bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilization of accelerated partial-breast irradiation (APBI) and guideline concordance: Analysis of the National Cancer Database.
Authors: Shaitelman Simona Flora , Lin Heather , Shen Yu , Bedrosian Isabelle , Bloom Elizabeth S. , Babiera Gildy
Published: February 2017

54

Background: ASTRO published a consensus statement on patient suitability for APBI treatment to guide physician practice. The purpose of this study was to examine utilization trends of APBI in the American College of Surgeons’ National Cancer Database and to assess changes in APBI use following publication of the ASTRO guidelines in 2009. Methods: A total of 337,910 women were identified who were diagnosed from 2004 to 2010 with non-metastatic invasive breast cancer or ductal carcinoma in situ who were treated with breast conserving surgery and radiation therapy (RT) to the breast. Patients were divided by the type of treatment received (whole breast irradiation (WBI) or APBI) and by suitability to receive APBI as defined by the ASTRO Consensus Statement. Logistic regression was applied to study APBI use overall and within consensus statement categorization. All p-values are two-sided. Results: For all patients, APBI usage increased as an alternative to WBI over time, from 3.8% in 2004 to 10.8% in 2008, with a subsequent decline to 9.9% in 2010, due to a decline in APBI use for “cautionary”/“unsuitable” patients (p<0.0001). Overall rates of APBI utilization were higher among “suitable” than “cautionary”/“unsuitable” patients (range 6.9% to 16.9% vs. 3.1% to 7.8%, p<0.0001). Among all patients, the most common modality of delivering APBI was brachytherapy (82%), followed by external beam RT (17%) and intraoperative RT (1.0%). For both “suitable” and “cautionary”/“unsuitable” patients, factors associated with treatment with APBI included treatment after 2004 (p<0.0001), well differentiated histology (p<.0001), and smaller tumor size (p<0.0001). For “cautionary”/“unsuitable” patients, those with grossly negative tumor margins were more likely to receive APBI, as were “suitable” patients treated at an academic or comprehensive community cancer program compared to a community cancer program (both p<0.0001). Conclusions: The highest absolute rate of use of APBI was seen in the group considered “suitable” by ASTRO guidelines. Although significant increases have also been seen among less suitable cohorts, these rates have declined since the publication of the ASTRO guidelines in 2009.
Identifying women at high risk for invasive breast cancer at the time of screening mammography.
Authors: Lopresti Mary Lorraine , Edmiston Kathryn L. , Sood Rahul , Khanna Shrinkala
Published: February 2017

6

Background: Most mammography centers collect reproductive, family, and environmental data on patients presenting for screening mammograms. These data, if entered into a Gail Model Risk Assessment Tool, can help identify those patients at increased risk. These patients can then be referred to high-risk centers that will focus on risk-reduction strategies. Methods: This study is an observational prospective cohort of 1,000 women presenting for mammographic screening or diagnostic evaluation at mammography clinics affiliated with a single institution. Women at the time of their mammogram were asked to fill out a standard intake sheet by the institutional clinic. These data sheets were gathered and Gail model risk scores were calculated. Women with a 5-year risk of invasive breast cancer of 1.7% or greater were identified. Patients with a history of breast cancer or who underwent diagnostic mammography were excluded. A high risk subgroup was identified and risk factors were analyzed. Women at particularly high risk ( ≥ 3.4% or double the 5-year risk) were analyzed separately. Results: Of 1,000 women screened, 366 had ≥ 1.7% 5-year risk of invasive breast cancer. 26% (96) of these women were under 60 years old while 74% (270) were ≥ 60 years old. Among the latter group, 19.6% (53) were found to have ≥ 3.4% of developing invasive cancer. In these women with double the 5-year risk, 96.2% had a family history of breast cancer and 92.4% had a prior biopsy. Similarly, in women under 60, greater than half were high risk secondary to a prior biopsy or family history. Conclusions: 1/3 of patients who receive annual screening are at high risk for breast cancer. These patients can be identified from data routinely obtained at the time of screening mammography. Many were found to be at increased risk due to a strong family history or prior biopsy. Mammography centers may be the ideal setting in which to alert these patients of their risk and refer them to high risk centers for genetic counseling and consideration of chemoprevention.
A pilot study of preoperative (Pre-op), single-dose ipilimumab (Ipi) and/or cryoablation (Cryo) in women (pts) with early-stage/resectable breast cancer (ESBC).
Authors: Diab Adi , Solomon Stephen Barnett , Comstock Christopher , Maybody Majid , Sacchini Virgilio , Durack Jeremy C. , Blum Brian , Yuan Jianda , Patil Sujata , Neville Deirdre A. , Sung Janice S. , Kotin Alan , Morris Elizabeth Ann , Brogi Edi , Morrow Monica , Wolchok Jedd D. , Allison James , Hudis Clifford , Norton Larry , McArthur Heather L.
Published: February 2017

67

Background: Intratumoral cryo combined with immune modulation generates a potent systemic anti-tumor immune response that might improve recurrence free survival in ESBC. In this study, we evaluate the safety of pre-op cryo and/or ipi (10mg/kg) in pts with ESBC. Radiographic correlates and intratumoral/serologic immune responses are also explored. Methods: Eligible pts are ≥18y of age with operable ≥1.5 cm invasive ESBC, no history of autoimmune disease and planned mastectomy. Pts are sequentially assigned to receive pre-op: cryo alone (Group-A), ipi alone (B), or ipi with cryo (C). Cryo is administered 7-10d prior to surgery. Ipi is administered 8-15d prior to surgery (1-5d prior to cryo). If at least 5/6 pts in each group proceed with surgery without delay, the regimen will be considered safe/tolerable. Toxicity evaluation continues for 12 wks after ipi administration for Groups B and C. Results: As of May 1, 2013, 7/7 pts were enrolled to Group-A (expanded after a possible technical failure in 1 pt) and 6/6 pts were enrolled to Group-B. The median age was 45y (range 39-69y). All 13 pts in Groups A and B underwent mastectomy without delay. Group C is now accruing with 1/6 patients enrolled and awaiting surgery. 6/7 pts in Group-A and none in Group-B had ischemic tumor necrosis/infarction in the mastectomy tissue. Overall, pre-op cryo or ipi alone have been well tolerated with no study related grade 3/4 adverse events (AE) reported (Table). Conclusions: To date, pre-op cryo or ipi is safe and tolerable in pts with ESBC. A Phase II study of pre-op ipi and cryo in ESBC is planned. Clinical trial information: NCT01502592. [Table: see text]
Do locoregional recurrence and survival outcomes differ in women with node-negative, HER2-positive breast cancer treated with breast-conserving therapy versus mastectomy?
Authors: Peterson David John , Truong Pauline , Sadek Betro , Shenouda Mina , Taghian Alphonse , Alexander Cheryl
Published: February 2017

69

Background: Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer subtype is an adverse prognostic factor, it is unclear whether there are differences in outcomes according to the type of locoregional treatment used in this population. This study compared locoregional recurrence and survival outcomes in women with node-negative, HER2-positive breast cancer treated with Breast Conserving Therapy (BCT) versus Modified Radical Mastectomy (MRM). Methods: Independent datasets from the BC Cancer Agency (BCCA) and the Massachusetts General Hospital (MGH) were pooled and analyzed. Study subjects included 748 patients between 2003-2009 with pT1-2, N0, M0 Her2+ breast cancer, treated with BCT or MRM. Standard clinico-pathologic factors were analyzed. Kaplan-Meier locoregional recurrence (LRR), breast cancer specific survival (BCSS) and overall survival (OS) were compared between cohorts treated with BCT vs. MRM. Multivariable analysis (MVA) with Cox regression modeling was performed to evaluate the prognostic significance of type of locoregional treatment on outcomes. Results: Median follow-up time was 4.2 years for BCCA and 6.0 years for MGH. Comparison of clinico-pathologic factors according to type of locoregional treatment found that patients treated with MRM had higher proportions of grade 3 histology (69% vs. 60%, p = 0.004) and PR-negative disease (56% vs. 44%, p = 0.008) and lower rates of endocrine therapy (51% vs. 64%, p <0.001) and herceptin therapy (50% vs. 57%, p = 0.04). There were no significant differences between BCT and MRM groups in 5-year Kaplan-Meier LRR (2.0% vs. 1.7%, p=0.88), BCSS (97.2% vs. 96.1%, p=0.70), and OS (95.5% vs. 93.4%, p=0.19). On MVA, BCT and MRM were associated with similar LRR, BCSS, and OS. The only factor associated with reduced OS was T2 disease (HR 3.1, p=0.01). Conclusions: In this multi-institutional study, no significant outcome differences were found among women with T1-2 N0, HER2-positive breast cancer treated with BCT or MRM. Breast conserving therapy is safe in this population, providing high rates of locoregional control and survival equivalent to mastectomy.
Radiation-induced lung and heart toxicity in patients with early-stage breast cancer treated with hypofractionated radiotherapy following breast-conservative surgery.
Authors: Fragkandrea-Nixon Ioanna
Published: February 2017

73

Background: Hypofractionated RT for breast cancer (BC), although reducing cost and time, could have negative impact on normal underlying lung and heart. We studied and compared lung function and the post –RT radiological changes using High–Resolution CT (HRCT) in early BC patients, treated with 3-D conformal whole breast radiotherapy (WBRT) using either conventional or hypofractionated regime. Additionaly, in patients with right-sided breast cancer, we monitored changes in LVEF performing MUGA scans. Methods: Between 2008 and 2009, 61 early BC patients (TI-2N0M0) were randomised into Group A (n=31) and Group B (n=30) receiving standard radiotherapy with 50Gy/25f/5w plus boost 10Gy/5f/1w to tumour bed or 43.2Gy/16f/22d plus same boost dose respectively. All patients were subjected to dynamic lung testing, on D0 (before RT), during and after RT at 3 and 6 months. HRCT scans were performed at baseline, and 3, 6, 12 months after RT. Dosimetric factors (CLD, V20, D25, MLD) were calculated. MUGA was performed in patients with right sided BC prior and 6 and 12 months post RT. Results: At 3 months after RT, pulmonary changes were classified at HRCT as follows: 91.8% were Grade 0, 8.19% Grade 1, and 0% Grade 2. At 6 months, 86.98% were Grade 0, 11.47 % Grade 1, and 1.6% Grade 2. At 12 months, 88.52% were Grade 0, 9.19 % Grade 1 and 3.27% Grade 2. Univariate analysis showed strong association between radiation pneumonitis, age and all dosimetric parameters. There was no association between fractionation type and incidence of RN. FEV1, FVC, FEV 25, FEV 50 and DLCO showed no statistically significant reduction in both treatment groups in 3 and 6 months following RT, compared to baseline. Multivariate analysis showed no relation between HRCT findings and age, smoking, chemotherapy, hormonotherapy, V20. No changes were found in LVEF prior and 6 and 12 months post radiotherapy. Conclusions: Lung toxicity as assessed with HRCT and PFTs was minimal in both treatment arms and our results are in consistency with other published data. In our series, no significant changes were found in LVEF in both treatment arms.
Identifying the surgical cavity following oncoplastic surgery: Utility of a novel tissue marker.
Authors: Harman John , Govender Stan , Benjamin Benji , Simpson John
Published: February 2017

76

Background: Oncoplastic surgery has helped improve outcomes following partial mastectomy. However, in most cases, patients still require post-operative radiotherapy, which can cause significant complications. While recent advances have made it feasible to perform external beam radiation in a more targeted and accelerated fashion, these methods are not commonly used in the treatment of breast cancer. This is due to the difficulty in identifying the margins of the surgical site, and can be particularly challenging with oncoplastic surgery (OPS). In this pilot study, we evaluated a new method for marking the margins of the surgical cavity when using oncoplastic techniques. Methods: 15 patients were selected to have a 3-D tissue marker implanted at the time of lumpectomy. All patients were candidates for partial mastectomy, sentinel lymph node biopsy and breast reconstruction using OPS. Post-operative treatment plans including radiation and/or adjuvant chemotherapy were completed as recommended. Patients were followed and imaged with standard breast imaging following completion of their treatment. Results: The marker was easily identified and clearly delineated the margins of the lumpectomy cavity. It allowed for 3-D characterization of the borders surrounding the cavity, and it was easily distinguishable from the seroma and other surgical tissue changes. Respiratory motion was easily tracked using the device making it possible to apply advanced radiation treatment methods such as IMRT and accelerated protocols. When compared to conventional methods of determining the target area, use of the marker resulted in treatment volumes that were reduced by >60%. In appropriate patients, the marker also facilitated the use of an accelerated protocol, decreasing total treatment time from 6 weeks to 5 days. No complications were reported. Conclusions: This novel 3-D marker was consistently visualized, was readily incorporated into standard and advanced dose planning methods, and had appreciable benefits when designing optimal treatment plans. Its unique features were also helpful when using oncoplastic techniques, and proved valuable for long-term follow-up using standard methods of breast imaging.
Clinical and pathologic characteristics of patients with PI3K-mutant breast cancers.
Authors: Lloyd M. Cooper , Sanders Melinda , Kuba Maria Gabriela , Farley Jaime , Lai Darson , Su Zengliu , Mayer Ingrid A. , Means-Powell Julie Ann , Vnenzak-Jones Cindy , Levy Mia Alyce , Pao William , Arteaga Carlos L. , Abramson Vandana Gupta
Published: February 2017

8

Background: Mutations in PIK3CA are the most common somatic alterations in breast cancer and represent a potentially useful therapeutic target. As more PI3K pathway inhibitors enter the clinical arena, it is important to understand the characteristics of patients harboring mutations. This study seeks to identify the clinico/pathological characteristics of PI3K mutant breast cancers in patients evaluated at Vanderbilt University Medical Center. Methods: Molecular profiling (SNaPShot) was used to detect mutations in three genes in the PI3K pathway (PIK3CA, PTEN, AKT1). Electronic medical records of breast cancer patients whose tumors underwent testing from June 2010 to January 2013 were reviewed. PI3K mutation rates, histological tumor grade, receptor status (ER/PR/HER2), and recurrence-free survival were tabulated. Results: Three hundred evaluable tests were identified, with PI3K mutations detected in 83/300 (28%). Patients with PI3K mutations were more likely to be ER/PR positive (73% vs. 48%; p<0.001) and less likely to be HER2 positive (6.0% vs. 20.7%, p=0.0022). Only 6/83 patients (7.2%) with triple negative cancers harbored PI3K mutations. 32% of patients with PI3K mutations participated in clinical trials, versus 25% without. Conclusions: Tumors with PI3K mutations were more likely to be ER/PR positive, of intermediate grade, and associated with longer recurrence-free survival. Patients with PI3K mutations were more likely to participate in clinical trials. These data and the potential eligibility of patients harboring mutations for clinical trials support the prognostic and clinical utility of SNaPShot testing for all breast cancer patients at a tertiary care center. [Table: see text]
Technical feasibility and cosmetic advantage of hybrid endoscopy-assisted breast-conserving surgery.
Authors: Ozaki Shinji , Ohara Masahiro , Shigematsu Hideo , Kadoya Takayuki , Kataoka Tsuyoshi , Okada Morihito
Published: February 2017

80

Background: We developed a new procedure called hybrid endoscopy-assisted breast-conserving surgery (EBCS), which consists of a combination of plastic surgery and endoscopic surgery techniques. The purpose of this study was retrospectively to analyze the clinical outcome of hybrid-EBCS and compare the cosmetic outcomes between hybrid-EBCS and conventional breast-conserving surgery (CBCS). Methods: We reviewed medical records of patients who had undergone hybrid-EBCS (n = 73) or CBCS (n = 90) between May 2005 and April 2011 and had been followed-up in our department until March 2012. The clinical outcomes, and cosmetic outcomes of these 2 groups were compared. The safety of hybrid-EBCS was also analyzed by confirming its complications and pathological surgical margin. Results: In the hybrid-EBCS group, operation time was longer by 30–50 minutes. Blood loss was not significantly different between the 2 groups. The surgical margin of hybrid-EBCS was as follows: 1 patient (1.4%) had a positive margin; 4 patients (5.5%) had a margin of less than 2 mm; in 9 patients (12.3%), the margin was > 2 mm and < 5 mm; and in 59 patients (80.8%), it was more than 5 mm. Seven cases (9.6%) of postoperative complications occurred in 6 hybrid-EBCS patients. To date, no local recurrence has been observed in hybrid-EBCS patients (postoperative observation period: 18.1 ± 5.6 months). Compared with the CBCS group, the hybrid-EBCS group had better cosmetic results, especially with a less noticeable operative scar (p < 0.01). Conclusions: Hybrid-EBCS can provide sufficient free margin, and its surgical curability is acceptable. Additionally, this method is superior to CBCS in terms of cosmetic outcome.
The choice of IMRT for early-stage right breast cancer.
Authors: Edwards-Bennett Sophia , Andrews Stephen , Francke Patrick , Vicini Frank
Published: February 2017

81

Background: The benefit of Intensity Modulated Radiation Therapy (IMRT) has been established for left breast cancer. However, IMRT is not routinely employed for right breast cancer. The purpose of this study is to (1) compare dosimetric parameters in women with early stage right breast cancer undergoing whole breast radiation therapy using 3-dimensional conformal radiation (3DCRT) versus intensity modulated radiation therapy (IMRT) (2) determine treatment planning and/or anatomical correlates for patients who may benefit from IMRT. Methods: IMRT versus 3DCRT treatment plans were compared for 20 consecutive female patients with early stage (T1-T2 N0M0 ) right breast cancer treated at our center from 1/2012 to 12/2012. The planned target volume (PTV), contoured according to the RTOG atlas guidelines, was prescribed to 46-8-50.4 Gy in 26-28 fractions with PTV coverage goal of ≥ 95 % receiving the prescription dose. Dosimetric and anatomic parameters: % right lung receiving 20 Gy (lung V20), maximum breast dose (Dmax), maximum skin dose (Dmax skin), chest wall separation (CWS) and medial gantry angle (MGA) were determined for each paired treatment plan. Wilcoxon-signed rank test was utilized to compare IMRT and 3DCRT dosimetric parameters. Univariate analysis was used to identify planning or anatomic correlates associated with favorable dosimetric outcomes. Results: The lung V20Gy for IMRT ( 10.86±2.81%) was significantly lower than for 3DCRT (12.92±3.45 %, p < 0.043). IMRT significantly reduced Dmax to 53.79 ± 2.17 Gy from 56.7 ± 2.24 Gy with 3DCRT (p 0.001). 3DCRT yielded significantly higher Dmax skin (33.47±3.21 Gy) than IMRT (24.16 ±2.65 Gy, p< 0.0001). Mean CWS and MGA were 22.4 ± 2.6 cm and 126 ± 5.1° respectively. There was a significant association between CWS and Dmax for 3DCRT (p < 0.026). Conclusions: The most significant impact of IMRT for right breast cancer was the reduction of Dmax and Dmax skin, with a more tempered advantage in the reduction of lung V20. Reduction of maximum breast and skin dose harbors clinical relevance as it relates to acute skin toxicity, long- term fibrosis and adverse cosmetic outcomes. Chest wall separation may be a potential planning surrogate marker to determine which right-sided breast cancer patients may benefit from IMRT.
Evaluation of the anticarcinogenic effect of solanumrastratum dunal (Mexican thistle) on breast cancer cells MDA.
Authors: Valadez Vega Maria Del Carmen , Garcia Velasco Laura , Zuniga Perez Clara , Sanchez Gutierrez Manuel , Morales Gonzales Jose Antonio
Published: February 2017

84

Background: The use of medicinal plants has been very common since ancient times, used for the treatment of several diseases such as cancer. In many towns in Mexico are used extracts from plants such as Solanum rastratum Dunal (buffalo bur, spiny nightshade, Colorado bur, Kansas thistle, Mexican thistle, and Texas thistle), which has shown to be effective in improving symptoms of some diseases conditions, there are reports indicating its use in the treatment of some types of cancer, such as the breast and cervical cancer. For this reason, in this work the aim was to evaluate the anticarcinogenic effect of extracts of Solanum rastratum Dunal on human breast cancer cells MDA. Methods: The plant was collected, cleaned, separate the different sections, were dried in darkness in special panels at room temperature; subsequently the extracts were prepared from the leaf, stem and flower-fruit using solvents of different polarity (methanol, ethyl acetate and hexane). Extracts were analyzed in cultured MDA cells line and the cytotoxic effect was evaluated by MTT technique. Results: The results showed that the stem and leaf extracts were those which showed higher inhibitory effect on cell viability, with those obtained with ethyl acetate which showed better anti-carcinogenic effect, while the hexane extract of the flower and fruit mixture which was showed higher inhibitory effect on this part of the plant; however generally the ethyl acetate extract obtained from the leaf was the one with greater cytotoxic effect in this cell line. Conclusions: The results of this work lead to the conclusion that is greater cytotoxic effect of ethyl acetate extract of the leaf than the other extracts tested. These results are contrasting with the traditional use of the extract of this plant, since traditionally people employ the aqueous extract of this plant, which would be equivalent to methanolic extract used in this study, which was who presented the lower cytotoxic effect of three solvents studied.
Role of sentinel lymph node biopsy (SLNB) and preoperative MRI in the management of patients with pure high-grade ductal carcinoma in situ (DCIS).
Authors: Sunkara Rajitha , Taneja Charu , Chi Dorcas , Wolfe Gail , Segal Christine , Keel Allison , Olhava Phoebe , Martin Leslie A.
Published: February 2017

87

Background: The overall incidence of SLN metastases in pure DCIS is < 1% and the results of SLNB do not usually impact treatment or survival but adds significant surgical morbidity. In addition, there is no evidence regarding the role of preoperative MRI in the management of DCIS. The purpose of our study was to identify the efficacy of SLNB and the benefit of preoperative MRI in high-grade DCIS. Methods: We performed retrospective review of 364 patients with DCIS, identified through our cancer registry database, that were seen from 2003 to 2012 at our institution. Of these, 62 patients were diagnosed with high-grade DCIS (Grade 3 or 2 with comedonecrosis) by core needle biopsy, and underwent SLNB. The remaining 302 patients had either low-grade DCIS or did not have a SLNB. Results: Median age was 56 years (range 33-80). Sixty two patients had high-grade DCIS on definitive excision and 2/62 patients were noted to have small invasive focus of disease. 15/62 (24.19%) patients underwent mastectomy and 47/62(78.1%) underwent lumpectomy. No patient had a positive SLN (0/62). 15/62 (24.2%) patients had breast MRI preoperatively and among them, in 5 (33.3%) patients, MRI findings changed the surgical decision to mastectomy. Among these 5 mastectomy patients, four of them (80%) had pathologically confirmed findings consistent with preoperative MRI suspicions. In lumpectomy patients, close margin of less than 1mm was seen in 4/9 (44.4%) patients with staging MRI and in 24/38 (63.15%) patients without MRI (p = 0.45. Fisher’s exact test). However the positive margin leading to re-excision was seen in 2/9 (22.2%) patients who underwent lumpectomy with staging MRI, and 9/38 (23.6%) patients who underwent lumpectomy without staging MRI. Conclusions: In our study, no patient with high grade DCIS had a positive sentinel node suggesting that routine sentinel node biopsy is not necessary in DCIS patients. The use of MRI changed the surgical planning in 33.3% of patients, but did not improve the surgeon's ability to achieve clear margins.
Lymphatic and proinflammatory candidate gene variations and lymphedema.
Authors: Fu Mei R. , Axelrod Deborah M. , Guth Amber , Goldberg Judith D. , Li Xiaochun , Cartwright Francis , Haber Judith , Conley Yvette
Published: February 2017

9

Background: Traditionally, breast cancer-related lymphedema is considered to be mainly due to the mechanical injury from cancer surgery. Recent research identified that inflammation-infection may be one of the important predictors for lymphedema. This pilot study aimed to explore the associations between lymphatic and pro-inflammatory candidate gene variations and lymphedema. Methods: A prospective, longitudinal, repeated-measure, and comparative design was used to recruit 178 breast cancer survivors. To ensure the accuracy of lymphedema phenotype, lymphedema was classified into lymphedema of arm and breast. Arm lymphedema must have been validated by infra-red perometer and a bioimpedance device. Breast lymphedema was validated by an observational scale since no objective measure is available. Saliva samples were collected for DNA extraction. Candidate Gene Association Research Method was used to examine the eight genes known for inflammation and lymphatic specific growth factors: cytokines (IL1A, IL6, IL8, IL10, IL13) and PTGS2 (COX2), and lymphatic specific growth factors [VEGF-C and D]. Descriptive statistics, Chi-Squared tests for contingency tables and one-way analysis of variance for continuous variables were used to compare the genotypes for each of these genes in patients with and without lymphedema. Odds ratios of developing lymphedema are estimated. Results: Among 178 survivors, 39 women were confirmed to have arm lymphedema and 43 women had breast lymphedema. Five genes were significantly associated with breast cancer-related lymphedema. Specific single nucleic polymorphisms (SNPs) for lymphatic specific growth factors VEGF-C (rs4604006) and cytokine IL13 (rs1800925) were related to arm lymphedema. Specific SNPs of cytokine IL1A (rs1800587) and PTGS2 (COX2) (rs20417) were associated with breast lymphedema. Conclusions: Our findings provided preliminary data on genetic susceptibility as a risk factor for breast cancer-related lymphedema. Findings of our study may serve as a preliminary foundation for a priori recognition of genetic risk that may facilitate lymphedema risk prediction prior to surgery and raises the potential for early intervention for a high-risk group.
How accurately can clinicians predict the Oncotype DX DCIS score?
Authors: Cate Sarah Patricia , Gillego Alyssa , Chadha Manjeet , Rescigno John , Gliedman Paul R. , Radzio Agnes , Boolbol Susan K.
Published: February 2017

90

Background: The Oncoype DX DCIS Score was developed to assess the risk of recurrence for ductal carcinoma in situ, as well as an invasive breast cancer. It is a 12 gene assay performed on an individual patient’s tumor and is used to predict the ten year local recurrence risk of an ipsilateral breast event, which can be either an invasive breast cancer or ductal carcinoma in situ. It is also used to predict the 10 year risk of an invasive cancer. The DCIS Score was clinically validated using patients from ECOG 5194. The purpose of this study was to investigate how often clinicians, (medical oncologists, breast surgical oncologists, and radiation oncologists) can predict the DCIS Score. Methods: In this IRB approved study, we retrospectively reviewed the charts of 27 patients at our institution who underwent unilateral or bilateral partial mastectomy for DCIS from April 2012 to February 2013 and who had their pathology specimens submitted for DCIS Scores. Patient age range was 40-79 years old, with a mean of 56.8. All patients underwent consultation with radiation oncology. A chart was compiled to include the patient’s age and tumor histology. This included grade of DCIS, extent of DCIS, presence of necrosis, margin width, and hormone receptors. We then removed all identifying factors from the patients’ data, and surveyed our radiation oncologists, medical oncologists, and breast surgical oncologists on whether patients had a low, intermediate, or high DCIS Score. Results: Breast surgical oncologists accurately predicted the DCIS score 49% of the time. Medical oncologists predicted the DCIS score 35% of the time, while radiation oncologists were accurate 51% of the time. Conclusions: This study demonstrates the difficulty in predicting the DCIS Score. The information obtained from the DCIS Score is specific to the genetic behavior of each individual tumor, whereas traditional methods of predicting risk of recurrence and benefit of radiation are based on standard pathologic and clinical criteria. Further studies on larger patient populations need to be performed prior to wide scale acceptance of this genomic test. [Table: see text]
Does the Oncotype DCIS score impact treatment decisions?
Authors: Cate Sarah Patricia , Gillego Alyssa , Chadha Manjeet , Rescigno John , Gliedman Paul R. , Kats Ilana , Boolbol Susan K.
Published: February 2017

91

Background: The Oncotype Dx DCIS Score has been developed and validated for risk recurrence in ductal carcinoma in situ. It is a 12 gene assay performed on an individual patient’s tumor. The results give information about the 10 year risk of any in-breast event and the 10 year risk of an invasive breast cancer. The clinical validation study was based on patients enrolled in ECOG 5194. The purpose of our study was to evaluate the impact of the DCIS Score on recommendations for adjuvant radiation therapy. Methods: In this IRB approved study, 27 patients at our institution underwent evaluation with the DCIS Score from April 2012 to February 2013. All patients had specimens submitted for DCIS Scores. 14 patients had margins of 3 mm or greater. 12 patients had margins of 1 mm to 2.5 mm, and 1 patient had margins that were less than 1 mm from the DCIS. The mean age was 56.8 years, with a range of 40-79 years old. The DCIS Score is reported on a scale of 0-100. All patients underwent consultation with radiation oncology. The radiation oncologists formulated their preliminary recommendation prior to reviewing the patients’ DCIS Scores. The final recommendation for radiation treatment was rendered after reviewing the DCIS Score. We then compared the pre-DCIS Score and post-DCIS score treatment recommendations. Results: 21 patients (78%) were advised to have adjuvant radiation therapy. 6 patients (22%) were advised not to undergo adjuvant radiation based on their clinical and pathologic features. Although the DCIS Score did not change treatment recommendations for any patient in this study group, it did confirm initial treatment recommendations. For the patients who were advised not to have radiation, their DCIS Scores were 0-31. Conclusions: The DCIS Score is a validated tool to assess the local risk of recurrence for ductal carcinoma in situ. In our study population, the results of the DCIS Score did not alter treatment in any patient. It is important to note that in the 6 patients who were advised not to have radiation, the low DCIS Score confirmed the radiation oncologist’s perceived low risk of recurrence. In order to increase confidence in results of the DCIS Score, further studies need to be performed.
Comparison of ultrasound with ultrasound-guided fine-needle aspiration biopsy and core needle biopsy for initial axillary staging of breast cancer patients.
Authors: Ahn Hye Shin , Kim Sun Mi , Jang Mijung , Yun Bo La
Published: February 2017

96

Background: The sensitivity and specificity of FNAB and CNB performed in suspicious axillary LNs have ranged from 56% to 86% and from 91% to 100%, because FNAB and CNB are operator- and institution-dependent procedures. In addition, previous studies concerning the diagnostic accuracy of these procedures have reported results from only FNAB or CNB. So, the purpose of this study was to determine the diagnostic accuracy of axillary US and compare that of US-guided FNAB with CNB for axillary staging in the same breast cancer population. Methods: Of 220 breast cancer patients who underwent preoperative or prechemotherapy axillary US for axillary staging, 52 patients who underwent US-guided FNAB and CNB of cortical thickening and/or compressed hilum of lymph nodes on US were prospectively enrolled. US and FNAB/CNB findings were compared with final pathology from sentinel lymph node biopsy or axillary lymph node dissection. Results: Forty-eight patients met the final study criteria; we excluded 4 who had received primary systemic chemotherapy and showed negative FNAB/CNB results with negative final post-operative pathology. Positive predictive value (PPV) of axillary US was 54%. The sensitivity and specificity of FNAB were 73% and 100%, and those of CNB were 77% and 100%. Results did not significantly differ between US-guided CNB and FNAB. The complication rates of FNAB and CNB were 4%, and FNAB and CNB cost $180 and $350, respectively. Conclusions: Both US-guided CNB and FNAB were useful for axillary staging in breast cancer patients with high sensitivity. However, FNAB is recommended based on the advantages of low cost and minimal invasiveness.
Visualization rate of internal mammary sentinel lymph nodes with modified technique of radiotracer injection.
Authors: Wang Yong-sheng , Qiu Peng-fei , Yang Guo-ren , Liu Yan-bing , Cong Bin-bin , Zhao Tong , Chen Peng , Sun Xiao , Wang Chun-jian , Zhang Zhao-Peng , Yang Tao , Bi Xiang
Published: February 2017

99

Background: Even though the 2009 AJCC incorporated the internal mammary sentinel lymph node biopsy (IM-SLNB) concept, there has been limited change in surgeons practice patterns due to the low visualization rate of the internal mammary sentinel lymph nodes (IM-SLNs) with the conventional injection technique (average 13%, 0~37%). In this prospective study, different radiotracer injection techniques were evaluated to achieve a relative high visualization and detection rate of IM-SLNs (NCT01642511). Methods: The 190 patients enrolled in this study were divided into three groups according to the study period and radiotracer (99mTc-labeled sulfur colloid) injection technique. Group A: conventional technique (radiotracer injection only into the tumor quadrant) for the initial 58 cases; Group B: two-quadrant injection at the 6 and 12 o’clock positions, 2.0~3.0 cm from nipple in the latter 132 cases. Group B was then separated into two groups according to the radiotracer injection volume: Group B1, low volume (<0.5ml/point, n=41); Group B2, high volume (≥0.5ml/point, n=91). Radiotracer was injected into the parenchyma under the ultrasonographic guidance for all patients. IM-SLNB was performed for patients with IM-SLNs visualized on preoperative lymphoscintigraphy and/or detected by intraoperative gamma probe. Results: Group B was associated with a significantly higher IM-SLNs visualization rate (76.5%, 101/132) compared to Group A (15.5%, 9/58, P=0.000), and Group B2 with the highest visualization rate (86.8% vs. 53.7% Group B1, P=0.000). All techniques had the same visualization rate of the axillary SLNs (P=0.915). The visualization rate of IM-SLNs was related to the patient’s age (P=0.037) and injection volume (P=0.000). The successful rate of IM-SLNB was 92.3%, and arrived 100% after 20 cases learning curve. The postoperative IM-SLNB complications were 0. Conclusions: Modified technique of radiotracer injection (Qiu's injection technique: two-quadrant, high volume and ultrasonographic guidance) significantly improved the visualization rate of IM-SLNs, provided an effective technique to evaluate the status of internal mammary, and would promote research on the IM-SLNB.
Taking control of cancer: Women’s choice for mastectomy.
Authors: Covelli Andrea Marie , Baxter Nancy , Fitch Margaret , Wright Frances Catriona
Published: February 2017

11

Background: Rates of both unilateral (UM) and contralateral prophylactic mastectomy (CPM) for early stage breast cancer (ESBC) have been increasing since 2003. Studies suggest that the increase is due to women playing an active role in decision-making. We do not know what factors are influencing the choice for more extensive surgery. Methods: To identify these factors we completed a multi-method study; conducting a systematic review of quantitative literature and qualitative interviews. Decision-making literature was identified from 5 databases and underwent thematic analysis. Purposive sampling identified women across the Toronto Area (Ontario, Canada), who were suitable candidates for breast conserving surgery (BCS) but underwent UM or CPM. Data saturation was achieved after 29 in-person interviews. Constant comparative analysis identified key concepts and themes. Results: ‘Taking control of cancer’ was the dominant theme. Literature illustrated that patients markedly overestimate risk of local recurrence, contralateral cancer and particularly, mortality. Similarly, interviews revealed that fear of breast cancer was expressed at diagnosis and drives the decision-making process. Despite surgeons discussing survival equivalence of BCS and UM, patients chose UM due to fear of recurrence and an overestimated survival advantage. Similarly, patients chose CPM to eliminate contralateral cancer and a misperceived survival benefit. Women were actively trying to Control Outcomes, as more surgery was believed to offer greater survival and therefore greater control. Conclusions: Both the literature and our interviews have illustrated that women seek UM and CPM for treatment of their ESBC to manage their fear of cancer mortality by undergoing more extensive surgery; this in turn drives mastectomy rates. It is important to understand this process so that we may improve our ability to communicate issues of importance to women and facilitate informed decision-making.
Adherence to national quality guidelines for nodal staging and treatment of cutaneous melanoma.
Authors: Hieken Tina J. , Comfere Nneka I. , Grotz Travis Edward , Inselman Jonathan W. , Habermann Elizabeth B.
Published: February 2017

110

Background: Assessment of compliance with national quality guidelines for the management of melanoma may be complicated by controversy about selection of patients for nodal surgery and limited by a lack of data on quality metrics. Previous reports suggest suboptimal overall compliance, with sentinel lymph node biopsy (SLNB) not performed for many suitable patients and completion lymph node dissection (CLND) omitted in many biopsy-proven node-positive (LN+) cases. The purpose of this study was to assess compliance with national ASCO/SSO guidelines for lymph node (LN) surgery for T2 and T3 (intermediate thickness, 1.01-4.00 mm) primary cutaneous melanoma patients and elucidate factors associated with non-compliance. Methods: All cases of T2 and T3, M0 melanoma were identified from 2004-2010 SEER data. Multivariable logistic regression was utilized to identify independent predictors of compliance. Five-year cancer specific survival (CSS) was estimated using the Kaplan-Meier method. Results: Overall, 75.3% (6,609/8,782) of T2-T3 primary cutaneous melanoma patients underwent LN staging including SLNB in 6,330 (74.5%) of 8,492 clinically LN negative patients. Among these 6,609 patients, 1,279 (19.4%) had one or more LN+. 940 LN+ patients (73.4%) underwent CLND with removal of a mean (median, IQR) of 20.7 (18, 11-27) LNs. Compliance with LN staging and management guidelines was associated with truncal primary site (for SLNB), p<0.001 and with patient age <65 yrs and increasing number of metastatic LNs (for CLND), both p<0.0001. Compliance with CLND for LN+ patients was associated with improved 5 year CSS: 70.0% vs 64.6%, p<0.001. Conclusions: Compliance with guidelines for LN surgery in T2 and T3 melanoma is poor despite the well-defined benefit for this group of patients. These data suggest that non-compliance is multifactorial and not simply due to practice differences arising from the controversial aspects of melanoma management. Room for improvement exists. Assessment of modifiable factors associated with poor compliance, design of strategies to improve compliance and the development of performance measures around appropriate LN staging and management of T2 and T3 melanoma deserve further investigation.
Resource utilization, costs, and quality of end-of-life cancer care: A systematic review of retrospective cohort studies based on routinely collected data (1990-2011).
Authors: Langton Julia M. , Blanch Bianca , Drew Annabelle , Haas Marion , Ingham Jane M. , Pearson Sallie
Published: February 2017

111

Background: The last year of life is one of the most resource intensive periods in cancer care. The aim of this systematic review is to synthesize retrospective observational studies examining resource utilization and costs at the end-of-life period in adult cancer patients. The purpose is to examine study methodology and outcomes, with a particular focus on studies using quality indicators. Methods: We searched Medline, Embase, CINAHL, and York Centre for Research and Dissemination (1990-2011). Two reviewers screened titles and abstracts of 14,424 articles and 835 full-text, potentially relevant articles. Inclusion criteria were: English-language; at least one resource utilization or cost outcome in adult cancer decedents with solid tumors; outcomes derived from health administrative data; and an exclusive end-of-life or palliative focus. Results: We reviewed 78 studies examining end-of-life care in over 3.7 million cancer decedents; 55 were from the North America; and 33 published since 2008. We observed exponential increases in service use and costs as death approached. Hospital services were the main cost driver. Palliative services were relatively underutilized, and associated with lower expenditures than hospital-based care. The 15 studies using quality of care indicators demonstrated significant proportions of up to 33% of patients receive chemotherapy or life sustaining treatments in the last month of life; up to 66% do not receive hospice/palliative services. Conclusions: Observational studies using routinely collected health administrative data have the potential to drive evidence-based palliative care practice and policy. Further refinement of quality of care markers will enhance benchmarking activities across health care jurisdictions, providers, and patient populations.
The impact of screening mammography in women age 40-49 as a function of tumor biology.
Authors: Ruckdeschel John C. , Rees William V. , Parkinson Brett T , Belnap Thomas , Rowley Braden D. , Pena Kenneth
Published: February 2017

113

Background: Mammographic screening for women 40-49 years of age remains controversial based on results from earlier large scale, controlled mammography trials. Methods: From 2002-2006, 871 women aged 40-49 were diagnosed with breast cancer at Intermountain. The charts of all patients without a record of a screening mammogram at Intermountain (n= 436) were reviewed to confirm that they had not had a screening mammogram in the prior two years at any facility (Interval Cancers) and their survival was compared to 435 women who had their cancer diagnosed on a screening exam (Screen Detected). All patients were followed for at least 5 years via the tumor registry. Results: Stage distribution for Screen Detected/Interval cancers was 25.3/6.4% stage 0, 36.8/24.8% stage I, 24.6/35.6% stage II, 6.9/20.4% stage III and 0.5/3.4% stage IV. Overall, 67 patients (7.7%) did not have complete staging data. Overall survival was significantly better (p<.0001) for 40-49 year old women with Screen Detected compared to those with Interval cancers. 702 (79.6%) had ER/PR status recorded (83.5% ER/PR positive). Women with DCIS or LCIS did not have tissue sent for markers. 679 patients (76.9%) had HER2 status recorded (78.8% HER2 neg). Of the patients with both HER2 and ER/PR status recorded 10.4% were “triple negative.” Survival following screening mammography was significantly enhanced for women who were ER/PR positive (p<0.0001), HER2 negative (p=0.0065), or HER2 positive (p=0.0013). Survival was not improved by screening mammography for women who were ER/PR negative (p=0.3818) or for women who were triple negative (p=0.416). Conclusions: A minority of women age 40-49 who develop breast cancer (13%) have biologic features suggestive of aggressive disease and, after 5 years of follow up, they are not benefitted by screening mammography. The remaining 87% are clearly benefitted by screening mammography. Our results suggest that the discrepancies noted in the screening mammography trials in 40-49 year old women may have resulted from population variations in the proportion of women with unfavorable biology. Based in part on these results, we continue to recommend regular screening in the 40-49 year old cohort.
Identifying opportunities to improve quality of cancer care: An evaluation of the use of routine surveillance imaging scans in women with early breast cancer (EBC) treated in Ontario, Canada.
Authors: Enright Katherine , Ghannam Mohammed , Yun Lingsong , Taback Nathan , Booth Christopher M. , Trudeau Maureen E. , Krzyzanowska Monika K.
Published: February 2017

115

Background: Over use of routine surveillance imaging to detect recurrence in women with EBC was recently identified as one of the top five opportunities to improve the quality of cancer care by the American Society of Clinical Oncology. We undertook a population level assessment of the current practice of surveillance imaging in EBC women treated in Ontario Canada. Methods: Incident EBC patients diagnosed 01/07 – 12/09 in Ontario, Canada were identified from the Ontario Cancer Registry. Patient records were linked deterministically to provincial health care databases to provide comprehensive medical follow-up. Basic (chest x-ray, abdominal x-ray and abdominal ultrasound) and advanced (computed tomography [CT] or bone scans) surveillance imaging scans completed during the first and second year of follow-up (starting 6 months after surgery or upon completion of chemotherapy) were identified. Logistic regression models were used to identify covariates associated with advanced surveillance imaging. Results: 16,981 EBC patients were included in the analysis of which 7,907(46.6%) received chemotherapy. In the first year of follow up care, 8,311 (48.9%) had at least 1 basic imaging test, while 4,916 (29.0%) had advanced imaging. This fell to 45.7% (basic) and 25.1% (advanced) in the second year of follow-up. Bone scans were the most common advanced imaging test (14.5%), followed by CT thorax (10.8%). On multivariable analysis age, stage, the use of chemotherapy and comorbidity were associated with increased use of advanced surveillance imaging (Table). Conclusions: Surveillance imaging was common in the first two years of follow-up for EBC patients. While appropriate for symptom driven investigation, the high rate of advanced imaging scans suggests an opportunity for improvement with the Ontario cancer system. [Table: see text]