bluuebunny/crossref_metadata_2025 huggingface dataset:
The elderly breast cancer patient: Association of age, tumor size, and grade with sentinel lymph node status.
Authors: O'Malley Meaghan Working , Griffith Kent A. , Sabel Michael S. , Newman Lisa A. , Breslin Tara M. , Chang Alfred E. , Cimmino Vincent M. , Kleer Celina G. , Diehl Kathleen M.
Published: February 2017

15

Background: Nodal evaluation of the elderly breast cancer patient remains controversial, and some have suggested that selected older women with breast cancer may not require sentinel lymph node biopsy (SLNB). Methods: An IRB-approved database was queried for patients undergoing SLNB for invasive breast cancer from 2000-2006. We compared 8 cohorts: age <40 years, 40-44, 45-49, 50-54, 55-59, 60-64, 65-69, and >70 years. Logistic regression and chi-square test were used. Results: Procedure success rate was above 95% for all groups in a total sample size of 1268 patients. Patients >70 years had lower grade tumors than patients <40 years (Grade 1: 25% vs. 7%; Grade 2: 53% vs. 47%; Grade 3: 17% vs. 40%, p<0.0001) and higher ER expression (ER+: 83% vs. 59%, p<0.0005). Patients <40 years also had a higher proportion of multifocal disease (21% vs. 9%, p<0.002), lymphovascular invasion (20% vs. 10%, p<0.007), and number of positive sentinel lymph nodes (PSLN) removed (mean: 3.7 vs. 2.7, p<0.028). Upon multivariate analysis, the odds of a PSLN decrease 9% for every 5-year increase in age (OR 0.91, p<0.003), but increase significantly with certain tumor characteristics (ER+ vs. ER-: OR 1.7, p=0.002), larger size (0.5 cm increase: OR 1.26, p<0.0001), and higher grade (Grades 2-3: OR 1.99, p<0.0007). The predicted probability of a PSLN for patients age 35, 55, and 70 years is 27%, 22%, and 16%, assuming each had a ER+, low grade, 2 cm tumor. Conclusions: Older breast cancer patients have more favorable pathology, and the chance of a PSLN decreases as age increases. However, the odds of a PSLN are significantly higher in patients with certain tumor characteristics, which are known prior to definitive surgery. Given recent reports that older patients are less likely to receive standard treatment for breast cancer and prognosis may worsen as a result, tumor size and characteristics rather than age should dictate the decision to perform SLNB, and we should continue appropriate, aggressive staging of the older breast cancer patient.
Effect of IL-8 on integrin αvβ3 expression and cell motility via PI3K, Akt, and NF-κB-dependent pathway in human breast cells.
Authors: Shao Nan , Wang Shenming , Zhang Yunjian , Lin Ying
Published: February 2017

158

Background: αvβ3 integrin-overexpression in tumor associated vasculature is a marker of poor prognosis in breast cancer. A positive correlation between αvβ3 integrin and overexpression of Interleukin-8 (IL-8), a multifunctional cytokine associated with breast cancer aggressiveness was recently demonstrated. Here, we addressed the effects of IL-8 in migration and integrin expression in breast cancer cells. Methods: The IL-8 overexpressing breast cancer cells MDA-MB-231 and HS 578t were treated with IL-8 siRNA and evaluated for cells motility and alterations in the expression of αvβ3. Western Blotting to identify the status of PI3K, Akt and NF-κB. Results: In this study, we found that αvβ3 expression was decreased by IL-8 siRNA, especially the expression of β3. Treatment with αvβ3-blocking antibody LM609 and β3 siRNA significantly reduced invasion in the IL-8 overexpressing cells MDA-MB-231 and HS 578t. The phosphorylation of PI3K, Akt and NF-κB was abrogated after IL-8 siRNA treatment. The IL-8 siRNA can also decrease the binding of β3 promoter and the NF-κB-P65. Conclusions: These results indicate that IL-8 enhances the motility of highly invasive breast cancer cells by regulating αvβ3 expression partially through PI3K/Akt/ NF-κB signal transduction pathway.
Estrogen receptor-positive, progesterone receptor-negative tumors: Pathology and outcome correlations from a single-center cohort.
Authors: Danciu Oana Cristina , Thakkar Jigisha P. , Mehta Divyesh
Published: February 2017

160

Background: Estrogen receptor (ER) + progesterone receptor (PR) - tumors are a distinct subset of breast cancers characterized by aggressive behavior and tamoxifen resistance in spite of being ER+. We sought to describe the characteristics of the patients treated for this type of breast cancer at a large, urban, academic center, compare them with ER+PR+ patients and evaluate the outcomes achieved with the current modern treatments and establish the predictors of worse outcomes. Methods: All patients with the diagnosis of breast cancer who underwent a biopsy at our center between January 1st, 2005 and December 31st 2010 were included into a database. We compared ER+/PR- with ER+/PR+ patients. Demographic data, comorbidities, obstetric data, pathology data, type of treatment and outcome data were collected retrospectively through extensive electronic medical records review. The study was approved by the local IRB. Standard statistical methods were used and a p value <0.05 was considered significant. Results: We found 101 ER+/PR- and 150 ER+/PR+ breast cancer patients. Baseline characteristics, pathology data, treatment and outcomes are shown in the table. Within the ER+/PR- group the degree of Ki67 expression was directly associated with recurrence rate (p 0.0039). Conclusions: ER+/PR- breast cancer is an aggressive type with high recurrence rate and mortality, that affects mainly postmenopausal women. This subtype is associated more frequently with p53 and Ki67 overexpression, and the later levels appear useful in predicting recurrence in this subtype of breast cancer. Novel treament paradigms guided by molecular studies are currently being implemented. [Table: see text]
Subpectoral implants in oncoplastic-reconstructive breast surgery: Habit or necessity?
Authors: Paepke Stefan , Dittmer Sissi , Rezai Arian , Klein Evelyn , Kiechle Marion
Published: February 2017

161

Background: We perform nipple-sparing subcutaneous mastectomies since 2002. Herein we report on 352 cases, in 156 of which acellular dermis (ADM) or meshs (tetanized polypropylene-mesh) as tissue interponates were used. The standard procedure of subpectoral implant positioning with or without caudo-lateral tissue interponates (acellular dermis or mesh) can lead to postoperative problems due to detachment of muscle. Against this background we did not form a submuscular pocket in individual cases, but instead placed the implant in a cranially and caudally covering ADM or mesh pocket. Methods: Between 06/11 and 03/12 17 patients were operated according to the above protocol, and the short-term follow up analyzed. Patients that had to get radiation therapy were not admitted to the study. Furthermore, we only included patients that were planned to get a second, contralateral operation so that corrections of the first operation were possible. Patients were between 34 and 58 years old. One patient had to receive radiotherapy due to a nodal involvement not diagnosed before. Results: Four patients had received prior surgery. Indications for subcutaneous mastectomies comprised invasive carcinomas with large DCIS, R1 resections or secondary prophylaxis. Mastectomy weights ranged between 225 and 1100 g; implant volumes ranged between 225 and 800 cm3. The cosmetic outcome was excellent, the margins of the implants were not visible. In three cases there was a partial necrosis of the nipple and in two cases a partial skin necrosis with the necessity of a wound revision. Conclusions: Using a ADM- or mesh-pocket instead of subpectoral positioning of the implant makes the operation in individual cases easier. Post-operative mobility is immediate and unrestricted. Since the implant size has to be chosen according to the tissue weight removed, a bilaterally identical cosmetic result can be archieved. Complications inculde a mild seroma formation without the necessity to puncture. However, the small number of cases and the short term follow up do not allow to make any statements about consecutive capsular fibrosis.
Clinical and histopathologic tumor characteristics in patients with invasive breast carcinoma receiving metformin.
Authors: Besic Nikola , Gazic Barbara , Satej Nika
Published: February 2017

165

Background: Although both diabetes mellitus (DM) and breast carcinoma (BC) are common diseases, the data about histopathology characteristics and extent of disease of these patients in the literature are scarce and conflicting. Metformin may exhibit inhibitory effects on cancer cells by inhibiting mTOR signaling pathway. Our hypothesis was that use of metformin has an impact on slower progression of breast carcinoma in comparison to other types of anti-diabetic drugs. The aim of our retrospective study was to examine if the patients with BC and DM receiving metformin have lower tumor stage in comparison to patients not receiving metformin. Methods: A chart review of 252 patients (mean age 66.6; range 38-93 years) with invasive BC and DM was performed. They were surgically treated at our institute from 2005-2011. Data on clinical and histopathology factors were collected. Statistical analysis of these factors (i.e., comparison of metformin group vs. no metformin group) was performed by contingence tables and non-parametric tests. Results: DM type 1 and DM type 2 was present in 14 and 238 cases, respectively. Altogether 126 patients were on metformin, while 126 were not receiving metformin. Larger proportion of patients on metformin in comparison to patients not receiving metformin was younger than 71 years of age (p<0.05). No statistical difference between the study groups (metformin vs. no metformin) were found in TNM stage (T1: 48% vs. 46%; T2: 36% vs. 28%; T3: 7% vs. 5%; T4: 9% vs. 21%, p=0.071; N0: 51% vs. 50%, N1 49% vs. 50%; M0: 97% vs. 97.5%, M1: 3% vs. 4%, p=0.74, respectively). However, patients on metformin had lower proportion of T3 or T4 tumors than patients who were not receiving metformin (16% vs. 26%; p<0.05). Patients on metformin had lower rate of lobular carcinoma than patients who were not receiving metformin (9.5% vs. 19%; p<0.05). Tumor size, tumor grade, mean number of metastatic lymph nodes, hormone receptor status or HER-2 status did not show any statistical difference between both study groups. Conclusions: Patients with BC and DM on metformin have lower proportion of T3 or T4 tumors and lower proportion of lobular carcinoma in comparison to patients not receiving metformin.
Feasibility study of nipple-sparing mastectomy for Japanese breast cancer patients.
Authors: Takahashi Maiko , Jinno Hiromitsu , Hayashida Tetsu , Kitagawa Yuko
Published: February 2017

166

Background: Nipple-sparing mastectomy (NSM) has been gathering increased recognition as an alternative to more traditional mastectomy approaches. However, the oncological safety of these procedures is still to be elucidated. The purpose of this study is to investigate technical feasibility of NSM without increasing the risk of local recurrence and complications. Methods: Ninety-eight stage 0-III breast cancer patients received NSM between January 2001 and April 2012 at Keio University Hospital. Eligible patients were without skin involvement and not indicated for breast-conserving therapy by preoperative imaging. The pathological analysis of the subareolar tissue was performed and nipple-areolar-complex (NAC) would be removed if positive. Four hundred seventy-four breast cancer patients who had mastectomy during the same period were used as a control group. Results: The median age was 46.0 years (range 29–68). The mean clinical tumor size was 2.8±1.2cm and the mean distance between the nipple and the tumor was 2.5±1.7cm. Ninety-one patients (92.9%) had clinically node-negative status. NAC involvement was observed in 3 patients (3.1%). Three patients (3.1%) presented with epidermal necrosis. After a median follow-up period of 37.3 months (range 1-136), there were 7 recurrences (7.1%), including 4 local recurrences (4.1%) and 3 distant metastases (3.1%). There was no statistically significant difference in local recurrence between the patients with NSM and mastectomy (4.1% vs. 3.2%; p=0.16). Immediate and delayed reconstruction was performed in 2 cases (2.0%) and 41 cases (41.8%), respectively. Conclusions: Our results suggested NSM may provide oncologic safety for strongly motivated and carefully selected patients.
Predictors of residual disease after breast-conserving surgery.
Authors: Aneja Sanjay , Lannin Donald R. , Killelea Brigid K. , Horowitz Nina Ruth , Chagpar Anees B.
Published: February 2017

168

Background: Locoregional failure after breast conserving surgery (BCS) is often due to undetected residual disease, and the risk of such residual disease frequently guides management. We sought to determine clinical and pathologic factors correlating with the finding of residual invasive cancer and/or DCIS in patients undergoing BCS. Methods: We performed a retrospective cohort study for all invasive and in situ breast cancer treated with BCS at a single institution in 2009. The main outcome variable of interest was residual disease determined by pathologic examinations of cavity shave margins or reexcision. Chart review and statistical analyses were performed to evaluate clinical and pathological factors correlating with residual DCIS or invasive cancer. Results: 256 in situ or invasive breast cancers were treated with BCS in 2009. Of these, 207 (80.9%) underwent additional resection either for close margins or as routine practice. These formed the cohort of interest for this study. 39 patients (18.8%) had residual DCIS and 22 (10.6%) had residual invasive disease. Age, race, histology, ER, PR, her-2-neu and margin distance for invasive disease did not predict the finding of residual DCIS nor invasive cancer. Lymphovascular invasion, while not predicting residual DCIS, was correlated with the finding of residual invasive disease (28.0% vs. 7.9%, p=0.007). Margin distance for DCIS was not predictive of residual invasive cancer but was predictive of residual DCIS. 33.8% of lesions with DCIS margins <1mm were associated with residual DCIS, while 3.4% of those with DCIS margins >5mm were associated with residual in situ disease (p=0.002). Increasing tumor size for invasive and in situ disease were associated with residual DCIS (median 19.5 vs. 13.0 mm, p=0.001 and 22.5 vs. 15.0 mm, p<0.001, respectively); however, neither size component was associated with residual invasive disease. Conclusions: While margin distance and tumor size are associated with residual DCIS in patients undergoing BCS, these are not correlated with residual invasive disease. Conversely, the finding of lymphovascular invasion predicts residual invasive cancer, but not DCIS. These factors may aid in risk stratification of patients and guide postoperative management.
Experience with nipple-sparing mastectomy after prior whole-breast radiation.
Authors: Mackey Aimee Marlena , Taback Bret , Ananthakrishnan Preya , Feldman Sheldon M.
Published: February 2017

173

Background: Nipple-sparing mastectomy (NSM) is being performed more frequently for risk reduction and breast cancer treatment. Prior whole breast irradiation (WBI) has been considered a contraindication to NSM. This study reviews our NSM experience following prior WBI. Methods: We reviewed our prospective mastectomy database from April 2007 to April 2012 for patients undergoing NSM. Ten patients out of a total 169 NSM were identified that underwent NSM following prior WBI. Data collected included incision type, follow-up, complications, cosmesis, and recurrence. Results: Of the ten NSM patients who received prior WBI, 6 had recurrent ipsilateral breast cancer at the lumpectomy site, 3 developed contralateral breast cancers and opted for bilateral NSM, and 1 patient opted for bilateral NSM after finding a BRCA mutation following BCT. Mean patient age was 53. Two patients had comorbities: 1 hyperlipidemia and 1 former smoker. Three of 10 (30%) developed complications, with 2 partial necrosis of nipple-areola complex (NAC) and 1 complete loss of the NAC (Table). No patient required return to the operating room (local resection in the office was performed for the complete NAC loss) and all patients had good final cosmesis. All patients underwent immediate reconstruction: 5 tissue expanders (TE), 2 DIEP and 3 TRAM flaps. Mean follow up is 23 months with no local recurrences to date. Conclusions: This study demonstrates that NSM with immediate reconstruction can be performed in selected patients with prior WBI with an acceptable rate of nipple preservation and good cosmesis. NAC preservation is the ultimate goal in patients undergoing NSM. Current studies are ongoing to identify risk factors that may be associated with nipple necrosis. [Table: see text]
KLF4 and ER as biomarkers for prognosis of breast cancer patients.
Authors: Nagata Takuya , Matsui Kousi , Shimada Yutaka , Tsukada Kazuhiro
Published: February 2017

174

Background: Some of the induced pluripotent stem cell (iPS cell)-inducing factors have been reported to be expressed in breast cancer. The aim of the present study was to examine the relationship between the expression of KLF4 that was one of iPS cell-inducing factors and the prognosis of breast cancer patients. Methods: In 162 breast cancer patients, the expression of KLF4 was determined by immunohistochemistry using a tissue microarray analysis. The relationship with the expression of the estrogen receptor (ER) was also examined. Results: Patients with strong expression of KLF4 (KLF4 high: n=76, 46.9%) had significantly better disease-free survival (DFS; p=0.002) and overall survival (OS; P=0.0006) rates than those with weak expression of KLF4 (KLF4 low: n=86, 53.1%). And also, patients with expression of ER (ER+; n=135, 83.3%) had better DFS (p=0.018) and OS (p=0.0018). About the relationship of KLF4 and ER, KLF4low, ER+ group were better DFS (p=0.0024) and OS (p<0.0001) than KLF4low, ER- group. Conclusions: It was suggested that expressions of KLF4 and ER were useful as biomarkers of prognosis for breast cancer patients respectively. It was also suggested that KLF4 was not cooperative with ER to control the metastasis or progression of breast cancer cells.
Nipple-sparing mastectomy and subareolar biopsy: To freeze or not to freeze?
Authors: Alperovich Michael , Blechman Keith M. , Samra Fares , Shapiro Richard , Axelrod Deborah M. , Choi Mihye , Karp Nolan S. , Guth Amber Azniv
Published: February 2017

185

Background: Advances in breast cancer screening and treatment have fostered the use of surgical procedures that increasingly optimize cosmetic outcome, while ensuring oncologic safety remains the primary concern of the oncologic surgeon. The role of nipple-sparing mastectomy (NSM) for risk-reducing surgery and breast cancer is evolving. It can be difficult to demonstrate involvement of the nipple-areolar complex (NAC) preoperatively, and and in this report we examine the utility of intraoperative subareolar frozen section (FS). Methods: Records of patients undergoing NSM at the NYU Langone Medical Center from 2006-2011 were reviewed retrospectively. Use of subareolar FS was at surgeon’s discretion. Results: 237 NSM were performed (146 prophylacytic, 91 theraputic). FC was not utilized in 58 mastectomies (28 prophylactic), with 2 (+) on paraffin. Among the remaining 180 mastectomies, 11 biopsies were (+)(7.2%); 5 subareolar biopsies were (+) on FS and paraffin histologic slides (PS) (2.8%); 6 were negative on FS and (+) on PS. Among the 3 prophylactic NSM with (+) subareolar biopsies there was 1 (+) FS, 1 (-) FS, and 1 with no FS performed. There were no false (+) FS. Four of the 5 patients with (+)FS underwent simultaneous excision of the NAC. The 5th patient had atypia on FS and DCIS on PS, and returned to the OR during the same hospitalization for removal of NAC. The remaining patients underwent subsequent excision of the NAC either during planned 2nd stage reconstruction or following completion of chemotherapy. 8 NAC were free of disease and 5 were positive for in situ or invasive disease. There has been no local recurrence in these patients to date. Conclusions: The rate of NAC involvement is low, 5.5% in this series, and FS, while utilized in the majority of these cases, detected only 46% of subareolar disease. While FS can direct intraoperative decision making, the predictive power is low, and these considerations must be addressed in preoperative patient discussions. Furthermore, among those patients with (+) subareolar biopsies, only 39% had residual disease on NAC excision. Thus, optimal oncologic management of the NAC must still be considered an unresolved issue.
Indication of sentinel lymph node biopsy with breast-conserving surgery for ductal carcinoma in situ considering lymphatic flow.
Authors: Yamaguchi Ayane , Tsuyuki Shigeru , Okamura Miru , Kawata Yukiko , Kawaguchi Kosuke , Kawaguchi Nobuko , Kohno Yukihiro
Published: February 2017

192

Background: Ductal carcinoma in situ (DCIS) has been regarded as curable with resection, but axillary lymph node metastases have been reported in 2% of DCIS patients. Even when DCIS has been diagnosed by preoperative core needle biopsy (CNB), 8% to 38% of the patients have been found to have invasive ductal carcinoma (IDC) on the basis of pathological diagnosis after surgical treatment. The indication of sentinel lymph node biopsy (SLNB) and breast-conserving surgery (BCS) for DCIS is still controversial. Methods: SLNB is a standard surgical technique for early breast cancer treatment, and indocyanine green (ICG) fluorescence method is remarkable in terms of the visualization of lymphatic flow. We analyzed the variation in lymphatic drainage routes from the nipple to the SLN (sentinel lymphatic routes) by using the ICG florescence method in early breast cancer patients and investigated the effects on the localization of the tumor to the sentinel lymphatic routes after BCS. Results: From November 2010 to April 2012, we recorded the sentinel lymphatic routes in 118 patients. All the routes passed through the upper outer quadrant (UOQ) area, and there were more than 2 routes in 53 cases. Of these routes, 73% passed through only the UOQ area and 27% passed through the UOQ via the upper inner, lower inner, and/or lower outer quadrant area. Conclusions: We should confirm the sentinel lymphatic routes by using the ICG florescence method before BCS for preoperatively diagnosed DCIS. If the lymphatic routes do not pass over the extent of resection of BCS, we can omit SLNB in the first surgical treatment and await the final pathological result. However, we should perform SLNB in addition to BCS in cases in which the lymphatic routes pass over the tumor in the region except the UOQ area.
Adjuvant docetaxel and cyclophosphamide (DC) with prophylactic growth colony stimulating factor (GCSF) on days 8 and 12 in breast cancer patients: A retrospective analysis.
Authors: Yerushalmi Rinat , Stemmer Salomon M. , Hendler Daniel , Neiman Victoria , Ciuraru Noa Beatrice , Bonilla Luisa , Ben-Aharon Irit , Amit Limor , Granot Tal , Zer Alona , Sulkes Aaron , Rizel Shulamith
Published: February 2017

202

Background: Four cycles of docetaxel/cyclophosohamide (DC) produced superior survival compared with doxorubicin/cyclophosphamide in the treatment of early breast cancer. The study reported 5% of febrile neutropenia (FN) events using prophylactic antibiotics with no growth factor (GF) support. The worldwide adoption of this protocol yielded several reports on substantially higher rates of FN events (up to 46%), prompting the addition of GCSF by most centers. We explored the use of GF support on days 8 and 12 to the original DC protocol. This report summarizes treatment related morbidity of the DC protocol with GF support given on days 8 and12. Methods: All consecutive patients with stages I-II breast cancer who were treated with the DC protocol in our institute from April 2007 to March 2012 were included. Patient characteristics and toxicity were reported. Results: 131 patients were identified. Median age- 60y (25-81), 65y and older- 25%; 5 patients did not complete the 4 planned cycles (12/524 cycles were missed). Fifteen patients (11.5%) experienced at least one event of FN (4 patients had 2 events), all requiring hospitalization. FN events occurred in 19 out of 512 cycles (3%). Median age of the patients who required hospitalization due to FN was 60y (42-73). Results were comparable in the older group (≥65): 15% developed FN with 6 NF events out of 130 cycles (4.6%), p>0.05. There were additional 14 hospitalizations events due to other causes (diarrhea n=2, chest pain=2, cellulitis n=2, COPD n=1, tonsillitis n=1, fever n=2, bone pain n=1, observation after treatment n=1 and hearing problem n=1, unknown n=1). Six patients had grade 2-3 diarrhea. 2/6 required hospitalization. There was no treatment related mortality. Conclusions: Primary prophylactic growth factor support on days 8 and 12 provides a safe and economic option to deliver the DC protocol. Our results are in line with other retrospective protocols using longer schedules of GF support.
Sentinella: Portable gamma camera versus conventional scintigram for intraoperative sentinel lymph node detection in breast cancer.
Authors: Ghosh Debashis B. , Michalopoulos Nikolaus , Wickham Caspar , Davidson Timothy , Keshtgar Mohammed R.
Published: February 2017

22

Background: Sentinel lymph node biopsy (SLNB) is a standard practice for staging the axilla in breast cancer. Access to nuclear medicine department and sentinel node imaging remain an issue in number of hospitals in the UK and rest of the world. Preoperative scintigrams are performed to confirm uptake of radioactivity and localisation of nodes in centres where facilities are available. Sentinella is a portable imaging camera used intraoperatively to produce real time visual localisation of SLNs. Sentinella was tested in a controlled laboratory environment at our centre followed by the first use of this device in breast cancer patients from UK. Methods: Sensitivity and spatial resolution of Sentinella was compared with conventional gamma camera (CGC).Intraoperative Sentinella Scans were performed in 130 patients and their yield compared with Lymphoscintigrams from CGC. Further Sentinella scans were performed after the axilla was deemed clear by silent activity of hand held gamma probe. Results: Sentinella resolution is comparable with the CGC for objects close to the camera. Sentinella detects high radioactivity (500 kBq) faster than CGC (1 vs 2.5min). In cases of low radioactivity (10kBq) Sentinella was equally accurate and faster than CGC, when placed nearer to skin.Intra-operative Sentinella scans detected an average of 2 sentinel nodes compared to 1.4 nodes by CGC scans. Sentinella demonstrated a serial decay in activity with removal of every hot node and its LED guidance helped in detecting residual nodes. Sentinella picked up extra nodes in 5/130 cases after the axilla was found silent using hand held gamma probe. In 2/130 cases extra nodes found using Sentinella had presence of cancer that led to a complete axillary clearance. Conclusions: This data confirms the excellent sensitivity and specificity of the machine in localisation of radioactive nodes. This new imaging technique increases our pick up of SLNs intraoperatively that are missed due to inadequate visualisation and provide a superior detection compared to static scintigram imaging. This portable gamma camera can replace the use of conventional lymphoscintigrams saving camera time and cost.
Metformin and breast cancer risk: A meta-analysis and critical literature review.
Authors: Col Nananda , Ochs Leslie , Springmann Vicky , Aragaki Aaron K , Chlebowski Rowan T.
Published: February 2017

25

Background: Observational studies have suggested that metformin, commonly used for diabetes treatment that increases insulin sensitivity and improves glycemic control, decreases the incidence of several common cancers. However, findings regarding metformin and breast cancer incidence have been mixed. To explore this issue, a systematic literature review and meta-analysis were performed with a focus on potential biases. Methods: We conducted a comprehensive literature search for all pertinent studies addressing metformin use and breast cancer risk by searching Pub Med, Cochrane Library, Scopus (which includes Embase, ISI Web of Science) using the Mesh terms: "metformin" or "biguanides" or "diabetes mellitus, type 2/therapy" and "cancer" or "neoplasms". When multiple hazard ratios (HR) or odds ratio (OR) were reported, the most adjusted estimate was used in the base-case analysis. We pooled the adjusted HR using and performed sensitivity analyses on duration of metformin use (> or < 3 years use), study quality (assessed using the GRADE system), and initial observation year of the cohort (before vs after 1997). Results: From a total of 421 citations, 13 full-text articles were considered, and 7 independent studies were included. All were observational (4 cohort and 3 case control). Our combined OR for metformin association with invasive breast cancer of all 7 studies was 0.83 (95% CI, 0.71-0.97). Funnel plot analyses did not suggest publication bias. Stronger associations were found when analyses were limited to studies estimating the impact of longer metformin duration (OR = 0.75. 95% CI, 0.62-0.91) or among studies that began observing their cohort before 1997 (OR=0.68. 95% CI, 0.55-0.84). Stratification according to study quality did not affect the combined OR but higher quality studies had smaller CI and achieved statistical significance. Interpretation is limited by the observational nature of reports and different comparison groups. Conclusions: Our analyses support a protective effect of metformin on invasive breast cancer incidence among postmenopausal women with diabetes. Clinical trials are needed to determine whether metformin reduces breast cancer risk.
Screening mammography in southeastern Kentucky: Is it a predictor of ongoing health disparities?
Authors: Elsoueidi Raymond , Hanna Elias , Dignan Mark
Published: February 2017

28

Background: Studies have shown that women living in rural areas have a significantly lower rate of screening mammography than women living in urban areas. Despite the dramatic improvement in the use of screening mammography in the United States, disparities are still present. Southeastern Kentucky is a rural area with a low income population and barriers such as distance and lack of public transportation to access health care. We reviewed the use of screening mammography in this population. Methods: Data for women age 50 and older who did not have a screening mammography within the past 2 years were obtained from the behavioral risk factor surveillance system for the years 2000 through 2008. Results: The rates of screening mammography in the state of Kentucky for women age 50 and older ranged from 77% in 2000 to77.6% in 2008. The rates for urban areas in Kentucky ranged from 79.5% in 2000 to 79.4% in 2008 and those for the rural southeastern part of the state ranged from 62.6 % in 2000 to 63.7 in 2008. On average, the rates of screening mammography in southeastern Kentucky were 23% lower than state rates from 2000-2008, a difference that is statistically significant (p<.05). Additionally, from 2000 to 2008 there was no statistically significant improvement in the rates of screening mammography in southeastern Kentucky. Conclusions: The results of this study showed that the rates of participation in screening mammography are substantially lower in rural southeastern Kentucky. Continued efforts are needed to improve understanding the factors that contribute to these low rates and to help develop interventions to overcome the obstacles for obtaining screening mammography in rural populations.
Does lobular carcinoma in situ (LCIS) affect biology of future breast cancer? Surveillance Epidemiology and End Results (SEER) database review.
Authors: Tesfaye Anteneh A. , Mozayen Mohammad , Morariu Ioana , Eilender David S.
Published: February 2017

37

Background: Lobular carcinoma in situ (LCIS) is a recognized risk factor of breast cancer. Data evaluating the behavior of breast cancer arising after LCIS is lacking. Our study compared the characteristics of breast cancer arising after LCIS with the breast cancer arising de novo. Methods: From the 1973-2009 SEER database, women with breast cancer who were diagnosed and treated between 1990 and 2009 were abstracted. Patients were divided to group A: breast cancer after LCIS, group B: de novo breast cancer. Age, ethnicity, staging, tumor size, grade and hormone receptor status were reviewed. Data were analyzed using chi square, Kaplan-Meier, Life table, and Cox proportional hazard model. Results: Patients with LCIS were 7,258 with 547 (7.5%) developing breast cancer subsequently. The mean (SD) time to develop breast cancer after LCIS was 68 (2.14) months. Of the total 557,309 patients with breast cancer, group A had 547 patients and group B had 556,762 patients. The median tumor size was 1.3 and 1.8 cm in groups A and B respectively (p<0.0001). Grade 1 and 2 tumors were 78.5% and 60.8% in groups A and B respectively (p<0.0001). Local disease alone was seen in 70% and 61% of groups A and B respectively (p<0.0001). ER-PR negative tumor was seen in 14.9% and 24.5 % in groups A and B (p<0.0001). On univariate analysis, 5 year cancer specific survival was 91% and 85% in groups A and B respectively (p< 0.0001). Unlike grade, hormone receptor status and stage, prior history of LCIS was not an independent predictor of survival on multivariate analysis (see Table). Conclusions: Breast cancer diagnosed after prior LCIS has favorable features like smaller tumor, lower grade, earlier stage and less ER-PR negativity. Some of these might be a result of more diligent subsequent screening. A history of LCIS per se is not an independent prognostic factor in breast cancer. [Table: see text]
Impact of breast cancer and BRCA mutations on thoughts and feelings of future pregnancies.
Authors: Woodson Ashley Henriksen , Muse Kimberly I. , Jackson Michelle , Arun Banu , Litton Jennifer Keating
Published: February 2017

38

Background: Many women diagnosed with premenopausal breast cancer are concerned with treatment-related infertility. Identifying a BRCA mutation associated with hereditary breast and ovarian cancer may affect attitudes regarding future childbearing. We evaluated attitudes regarding the impact of cancer or potentially being a BRCA mutation carrier on future childbearing. Methods: Women with childbearing potential were invited to participate in an IRB-approved questionnaire study administered prior to genetic counseling and after results disclosure, if applicable. Women were provided a series of 15 statements and asked to rate how often they thought about the impact of cancer or of having a BRCA mutation on the ability to conceive or carry a pregnancy on a 4-point scale ranging from not at all to often. Descriptive statistics were used. Results: We received 148 pre-questionnaires and 114 post-questionnaires. Thirteen women tested positive for a BRCA 1 mutation and 5 with a BRCA 2 mutation. The mean age was 35 (range 20-45) with 71% having breast cancer. The majority (62%) had at least 1 biological child prior to diagnosis and 45% desired a future child. Across 15 statements, 57% of women did not have any thoughts or feelings about the impact of cancer or a BRCA mutation on a future pregnancy at initial visit. Across the same 15 statements, 52% of women who tested positive for a BRCA mutation changed their answer from the pre-questionnaire to post-questionnaire. Of these women, 70% thought about the impact more often than they reported initially. When compared to women who tested negative for a BRCA mutation (n=78), only 40% of women changed their answer choice, with 54% thinking about the impact less often. Conclusions: Women testing positive for a BRCA mutation were more likely to have an increase in thoughts and feelings regarding the impact of cancer or of being a BRCA mutation carrier on the ability to have a future pregnancy, while women who tested negative showed a decrease. Therefore, women with a BRCA mutation may be influenced in their decisions regarding future childbearing.
Radiation therapy after breast-conserving surgery: When are we missing the mark?
Authors: Nassif Mohammed , Trabulsi Nora , Reidel Kristen , Meterissian Sarkis H. , Tamblyn Robyn , Mayo Nancy , Meguerditchian Ari-Nareg
Published: February 2017

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Background: Postoperative radiotherapy (RT) after breast conserving surgery (BCS) represents the standard of care for local control of breast cancer (BC). Despite wide dissemination of clinical guidelines, variations in practice persist. Our objective was to identify patient, disease, and physician characteristics that predict lack of consideration for RT after BCS. Methods: Cancer registry data and administrative claims for all BCs diagnosed in Quebec from 1998 to 2005 were collected. Receipt of a consultation for RT in women with non-metastatic BC treated with BCS was measured. Multivariate logistic regression was used to assess the association between patient, disease, and physician characteristics and having an RT consult. Results: 27,483 women were included. Mean age was 59 years, 76.5% had no comorbidities, and 27.6% had stage III BC. Overall, 90.1% of women were considered for RT within 1 year of diagnosis. Patients at age extremes were less likely to be considered as compared to women 50-69: those 30-49, 70-79 and 80+ had odds ratios (OR) of 0.82 (CI 0.73-0.93), 0.54 (CI 0.48-0.61) & 0.11 (CI 0.09-0.12), respectively. Women with any ER visit and women with a hospitalization (unrelated to BC) had 15% and 17% lower odds of having an RT consult, respectively. In patients with advanced disease, receiving a consultation for chemotherapy within 4 months of BCS increased the likelihood of also being considered for RT within 1 year (OR 1.54, CI 1.19-2.00). Increases in physician BCS volume in the year prior to patient diagnosis increased the chance of their patient receiving an RT consult by 7% for every additional 10 BCS performed. Conclusions: Patient age, use of non- BC-related health services and physician volume of BCS predicts use of RT. Guideline deviations in chemotherapy administration also predicts variation in RT use.
Papillary lesions of the breast: Can larger core needle biopsy samples identify patients who may avoid surgical excision?
Authors: Chung Alice P. , Huynh Kelly T. , Shamonki Jaime , Sim Myung-Shin , Lawrence Camelia , Kinnaird Michelle , Giuliano Armando E.
Published: February 2017

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Background: Papillary lesions of the breast are frequently diagnosed on core needle biopsy (CNB). The ability to distinguish benign from atypical/malignant papillary lesions is limited by the representative nature of the biopsy method; thus follow-up excision is usually recommended. We aimed to determine if larger CNB samples can more reliably predict the true benign nature of a papillary lesion, thereby sparing certain patients a formal surgical excision. Methods: We reviewed medical records of 53 female patients diagnosed with histologically benign papillary lesions on CNB from 2000 to 2010, who subsequently underwent surgical excision. Pathology slides of the CNB were reviewed to document the benign histologic features of the papilloma, the number of cores sampled and the area of tissue biopsied (mm2). Statistical analysis was performed to identify the characteristics of the CNB that were associated with retention of benign histology on excision. Results: Atypical ductal hyperplasia (ADH) and carcinoma were identified in 6% (3/53) and 8% (4/53) of papillary lesions, respectively, when excised. Clinical and radiographic characteristics did not distinguish the ADH/malignant lesions from benign papillomas. The CNB needle sizes ranged from 9- to 18-gauge (median 14). The number of cores sampled ranged from 3-16 (mean 4.5). Patients with benign excisions had a significantly larger area of tissue sampled by CNB than those found to have ADH/malignant lesions on excision (mean ± SD: 95.6 ± 101.2 vs. 41.7 ± 21.9, respectively, p=0.003). By logistic regression, CNB tissue samples consisting of ≥7 cores, or measuring >96 mm2 in aggregate, had a negative predictive value for ADH/malignancy of 100% (AUC of 0.69 and 0.68, respectively). Conclusions: Although no clinical or radiologic features distinguished benign from pathologically significant papillary lesions, larger sample sizes significantly improved the predictive value of benign histology on CNB. A papilloma sampled by ≥ 7 cores or > 96 mm2 showing benign histology at CNB, retained benign features upon excision. Close surveillance may be a reasonable option for patients whose benign papillomas are generously sampled at the time of CNB.
Molecular differences between normal breast epithelia, pure DCIS, and DCIS adjacent to invasion.
Authors: Guvakova Marina
Published: February 2017

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Background: With the use of screening mammography, the diagnosis of breast ductal carcinoma in situ (DCIS) is increasing worldwide. Currently there are no applied molecular markers to aid in predicting risk of DCIS progression to invasive breast cancer (IBC). Studies predicted that the transition from DCIS to invasive disease was associated with quantitative rather than qualitative differences in gene and protein expression. Methods: We developed monochrome imaging-based method to measure protein expression as a continuous variable in fixed tissue (Furstenau et al. BREA 2010). The insulin-like growth factor I receptor (IGF-IR), Ras oncogene –like protein 1 (Rap1), and a Rho GTPase guanine nucleotide exchange factor Vav2 implicated in the regulation of invasion in preclinical models have been chosen for protein analysis in tissue. In pilot study, we performed quantitative protein profiling on 90 samples of the breast: 17 histologically normal tissues, 16 benign lesions; 15 CIS, and 42 IBC. In addition, we analyzed 24 DCIS: 12 pure and 12 associated with IBC. Results: The expression of the IGF-IR and Rap1 was increased in pure CIS; significantly (P ≤ 0.001) increased in CIS adjacent to IBC as well as in IBC compared with non-cancerous tissue. In the majority of pure DCIS the levels of Vav2 were similar to that in normal epithelia; however, the Vav2 levels were significantly (P<0.01) higher in DCIS adjacent to invasion and in IBC. Moreover, IGF-IR, Rap1 and Vav2 significantly discriminated invasive from non-invasive tissues, with receiver operating characteristic (ROC) area under curve, AUC=0.8. Interestingly, younger women (< 50 years of age) were more likely to develop IBC with increased expression of the Vav2 protein (OR= 2.05; 95% CI 1.08-3.86). No significant correlation was found between IGF-IR, Rap1 expression levels and patient’s age. Conclusions: We conclude that our assessment of protein expression in breast tissue revealed previously unidentified quantitative differences in the IGF-IR, Rap1, and Vav2 protein expression in breast cancer progression series. These findings open door for studies on molecular-based prediction of individualized risk for developing invasion in early diagnosed DCIS.
Estimation of additional MRI resources needed in British Columbia for screening high-risk women for breast cancer.
Authors: Rajapakshe Rasika , Bitgood Christabelle , McAvoy Steven , Araujo Cynthia , Gordon Paula , Coldman Andy
Published: February 2017

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Background: Screening women at high risk with MRI has been shown to detect breast cancer at an early stage. Therefore, MRI screening has been recommended in the UK and USA for women who are at a high risk of developing breast cancer. However, there is no information available in the province of British Columbia (BC) about the number of women who have a high risk of developing breast cancer. Therefore, we carried out a study to estimate the breast cancer risk distribution in three sample populations in BC using Tyrer-Cuzick (TC) risk prediction model so that additional resource requirement for MRI breast screening can be calculated. Methods: A survey questionnaire was designed based on the TC model, which includes family history, hormonal factors, and benign breast disease. Additional questions also include factors that are used in other models (Gail, Claus, and BCRAPRO) as well as factors that may be included in the future. Women were recruited by staff and volunteers at three screening mammography clinics: Kelowna, Victoria General Hospital, and BC Women’s Health Centre in Vancouver. The survey was available to women to complete on the web, by phone, or on paper. An online database was constructed to store and query the data. The 10-year risk of developing breast cancer for each woman was calculated using the Tyrer-Cuzick IBIS Risk Evaluator software and the risk distribution of the survey population was analyzed. Results: Data from 3,200 women recruited from three sites, gives a risk distribution showing 2.6% are at high risk of developing breast cancer, 31.2% are at moderate risk, and 66.2% are at low risk. Based on NICE guidelines (UK), high risk is defined as having a 10-year risk of greater than 8%, moderate risk as 3-8%, and low risk as less than 3%. Extrapolating this to the approximately 500,000 women who are eligible to attend for screening mammography in BC, 13,000 women are considered at high risk. Conclusions: Our results indicate that 2.6% of women ages 40-79 attending screening mammography in BC may have a very high risk of developing breast cancer based on personal and family history. Based on a 14-hour work day, three additional MRI scanners would be required to implement MRI screening for these high-risk women in BC.
Does breast density affect the ability of MRI to detect mammographically occult cancers?
Authors: Freedman Beth Cutler , Luongo Jocelyn , Gillego Alyssa , Fulop Tamara , Boolbol Susan K.
Published: February 2017

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Background: In breast cancer patients, the use of preoperative MRI is increasing. A change in the operative plan due to MRI findings occurs in 8%-20% of cases. Preoperative MRI is used routinely by many surgeons and radiologists, but debate persists with regard to its indications. We evaluated whether mammographic breast density affected MRI findings. We also examined whether the number of MRI detected synchronous cancers were affected by breast density. Methods: A retrospective chart review was performed of newly diagnosed breast cancer patients who underwent preoperative MRI from 2008-2011. There were three categories of breast density: fat-replaced, scattered fibroglandular densities, and dense. We determined the number of patients in each group who underwent biopsies based on MRI findings, and evaluated the number of occult cancers diagnosed as a result of these biopsies. Results: 301 patients were included. Overall, 64 patients (21%) who underwent an image guided biopsy based on pre-operative breast MRI were diagnosed with an additional focus of cancer. Of the 17 patients with fat-replaced breasts, 4 underwent additional biopsy, and carcinoma was identified in all patients. 149 patients had scattered fibroglandular densities; 53 (36%) underwent additional biopsies. New cancers were diagnosed in 28 patients (19%). Of 135 patients with dense breasts, 61 patients (45%) had additional biopsies, and new cancers were diagnosed in 24 % of these patients. Conclusions: MRI detected additional cancer in 21% of patients in this study. MRI is sensitive and specific in patients with fat-replaced breasts (100%), but due to the small number of patients in this group, additional studies must be done to evaluate the usefulness in this group of patients. We conclude that MRI is useful for detecting additional cancers in patients of all breast densities, and may change the surgical options of the patient when multicentric or contralateral disease is diagnosed.[Table: see text]