bluuebunny/crossref_metadata_2025 huggingface dataset:
Distant disease-free survival (DDFS) discrimination capacity of various pathologic complete response (pCR) definitions according to breast cancer subtypes.
Authors: Hattori Masaya , Matsuo Keitaro , Ichikawa Mari , Fujita Takashi , Sawaki Masataka , Kondo Naoto , Horio Akiyo , Yatabe Yasushi , Iwata Hiroji
Published: February 2017

162

Background: pCR has been postulated to be correlated with long-term clinical benefits in some subtypes of breast cancer. Here, we analyzed the discriminatory ability and the predictive power of various pCR definitions for distant disease-free survival (DDFS) according to breast cancer subtypes. Methods: We analyzed 326 (114 Luminal A: ER+/PR+/HER2-, 44 Luminal B/HER2-: ER+/PR-/HER2-, 51 Luminal B/HER2+: ER+/PR+ and/or -/HER2+, 51 HER2: ER-/PR-/HER2+, and 66 Triple negative: ER-/PR-/HER2-) non-metastatic breast cancer patients (pts) who had received neoadjuvant chemotherapy at our institution between January 2003 and June 2012. Four pCR definitions were used: ypT0ypN0, ypT0/isypN0, ypT0/isypN0/+, ypT<1micypN0/+. DDFS was estimated by Kaplan-Meier method, and analyzed by log-rank test and Cox proportional hazard model. The receiver operating characteristic (ROC) curves analysis was used for comparing DDFS prediction models with and without various pCR definitions in addition to other covariates (tumor stage, nodal status, BMI, tumor grade, use of trastuzumab) as variables. Results: The pCR rate was comparatively low in Luminal A and high in HER2. 94.1% of HER2 and 74.5% of Luminal B/HER2+ received total 1 year of trastuzumab therapy. In multivariate analysis, no pCR definitions were associated with improved DDFS significantly in Luminal A, Luminal B/HER2-, Luminal B/HER2+ and HER2, whereas each pCR definition was associated with improved DDFS in Triple negative (ypT0ypN0: HR0.12, p=0.043, ypT0/isypN0: HR0.06, p=0.007, ypT0/isypN0/+: HR0.107, p=0.004, ypT<1micypN0/+: HR0.104, p=0.003). In the ROC curves analysis of triple-negative, a DDFS prediction model including pCR defined as ypT0/isypN0 showed the highest accuracy, but low statistical significance (AUC: 0.834 vs.0.749 p=0.076). Conclusions: pCR could discriminate good and poor prognosis groups only in Triple negative and pCR defined as ypT0/isypN0 has the potential to provide better discrimination in this subtype. The predictive power of pCR for long term clinical benefit in other subtypes may not be obvious due to the influence of effective adjuvant therapies.
Assessing breast cancer risk in primary care: What can we learn from cardiovascular disease?
Authors: Collins Ian M. , Keogh Louise A. , Steel Emma , Emery Jon , Pirotta Marie , Mann Bruce , Butow Phyllis , Trainer Alison , Moreton Jane , Antoniou Antonis C. , Cuzick Jack M. , Hopper John L. , Phillips Kelly-Anne
Published: February 2017

17

Background: Routine assessment of breast cancer (BC) risk by primary care clinicians (PCCs) might improve uptake of (BC) prevention and screening interventions and thus reduce morbidity and mortality. Methods: Australian PCCs were recruited through local professional networks. Facilitated focus group discussions about current practice of assessing and managing BC risk were audiotaped, transcribed verbatim and managed using QSR NVivo qualitative data management software. A coding framework was developed based on the transcripts, data was coded and each code further analyzed to identify key themes. Results: 17 PCCs (12 doctors, 5 practice nurses) participated in 2 focus groups. 41% were male, median age 49 years, median number of years as a PCC was 15. Approaches to assessment and management of BC risk differed markedly from that of cardiovascular (CV) risk. PCCs see assessment and management of CV risk as an intrinsic, expected part of their role. Sidebar prompts on practice software trigger CV risk assessment and PCCs often use an online tool (www.knowyournumbers.co.nz) to provide personalized risk estimates and to discuss management options for CV risk. Conversely, assessment of BC risk is haphazard, generally patient (not clinician) initiated, and management, beyond routine BC screening (e.g. chemoprevention), is considered outside the domain of the PCC. BC risk assessment is not prompted by practice software. Most PCCs are not familiar with, or using, BC risk assessment tools. PCCs suggested they could potentially routinely assess and manage BC risk, but such an approach would need to be widely endorsed as within the remit of primary care and would be enhanced by an online tool that is accessible, quick, visual (graphs and pictograms), evidence-based and regularly updated. Ideally, its use would be prompted by their practice software. Conclusions: There is a clear opportunity in primary care to enhance the capacity and motivation of clinicians to assess and manage BC risk. A risk assessment and decision aid tool, integrated into primary care software, might facilitate routine appropriate management of BC risk in the Australian primary care setting, modelling what has already been achieved for CV disease.
Detection of new or additional significant breast disease by MRI compared to standard imaging in “high-risk” and “non-high–risk” patients.
Authors: Banks Amy Lynn , Titus Rachel , Melnik Marianne
Published: February 2017

22

Background: Mammography is the standard of care for the early detection of breast cancer. Recently, studies have shown that Magnetic Resonance Imaging (MRI) has greater sensitivity in cancer detection. However, there have been reports identifying a high false positive rate. The aim of our study was to determine if breast MRI aids in the detection of new clinically significant disease, even in “low risk” patients, when compared to ultrasound (US) or mammography alone. Methods: A review of all patients who underwent breast MRI under the care of a single surgeon between 1/1/07 through 6/1/11 was conducted. Patients were categorized as high or non-high risk based on a history of breast cancer, genetic mutation, significant family history or >20% lifetime Gail model risk. For this study a clinically significant disease is defined as a new cancer or high-risk lesion that requires close follow-up and monitoring. Results: A total of 163 patients had a breast MRI and all had concerning findings. Compared to US or mammogram, MRI identified new or additional disease that changed plans in 150/159 (94.3%) patients. Of these, MRI added clinically relevant findings in 85 patients (56.7%, p<0.001). In those considered “high risk” MRI detected clinically significant disease in 37/76 (48.7%) and in 46/76 (60.5%) of the non-high risk group. 16 patients were <40 and MRI found new disease in 2/7 (28.6%) high risk patients compared to 3/9 (33.3%) non-high risk patients. 48 patients were 41-50 years old and MRI detected new disease in 12/24 (50%) high risk patients compared to 13/24 (54.2%) non-high risk. Of the 37 patients aged 51-60, MRI found new disease in 11/19 high risk patients (57.9%) compared to 14/18 (77.8%) non-high risk. 50 patients >60 years of age, MRI found new disease in 12/25 (48%) high risk patients compared to 16/25 (64%) who were non-high risk. Conclusions: We confirm that MRI provides extremely relevant data in identifying new or additional disease when compared to US or mammogram. MRI not only aided in finding additional disease in patients that were high risk but more importantly, MRI found pathology-proven new disease in non-high risk patients across all age groups. These results hold a substantial clinical implication in the ability to find new cancers or high-risk lesions early on, especially in non-high risk patients.
Induction of breast cancer progression and metastasis by HOXB9 gene’s activation by sequence specific binding factors.
Authors: Zhussupova Aisulu , Hayashida Tetsu , Takahashi Maiko , Jinno Hiromitsu , Kitagawa Yuko
Published: February 2017

26

Background: HOXB9 is a member of class I HOX genes and is known to be overexpressed in human breast cancer and related to EMT, tumor angiogenesis, and radio-resistance (PNAS 2010), being significant prognostic factor in breast cancer patients. (Ann Surg Oncol 2012). Methods: We analyzed the upstream promoter region to determine the critical sequence for HOXB9 transcription. The multiple lengths of HOXB9 promoter region were cloned into pGL3 luciferase vector and each of them were checked by luciferase assay. Then made E2F1 overexpressed cell-lines: MCF7, MCF10A and MDA-MB231 to check HOXB9 gene expression. ChIP assay performed using E2F1 induced MCF7 cell-line model and EMSA made with T47D cells and E2F1 antibody. Results: We demonstrated luciferase activity of MDA-MB231 cells and overexpressed HOXB9 was determined at the region from -404 to -392 bps, showing that the mentioned region plays the critical role for the transcription of HOXB9. Computer prediction system for the binding ability to critical sequence raised several candidate: E2F1, PAX-5, P53, ETS-1, NFY-A, Sp-1, which are known to be related with cancer progression and we confirmed these genes could induce HOXB9. E2F1 overexpressed breast cancer cell-lines indicate high expression of HOXB9 show the correlation between E2F1 and HOXB9 expression. Luciferase assay method done by constructing pGL3 with HOXB9 critical sequence and analyzed using wild-type MCF7 and E2F1 induced MCF7 cells showed high luciferase activity of HOXB9 critical sequence plasmid in E2F1 induced MCF7 cell-line by compare to WT. ChIP assay and EMSA assay methods performed using E2F1 overexpressed MCF7 and T47D cell-lines model revealed high precipitation rate with E2F1 antibody and HOXB9 expression than negative control. Conclusions: HOXB9 is plays the role as the accelerator of breast cancer progression and discovering the properties of the gene and related factors will help to understand new signaling pathways of breast cancer development. E2F1 is a strong candidate direct binds to HOXB9 critical sequence and correlates with HOXB9 expression. Manipulating of E2F1 expression may regulate HOXB9 and reduce cancer progression and metastasis.
Is MRI suitable for conclusive work-up of suspicious findings in mammography and ultrasound?
Authors: Strobel Kevin , Schrading Simone , Kuhl Christiane K.
Published: February 2017

3

Background: The current ACR practice guidelines discourage use of MRI for work-up of suspicious findings in mammography (Mx) and ultrasound (US). We investigated whether additional breast MRI assessment of suspicious Mx and U.S. findings could improve PPV and thus possibly help reduce the number of biopsies for false positive findings in Mx or U.S. Methods: Between 06/2010 and 04/2012, a total 2,754 patients underwent DCE breast MRI. Of these, 277 underwent MRI for further work-up of suspicious findings made in Mx (n=173, 57 patients with mass lesions, 33 with asymmetries, 12 with architectural distortions, and 71 with suspicious calcifications) or U.S. (n=104, 74 with masses, 30 with miscellaneous U.S. findings such as suspected intraductal pathology, focal acoustic shadowing or architectural distortions) . All lesions categorized as MR-BIRADS 4 and 5 underwent biopsy, lesions categorized as MR-BIRADS 1 or 2 did not proceed to biopsy, except for selected women with mammographic calcifications suggestive of DCIS. Lesions categorized as MR-BIRADS 3 underwent additional short term follow-up by MRI, US and/or Mx. All women who did not undergo biopsy (MR-BIRADS 1-3) underwent long term follow-up for so far 12-24 months. Results: For suspicious lesions in mammography, MRI increased PPV from 19.3% (11/57) to 92.3% (12/13) for masses, from 3% (1/33) to 33.3% (1/3) for asymmetries, from 8.3% (1/12) to 25% (1/4) for architectural distortions and from 21.1% (15/71) to 62.5% (15/24) for calcifications. For suspicious lesions in ultrasound, MRI increased PPV from 13.5% (10/74) to 71.4% (10/14) for masses and from 3.3% (1/30) to 50% (1/2) for non-mass U.S. findings. In 4/277 patients, MRI showed additional suspicious findings, requiring MR-guided biopsy, one of which was histologically proven malignant. So far, none of the patients who, because of an MR-BIRADS 1-3, did not undergo biopsy has been diagnosed with invasive cancer or DCIS or with progressive conventional imaging findings necessitating secondary biopsy. Conclusions: MRI improves PPV for both suspicious Mx and U.S. findings, especially mass lesions. In experienced hands, careful use of MRI can help avoid biopsies for false positive diagnoses made in Mx and U.S.
Time-resolved gadolinium-enhanced MR imaging of the breast: Impact on accuracy of diagnosis of breast carcinoma.
Authors: Sherif Hanan , Al-Obaidly Amal , Albosom Issam , Mahfouz Ahmed-Emad
Published: February 2017

33

Background: The purpose of the study is to differentiate benign and malignant breast lesions based on very early enhancement of the lesion on time-resolved gadolinium-enhanced MR imaging. Methods: 100 women with breast lesions were examined at 1.5 T (Siemens, Erlangen, Germany), by fast T1-weighted GRE images every 5 s for 1 min after injection of Gd-DOTA (Dotarem, Guerbet, France), followed by 5 spacially-resolved MR image series every 30 s. Images were subtracted; maximum-intensity-projection images were obtained; and images were randomized and reviewed by two blinded readers, who reviewed only the spacially-resolved MR images and gave BIRADS diagnosis. After one month, they evaluated only the time-resolved MR images and noted the time of first appearance of enhancement. Results: The patients had 249 enhancing lesions: 66 malignant on histopathology and 183 benign on basis of histopathology or 1-year imaging follow-up. On time-resolved MR imaging, 15 lesions enhanced at 0-5 s (all malignant), 23 at 5-10 s (21 malignant, 2 benign), 34 at 10-15 s (28 malignant, 6 benign), and 117 at 15-20 s (2 malignant, 115 benign). All malignant lesions enhanced before 20 s. Taking 15s as the cut-off point, early enhancement had sensitivity of 96.9%, specificity of 95.6%, positive predictive value of 88.8%, negative predictive value of 98.8%, and accuracy of 95.9% for diagnosis of carcinoma. Enhancement before 15 s corrected BIRADS diagnosis of the spacially-resolved MR imaging in 14 lesions (5.6%). Conclusions: Lesion enhancement in the first 15s on time-resolved MR imaging is a useful sign for the diagnosis of breast carcinoma.
Novel factor to improve prediction of sentinel node positivity in patients with clinical T1/T2 breast cancer.
Authors: Shah-Khan Miraj G. , Torstensen Tiffany , Hoskin Tanya L. , Morton Marilyn , Adamczyk Darcy , Jones Katie N. , Chartier Stephane , Boughey Judy Caroline
Published: February 2017

49

Background: Predicting nodal positivity can guide surgical planning in breast cancer. Memorial Sloan-Kettering Cancer Center (MSKCC) and MD Anderson Cancer Center (MDACC) have established nomograms to predict sentinel node positivity. We propose that addition of distance of tumor from the nipple (DFN) can improve their performance. Methods: With IRB approval clinical T1/T2 tumors with pre-biopsy ultrasound were reviewed. MSKCC and MDACC nomogram predictions and the AUC-ROC were calculated. The addition of DFN was examined using multiple logistic regression and comparison of AUC-ROC values. Results: 401 breast cancers with clinical T1 (85%) or T2 (15%) tumors in 395 patients were included; of which 79/401 (19.7%) were node positive. Tumors were significantly closer to the nipple in those with positive nodes. 17/33 (51.5%) tumors within 2 cm of the nipple were node-positive versus 62/368 (16.8%) tumors > 2 cm from the nipple (p<0.0001). The MSKCC and MDACC nomograms each demonstrated good discrimination between node positive and negative patients with AUC-ROC values of 0.71 (95% CI: 0.64-0.77) and 0.74 (95% CI: 0.68-0.81), respectively. When added to the MSKCC nomogram, DFN ≤2 cm contributed significantly (OR 4.78, p=0.0001) to prediction of node positivity and improved the AUC-ROC to 0.73 (95% CI: 0.67-0.80). Similarly, DFN ≤2 cm was significant (OR 4.73, p=0.0002) when added to the MDACC nomogram and improved the AUC to 0.76 (95% CI: 0.70-0.82). Within nomogram probability categories, the proportion with positive nodes was consistently higher with DFN ≤2 cm. Conclusions: Tumor distance from nipple is associated with nodal positivity. When added to nomograms it improves prediction of node positivity. DFN should be considered when considering likelihood of nodal positivity for treatment planning. [Table: see text]
Resource and quality information provided by compliance with NCCN hereditary breast cancer guidelines.
Authors: Levonian Peter J. , Landercasper Jeffrey , Vang Choua , Marcou Kristen , Al Hajj Rima , Al-Hamadani Mohammed
Published: February 2017

5

Background: NCCN provides guidelines for breast cancer genetic risk assessment and testing. Measuring compliance with NCCN Guidelines (NG) can identify quality gaps. Methods: After IRB approval, a retrospective review of a prospective database of breast cancer patients was conducted to measure compliance with NG for genetic counseling and BRCA testing. Entry criteria were breast cancer patients with diagnosis and treatment at our center, during the 3 year period ending 12/31/11. Genetic counselors (GC) used NG and BRCAPRO modeling in all patients. Surgeon and GC pedigree analyses were compared. Results: Surgeons constructed pedigrees in 675 breast cancer patients and referred 42% (286/675) to the GC. The decision to refer was NCCN compliant in 671/675 (99%). The GC corrected the pedigree in 14% (39/286); nearly all due to the GC identifying extra breast or ovarian cancers. The mean BRCAPRO probability in referred patients was 7.2%. Fifty-nine percent (170/286) of patients seen by the GC received a recommendation for BRCA testing. The NG compliance rate for testing was 98% (170/174). Of 174 BRCA tests offered to patients, 74% (128/174) underwent testing. In tested patients, there were 4% BRCA1+, 5% BRCA 2+, and 1% uncertain variants. Total patient charges for 128 tests were $696,000 ($4,000/test). If the threshold for testing was BRCAPRO > 5% or >10%, then 69 ($276,000) and 45 ($180,000) (p<0.001) patient charges would have occurred, and no patient with BRCA + status would have been missed. Conclusions: High rates of NCCN guideline compliance for genetic counseling and testing are achievable. Our GC's improve accuracy of pedigree assessment and demonstrate adherence to NCCN guidelines, resulting in more testing compared to BRCAPRO modeling. The balance between different methods to trigger testing, their sensitivity, and cost deserves more study, but the observational data contained herein provides information for provider and payer stakeholders regarding estimated GC resources and cost of care.
Triple-negative breast cancer and likelihood of nodal metastates.
Authors: Gangi Alexandra , Mirocha James , Leong Trista , Giuliano Armando E.
Published: February 2017

50

Background: Axillary lymph node metastases are a prognostic indicator for breast cancer. Studies suggest that breast cancer subtypes are associated with the presence of lymph node (LN) metastases. The purpose of this study was to determine if patients with triple negative breast cancer (TNBC) have a higher risk of LN metastases than those with non-TNBC. Methods: Prospective database review identified 2,967 female patients with invasive breast cancer treated with mastectomy or breast conserving surgery (BCS) between January 2000 and May 2012. Only patients who underwent sentinel node biopsy (SNB) and/or axillary lymph node dissection (ALND) were included. Those receiving neoadjuvant therapy were excluded. Patient and tumor characteristics evaluated included age, race, tumor size, grade, stage, histologic subtype, presence of lymphovascular invasion (LVI), estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER2) status. Results: BCS was performed in 1,889 and mastectomy in 1,078 patients. Breakdown by subtype included 2,201 (74%) patients with Luminal A, 344 (12%) with Luminal B, 144 (5%) with HER2, and 278 (9%) with TNBC. SNB was performed in 1,094 (37%), ALND in 756 (25%), and 1,117 (38%) patients had both. LN metastases were detected in 1050 (35%) patients. The LN positivity rate varied across subtypes with 734/2,201 (33%) in Luminal A, 143/344 (42%) in Luminal B, 108/278 (39%) in TNBC, and 65/144 (45%) in HER-2 (p = 0.0007). However, on multivariable analysis, there was no difference in LN positivity among subtypes (p=0.24). Only age < 50 (HR 1.5, CI 1.3 to 1.8), grade 2 or 3 tumors (HR 1.8, CI 1.4 to 2.5), size greater than 2cm (HR 3.2, CI 2.7 to 3.9), and presence of LVI (HR 3.9, CI 2.4 to 6.3) were significant predictors of LN positivity. Four or more involved nodes were seen most commonly in the HER2 (28/144; 19%) and Luminal B (47/344; 14%) subtypes, but not TNBC (26/278; 9%) or Luminal A (199/2201; 9%) (p < 0.0001). Conclusions: Predictors of LN metastases include younger age, higher grade, larger tumor size, and presence of LVI. Patients with TNBC are not more likely to have involved nodes than those with non-TNBC.
Mean radiation dose to the heart in patients with breast cancer.
Authors: Jacobson Geraldine Meerbott , Wen Sijin , Zhang Jianjun , Hazard Hannah , Abraham Jame
Published: February 2017

56

Background: Breast irradiation may expose a portion of the heart to radiation. Heart irradiation is associated with late risk of ischemic heart disease, proportional to dose. A recent publication of patients treated with 2-D planning prior to 2001 noted average mean heart dose (MHD) of 6.6 Gy for left breast tumors, 2.9 Gy for right breast. Current treatment planning can minimize the MHD, reducing the risk of late heart injury. Methods: We reviewed treatment plans of 78 patients (86 breasts) treated 1/2012-3/2013 to obtain MHD. Treatment plans were CT-based, field-in-field forward planning with heart blocking. Two treatment regimens were used; hypofractionation (HF) (16 x 2.66 Gy, no boost) or standard (SF) (46.8-50.4 Gy +/- 10 Gy boost). Statistics were obtained for MHD based on right (N = 44) or left breast (N = 42); HF (N = 31) vs SF (N = 55), and total dose. Results: Average (av) MHD for left breast was 1.45 Gy (range 0.19-3.12), for right breast 0.70 Gy (0.12-1.54). For HF patients av MHD left was 1.16 Gy (0.19-1.90), MHD right was 0.48 Gy (0.12-0.91). For SF av MHD left was 1.60 Gy (0.80-3.12), MHD right was 0.84 Gy (0.39-1.54). There was a significant difference in MHD between left and right breasts (p = 0.002) and significant correlation between breast dose and MHD (p = 0.026). Conclusions: MHD from breast RT with current treatment planning is much lower than published reports from 2-D planning. MHD correlates with total breast dose and is greater for the left than right side. Techniques to reduce MHD should be utilized, especially for left-sided breast cancer.
Cardiovascular morbidity and mortality in patients treated for ductal carcinoma in situ of the breast.
Authors: Boekel Naomi B. , Schaapveld Michael , Gietema Jourik A. , Rutgers Emiel J. , Versteegh Michel I.M. , Visser Otto , Aleman Berthe M. , van Leeuwen Flora E.
Published: February 2017

58

Background: Recent concerns about potential overdiagnosis and overtreatment of ductal carcinoma in situ of the breast (DCIS) render evaluation of late effects of treatment, such as cardiovascular disease (CVD), of great importance. We studied cardiovascular morbidity and mortality in a large population-based cohort of DCIS patients. Methods: Data on all incident DCIS diagnosed before the age of 75 years between 1989 and 2004 in the Netherlands were obtained (n = 10,468). Cardiovascular morbidity and mortality data was acquired through linkage with population-based registries. Risk of CVD in the study cohort was compared with general population rates and evaluated in Cox proportional hazards regression models. Results: Compared with the general population, five-year survivors of DCIS had a similar risk of dying due to any cause (standardized mortality ratio (SMR)=1.04 95% confidence interval (CI) 0.97-1.11), but a lower risk of dying of CVD (SMR=0.77 95% CI 0.67-0.89). When comparing treatment groups within the cohort, no difference in risk of CVD was found when comparing patients treated with radiotherapy to surgery only. Left- versus right-sided radiotherapy did also not increase this risk (hazard ratio (HR)=0.93 95% CI 0.67-1.30). In a subgroup analysis of patients diagnosed between 1997 and 2005, accounting for overall history of CVD before DCIS diagnosis, we did not observe a risk difference between treatment groups (left- versus right-sided radiotherapy HR=0.95 95% CI 0.69-1.30). When taking into account CVD that occurred two years prior to DCIS diagnosis only, however, a statistically non-significantly increased risk was seen for patients with a history of CVD (HR=1.84 95% CI 0.45-7.50). Conclusions: After a median follow-up of ten years, we did not find an increased risk for cardiovascular morbidity or mortality after radiotherapy for DCIS when comparing surgery and radiotherapy versus surgery only, nor when comparing radiotherapy for left- versus right-sided DCIS. Compared to the general population, DCIS patients have a decreased risk of cardiovascular death, independent of treatment.
Does the number of surgical excisions before delivering intraoperative radiotherapy (IORT) affect skin toxicity?
Authors: Dai Kubicky Charlotte , Donovan Cory , Diggs Brian S. , Naik Arpana , Marquez Carol , Pillai Susha , Vetto John T. , Pommier Rodney F.
Published: February 2017

72

Background: The TARGIT-A trial allowed administration of IORT both pre- and post-pathology. The advantage of post-pathology is the ability to determine eligibility based on margins, pathologic tumor size and nodal status, prior to delivering radiation. However, it is unclear whether having more than one operation before IORT is associated with worse skin toxicity. In this study, we aimed to examine the relationship of the number of operations and skin toxicities in women receiving IORT. Methods: We conducted a retrospective analysis of 57 consecutive patients who underwent IORT from 2009-2013. All patients received 20 Gy in 1 fraction prescribed to the applicator surface using the Carl Zeiss Intrabeam System. Skin toxicities were determined using CTCAE 4.0 and RTOG criteria. In addition, infection, skin erythema, desquamation, symptomatic seroma, and necrosis were scored individually and used as outcome measures. Pearson’s Chi-squared test was used to assess the association of the number of operations and skin toxicities. A multivariate analysis was performed and included age, applicator size, max skin dose, number of operations, DM, HTN, BMI, co-morbidity, and depth from skin on mammogram as variables. Results: The median follow-up was 11 months (range 1-33). The median age and applicator size were 68 yrs (range 49-85) and 4 cm (range 2.5-5). 20 (35%) patients had 1 operation (lumpectomy, SLNB and Intrabeam all in 1 setting). 36 (63%) patients had 2 operations (initial surgery, followed by Intrabeam +/- margin re-excision). One (2%) patient had 3 operations (initial surgery, re-excision, followed by Intrabeam). On univariate analysis, the number of operations was associated with increased infection (p = 0.044), but not other skin toxicities. On multivariate analysis, the association was no longer significant (p = 0.97). Conclusions: Our study suggests that delivering IORT post-pathology was not associated with worse acute or late skin complications. Delivering IORT after the initial operation decreases the uncertainty of margin status and avoids the controversy of excising an irradiated positive margin and/or the need for additional whole breast radiation.
Significance of core needle biopsies with ductal carcinoma in situ suspicious for microinvasive carcinoma.
Authors: Namm Jukes P. , Mueller Jeffrey , Kulkarni Swati
Published: February 2017

86

Background: Sentinel lymph node biopsy (SLNB) is not routinely recommended for women diagnosed with ductal carcinoma in situ (DCIS); however, when the pathologist cannot rule out microinvasion on core biopsy (CB), the surgeon must decide whether to perform a SLNB at the time of surgical excision. Up to 10% of patients with T1mi are found to have breast cancer cells in the axillary lymph nodes, but less than 2% contain macrometastasis making the utility of SLNB in this setting unclear. Methods: The University of Chicago pathology database was queried for patients whose CB showed DCIS suspicious for microinvasion (Smic) or definite microinvasion (Mic) from 2000 to 2012. We analyzed histology, imaging, nodal status, core needle size, and the use of myoepithelial immunohistochemistry (IHC) markers to identify microinvasion. Results: We identified 60 women with Smic and 19 women with Mic on CB. In the Smic group, 33% had infiltrating ductal carcinoma (IDC) in the surgical specimen (35, 30, 30, 1 and 0% for T1mi, T1a, T1b, T1c, and T2 respectively compared to 58, 21, 0, 10.5 and 10.5% in the Mic group). A SLNB was performed at the initial surgery in 38/60 (63%) of Smic and in all Mic biopsies; they were positive in 3/42 (7%) and 2/19 (11%) respectively (p=0.64). When N1mic was excluded, the incidence of macroscopic nodal disease was 1/42 (2.4%) and 1/19 (5.3%) p=0.53. Of those with Smic, we observed a higher proportion of IDC associated with a lesion size ≥ 14 mm on imaging (75% versus 15% for < 14 mm, p<0.02); smaller CB needle size (69% with 11, 12 and 14 gauge versus 0% with 9 gauge, p<0.01); and the use of IHC on the CB to identify microinvasion (58% versus 22% without IHC, p<0.01). There was no association to IDC with respect to grade, necrosis, mass on imaging, or biopsy guidance. Conclusions: The incidence of clinically positive nodal disease in patients with Smic on CB is extremely low. However, those with tumors ≥ 14 mm, the use of smaller gauge CB needles, and Smic based on myoepithelial IHC may be at higher risk for IDC. Of the Smic group with DCIS after excision, none harbored nodal disease; therefore, the use of SLNB only after a definitive diagnosis of IDC may prevent overtreatment.
Predicting the extent of nodal disease in early breast cancer.
Authors: Caudle Abigail Suzanne , Kuerer Henry Mark , Le-Petross Huong T. , Yang Wei Tse , Bedrosian Isabelle , Krishnamurthy Savitri , Lucci Anthony , Hunt Kelly , Mittendorf Elizabeth Ann
Published: February 2017

95

Background: In early-stage breast cancer patients, the number of positive lymph nodes (LN) is considered in decisions regarding surgery and radiation. The goal of this study was to characterize the extent of axillary nodal involvement based on clinicopathologic and imaging features. Methods: A prospective database was used to identify T1-2 patients who underwent regional nodal ultrasound (US) and axillary lymph node dissection (ALND) from 2002-2012. Patients who received neoadjuvant chemotherapy or had extra-axillary LN metastases were excluded. Subjects were grouped by whether axillary metastases (AxM) were identified by US confirmed by needle biopsy or by sentinel lymph node dissection (SLND) after a negative US, then compared using X2 and Rank-Sum tests as appropriate. Results: AxM were identified by US in 190 patients and SLND in 518 patients. When compared to US-detected patients, SLND patients had fewer positive nodes (2.2 vs. 4.1, p < 0.0001), smaller metastases (5.3 vs. 13.8 mm, p < 0.0001), and a lower incidence of extranodal extension (ENE) (24% vs. 53%, p < 0.0001). Limiting analyses to patients with ≤ 2 abnormal LN on US, US-detected patients still had more positive LN (3.6, p < 0.001), larger metastases (13.4 mm, p < 0.0001), and a higher incidence of ENE (50%, p < 0.001) with more than 2 positive LN found in 45% of the US group versus 19% of the SLND group (p < 0.001). In patients with lobular histology there were no differences in number of positive LN (4 in SLND vs. 3.6 in US, p = 0.36), or ENE (34% SLND vs. 36% US, p = 0.9). Positive non-SLN were found in 23% (96/415) of patients with ductal tumors and 36% (21/59) of those with lobular tumors. In multivariate analysis, having metastases found by US (OR 4.01, 95% CI 2.75-5.84) and lobular histology (OR 1.77, 95% CI 1.06-2.95) predicted having > 2 positive LN adjusting for tumor size, receptor subtype, and histology. Conclusions: Patients with AxM found by US have more positive nodes, larger metastases, and higher risk of ENE, even if ≤ 2 suspicious LN are seen on US compared to patients with SLND-detected AxM. Tumor histology also predicts nodal burden. Clinicians can use imaging and clinicopathologic features to predict extent of nodal involvement and appropriately counsel patients regarding treatment decisions.
Quality cancer-survivorship care: Receipt of guideline-recommended cardiovascular disease (CVD) preventive care among healthy cancer survivors in the United States.
Authors: Pearlstein Kevin A. , Hendrix Laura H. , Chen Ronald C.
Published: February 2017

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Background: Improving cancer survivorship care is a high priority research area. CVD is a major cause of mortality in cancer survivors. Preventive care reduces CVD mortality and is part of guideline recommended care for all individuals. We examined receipt of CVD preventive measures among healthy cancer survivors compared to the non-cancer population using the National Health Interview Survey (NHIS). Methods: NHIS is a population-based, annual survey designed to provide data representative of the health care received by the U.S. population. For this analysis, 1,860 survivors without CVD risk factors (hypertension, diabetes, or hyperlipidemia) were matched to 7,393 controls without CVD risk factors based on age, race, gender, and survey year. Multivariate logistic regression models examined factors associated with receipt of each preventive measure. Results: Cancer survivors were more likely than controls to visit a general doctor and a specialist during the past year (Table). Further, survivors were more likely to have received CVD preventive care (blood pressure and cholesterol check) and undergone behavior modification (tobacco cessation and exercise). Survivors > 5 years versus < 2 years from diagnosis were no better in CVD preventive measures, except slightly higher rate of exercise (51 vs. 48%, p < 0.001). On multivariate analysis, general doctor visitation was associated with receipt of blood pressure check (OR 7.0), cholesterol check (OR 2.9), smoking cessation attempt (OR 1.4) and exercise (OR 1.3); survivors vs. control were no different in CVD preventive care. Conclusions: Care by a general doctor improves receipt of CVD preventive measures for cancer survivors and non-cancer individuals alike. This study supports the integral involvement of primary care physicians in a “shared care model” for the delivery of quality cancer survivorship care. [Table: see text]
Community oncology treatment patterns and clinical effectiveness in metastatic castration-resistant prostate cancer (mCRPC) patients who progressed after docetaxel.
Authors: Houts Arthur C. , Hennessy Daniel , Walker Mark S. , Nicacio Leonardo , Thompson Stephen F. , Miller Paul J. E. , Somer Bradley G.
Published: February 2017

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Background: Cabazitaxel (C) and abiraterone (A) improve survival in mCRPC after progression on docetaxel (D). We examined whether mCRPC patients progressing on D received C and/or A, in which sequence, and how they compared with patients not receiving C or A. Methods: This retrospective study used medical records from the ACORN Data Warehouse. Eligible patients were: diagnosed with mCRPC, progressed after 1st-line D, treated 2nd-line with C (DC) or A (DA). Some went to 3rd-line C or A (DCA, DAC). A random sample of comparable patients without A or C (DO) was included. Demographic and clinical characteristics were extracted. Cox regression analyses assessed PFS and OS by 2nd-line group after D. Results: Screened out patients were: 60 with no progression on D; 41 absent records; 18 with another cancer. Table below shows patients by treatment sequence group. Age, PS, and PSA did not differ significantly. More patients appear to have received A after C (56.7%) than C after A (25.7%). In the 3-drug sequence groups, more patients received DCA in the 6-month period from April-October 2011 (n = 17/19) than in the 6-month period from June-December 2012 (n = 2/10), suggesting a drop-off in use of C immediately after D. Cox PFS treatment effect was not significant. Cox OS treatment effect was significant (DA vs DC, HR = 1.693 [95% CI: 1.066, 2.691], p = 0.0258). Conclusions: Patterns suggest comparable outcomes in PFS. Controlling for patient characteristics, OS may be longer in DC vs DA. Patients appear undertreated in third line with fewer receiving C after A than the opposite sequence. We hypothesize that DAC may not be as feasible as DCA. Reasons for underutilization of C are being examined. [Table: see text]
Use of clinical care registries to facilitate research study recruitment.
Authors: Messer Karen , Layton Tracy M. , Chen Tony , Nandigam Viswanath , Abihider Katherine , Chase Peter W. , Pierce John P. , Madlensky Lisa , Cadmus Lisa , Patterson Ruth E. , Faerber Susan , Schwab Richard B. , Blair Sarah , Wallace Anne M. , Ojeda-Fournier Haydee , Parker Barbara A.
Published: February 2017

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Background: We developed IRB-approved secure research registries for our Breast Imaging and Breast Care Clinics at Moores UC San Diego Cancer Center, as part of the UC statewide Athena Breast Health Network. Our clinical care registries securely store patient-reported intake data, which are summarized and uploaded into the medical record for patient care. Following consent, data are securely maintained in a separate research registry. In addition to facilitating quality assurance data collection, these registries aim to 1) maintain a data-rich research registry, 2) offer patients research opportunities, and 3) facilitate participant screening and recruitment into research studies. Methods: Breast Imaging or Breast Care clinic patients complete an online clinical intake form prior to their appointment, either at home or using an iPad in clinic, and are given the opportunity to be involved in research. Patients are asked for site-specific consent to keep personally identifiable intake data in a research registry, for consent to be approached about providing a biospecimen sample, and for consent to be contacted for future research opportunities. Data from consented participants are pulled into secure databases available to study personnel. Results: Participants to date include 4,480 patients, of whom 3,246 consented to use of data for research (72%), and 2,627 have agreed to be contacted for future research opportunities (59%). In a pilot biospecimen collection protocol, 46% of patients agreed to be approached and we have collected over 360 blood or saliva and 51 tissue samples. Additionally, with the use of future contact consent, we have facilitated recruitment of more than 370 participants to multiple lifestyle and survey-based clinical studies. Conclusions: Patients are willing to participate in research, especially in a research registry that requires little additional time on their part. The use of research registries allows collection of a variety of data elements useful for prescreening participants for research studies, including body mass index, age, menopausal status and breast cancer diagnosis. Data- and participant-rich research registries facilitate efficient screening and recruitment for other research studies.
Impact of a clinical care online intake form in a breast care clinic.
Authors: Layton Tracy M. , Messer Karen , Pierce John P. , Madlensky Lisa , Cadmus Lisa , Patterson Ruth E. , Chase Peter W. , Faerber Susan , Schwab Richard B. , Blair Sarah , Wallace Anne M. , Parker Barbara A.
Published: February 2017

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Background: An online self-reported clinical care intake form was provided to new surgery patients of the Moores UCSD Breast Care Clinic, as part of a pilot project in collaboration with the University of California Athena Breast Health Network. Clinical care goals were 1) to reduce clinic time by pre-visit collection of patient histories, co-morbidities, and medications and 2) provide patient reported data to clinicians and the electronic medical record (EMR). Clinical research goals were to 1) identify individuals diagnosed with breast cancer, 2) collect baseline measures related to co-morbidities, psychosocial parameters, and lifestyle factors and 3) increase research opportunities and enrollment. Methods: We developed an online intake form for patients to complete at home prior to their appointment. Patients were informed to complete the intake form before their appointment and were sent instructions via email. Patients without an email address had the opportunity to complete their intake form on an iPad in clinic. A summary of intake form answers was uploaded into the EMR for all patients. Patients could consent to future contact, to have their intake data kept in a research registry and/or to provide a blood or tissue sample. Results: From March 2010 to May 2013, 1,224 sequential new breast surgery clinic patients were contacted to complete the online intake form as part of their clinical care. 890 patients completed the intake form prior to their visit (73%). 802 of the 890 patients consented to contact for future research opportunities (90%) and 624 of the 802 consented to share data and EMR access for research (78%). We have coordinated enrollment with our ongoing UCSD biorepository study and have collected 210 blood and 51 tissue samples. Additionally, using future contact consent, we recruited more than 100 participants to multiple lifestyle and survey-based clinical studies. Conclusions: The use of an online intake form is well accepted by patients and provides patient reported data to all clinicians involved in patient care. In conjunction with consented EMR access, these data can be evaluated routinely for quality and efficiency purposes. Initial consent for future contact greatly facilitates participant recruitment to research studies.
Patients’ perceptions of early palliative oncology care: A qualitative analysis.
Authors: Hannon Breffni , Swami Nadia , Krzyzanowska Monika K. , Leighl Natasha B. , Oza Amit M. , Moore Malcolm J. , Rodin Gary , Tannock Ian , Zimmermann Camilla
Published: February 2017

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Background: Early palliative care referral is encouraged for patients with advanced cancer. However, little is known about patients’ perceptions of the impact and relevance of early referral. We conducted a qualitative study in which patients with advanced cancer were interviewed following completion of a randomized controlled trial comparing early palliative care with standard oncology care. Our aim was to delineate what, in the opinion of patients, were the respective roles of the oncology and palliative care teams in an outpatient setting. Methods: We conducted qualitative interviews with patients following completion of a cluster randomised controlled trial of early versus routine palliative care referral. Participants were recruited from 24 medical oncology clinics at a comprehensive cancer center. Selective sampling was employed to ensure equivalent numbers of participants from intervention vs. control arms, male vs. female, age ≥60 vs. <60 years, with high vs. low self-reported quality of life, and with high vs. low satisfaction with care. Forty-eight patients (26 intervention and 22 control) with advanced lung, breast, gynecological, gastrointestinal and genitourinary cancers completed interviews lasting 25 to 90 minutes. Control patients were asked about the role of oncology; intervention patients were asked about both teams. Interviews were recorded, transcribed and analysed using NVivo. A grounded theory approach was used to explore emerging themes. Results: Several themes emerged in relation to the contrast between oncology (OC) and palliative care (PC) including (1) the focus of the consultation, with OC tending to focus on cancer or treatment options while PC was regarded as being more holistic, including physical, psychological and family domains; (2) the model of care delivery, with OC described as being clinician-led and time-limited, in contrast with PC where time was more flexible and the patient set the agenda; and (3) the complementary nature of early palliative care alongside standard oncology care in terms of overall well-being. Conclusions: From a patient perspective, palliative care and medical oncology have distinct and complementary roles, supporting the relevance of early referral.
Influenza vaccine immunization in a pediatric oncology ambulatory practice.
Authors: Tishler David , Escobedo Erika , Alhushki Waseem , Margol Ashley S. , Mehta Bhakti , Rushing Teresa
Published: February 2017

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Backround: Complications from Influenza infection remain an important cause of morbidity and mortality among immunosuppressed children and adolescents. Seasonal Influenza vaccine has been shown to be both safe and effective in pediatric and adolescent patients on chemotherapy treatment although at the Childrens Center for Cancer and Blood Diseases (CCCBD), immunization rates remain suboptimal. We initiated a comprehensive campaign for the 2012-13 flu season with these objectives: 1) evaluate provider attitudes regarding Influenza vaccine, 2) provide a data capture form in the patient medical record to improve vaccine compliance and 3) retrieve electronic medical record (EMR) data on immunization incidence. Methods: The study period was October 1, 2012 through January 31, 2013; a hybrid hard copy/EMR was in use. A Survey Monkey questionnaire was given to CCCBD oncology providers to assess individual influenza vaccine practices. Information was provided how to document vaccination in the EMR. A reminder/data capture form was attached to the hard copy medical record and collected following each patient visit. Forms were tracked to ensure completion for each active oncology patient seen during the campaign period. Patient medical record numbers were cross-referenced with EMR data to determine immunization incidence and the success of the campaign. Results: 100% of providers (46/46) responded to the survey. All respondents believed that the flu vaccine was both safe and efficacious; many reported that the priority of oncology care pre-empted ordering vaccine (27%). Total vaccine doses dispensed increased by 28 % over the previous season (502 doses in 2012-13 vs. 361 doses in 2011-12). 61% of eligible patients with Acute Lymphoblastic Leukemia (ALL) were immunized in 2012-13 compared to 40% of ALL patients in 2011-12. EMR documentation of vaccination also improved during the campaign. Conclusions: A comprehensive campaign to promote Influenza immunization during the most recent flu season was overwhelmingly successful. In-progress improvement in the institutional EMR will further advance our ability to document and retrieve influenza vaccine data for this at-risk population of children and adolescents.