observed in the ongoing progress.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-16.
P3-07-31: Intra-Operative Assessment of Sentinel Lymph Nodes in Breast Cancer with Touch Imprint Cytology (TIC) in 460 Consecutive Patients.
Authors: Iqbal M , Shetty G , Randhawa S , Sandhu F , Chachlani N , Simon J , Harries S , Jones L , Clarke D
Published: June 2012

Background

Sentinel node biopsy (SNB) accurately predicts the axillary lymph node status in patients with breast cancer. The sentinel lymph node (SLN) is evaluated by routine histology, requiring 3–5 days for the results and a second operation if the SLN is positive. However a second operation can be avoided if a reliable intraoperative assessment of the SLN was available. The techniques used for intra-operative assessment of the SLN include frozen section, touch imprint cytology (TIC) and more recently molecular biology assays. The aim of this study was to evaluate the accuracy of TIC in the assessment of the SLN.

Methods: A prospective study to include 460 patients with breast cancer who underwent SNB and had the sentinel node assessed intra-operatively with TIC. The SLN was bisected and a touch imprint was made on to a slide. The imprint was stained with Giemsa stain. Permanent sections were evaluated with H&E and immunohistochemical staining. The TIC results were compared with the final histology of the SLN.

Results: 766 SLN's were harvested from 460 patients (Mean - 1.66). Of the 460 patients, TIC was falsely negative in 50(24%) patients. No patients had false positive results. Negative predictive value was 87%. The accuracy rate was 89%. 94 patients were positive on histology. TIC was positive in 44 patients and negative in 50. The sensitivity, specificity and positive predictive value of TIC was 47%, 100% and 100% respectively. By acting on the results of TIC, 44 patients (47%) had an axillary clearance at the primary operation and were thus spared a second operation.

Conclusion: TIC in our cohort of 460 patients and 766 sentinel lymph nodes had an accuracy rate of 89% and specificity of 100%. Our study compares favourably with published literature, confirming that TIC is a simple, quick, reliable and reproducible technique that can be used for intra operative assessment of the SLN. A sensitivity of 47% means that about half of the SLN positive patients were spared a second operation. We had hoped that with more experience, our sensitivity would improve but since this has not been the case we are now moving towards molecular biology assays (OSNA) to assess the SN intra-operatively.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-31.
P3-07-41: Sentinel Lymph Node Biopsy Is a Reliable Method for Lymph Node Evaluation in Neoadjuvant Chemotherapy Treated Breast Cancer Patients.
Authors: Kaplan R , Qiu Q , Monni S , Swistel A , Shin S
Published: June 2012

Background: Successful sentinel lymph node mapping in breast cancer patients treated with neoadjuvant chemotherapy has been debated by practicing surgeons due to the potential compromise of the lymphatic drainage system after treatment. Furthermore, whether clinicopathologic variables associated with sentinel lymph node positivity in breast cancer patients differ from similar patients who have been treated with neoadjuvant chemotherapy has not been well-studied.

Materials and Methods: Breast cancer patients who received neoadjuvant chemotherapy were identified in our files. A similar number of breast cancer patients who did not receive such therapy was also selected as a comparison group. Clinicopathologic parameters such as age, type of surgical procedure, number of sentinel lymph nodes removed and/or positive, number of non-sentinel lymph nodes removed and/or positive, tumor size, histologic type/grade, presence of lymphovascular invasion, biomarker expression (ER,PR, HER-2/neu) and multifocality were recorded for each patient in both cohorts. Statistical analysis was performed for each cohort to identify variable(s) that correlated with sentinel lymph node positivity. Additional analysis was performed by computing the odds ratio of sentinel lymph node positivity after adjusting for selected variables. Results: Ninety-seven and ninety-three patients who were and were not treated with neoadjuvant chemotherapy, respectively, were identified. In all patients, successful sentinel lymph node mapping was achieved. When these cohorts were separately analyzed, tumor size, lymphovascular invasion, and non-sentinel lymph node positivity were associated with sentinel lymph node positivity in the cohort that did not receive neoadjuvant chemotherapy. In the cohort that received therapy, lymphovascular invasion and non-sentinel lymph node positivity were associated with sentinel lymph node positivity. In addition, after adjusting for tumor size, lymphovascular invasion and histologic grade, patients treated with neoadjuvant chemotherapy were more likely to have sentinel lymph node positivity than those who did not have this treatment (odds ratio: 5.4, 95% CI 2.4, 12.1).

Conclusions: Successful sentinel lymph node mapping was achieved in all ninety-seven breast cancer patients studied. Regardless of whether neoadjuvant chemotherapy was administered, the presence of lymphovascular invasion and non-sentinel lymph node positivity were found to predict sentinel lymph node positivity. By comparing two cohorts of breast cancer patients differing only in the use of neoadjuvant chemotherapy and adjusting for select variables, those in the treated cohort still remained more likely to have a positive sentinel lymph node.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-41.
P3-08-01: Effects of an Integrated Yoga Program on Mood States, Distress, Quality of Life, Diurnal Cortisol Rhythms and Natural Killer Cell Counts in Metastatic Breast Cancer Survivors.
Authors: Gopinath SK , Rao RM , Sanjeevarao VH , Diwakar RB , Basavalingaiah AS , Patil S , Raghuram N , Ramarao N , Usharani RM
Published: June 2012

Background and objectives: Metastatic breast cancer patients experience tremendous psychological distress due to treatment, disease and uncertainty of their survival. In this study we evaluated the effects of an integrated yoga program versus supportive counseling in advanced breast cancer survivors.

Methods: Ninety one Metastatic breast cancer survivors (group mean age 50.54 yrs ± 8.53 yrs) registered in hospital based cancer registry were recruited if they satisfied selection criteria and gave written consent for participation in the study. The study was approved by the institutional review board. Subjects were randomized to either receive yoga intervention (n=45) or supportive therapy (n=46) counseling as a standard of care for 3 months of intervention period. Subjects were assessed at baseline and after intervention for mood states using hospital anxiety and depression scale, sleep quality using Pittsburg Insomnia rating scale, quality of life using EORTC Qol C30 for breast and perceived stress using perceived stress scale. Saliva samples were collected for three consecutive days at 0600hrs, 0900hrs and 2100hrs before and after intervention for cortisol rhythms using Enzyme Immune Assay kits from Salimetrics and blood samples were collected between 0800hrs to 01000hrs for NK cell enumeration using flow cytometry. 35 subjects in yoga and 31 subjects in controls completed the post measures. Data were analyzed using both parametric (ANCOVA with respective baseline measure as a covariate) and non parametric tests (Mann whitney U test) to evaluate effects of intervention on the above outcome measures. Data for salivary cortisol data was log transformed, area under the curve and cortisol slope computed using linear mixed effects model.

Results: There was a significant decrease in anxiety (p < 0.001), depression (p < 0.001), perceived stress (p = 0.01), fatigue severity (p < 0.001) and interference (p < 0.001) in yoga group compared to controls post intervention. There was a significant improvement in emotional function (p < 0.001), role function (p = 0.03) and cognitive function (p < 0.001) and global quality of life (p < 0.001) in yoga group compared to controls. There was significant decrease in 0600 hrs cortisol within the yoga group (p =0.03) alone. There was a significant increase in Natural killer cell percent in yoga group (p =0.03) compared to controls after intervention. Conclusion: The results suggest biobehavioral effects of yoga intervention could possibly improve quality of life, reduce psychological distress and modulate abnormal cortisol profiles and immune responses in metastatic breast cancer patients.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-08-01.
P3-09-02: Intermittent Dietary Carbohydrate Restriction Enables Weight Loss and Reduces Breast Cancer Risk Biomarkers.
Authors: Harvie M , Wright C , Pegington M , Mitchell E , Evans DG , Jebb S , Clarke R , Goodacre R , Dunn W , Mattson M , Howell A
Published: June 2012

Background: Energy restriction is a potential strategy for breast cancer prevention but is difficult to achieve and maintain. We found that intermittent energy restriction (2 days strict dieting week) is comparable to the standard approach of moderate daily restriction for weight loss and marginally better for improving insulin sensitivity, but no easier to follow1. In this follow on study we wished to test whether 2 novel intermittent low carbohydrate/low energy diets were feasible and easier to follow than a standard daily energy restriction. Design: Randomised comparison of 3 dietary types over 4 months in 115 overweight or obese (mean body mass index 31.0 [±5.3 SD] kg/m2) women at increased risk of breast cancer (lifetime risk > 1 in 6).

Diets:

1. A restricted low carbohydrate diet (RLCD): 650 kcal and <50g carbohydrate / day for 2 days per week

2. Ad lib low carbohydrate diet (ALCD): <50g / day for 2 days per week with other food types (e.g. protein) ad lib

3. A standard daily restricted Mediterranean diet (DRMD): ∼ 1500kcal/day for 7 days per week

Methods: Weight, anthropometrics, blood markers for breast cancer; insulin resistance, oxidative stress markers, leptin, adiponectin, lipids, inflammatory markers IGF-1 were assessed at baseline, 1, 3 and 4 months.

Results: 88/114 completed the study (77%, drop outs 6 RLCD, 8 ALCD 12 DRMD). Last observation carried forward analyses show both intermittent low carbohydrate diets were superior to standard daily restriction for reducing weight and body fat: mean (95% confidence interval [CI]) change in body fat for RLCD was −4.3 (−5.6 to −3.0) kg, for ALCD −4.1 (−5.2 to −3.1) kg vs. −2.4 (−3.4 to −1.2) kg for DRMD (P value for difference between groups = 0.02). The intermittent groups had greater improvement in insulin resistance: mean (95% CI) change for RLCD was −22 (−35 to −11) %, ALCD −14 (−27 to −5%) % vs. −4 (−16 to 9) % for DRMD (P = 0.02). Other biomarkers are being assayed currently.

Conclusion: Greater weight loss, fewer drop outs and greater reductions in insulin resistance with the novel intermittent low carbohydrate diets indicate that these are alternative approaches for energy restriction for potentially reducing risk of breast cancer and other diseases.

Reference:

1Harvie MN, Pegington M, Mattson MP, Frystyk J, Dillon B, Evans G et al. The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. Int.J Obes (Lond) 35; 714–27, 2011. This study is funded by the Genesis Breast Cancer Prevention Appeal: www.genesisuk.org

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-09-02.
P3-11-06: A Pilot Study of RPFNA in Overweight and Obese Postmenopausal Women.
Authors: Korde LA , Grieco VS , Imayama I , Kumai C , Mason C , Duggan CR , Wang C-Y , McTiernan A
Published: June 2012

Background: Random periareolar fine-needle aspiration (RPFNA) is a research-based procedure used to obtain breast epithelial cells and fluid. Data suggest that atypia in epithelial cells from RPFNA specimens is associated with an increased risk of breast cancer, and changes in the degree of atypia may be a viable biomarker for response to chemopreventive interventions.

Methods: We performed RPFNA on 37 overweight or obese (body mass index (BMI≥ 25.0 kg/m2) postmenopausal (50-75 y) women enrolled in a randomized clinical trial of Vitamin D vs placebo in combination with a lifestyle (diet + exercise)-based weight loss program. Eligibility criteria included serum vitamin D concentrations 10–32 ng/mL. The procedure was performed by two trained clinicians prior to randomization to assess baseline cell counts and degree of atypia. Two areas in the breast (10:00 and 2:00 positions) were infiltrated with lidocaine, and 8 to 10 aspirations of cellular material were performed using 1.5 inch, 21-gauge needles. The aspirated fluid was placed in 9 cc of Cytolyt Thinprep (Hologic Inc.) with 1 cc of 1% neutral buffered formalin and slides were prepared according to the University of Washington Department of Pathology non-gyn protocol.

Results: Thirty-seven women were included in this analysis. The mean age and BMI of study participants was 59.3 years and 32.5 kg/m2, respectively. The mean 5-year Gail risk score for study participants was 1.96%; 52% of women had a 5-year Gail risk >1.66%. Eight participants (21.6%) had >50 cells present on cytology examination. One additional participant had 10–50 cells, and one had <10 cells. No specimens showed cellular atypia. The remainder of study participants had only blood or fibroadipose tissue on cytology specimens. Women with epithelial cells present were younger (mean age 55.0 vs. 60.2 years, p=0.05). There were no significant differences in BMI or Gail risk score between those with and without epithelial cells.

Conclusions: RPFNA in our sample of overweight/obese postmenopausal women did not yield epithelial cells in a majority of participants. Younger age was associated with a greater cell count. We are planning further studies to determine whether other markers in RPFNA specimens can be used to assess breast tissue changes in response to chemopreventive interventions.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-11-06.
P3-12-02: Intra-Operative Margin Assessment of Diffuse Disease with MarginProbe” as an Adjunct to Standard of Care, Results from a Randomized Prospective Multi Center Study.
Authors: Boolbol SK , Cocilovo C , Tafra L
Published: June 2012

Background

The ability to obtain negative margins with a single surgical procedure remains a challenge, particularly in patients with diffuse disease such as DCIS and lobular pathology. A novel device (MarginProbe, Dune Medical Devices, Inc.) is intended to provide surgeons with real time, intraoperative detection of cancerous tissues at the margins of excised specimens. A study was performed to determine if there was a device-associated improvement in complete surgical resection (CSR) and therefore a decrease in the rate of patients requiring re-excision with these disease types. The current analysis stratified the data based on tumor type with a special focus on DCIS patients, patient with a DCIS component, and lobular patients.

Methods: All 596 patients underwent breast conservation, with image-guided localization, and were randomized in a prospective, international, multicenter (n=21) study. Randomization occurred in the operating room, following standard lumpectomy procedure, including palpation followed by additional cavity resections as indicated. In the device arm, MarginProbe was used on each specimen margin and device positive readings required additional resections of the cavity. Pathologists were blinded to study arm. Re-excision criteria were not dictated by the protocol.

A primary endpoint of this study was CSR, defined as the correct intraoperative identification and resection (if not skin or fascia) of all positive margins on the main lumpectomy specimen. Positive lumpectomy specimens were defined as those having at least one margin having cancer ≤1mm from the surface. Successful CSR results in reduced positive margin rate after lumpectomy.

Results: Results are presented in Table 1. The improvement in CSR was significant for all diagnosis types. The decrease in candidates for re-excision due to failed CSR was significant for all DCIS and mixed tumor types.

Conclusions: Use of the device resulted in significant improvement in CSR and therefore a significant decrease in the need for reexcisions. Further studies should be conducted to evaluate the use of the device for additional patient cohorts, such as patients receiving neoadjuvant treatment and patients who have undergone prior breast surgery.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-12-02.
P3-12-04: Involved Anterior Margins after Breast Conserving Surgery: Is Re-Excision Required?
Authors: Mullen R , Macaskill EJ , Khalil A , Elseedawy E , Brown DC , Lee AC , Purdie C , Jordan L , Thompson AM
Published: June 2012

Background: Complete tumour excision in breast conserving surgery (BCS) is critical for successful treatment; involved circumferential resection margins are associated with increased disease recurrence. However, the importance of an involved anterior margin is less clear. The purpose of this study was to audit an aggressive approach to involved anterior margins and hence assess whether anterior margin re-excision yields clinical benefit.

Material and Methods: A retrospective case note and pathology review was performed for all patients who underwent BCS between 2006 and 2010 through a single cancer centre. An involved margin was defined as <1mm clearance of invasive or in situ breast cancer. Results: 1667 patients underwent BCS for invasive and/or in-situ disease, of whom 114 (6.8%) underwent re-excision, most commonly for mixed invasive and in-situ pathology. The annual re-excision rate rose significantly (p<0.001), with no change in whole tumour diameter, specimen weight or specimen volume. A total of 170 involved margins were identified: most commonly the anterior margin (59 margins, 30.6%) followed by the posterior (39 22.9%) or inferior (31, 18.3%) margin. Patients with anterior margin involvement were more likely to have grade 3 invasive disease (p=0.0323) but less likely to have residual disease found at re-excision (2/49 vs. 32/101 margins, p=0.0033); there were no differences when in-situ characteristics were compared.

Conclusions: Re-excision of involved anterior margins rarely excises residual disease and may be unnecessary. Multidisciplinary teams should consider whether further therapy for an involved anterior margin is required on a patient by patient basis.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-12-04.