bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-breast tumor recurrence rate of breast CT-guided lumpectomy: A prospective multi-institutional study in Japan.
Authors: Sato Nobuaki 
Published: February 2017

170 Background: We have conducted the prospective multicenter study to evaluate the usefulness of breast CT in delineating tumor extent and preoperatively determining the optimal surgical procedure (Sadako Akashi-Tanaka et al, Ann Surg in press). Breast CT, carried out in the supine position, was useful since breast CT correctly changed the extent of surgery in 13.1% of patients. Here, we present the in-breast tumor recurrence (IBTR) of these patients undergoing CT guided breast conserving surgery. Methods: The follow-up records of 271 women treated with local excision (complete removal of gross tumor with a margin) for breast cancer at 3 Japanese hospitals were reviewed. CT guided surgery was performed as follows; the surgeon marked the line of planned excision prior to CT on the skin, which was also recorded on the CT image. Contrast-enhanced breast CT was performed in the supine surgical position. The CT results were used to determine the extent of surgery. IBTR was defined as a recurrence in the treated breast without regional or distant metastases. Results: The median age at surgery of them was 55 years (range, 21 to 88 years). The median palpable tumor size was 1.6cm (range, 0 to 3.5 cm). Tumor histology was as follows: ductal carcinoma in situ 13, invasive ductal carcinoma 234, invasive lobular carcinoma 10, mucinous carcinoma 6, and special type 8. The median follow-up after treatment was 3.8 years (range, 3.0 to 5.3 years). The rate of IBTR was 10/271 (3.7%). The 3.8-year rate of IBTR was 4.5%. Discussion: Without prospective randomized controlled studies, it is unlikely that a definitive conclusion can be reached on whether imaging-guided diagnosis of tumor extent will reduce the rate of IBTR. However, it seems almost ethically impossible to conduct such a clinical study in Japan, because preoperative imaging-guided diagnosis of tumor extent is routinely performed prior to surgery. Conclusions: Although this was not the randomized controlled study, CT-based preoperative diagnosis of tumor extent has the potential to improve the accuracy of breast-conserving surgery. The long-term results of IBTR need to be assessed.
Surgical treatment and outcome of patients with invasive breast carcinoma age 80 or older.
Authors: Besic Nikola , Zmuc Jan , Peric Barbara , Pilko Gasper , Petric Rok , Perhavec Andraz 
Published: February 2017

171 Background: Because the population ages, the proportion of breast cancer (BC) patients over age 80 is increasing. To date, there is no consensus as to what the best treatment is for older patients with BC. The aim of our retrospective study was to analyze data about surgically treated BC patients with ≥80 years of age and their outcome. Methods: A chart review of 158 early BC patients (mean age 83; range 80-90) that were surgically treated at our institute from 2000 to 2008 was performed. The data on the extent of disease, morphologic characteristics, mode of therapy, recurrence and survival were collected. Correlation between possible prognostic factors, mode of therapy and cause-specific survival was analyzed by univariate and multivariate test. Results: Extension of BC was local, locoregional and unknown in 37%, 46% and 17% of cases; pT1/pT2 and pT3/pT4 tumor stage was present in 75% and 25%, respectively. Conservative breast surgical procedure, mastectomy, axillary lymphadenectomy, sentinel lymph node biopsy and no lymph node surgery was done in 27%, 73%, 57%, 18%, and 25%, respectively. Adjuvant hormone therapy (tamoxifen in 56 and aromatase inhibitors in 47 cases), chemotherapy and external radiotherapy were used in 65%, 1.2% and 15% of patients. Recurrence occurred in 23% of cases during the follow-up period of 0.2-11 years (median 4.3 years); local, regional and/or distant in 10%, 6% and 22% of cases, respectively. Because of BC and other reasons died 20% and 20% of cases, respectively. The 5-year cause-specific survival in patients with local and regional extension of BC was 86% and 74%, respectively. Univariate statistical analysis showed that pT3/pT4 tumor, pN1 stage, mastectomy, sentinel node biopsy and lymphadenectomy correlated with shorter cause-specific survival. Multivariate analysis showed that only pT3/pT4 tumor and pN1 stage correlated with shorter cause-specific survival. Our results indicate that our patients were locoregionally treated adequately to tumor stage Conclusions: Short cause-specific survival indicates that BC in patients with ≥80 years of age and regional metastases may be aggressive. Adjuvant chemotherapy might be considered in selected cases to prolong survival.
Postmastectomy radiation for stage ll breast cancer patients with T1/T2 lesions.
Authors: Libson Shai , Ma Charles , Takita Cristiane , Avisar Eli 
Published: February 2017

175 Background: Post mastectomy radiation (PMR) is usually recommended for T3 or N2 breast cancer (BC). The role of PMR for stage ll BC with T1/T2 lesions remains controversial. The aim of this study was to assess the role of PMR in this subgroup of patients. Methods: A retrospective analysis of a prospectively collected database of all stage ll BC patients treated with mastectomy at our institution between 2005-2008 was performed. Demographics, tumor stage, histology, receptor status, adjuvant therapy, nodal status, failure patterns and disease free survival rates (DFS) were compared between the patients who received PMR vs.those who were not radiated. Results: Eighty-two patients underwent mastectomies for stage II disease with a T1/T2 lesion. Twenty two of those (27%) received PMR. The average follow up time was 47 months. The patients in the PMR group had significantly larger tumors (90% vs. 64%), more advanced stages (55% vs. 17%) and higher grade histology (59% vs. 32%). Menopausal status, nodal disease, histology, multifocality and receptors status did not differ significantly between the groups. Three patients in the non radiated (NR) group had a distant recurrence compared to 2 patients in the PMR group. There was one contra-lateral cancer in the NR group. The overall DFS was 86.6% in the NR group vs.91% in the PMR group, (p=0.72). Four patients had a chest wall recurrence (CWR) in the non-radiated (NR) group compared to none in the PMR group; however this was not statistically significant. In a sub-groups analysis comparing only T2, Stage IIB and high grade tumors respectively between the PMR and NR groups there was also no statistical difference in local or distant recurrence and in DFS. In the NR group, high grade tumors (p=0.0024) and estrogen receptors (ER) negativity (p=0.0168) were prognosticators of CWR. Conclusions: In our series PMR did not result in a statistically improved outcome for stage ll BC with T1/T2 lesions. A prospective trial randomizing patients with high grade or ER negative tumors only between PMR vs. NR could further clarify the role of PMR for stage II (T1/T2) lesions.
Analysis of interleukin-8, alpha1-antitrypsin, and tumor necrosis factor-alpha as biomarkers of breast cancer in women of northeastern Mexico.
Authors: Reyes-Lopez Miguel Angel , Sanchez-Meza Alberto Onofre , Bocanegra-Garcia Virgilio , Barrera-Saldana Hugo Alberto , Garza-Rodriguez Maria de Lourdes , Sanchez-Dominguez Celia Nohemi 
Published: February 2017

18 Background: Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease and variations of protein values in plasma. Interleukin (IL)-8, alpha 1-antitrypsin (AAT) and tumor necrosis factor-alpha (TNF alpha) have been related to carcinogenesis in breast tissue. Whether polymorphisms of the genes and protein values also influence breast cancer risk is unclear. The objective was to analyze the levels and polymorphisms of biomarkers in breast cancer patients for diagnostic purposes. Methods: In this cases-controls study a total of 30 patients with breast cancer confirmed by histopathology and 21 healthy individuals were studied, both groups were of three generations born in the Northeast of Mexico. Two polymorphisms of the AAT gene (Alleles Z and S), a polymorphism of IL-8 (-251 A/T polymorphism of the IL-8 promoter), and the polymorphism of TNF-alpha [-308 G/A (TNF1/TNF2) polymorphism of the TNF-alpha promoter gene] were analyzed using PCR-RFLP. Additionally, the plasma protein values of the biomarkers were measured by ELISA. Results: The IL-8 (-251T) and TNF-alpha (-308G) polymorphisms were significantly associated with breast cancer. Odds ratios for women with one high-risk allele versus women homozygous for the low-risk allele were 4.06 for -308G TNF-alpha (95% confidence interval, 1.298-13.678; P = 0.006) and 2.44 for -251T IL-8 (95% confidence interval, 1.277-4.7; P = 0.003). Significant differences between protein values of patients and controls were observed (ATT U=63, Z=4.81, p (2) <0.0001; IL-8 U=112.5, Z=3.87 p (2) =0.0001; TNF-α U=135.5, Z=3.43, p (2) =0.0006), AAT and IL-8 were over-expressed in patients with breast cancer. The presence of the polymorphism does not influence the protein values (TNF rs=0.1203, IL-8 rs=0.2246), apparently. No association between presences of the polymorphism. Conclusions: In this study, the presence of the IL-8 (-251T) and TNF-alpha (-308G) alleles may increase the risk of breast cancer in these Mexican women. Over-expression of IL-8 and AAT may directly correlate to the pathogenesis of breast cancer. Both biomarkers may be combined with other markers for presumptive diagnosis.
Axillary recurrence (AR) after negative sentinel node biopsy (SNB): Who is at risk?
Authors: Farkas Rachel Leah , Hicks David G. , Tang Ping , Shayne Michelle , Huston Alissa , Ling Marilyn N. , Skinner Kristin A. 
Published: February 2017

180 Background: AR after negative SNB is a rare event. The purpose of this study was to identify factors associated with AR. Methods: A breast cancer (BC) database was reviewed identifying 4 cases of AR among 424 (0.9%) patients with a negative SNB over a 5 year period. Demographic, pathologic and treatment data were collected. Patients with AR were compared those without using standard methods for contingency tables to identify factors associated with AR. Results: Tumor and treatment factors are shown in the table. There was no difference in age, race, menopausal status, tumor size or palpability, or the average number of SLNs harvested between the groups. Recurrences were only seen in patients with triple negative (TN), high grade tumors. AR occurred in 12.5% of pN0(i+) BCs compared to 6% of pN0 BCs (p<0.05). AR occurred in 3.5% of BCs with LVI compared to 0.5% of BCs without LVI (p<0.05). AR occurred in 4.3% of high grade BCs compared to 0% of non-high grade BCs (p<0.05). When comparing those with AR to TN patients without AR, patients with AR were less likely to have received chemotherapy(CT) (3 of the 4 patients declined). Both AR patients who received radiation therapy (XRT) had fields limited by anatomic constraints and the recurrence occurred outside of the radiated fields. AR occurred in 2% of TN BCs treated with CT compared to 19% of TN BCs not treated with CT (p<0.05). Conclusions: For a patient to develop AR there must be retained occult disease in the axilla that is not controlled by adjuvant therapies given. Factors such as high grade tumors and LVI that increase the chances of node positivity or increase SNB false negative rates increase the chances of retained occult disease in the axilla. If these patients do not receive optimal adjuvant therapies, there is a substantial risk of AR. Care should be taken when using SNB in such high risk patients. [Table: see text]
Clinical outcomes of patients with tumor bed-to-skin distance (TBS) ≤ 7 mm treated with accelerated partial breast irradiation (APBI) using multilumen catheter.
Authors: Abboud Mirna , Nitsch Paige , Paulino Arnold , Blanco Angel Ignacio , Bass Barbara Lee , Shadle Kathleen M. , Teh Bin S. 
Published: February 2017

182 Background: The initial single-lumen Mammosite trial has shown that skin spacing had an important implication on cosmetic outcomes. In this study, we reviewed the patients who were treated with APBI using multilumen catheter and assessed the outcomes for patients with minimal TBS of ≤ 7mm. Methods: Between August 2008 and April 2011, 79 patients were treated with breast-conserving therapy and adjuvant APBI using the Contura Multi-Lumen balloon or strut-adjusted volume implant (SAVI) device. All patients received 3,400 cGy in 10 fractions delivered twice daily using high dose rate radiation with Iridium 192. The dose was prescribed to 1 cm from the applicator surface. Thirty-six patients had a TBS of ≤ 7mm. We analyzed the clinical outcomes according to RTOG 9517 and skin toxicities as per RTOG 9804 in this patient subgroup. Results: The median age was 65 years (range, 50-86 years). All patients had Tis-T1N0 carcinomas; 39% had DCIS and the rest had invasive carcinoma. The majority (92%) were treated with Contura Multi-Lumen balloon and 8% with SAVI. Median follow-up was 18 months (range 6-42 months). The average TBS was 4.8 mm (range 1-7). 21 patients (57%) had a TBS of ≤ 5mm. The median maximal skin dose was 116% (range 82-134%). The median V90, V95 and V100 were 98%, 96% and 92% respectively. The average V150 and V200 were 31.2 and 9.6 cc respectively. At a median of 3 weeks after treatment, 95% of the patients had good to excellent cosmetic outcome. 54% had grade 1, 21% patients had grade 2 skin toxicity and 25% did not have any skin reaction. At last follow-up, 82% of the patients did not have any residual late skin reaction. Grade 1 skin toxicity was reported in 13%, and grade 2 in 1 patient. Cosmesis was excellent in 72% and good in 28% of the patients. There was no loco-regional recurrence. Conclusions: In our patient population, APBI proved to be an effective treatment with a good to excellent cosmetic outcome and acceptable toxicity. Further investigation with larger patient populations and longer follow-up is warranted to confirm the safety and efficacy of APBI for patients with small TBS.
Evaluation of autophagy as a therapeutic target for DCIS.
Authors: Espina Virginia A. , Edmiston Kirsten H. , Liotta Lance A. 
Published: February 2017

189 Background: Survival of intraductal, preinvasive proliferating cells under stress may promote genetic instability and the selection of invasive carcinoma cells. Our analysis of the mechanisms used by DCIS cells to survive in the hypoxic, nutrient deprived intraductal niche has revealed autophagy as a therapeutic target. Methods: DCIS spheroid forming cells have been isolated and propagated from fresh human DCIS lesions. We characterized the DCIS cells by organ culture, xenograft transplantation, molecular cytogenetics (300,000 SNPs) and 59 signal pathway profiling endpoints (Reverse Phase Protein Microarray [RPMA]). Results: DCIS spheroid forming cells were tumorigenic in xenograft models. Autophagy is up-regulated in: human DCIS lesions, DCIS spheroid-forming cells, and the xenograft tumors they generate. Autophagy is a means for intraductal neoplastic cells, accumulating in the duct, to digest intracellular contents and generate energy to survive in the face of severe metabolic, oxidative, and hypoxic stress. Suppression of autophagy by chloroquine kills human DCIS spheroid forming cells in culture and prevents them from forming tumors in xenografts (p < .0003). Based on these preclinical insights we have opened a neoadjuvant therapy trial for DCIS (NCT01023477 PINC Trial) to examine the safety and effectiveness of oral 30-day chloroquine for patients with any stage/grade DCIS. At the conclusion of treatment, all patients receive standard of care surgical therapy. MRI is performed before and after the treatment period. Endpoints compared before, versus after, therapy are lesion shrinkage, pathologic regression, disruption of lesion autophagy and proliferation (Ki67), induction of apoptosis, and suppression of xenograft tumorigenicity. Each patient serves as her own control because effectiveness is judged by comparing the patient’s DCIS lesion before and after oral therapy. Conclusions: We hypothesize that the intraductal pre-neoplastic cellular niche will be preferentially sensitive to a short term, anti-autophagy based prevention therapy which targets survival pathways used by pre-invasive carcinomas. Our unique trial design offers a means to functionally screen investigational agents that kill premalignant breast lesions.
Association of dyslipidemia with the aggressive molecular subtypes and pathologic profile of newly diagnosed nonmetastatic breast cancer patients.
Authors: Luna Herdee Gloriane Cristal , Luna Cher Alaine Cristal , Cristal-Luna Gloria R. , Luna Cesar Vilela 
Published: February 2017

19 Background: To investigate the association of dyslipidemia with the aggressive pathologic profile and molecular subtypes among the premenopausal and postmenopausal breast cancer patients. Methods: A retrospective review of Filipino breast cancer patients from 1990 to 2010 from an oncology clinic was done. Patients were grouped to pre- and post-menopausal and each group were divided to those with and without dyslipidemia. Association of dyslipidemia with breast cancer aggressiveness, (1) by pathology (histopathologic diagnosis, grade, invasion, TNM stage) and (2) by molecular phenotype (using the hormone status: estrogen and progesterone receptor positivity) and HER-2 neu status (overexpression by immunohistochemical stain / gene amplification by fluorescent in situ hybridization), was assessed using Fisher exact test. Results: Among 728 breast cancer patients, 201 met the inclusion criteria with 103 premenopausal (36 with dyslipidemia, 67 without dyslipidemia) and 98 were postmenopausal (42 with dyslipidemia, 56 without dyslipidemia). Significant association was noted only among pre-menopausal in terms of the molecular phenotypes (p value 0.002) when compared to individual parameters: total cholesterol (p value <0.001), LDL (p value <0.001), HDL (p value 0.006), and triglyceride (p value <0.001). Conclusions: Dyslipidemia was not found to be a factor associated with aggressiveness of breast cancer in terms of the pathology for both pre-menopausal and post-menopausal groups. Only among premenopausal patients was dyslipidemia shown to be a significant marker of aggressiveness in terms of poorer molecular subset (luminal B, HER-2, basal like). This finding was not observed among post-menopausal group.
Evaluation of one-step nucleic acid (OSNA) molecular assay for intra-operative diagnosis of sentinel lymph node metastasis.
Authors: Banerjee Shramana Mitul , Davidson Timothy , Michalopoulos Nikolaus , McDermott Nuala , El Sheikh Soha , Tran-Dang My-annh , Davison Stephen , Keshtgar Mohammed R. 
Published: February 2017

194 Background: One step nucleic acid (OSNA) is a recently developed molecular diagnostic assay to detect lymph node metastases. Aim of the present study was to assess OSNA for intra-operative detection of sentinel node metastases with use of standard histopathology as the “gold standard.” Moreover, discordant cases were further investigated to assess their impact on patients’ management. Methods: 157 breast cancer patients with clinically and ultrasonographically negative axilla underwent axillary staging with sentinel node (SLN) biopsy. 244 SLNs were evaluated by OSNA and standard histopathology (alternate slices were submitted to OSNA and standard test). The “turn-around time” taken for an intra-operative OSNA result was recorded. Results: Sensitivity and specificity of OSNA were 92.3% and 95.6% respectively with positive predictive value of 80% and negative predictive value of 98.4%. The average time taken for an intra-operative result in this group was 34 minutes. Concordance rate was 95% while 12/244 nodes showed discordant results between OSNA and Histology. The discordant cases were re-evaluated by histopathologists and characteristics of this subgroup analysed. Patient’s management was altered by OSNA alone in 5 patients as they underwent axillary lymph node dissection on the basis of a positive OSNA when histopathology did not show evidence of metastasis. Two patients with nodes negative on OSNA had histopathology results showing metastases requiring delayed axillary clearance. The rest of the discordant nodes belonged to patients who had other nodes biopsied concurrently that were concordant in OSNA and histology. Conclusions: OSNA is a fast, valuable and highly accurate standardised method for the intra-operative evaluation of axillary lymph node metastasis and is part of our routine intra-operative assessment tool for sentinel nodes in breast cancer.
Clinical relevance of the use of FDG PET/CT in locally advanced breast cancer.
Authors: Vrancken Peeters Marie-Jeanne TFD , Koolen Bas , Rutgers Emiel J. , Rodenhuis Sjoerd , Valdés Olmos Renato O. 
Published: February 2017

195 Background: As opposed to patients with early-stage breast cancer who are in general treated with primary surgery, patients with locally advanced tumors are usually treated with neoadjuvant chemotherapy (NAC). Optimal locoregional treatment after NAC starts with optimal staging before the start of NAC. Methods: Patients with stage II-III breast cancer underwent an FDG PET/CT of the thorax in prone position with hanging breasts. A panel of experienced reviewers blindly interpreted PET/CT images. Results: In 154 patients the FDG PET/CT was compared with conventional staging procedures (bone scintigraphy, ultrasound of the liver and chest radiography). We have shown that PET/CT has a higher sensitivity for the detection of distant metastases as no metastases were missed with the PET/CT and in 16 (80%) of 20 patients with proven metastases, one or more lesions were exclusively found with PET/CT. This resulted in a change of treatment in 13 (8%) of 154 patients. Furthermore we have shown that the FDG PET/CT offers a non-invasive procedure for the assessment of number of tumor-positive axillary nodes prior to NAC, enabling guidance for postoperative radiotherapy planning. In 311 patients a PET/Ct scan was performed prior to the start of NAC for this purpose. A substantial proportion of patients (16%) has been upstaged because of the detection of occult lymph node metastases in the internal mammary chain and periclavicular region, changing treatment in the majority of them. Conclusions: Based on these results we recommend performing an FDG PET/CT as a standard diagnostic procedure in stage II and III breast cancer patients prior to NAC. Current research regarding the use of PET/CT in breast cancer focuses on monitoring the response of the primary tumor and axillary node metastases to NAC in order to optimize locoregional treatment after NAC according to the tumor response.