bluuebunny/crossref_metadata_2025_split huggingface dataset:
IO-125: A novel supramolecular platinum chemotherapy for triple negative breast cancer.
Authors: Sengupta Aniruddha , Mylavarapu Sanghamitra , Kumari Smita , Hossain Samad , B Heeralal , Gupta Nimish , Sarkar Arindam , Ansari Aasif , Velpandian Thirumurthy , Roy Monideepa , Sengupta Shiladitya 
Published: February 2017

153 Background: Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancer patients, with a median survival of 13 months and limited treatment options. Recent studies have indicated clinical benefits in TNBC with platinum agents. We designed a novel platinum chemotherapeutic (IO-125), with platinum (II) tethered to cholesterol-based leaving group via a novel coordination environment, conferring properties unique from current platinum-based chemotherapies. In this study, we investigated the anti-tumor activity of IO-125 in pre-clinical models of TNBC. Methods: Cellular viability of IO-125 was assessed in TNBC cell lines using MTT assay, while Pt levels in cells, plasma and tumors were quantified using atomic absorption spectroscopy. Antitumor activity was assessed in MDA-MB-231 xenograft model. Results: We reportthat IO-125 shows enhanced cellular cytotoxicity and higher intracellular uptake as compared to oxaliplatin in TNBC lines. In addition to uptake by organic cation transporters known for transporting current platinum chemotherapies, IO-125 is also internalized via caveolin-mediated endocytic pathway, resulting in 10-20 fold greater uptake into cells as compared to oxaliplatin. Studies have implicated caveolin in TNBC progression and drug resistance, and harnessing this mechanism could confer enhanced activity. In animals bearing MDA-MB-231 xenografts, three cycles of IO-125 at well-tolerated doses (35 mg Pt/kg) resulted in significant tumor growth inhibition as compared to reported tumor inhibitions seen with existing platinum chemotherapies. Pharmacokinetic studies conducted in mice and rabbits indicate markedly improved profile of IO-125 as compared to oxaliplatin, showing a significantly higher area-under-the-curve (AUC), a substantial reduction in clearance and volume of distribution, with an enhanced half-life. Conclusions: Collectively, our findings demonstrate that IO-125 exhibits superior pharmacokinetics profile and biodistribution to tumors, resulting in enhanced anti-tumor activity in a TNBC xenograft model. Based on these observations, we propose that IO-125 may emerge as a potentially effective platinum-based drug for TNBC patients.
Utilization of Oncotype DX testing in a community hospital system: How did this affect patient care?
Authors: Snow Jennifer , Halaharvi Deepa R. , Pastorino Alyssa , Wooster Meghan , Dusseau Brian , Cripe Mark H. 
Published: February 2017

19 Background: The Oncotype DX Breast Cancer Assay is a multigene assay which quantifies risk of distant recurrence at 10 years and predicts benefit of chemotherapy in women with stage I/II, lymph node negative, estrogen receptor positive breast cancer. This retrospective study examines utilization of Oncotype DX for appropriate patients in a community hospital system. We hypothesize that chemotherapy administration follows the Oncotype DX score recommendation that patients with low recurrence scores not receive chemotherapy and patients with high recurrence scores receive chemotherapy and intermediate recurrence scores receive chemotherapy half of the time. Methods: In this retrospective study, 302 female patients from 1/1/12 – 1/1/14, were identified by breast cancer ICD9 codes from the system’s cancer registry. Data including imaging findings, pathology, and treatment information was then compared using chi square tests for categorical variables and two sample t tests or Wilcoxon rank sum tests for continuous variables. Results: Three hundred two female patients with stage I/II, lymph node negative, HR+, HER2/neu, breast cancer from a community hospital system were identified as appropriate candidates by NCCN guidelines, for Oncotype DX testing between 1/1/12 - 1/1/14. In patients receiving Oncotype DX, mass sizes were larger and were a higher proportion of stage 2 cancers (p < 0.001). Utilization of Oncotype DX in our CoC and NAPBC accredited hospital system was lower than hypothesized with only 73% of patients receiving testing. Following Oncotype DX testing, appropriate treatment ensued 94% of the time (low and high recurrence risk). Intermediate recurrence scores received treatment 36% of the time. Conclusions: In our CoC and NAPBC accredited hospital system, utilization of Onocotype DX testing was lower than hypothesized. For the patients who received testing, expected treatment was administered. Oncotype DX testing when performed influences patient care, however with 27% of patients not receiving testing and 25 % of the time this was due to patient preference, this observation supports that testing not be ordered reflexively, but rather with patient input and appropriate consent.
Germline mutations in early-onset or hereditary breast cancer from the Middle East.
Authors: Marafie Makia J , Al-Temaimi Rabea , Megarbane Andre , Al-Mulla Fahd 
Published: February 2017

20 Background: Breast cancer is the most common cancer affecting women of Middle Eastern origin. Epidemiologically, breast cancer in the Middle East clusters in families and usually affects women a decade younger than Western women. This dilemma is compounded by the lack of curated databases and ambitious studies that address the roles genetic or genomic may play in breast cancer. Methods: We have exome sequenced 60 Middle Eastern women with moderate and strong family history of cancer or young women without significant family history of cancer. DNA extracted from peripheral blood of patients and matching normal Middle Eastern women without history of familial or sporadic cancers, were subjected to whole-exome sequencing using the HiSeq 2500 Illumina platform and MLPA to map major breast cancer–activating genetic defects. Results: Several novel BRCA1/2 mutations were identified in the minority of these women. However, other complex mutations in non-BRCA1/2 genes appear to play a more subtle role in breast cancer in the Middle Eastern women. Germline mutations in TP-53, BARD1 and mismatch repair genes were more frequent than expected by chance. Conclusions: BRCA1/2 gene mutations are not a significant cause of heritable cancers in the Middle East. The region may benefit from a well-curated region-specific database accessible to clinicians and scientists where clinical and variants information can be deposited from all over the Middle East.
Breast surgeons' attitudes towards bilateral risk-reducing mastectomy: A National Survey of American Surgeons.
Authors: Basu Narendra Nath , Den Heijer Mariska , van Asperen Christi J , Harris Hilary , Nippert Irmgard , Schmidtke Joerg , Bouhnik Anne Deborah , Julian-Reynier Claire , Beitsch Peter D. , Tibben Aad , Hodson James , Evans D. Gareth 
Published: February 2017

25 Background: Bilateral risk-reducing mastectomy (BRRM) confers the greatest risk-reduction in women at high-risk of developing breast cancer. Uptake of BRRM is influenced by the attitudes of these women as well as the breast surgeons offering these procedures. We surveyed surgeon members of the American Society of Breast Surgeons to assess their attitudes and knowledge. Methods: An International Cancer Risk Communication Study (InCRisC) questionnaire, previously used to assess attitudes of European physicians and surgeons was sent to 2648 members. Personal and occupational characteristics were recorded and knowledge of cancer genetics and attitudes to BRRM were assessed using clinical vignettes. Results: 439 breast surgeons responded. 98% of surgeons actively took a family history of the father. Almost 100% of surgeons reported a positive attitude towards BRRM. Female surgeons and those treating greater than 100 breast cancers a year were predictors of knowledge of breast cancer genetics and a positive attitude towards BRRM. Conclusions: Multiple factors contribute to surgeons' attitudes towards BRRM. Gender of surgeon and workload contribute to theses observed variations.
Recurrence rates for ductal carcinoma in situ: Analysis of 2,996 patients treated with breast-conserving surgery over 30 years.
Authors: Van Zee Kimberly J. , Subhedar Preeti , Olcese Cristina , Patil Sujata , Morrow Monica 
Published: February 2017

32 Background: Randomized trials of radiation after breast-conserving surgery (BCS) for DCIS found substantial rates of recurrence, with half of recurrences invasive. Decreasing local recurrence rates for invasive breast carcinoma have been observed, and are largely attributed to systemic therapy improvements. Here we examine recurrence rates after BCS for DCIS over 3 decades at one institution. Methods: We retrospectively reviewed a prospectively maintained database of DCIS patients undergoing BCS from 1978–2010. Cox proportional hazard models were used to investigate the association between treatment period and recurrence, controlling for other variables. Results: 363 (12%) recurrences among 2996 cases were observed. Median follow-up for patients without recurrence was 75 months (range 0–30 years); 732 were followed for ≥ 10 years. The 5-year recurrence rate for 1978–1998 was 13.6% versus 6.6% for 1999–2010 (hazard ratio [HR] 0.62, p < 0.0001). After controlling for age, family history, presentation (radiologic vs clinical), nuclear grade (non-high vs. high grade), necrosis, number of excisions ( ≤ 2 vs ≥ 3), margin status (positive/close vs negative), radiation, and endocrine therapy, treatment period remained significantly associated with recurrence, with later years associated with a lower HR (0.74, p = 0.02) compared to earlier. After stratification by radiation use, and adjustment for 7 other factors, the decrease in recurrence rates was limited to those without radiation (HR 0.62, p = 0.003); there was no decline in recurrence rates among those receiving radiation (HR 1.13, p = 0.6). Conclusions: Recurrence rates for DCIS have fallen over time. Increases in screen-detection, negative margins, and use of adjuvant therapies only partially explain the decrease. The unexplained decline is limited to women not receiving radiation, suggesting it is not due to changes in radiation efficacy, but may be due to improvements in radiologic detection and pathologic assessment. The lower recurrence risk observed for DCIS patients treated in more recent years is important for patient education, especially in view of the widely reported recent increase in use of mastectomy.
Outcomes associated with adjuvant radiation after lumpectomy for elderly women with T1-2N0M0 triple-negative breast cancer: SEER analysis.
Authors: Szeja Sean , Hatch Sandra S. 
Published: February 2017

39 Background: Adjuvant Radiation (RT) may be omitted for elderly women with early stage breast cancer having favorable estrogen receptor status, however in the setting of triple negative breast cancer (TNBC), less evidence exists to guide decision making. As some findings thus far have shown TNBC to have an increased recurrence rate, this is an important subject to address. The purpose of this study is to use the Surveillance, Epidemiology, and End Result (SEER) database to evaluate how the addition of adjuvant radiation affects the survival of women ages 70 and above with T1-2, N0, M0 TNBC that undergo Lumpectomy (L). Methods: Cases diagnosed from 2010-2011 were downloaded from the SEER Database. Inclusion criteria were ages 70 and above, with T1-2N0M0 TNBC. Kaplan meier curves calculated overall survival (OS) and disease specific survival (DSS) in months (m). Log-Rank tests were performed to compare survival. Cox multivariate regression was performed to calculate Hazard Ratios (HR) and control for confounding variables including neoadjuvant chemotherapy, number of lymph nodes sampled, age, laterality, grade, T stage, extent of surgery, existence of other cancers. Results: From 2010-2011, SEER contained 109,559 cases of breast cancer with recorded results of Her-2-neu (H2N) status. Combining other receptor values, showed 12,620 triple-negative, which was 12% of cases. Of these, 6980 (55%) had stage T1-2, N0, M0. Lumpectomy was used in 4002 of these cases. There were 974 lumpectomy cases of women aged 70 and above. RT was given in 662 (68%) cases. After 23 months, L+ RT was associated with improved OS at 98.2% compared to 85.6% for L only (p=<0.001), as well as DSS at 99% for L+RT better than 94% for L only (p=0.003). Cox Regression showed radiation demonstrated improved OS (HR=0.14, p<0.001) and DSS (0.14, p=0.01). Conclusions: The use of adjuvant RT after lumpectomy for elderly women with early stage TNBC was associated with improved OS and DSS. Noting the potential for selection bias in this study, future prospective study is required to define the management of early stage triple negative breast cancer.
Prospective assessment of deep inspiration breath hold to prevent radiation-associated cardiac perfusion defects in patients with left-sided breast cancer.
Authors: Zagar Timothy , Tang Xiaoli lily , Jones Ellen , Matney Jason , Das Shiva , Green Rebecca L , Sheikh Arif , Khandani Amir H , McCartney William H , Wong Terence Z. , Marks Lawrence Bruce 
Published: February 2017

41 Background: Radiation therapy (RT) for left-sided breast cancer can cause regional cardiac perfusion abnormalities in nearly half of patients at 6 months post-RT. While the significance of these perfusion abnormalities remains unclear, RT is a well-accepted risk factor for heart disease. We herein report the results of a single-arm prospective clinical study to assess deep inspiratory breath hold (DIBH; using AlignRT) as a means to prevent the development of perfusion abnormalities in patients with left-sided breast cancer. Methods: Patients about to receive left-sided tangential RT had a pre-RT cardiocentric single photon emission computed tomography with CT based attenuation correction (IQ SPECT-CT) rest-cardiac gated perfusion scan (to assure a normal baseline). DIBH and conformal blocking was used to assure that the heart was excluded from the primary RT beam. Doses to the heart were computed. At 6-months post-RT, the SPECT-CT was repeated. The perfusion and motion images were assessed qualitatively by a nuclear medicine physician. Results: Twenty-four patients have been enrolled. Four were not evaluable (e.g. due to an abnormal pre-RT SPECT scan); one has been lost to follow-up. All patients received tangential radiation to the breast/chest wall (typical doses 200 cGy x 25 or 267 cGy x 16); five also received regional nodal RT as well; and 18/19 received a tumor bed boost. The mean heart dose ranged from 42-160cGy for all 19 patients (mean of the means = 78 cGy). Of the 19 potentially evaluable patients, post-RT SPECTs have been obtained in ten. All ten have a normal post-RT SPECT scan; and/or no change from pre-RT scan. Conclusions: In patients receiving tangential RT for left-sided breast cancer, cardiac avoidance with DIBH (e.g. with AlignRT) and conformal field shaping, appears to be able to prevent the development of RT-associated cardiac perfusion abnormalities. The mean dosages to the heart are quite low. Updated information on the remaining patients will be presented. Funded in part by VisionRT. Clinical trial information: NCT01849614.
Use of a 3-dimensional lumpectomy marker for targeting interstitial accelerated partial breast irradiation (APBI).
Authors: Smith Linda Ann , Nelums Erika N. , Snyder Margaret B. , Kuske Robert R. 
Published: February 2017

42 Background: APBI via high-dose-rate (HDR) interstitial catheter implants is an effective, highly customizable method of delivering radiotherapy in breast cancer patients. The technique is amenable to challenging anatomy such as pendulous and/or very small breasts, augmented breasts or superficial lumpectomy sites. The challenge for any APBI technique is identification of the lumpectomy cavity, which can be difficult to visualize after surgery due to post-surgical changes or tissue mobilization for oncoplastic closure. In the past we have used x-ray contrast injected into the cavity to facilitate the radiographic visualization of the cavity or individual clips. A new 3-D tissue marker (BioZorb, Focal Therapeutics, Inc.) has recently been used by surgeons to mark the area of the lumpectomy cavity at greatest risk for recurrence. In effect this acts as a communication tool to help guide the radiation oncologist for treatment planning and delivery. We examined this device for target volume localization in 15 patients receiving interstitial HDR APBI. Methods: The marker mimicking the tumor size was surgically sutured at the base of the lumpectomy cavity in 15 patients with T1T2N0N1 breast cancer with a variety of closure techniques. The clinical target volume (CTV) was taken as the 3-D outline made by the six embedded titanium markers and a 2 cm margin expanded around that structure (the planning target volume, PTV). Multiple interstitial catheters were spaced 1.5 cm apart within the PTV and 34 Gy was delivered in 10 fractions delivered over 5 treatment days. Results: The marker/CTV was easily visualized on CT images, without clips or injected contrast, making catheter insertion and planning more efficient, easier, and reproducible. The CTV volume was small (12.5 +/- 8.7cc; mean +/- SD, range 4.4–33.4cc) as was the PTV (137 +/- 60cc; mean +/- SD, range 75–327cc), relative to typical HDR APBI implants. Conclusions: The technique facilitated identification of the lumpectomy cavity in all patients treated regardless of surgical closure technique. The unambiguous margin demarcation facilitated target contouring and reproducibility for APBI.
Dosimetric study of 3-dimensional conformal radiotherapy, electronic compensator technique, intensity modulated radiation therapy, and volumetric arc therapy in whole-breast irradiation.
Authors: Nantavithya Chonnipa 
Published: February 2017

44 Background: Whole breast irradiation is an essential treatment after breast conserving surgery (BCS). Adverse effects are from inhomogeneity of PTV and excessive dose to normal tissues. Aim of this study is to compare dosimetry among standard technique, three-dimensional Conformal Radiotherapy (3D-CRT) and advanced techniques, Electronic Compensator (ECOMP), Intensity Modulated Radiation Therapy (IMRT) and Volumetric Arc Therapy (VMAT). Methods: Images from CT simulation of patients who underwent BCS were replanned. Clinical Target Volume (CTV) was contoured followed RTOG atlas as breast only and breast with chest wall respectively. Planning Target Volume (PTV) was expanded 0.7 cm from CTV. Each patient was replanned with all four techniques. Dose prescription was 50 Gy in 25 fractions. Results: Twenty five patients underwent CT simulation from November 2013 to November 2014 were included. Six patients with node positive were planned for breast with chest wall irradiation and 19 patients with node negative were planned for breast only irradiation. Primary outcome, homogeneity index (HI) of 3D-CRT, ECOMP, IMRT and VMAT were 0.865, 0.889, 0.890 and 0.866 respectively which ECOMP and IMRT were significant higher than 3D-CRT (p values < 0.001). Secondary outcome, conformity index (CI), Mean heart dose (MHD), heart V25, heart V30, mean lung dose (MLD), mean ipsilaterallung dose (MILD), mean contralateral lung dose (MCLD) and mean contralateral breast dose (MCBD) of advanced techniques were significant better than 3D-CRT technique. Conclusions: HI of ECOMP and IMRT were statistically significant higher compared with 3D-CRT technique. Advanced techniques showed statistically significant superior in CI dose to heart, lungs and contralateral breast.
Electrochemotherapy for cutaneous metastases in breast cancer: Experience from a designated treatment centre.
Authors: Banerjee Shramana Mitul , Newby Jackie , Khan Shahab , Homfray Virginia , Whittaker Diane , Keefe Christopher , Keshtgar Mohammed R. 
Published: February 2017

48 Background: Electrochemotherapy (ECT) combines the administration of poorly permeable chemotherapeutic agents with electroporation. It has been shown to be effective when compared with other treatments. This study assessed how breast cancer patients were benefited and identified potential problems at a designated treatment centre. Methods: This was a single centre prospective study of patients with cutaneous metastases from breast cancer. Patients who fulfilled NICE UK (National Institute Of Clinical Excellence) and local guidelines were treated. Gabapentin was given prior to general anaesthesia. Intravenous Bleomycin 15,000IU/m2 was given as a bolus. Treatment was commenced 8 minutes later with Cliniporator. Electrical pulses were delivered via an electrode inserted through the skin surface. Treatment response, disease progression free duration, post-operative pain and length of in-patient stay (LOS) were recorded. Patients recorded a symptom diary post treatment. Results: 20 treatments were performed in 16 patients from 2011-2015 with 53 separate areas treated. 8 patients had diffuse lesions, 5 had discrete lesions and 3 had both diffuse and discrete areas. 16 patients were being treated with ECT for the first time and 4 patients required 2 treatments. Median LOS was 3 days. Median follow up was 6 months (range 3-12).12 patients had complete response (75%) and 4 patients partial response. There was no disease progression for 6 months or more in 9 patients (56%) and 2 further patients had disease stabilised for 3 months with systemic or cutaneous progression in the remaining patients in 3 months or less. There were no deaths or immediate adverse events from ECT. 5 Patients (31%) with extensive diffuse chest wall disease reported persistent discomfort post treatment requiring extended period of post treatment analgesia. Conclusions: Electrochemotherapy is safe and effective treatment for cutaneous metastases. Appropriate patient selection for treatment, pre-emptive analgesia, post treatment support and follow up is essential in order to maximise the benefits and minimise potential side-effects particularly in extensive chest wall disease.