bluuebunny/crossref_metadata_2025 huggingface dataset:
Breast cancer detection among Irish BRCA1 and BRCA2 mutation carriers.
Authors: Walsh Elaine , Farrell Michael P. , Gallagher Fergal , Clarke Roisin , Nolan Carmel , Kennedy M. John , Daly Peter , McCaffrey John , Connolly Elizabeth M. , Boyle Terence , Kell Malcolm R. , Gallagher David J
Published: February 2017

59

Background: High-risk breast cancer screening for BRCA1/2 mutations carriers with clinical breast exam, mammography and MRI have sensitivities approaching 100%. Even with intensive screening BRCA mutation carriers can present with self-detected interval cancers. We investigate screening practices and presentation among a cohort of Irish BRCA1/2 mutation carriers. Methods: Females with breast cancer belonging to kindreds now known to harbour BRCA1/2 mutations were retrospectively identified. Records were reviewed for BRCA mutation, demographics, breast cancer diagnosis, stage, histology and screening. We assessed screening modalities and whether breast cancers were diagnosed at screening or as interval cancers. Results: 53 cases of breast cancer were diagnosed from 1968-2010 among 53 Irish hereditary breast ovarian cancer kindreds. BRCA mutation status was unknown at time of diagnosis but subsequently confirmed. Detection method was identified in 50% of patients: 84% by clinical breast exam (CBE), 4% mammography, 4% MRI and 8% by a combination of CBE and mammography. Fifteen women (28%) developed second breast cancer; 9(60%) were undergoing screening, 2 were not and 27% were unknown. 22% were detected by CBE alone; 34% mammography; 22% a combination of mammography and CBE and 22% by MRI. In 41%, histology changed between first and second diagnosis. Two women developed a third breast cancer. In one, her second was an interval cancer despite being in a screening programme. Her third was radiologically detected. Conclusions: In this cohort of Irish BRCA1/2 mutation carriers almost 25% of second breast cancers were not detected by screening. 4% of cases were phenocopies and in 41% histology changed between first and second diagnosis. [Table: see text]
Behavior of breast cancer in young women: A Surveillance Epidemiology and End Results (SEER) database review.
Authors: Tesfaye Anteneh A. , Mozayen Mohammad , Morariu Ioana , Eilender David S.
Published: February 2017

6

Background: Advanced age is a major risk factor for breast cancer in women. Small sized studies have reported variable outcome of breast cancer in young women. Our study was done to evaluate tumor characteristic and cancer specific survival among young women. Methods: The 1973-2009 SEER database was reviewed for women with breast cancer diagnosed between 2004 and 2009. Patients were grouped by age into: A (≤35 years), B (36-50 years) and C (>50 years). Age, ethnicity, staging, lymph nodes status, micrometastasis in negative lymph nodes, tumor size, tumor grade, hormone receptor status were extracted. Data and survival were analyzed using chi square, Kaplan-Meier, Life table, and Cox proportional hazard model. The primary outcome was 5-year cancer-specific survival. Results: A total of 248,280 patients were included in the study, group A, B and C making 2.8%, 25.5% and 71.7% of study subjects respectively. The median tumor size was 2.4, 1.9, and 1.6 cm in groups A, B and C respectively (p=0.0001). Positive lymph nodes were seen in 52.5%, 43% and 34% in groups A, B and C respectively (p=0.0001). Regional disease was seen in 47.5%, 39.5% and 29.9% in groups A, B and C respectively (p=0.0001). Higher Grade histology was seen in 63.5%, 44.3% and 33.8% in groups A, B and C respectively (p=0.0001). ER-PR negative were found in 42.1%,26.4%, 22.6% of Groups A, B and C respectively (p=0.0001). Five year cancer specific survival was 82%, 89%, 86% in groups A, B and C respectively (p=0.0001). Independent prognostic factors are given in the table. Conclusions: Breast cancer is uncommon among young women (age <35). Compared to other age groups, breast cancer in young women presents with bigger tumor, higher nodal positivity, an advanced stage, higher tumor grade, higher hormone receptor negativity, and worse 5-year cancer-specific survival. [Table: see text]
Socioeconomic and geographic disparities in immediate reconstruction after mastectomy in the United States.
Authors: Wexelman Barbara A. , Ma Xiangji , Estabrook Alison , Ma Ayemoethu
Published: February 2017

63

Background: Disparities are found in breast cancer diagnosis, treatment, and outcomes. We seek to determine if socioeconomic and geographic disparities exist nationally in immediate reconstruction type after mastectomy. Methods: This retrospective study compares socioeconomic and geographic features for 14,986 women who underwent mastectomy in 2008 using the Nationwide Inpatient Sample (NIS), an all-payer stratified statistical sample of all US hospital discharges. Statistical analysis was performed to understand variations between three groups: patients without reconstruction (NR), patients who underwent breast implant/ tissue expander reconstruction (TE), and patients with advanced reconstruction techniques such as free or pedicled flaps (FLAP). Results: The majority of women (63%) had no reconstruction (NR), while 25.3% had TE and 12% underwent FLAP. Compared to patients with NR, women with TE or FLAP were younger (64.9 years vs. 51.3 & 51.1 years, p<0.001), had fewer chronic conditions (3.85 NR vs. 2.60 TE & 2.54 FLAP conditions, p<0.001), and higher mean hospital charges ($22,300 NR vs. $42,850 TE and $48.680 FLAP, p<0.001). The length of stay was longest for FLAP patients (3.62 days) compared to the NR group (2.02 days) and the TE group (1.90 days), p<0.001. Caucasians were disproportionately more likely to undergo both TE and FLAP compared to Black and Hispanic women. Patients with FLAP reconstruction were more likely to have private insurance (81.1%), than TE (80.1%) and NR (35.2%) while women without reconstruction were more likely to have Medicare and Medicaid insurance. Compared to NR, those undergoing reconstructions were more likely to live in zip codes with higher average incomes and more likely to live in or near a major city (>1 million people). The states with the highest rates of FLAP reconstruction are New Hampshire (52.9%), Kansas (22.6%), New York (20.9%), and New Jersey (20.0%). Conclusions: This is the first national study analyzing patients of all insurance types and regions of the US to show statistically significant disparities in the type of immediate reconstruction after mastectomy based on age, race, insurance type, and geographic location.
Vascular toxicities of endocrine therapy in early-stage breast cancer: Encouraging observations in a nontrial setting.
Authors: Dent Susan Faye , Crawley Freya L. , Graham Nadine A. , Campbell Michelle M.
Published: February 2017

68

Background: Endocrine therapy (ET) is the standard of care for postmenopausal (PM) women with early stage breast cancer (EBC). Studies suggest higher risk of vascular toxicities (VT) on aromatase inhibitor (AI) therapy. We report incidence/discontinuation rates of VTs in a cardiac clinic. Methods: PM women with hormone receptor positive EBC treated with ET (tamoxifen (T) ± AI) at Ottawa Hospital Cancer Center 01/99-2/06. Data included: demographics, vascular co-morbidities (VCM), ET, duration, VTs. Results: 626 pts, median age 59 years (r: 30-92), median follow-up 98 months (m), stage: I (196 pts), II (341 pts) III (89 pts) EBC. Majority (52.5%) pts had VCM at ET initiation; hypertension (HTN) (36%), hyperlipidemia (HYLP) (17%), coronary disease (12%), thrombosis (9%), angina (6%) TIA (6%). Treatment discontinued due to VT 3x more with T vs. AI. Most common VTs: edema, arrhythmias (ARR), cardiovascular (CVS) event, and HYLP. With Letrozole and T, previous VCM significantly increased risk of developing VT (chi-square: P=0.022 and 0.009). Time to develop VT shortest for T and exemestane. Previous VCM did not affect this interval. Longer exposure to T correlated with higher VT rate (t-test: p=0.046) not seen with AIs. Exposure to multiple AIs associated with higher VT rate (t-test: p=0.009). Conclusions: This cohort study reports similar VT rates with AI therapy as reported in the literature. T was associated with higher discontinuation rates (10.5%) due to VTs compared to AIs (2.8-3.3%). Longer duration of AI therapy was not associated with increased risk of VTs. These encouraging results reflect the real-life experience of women exposed to ET. [Table: see text]
Contralateral breast cancer: Effect of stage on survival after unilateral breast cancer.
Authors: Uyeno Lori , Behrendt Carolyn E. , Kruper Laura , Chen Steven L. , Vito Courtney
Published: February 2017

69

Background: Contralateral breast cancer (CBC) is the most common malignancy among breast cancer survivors. We investigated the impact of CBC on overall survival (OS) after unilateral primary breast cancer (UPBC) in women treated with mastectomy. Methods: Using the Surveillance Epidemiology End Results registry, we identified women age 25-80 diagnosed 1998-2006 with UPBC stage 0-III, treated with mastectomy and free of CBC at 1-year landmark. Subjects were split into test and validation samples. Follow-up continued until the earliest occurrence: death, end of 2008, or age 85. Primary risk factor was incident CBC, a time-dependent variable categorized as advanced-stage (IIB-IV), early-stage (0-IIA), or none. Proportional hazards regression adjusted for primary tumor characteristics, treatment including contralateral prophylactic mastectomy (CPM), demographics, and aging. Results: Subjects (n= 109,411, age 53.7[+12.7] years at UPBC diagnosis) were followed median 51 months. Most UPBC were early stage (63%), moderately/poorly differentiated (78%), ER+PR+ (52%). Few (9.8%) women underwent CPM at primary diagnosis. Incident CBC (n=867, 0.79%) was diagnosed median 23.5 (95% CI 1.2-72) months beyond the 1-year landmark. Test and validation samples did not differ. Only CBC of stage IIB-IV increased mortality; early stage CBC had no effect on OS. Among CBC cases, advanced stage was independently associated with aggressive UPBC (more positive nodes; larger tumor; greater extension), African-American race, and shorter time from UPBC. Conclusions: Among women who undergo mastectomy +/-CPM for UPBC, few develop CBC, which impacts survival only when diagnosed at advanced stage. Efforts to improve survival after UPBC should emphasize earlier detection and prevention of advanced-stage CBC, especially in African-American women and women with more aggressive UPBC. [Table: see text]
Web-based standard-regimen selection (SRS) and cancer-care registry (CCR) systems of a nationwide network in Japan: An attempt to improve breast cancer treatment.
Authors: Sato Kazuhiko , Shinozaki Nobuaki , Iwai Masaru , Mizuno Yoshio , Shimoyama Rai , Takahashi Noriyuki , Niitsu Yoshiro
Published: February 2017

76

Background: Tokushukai group has a nation-wide network of 67 affiliated hospitals, and has started an “oncology project” to improve the quality of cancer care using web-based SRS and CCR systems. Methods: Every institution has been introduced the same electric-medical-record (EMR) to share the unified code to order chemotherapy regimens, and patient data could be collected on a database in the central office. 141 recommended regimens for 15 types of solid tumor have been approved in the cancer committee consisting of working-group and program-evaluation members. In breast cancer, 31 recommended regimens (7 for adjuvant and 24 for metastatic settings) were selected from the NCCN guidelines and approved by the committee. Not only recommended but also non-recommended regimens have their own specific codes in EMR, and the patterns of care in the selection of chemotherapy regimen were examined. Results: In 2011, 21 of 67 hospitals utilized these systems. 71.8% of 2,676 patients with cancer including 753 with colorectal, 317 with breast, 273 with gastric, 144 with non-small cell lung, 123 with pancreatic, and 73 patients with esophageal cancer had received 97 types of recommended therapies (11,022 cycles). In terms of breast cancer, 86% of 388 patients had been treated with recommended regimens (1,994 cycles). Among 71 patients received non-recommend therapies, only 6 patients (1.5%) had been treated with three regimens which were not regarded as standard regimens. Conclusions: The introduction of web-based SRS and CCR systems in a large medical group could facilitate standard chemotherapy regimen by an accurate examination of current treatment patterns.
Using computerized decision support to improve compliance of cancer multidisciplinary meetings with evidence-based guidance.
Authors: Patkar Vivek , Acosta Dionisio , Davidson Tim , Jones Alison , Fox John , Keshtgar Mohammed R.
Published: February 2017

79

Background: The cancer multidisciplinary team (MDT) meeting is regarded as the best platform to reduce unwarranted variation in cancer care through evidence-compliant management. However, MDT meetings are often overburdened with many different agendas, and hence struggle to achieve their full potential. Methods: We have developed an interactive computer system called MATE to facilitate explicit, evidence-based decision-making in MDT meetings for breast cancer care. MATE provides prognostication and risk assessment and also flags up patients eligible for recruiting into ongoing research trials. We describe the system; share our experience of implementing MATE and report initial audit and survey results. MATE was used to record the proceedings of breast MDT meetings between 2008-2009 to gather 1,295 cases discussed in the MDMs during this period and to audit the MDT decisions and MATE recommendations against NICE, NHSBSP, and NCCN guidelines. Results: MATE identified 61% more patients who were eligible for recruitment into clinical trials than the MDT and its recommendations demonstrated high concordance with MDT decisions (93.2 %). MATE is in routine use in breast MDT meetings at Royal Free Hospital, London, and deployment of the system in other NHS trusts is being explored. Conclusions: Sophisticated decision support systems can enhance the conduct of MDT meetings in a way that is acceptable to and valued by the clinical team. Further rigorous evaluations are required to examine cost-effectiveness, measure the impact on patient outcomes and test the generalizability of the system in different hospital setups and in different cancers.
Breast cancer patients' rights: How can they be respected in Iran?
Authors: Joulaee Azadeh , Joolaee Soodabeh , Bahrani Naser , Kadivar Maryam , Kalantari Mojgan
Published: February 2017

81

Background: The revolutionary concept in breast cancer diagnosis and treatment has significantly changed many aspects of cancer treatment in favor of patients' rights. The best useful targeted treatment is offered to them with the least harm and invasion. As the most common cancer, breast cancer incidence is 24/100, 000 or one-fourth of all new cancers. The aim of this study is to compare the international rights for breast cancer patients with actual situation in Iran. Methods: All published data in Iran are reviewed since 2001 to 2012 to see the actual care in Iran. Codification of new radiology, surgical and pathologic procedure and insurance coverage are searched through available national references. These data are compared with international references. Results: Diagnosis is done by excisional/incisional biopsy or frozen section. Trucut biopsy is done in a low minority of cases. Insurance system does not cover vacuum assisted biopsy. Only mastectomy and axillary dissection are accepted by insurance. No codification exists for conservative surgery, oncoplastic surgery and sentinel node biopsy and the rate for these surgeries are low. Breast reconstruction, conservative surgery as bilateral mammoreduction, and symmetrization of controlateral breast are considered as cosmetic surgery with no coverage. The majority of cases are treated in general surgical wards. There are very few breast nurses and few centers for rehabilitation, lymphedema treatment, and psychological support of survivor. Conclusions: The ministry of health insists on full respection of the patient’s rights in medical practice. The new rights of breast cancer patients based on new treatment strategy are not highlighted in Iran. Valid evidence must be provided for policy makers about the rights of these vulnerable patients to consider them in Iranian health care delivery system. Specialized breast unit can improve significantly the quality of breast cancer care toward the patients' right. Pre-operative confirmation of cancer by trucut biopsy seems to be the key point. This gives the patient the opportunity to know more about the disease and to search for the best therapeutic plan according to international guideline.
Time trends in survival in young women with breast cancer in a population-based study: Are there estrogen receptor status differentials?
Authors: Ademuyiwa Foluso Olabisi , Groman Adrienne , Hong Chi-Chen , Kumar Shicha , Levine Ellis Glenn , Miller Austin , Ambrosone Christine B.
Published: February 2017

85

Background: As mammography is not generally recommended to women under 40, it is reasonable to conclude that documented outcome improvements over time are attributable to treatment advances with screening playing a less important role. In order to determine the contribution of screening and treatment to improvements, we evaluated the odds of presenting with more advanced disease by time-period and examined the time-trends in outcome in a population-based cohort ≤50. We evaluated whether any outcomes differentials existed by ER status. Methods: Patients in SEER diagnosed with breast cancer were divided into 4 by year of diagnosis (1990-1994, 1995-1999, 2000-2004, 2005-2008). Patients were categorized into 2 age-groups: <40 and 40-50 years. Odds ratios for presenting with more advanced disease over the 4 time-periods were calculated for the 2 age-groups. Multivariate analysis was done to investigate the association of survival with time-period for the 2 age-groups by ER status. Results: 110,629 patient records were included. Patients 40-50 who were diagnosed in the 3 later time-periods (1995-1999, 2000-2004, 2005-2008) were more likely to have small tumors (≤2cm) compared with patients diagnosed in 1990-1994. Similarly, these patients were less likely to have larger tumors (≥3cm) comparing the 3 time-periods relative to 1990-1994. Conversely, patients <40 years had a higher odds of presenting with larger tumors (≥3cm) when the 3 later time-periods were compared to 1990-1994. In the ER positive patients, multivariate analysis showed that being diagnosed in the 3 later time-periods relative to 1990-1994 was associated with improved survival irrespective of age. In the ER negative cohort, those 40-50 years had a higher risk of death in the 3 later time-periods relative to 1990-1994; while there was a no effect of time-period on mortality for the younger age group of <40. Conclusions: Patients who are ER positive and between 40-50 years have had time-trend changes with improvements in breast cancer outcome and smaller tumors likely attributable to both screening and hormonal therapies. Patients who are <40 years and/or ER negative have not had improvements in breast cancer outcome.
Patient informational needs about breast reconstruction post-mastectomy.
Authors: Ahmed Ivy A. , Harvey Allison , Weiss Erica , Amsellem Marni
Published: February 2017

88

Background: For many women, receiving a breast cancer diagnosis is further complicated by decisions they will face about breast reconstruction post-mastectomy. While women are typically provided with some information about reconstruction options, little is known about the perceived value of this information and how it might ultimately affect their decision about reconstruction. The Cancer Support Community investigated these questions in a national sample of women with breast cancer to better understand their information-seeking experiences, knowledge, and decision-making about reconstruction. Methods: In 2011, 439 participants attending Frankly Speaking about Cancer: Spotlight on Breast Reconstruction, a national educational workshop, completed a post-workshop survey (56.4% response rate). 76.2% of respondents were women diagnosed with breast cancer, who reported their decisions about reconstruction as well as their experience receiving information about reconstruction. Results: Respondents were Caucasian (74.8%), black (11.4%), and Hispanic (10.1%), and the mean age was 48.9. Nearly half (42%) of respondents reported low levels of knowledge about breast reconstruction prior to the workshop. Of those eligible for breast reconstruction, 18.2% reported they had decided against reconstruction, 40.7% were considering their options, and 41.1% planned to undergo or had undergone reconstructive procedures. Women reported they would have liked to have had more information prior to reconstruction about a variety of topics, including more information about the procedure (43.6%), how they would look (31.1%) and feel (29.7%) after reconstruction, and information about their future breast health (31.8%). No differences were found in unmet informational needs based on their reconstruction decisional status with one exception: those who decided against reconstruction were more likely to endorse that they would have wanted more information about when to make their decision about reconstruction than the other two groups (chi square=24.6, p <.01). Conclusions: Findings suggest women facing breast reconstruction often are not equipped with comprehensive information about procedures, options, outcomes, and recovery.
The use of bioelectrical impedance spectroscopy (BIS) to detect subclinical changes potentially associated with the development of breast cancer-related lymphedema.
Authors: Vicini Frank , Arthur Douglas W. , Lyden Maureen , Shah Chirag
Published: February 2017

89

Background: The purpose of the study was to evaluate bioelectrical impedance spectroscopy's (BIS) ability to detect and monitor extracellular fluid accumulation of the upper limb as it relates to the extent of locoregional therapy for patients with breast cancer. Methods: A total of 125 patients from 4 clinical practices, with newly diagnosed breast cancer were evaluated at baseline and following locoregional procedures that could potentially affect fluid accumulation in the arm and signal the possible development of early lymphedema. In order to assess the ability of BIS to detect sub-clinical changes by treatment modality, the change in L-Dex score from baseline to measurements taken within 180 days following surgery were calculated. Results: Fifty-one patients (40.8%) underwent lumpectomy and 74 (59.2%) mastectomy; 68 patients (54.4%) underwent sentinel lymph node (SLN) sampling. Sixty-five patients underwent radiation therapy (RT) with RT patients being more likely to have undergone lumpectomy (66.2% v. 3.2%, p<0.001) and axillary dissection (41.5% v. 19.4%, p=0.04) compared with patients not receiving RT. However, no difference in the mean number of nodes sampled (7.7 v. 5.4, p=0.14) was noted for patients receiving RT compared with those not receiving RT. Patients receiving RT had a significantly increased change in L-Dex score (0.8 v. -2.5, p=0.03) compared with those patients not receiving RT. For all patients, ALND was associated with a significantly increased change in L-Dex score (5.0 v. 0.3, p=0.003) compared with SLN. When stratifying by the number of nodes removed, a statistically significant increase in the change in L-Dex score was noted (0.4 v. 0.4 v. 4.3 v. 6.4, p=0.04) for 0-3, 4-6, 7-10, and greater than 10 lymph nodes removed. Conclusions: In this limited analysis, L-Dex scores paralleled the extent of axillary sampling and the addition of radiation therapy; these results suggest that BIS can be used to monitor patients for the early onset of edema as differences emerged within 180 days of surgery.
Changing ER, PgR, and HER2 status between primary and recurrent breast cancer.
Authors: Matsumoto Akiko , Takahashi Maiko , Hayashida Tetsu , Hirose Shigemichi , Jinno Hiromitsu , Kitagawa Yuko
Published: February 2017

92

Background: Estrogen receptor (ER), progesterone receptor (PgR), and HER2 status are important biological markers for making decisions about breast cancer treatments. Although changes of hormone receptor (HR) and HER2 status with recurrence of breast cancer are clinically experienced, the frequency of discordance and clinical significance are still unknown. Thus, we investigated ER, PgR, and HER2 status with primary tumors and recurrent lesions, and assessed discordance rates and prognosis. Methods: We retrospectively identified recurrent breast cancer patients who had biopsies or resections of recurrent lesions between January 2007 to April 2012 at Keio University Hospital. HR status was assessed by immunohistochemistry (IHC) and determined using the Allred score. HR status was defined as positive when score was 3 and more. HER2 status was assessed by IHC and fluorescence in situ hybridization (FISH) analysis. We defined HER2 positivity as 3+ staining intensity by IHC or the presence of HER2 gene amplification by FISH. Results: Among 32 recurrences, 40% (13) were loco-regional recurrences (LLR) and 60% (19) were distant metastases (DM) (lung 14; liver 3; brain 1; pleura 1). Discordance rates in ER, PgR and HER2 status between the primary tumors and the recurrence lesions were 12.5%, 31.3%, and 13.8%, respectively. The most common change was loss of PgR. Changings from negative to positive in ER, PgR and HER2 status were found in 6.3%, 3.1%, and 3.4% of the patients, respectively. All gains were found in distant metastases. Discordance in ER and HER2 were more common in DM (15.8% and 17.6%) comparing with LRR (7.7% and 8.3%). Loss of HR status was not associated with a shorter time to progression (TTP) (ER: 19.3 vs. 8.5 months, p=0.185; PgR: 4.4 vs. 11.5 months, p=0.907). Patients with discordant HER2 status had significantly shorter TTP than with concordant status (0.9 vs. 11.5 months, p=0.012). Conclusions: Discordance of biological markers between primary and recurrent breast cancers were seen in 10-30%. Although HR discordance was not associated with prognosis, patients with HER2 discordance had poorer TTP. Tissue confirmation should be considered for making effective treatment decisions in recurrent breast cancer.
Proactive approach to risk reduction and early detection of breast cancer-related lymphedema.
Authors: Fu Mei R. , Guth Amber , Kleinman Robin , Cartwright Francis , Axelrod Deborah M.
Published: February 2017

95

Background: Advances in surgery and post-operative treatment continue to reduce the incidence of late effects of cancer treatment such as lymphedema. Yet, many breast cancer survivors still face considerable post-operative challenges as a result of developing lymphedema. The purpose of this study was to preliminarily evaluate an educational and behavioral program “The Optimal YOU” to enhance lymphedema risk reduction among patients with breast cancer. The intervention focuses on preventing inflammation-infection, promoting lymph drainage, and maintaining optimal BMI as well as preoperative and subsequent follow-up assessment of limb volume changes and symptoms. Methods: A quasi-experimental design with repeated-measures was used to assess outcomes of The Optimal YOU program at pre-operative baseline, post-operative, 6-month, and 12-month follow-up. A total of 147 patients newly diagnosed with breast cancer were recruited and received the program. The program outcome data include lymph volume changes by infra-red perometer-S350, lymphedema-related symptoms by Lymphedema Symptom Experience Index, and body mass index (BMI) by Bioimpedance DF50. Results: Among the 147 patients, 141 patients completed the study (4% attrition rate). Majority (94%) of patients maintained preoperative limb volume and improved their symptom experience at 12-month follow-up. During the 12-month study period, only five patients (6%) developed lymphedema and were referred for lymphedema treatment. At 12-month follow-up, among the five patients who developed measurable lymphedema, two patients’ limb volume returned to pre-operative level without compression therapy only by maintaining exercises of The Optimal YOU to promote daily lymph flow. About 80% of patients maintained or improved their preoperative BMI. Conclusions: The study shows that proactive approach to implementing The Optimal YOU program is effective to risk reduction and early detection of breast cancer-related lymphedema by focusing on preventing inflammation-infection, promoting lymph drainage, and maintaining optimal BMI.
Incidence complications following sentinel lymph node biopsy or axillary lymph node dissection after breast cancer surgery.
Authors: Bello Marcelo Adeodato , Bergmann Anke , Dias Ricardo , Thuler Luiz Claudio Santos , Tonellotto Fabiana , Pinto Renata Reis , Fabro Erica
Published: February 2017

97

Background: To reduce arm morbidity the sentinel lymph node biopsy was implemented in the breast cancer treatment. The aim of this study was to investigate the arm morbidity after sentinel lymph node biopsy or axillary lymph node dissection. Methods: This is a prospective cohort study of women who underwent surgical treatment of breast cancer at a single institution. Arm and shoulder morbidity were measured before, 1 and 6 months after the operation. Analyses were performed to compare morbidity between sentinel lymph node biopsy (SLND) and axillary lymph node dissection (ALND). This study obtained approval from the National Cancer Institute research and ethics committee. Results: Were included 203 patients and, during the study, 6 were excluded and there was 23 losses of follow-up. The average age of women was 58 years (DP=13). SLND was made in 31,6% with an average of 3 lymph nodes removed. Among those submitted to ALND, the average lymph node removed was 18 (p<0.0001). After 45 days of surgery, the incidence of arm morbidity was: 23% of shoulder restriction (ALND 22%, SLND 1%, p<0.001); 28% of axillar web syndrome (ALND 24%, SLND 4%, p<0.001); 38% of seroma (ALND 32%, SLND 6%, p<0.001); 5% of arm edema (ALND 4%, SLND 1%, p<0.001). In the final evaluation occurred 6 months after the surgery, it was observed de following incidence: 4% of shoulder restriction (ALND 3%, SLND 1%, p=0.371); 18% of arm pain (ALND 12%, SLND 6%, p=0.460); 18% of axillar web syndrome (ALND 16%, SLND 2%, p<0.002); 5% of arm edema (ALND 4%, SLND 1%, p=0.417). Conclusions: After 45 days of surgery, patients with SLND has less arm morbidity compared with patients submitted to ALND. After 6 months, it was observed less incidence of arm symptoms and only axillary web syndrome were more incident in patients with axillary dissection.
Evaluation of circulating biomarkers of bone metastases in early-stage breast cancer.
Authors: Dean-Colomb Windy Marie , Hess Kenneth R. , Young Elliana J. , Gornet Terrie , Handy Beverly Carol , Moulder Stacy L. , Ibrahim Nuhad K. , Pusztai Lajos , Booser Daniel J. , Valero Vicente , Hortobagyi Gabriel N. , Esteva Francisco J.
Published: February 2017

10

Background: Bone is the preferred site for metastases of breast cancer, affecting approximately 70% of women with advanced disease. N-terminal of procollagen type 1 (P1NP), c-terminal peptide crosslinks (CTX), osteocalcin (OC), and interleukin-6 (IL-6) are markers of bone turnover that may have clinical utility as predictors of breast cancer recurrence in the bone. Methods: Serum was collected prior to treatment from 162 patients with stage I-III and 83 patients with stage IV breast cancer from 09/2001 to 12/2008. Serum levels of P1NP, CTX, OC, and IL-6 were determined using the Roche’s Elecsys 2010 automated immunoassay system. Correlations of biomarker levels with stage and with time to bone metastases development were assessed with Cox proportional hazards regression analysis and the Kaplan-Meier method. Results: Patients with stage IV at the time of diagnosis had higher levels of serum P1NP (p<0.0001) and CTX (p<0.0001) compared with stage I-III patients. Fifty-five of the 162 patients with stage I-III breast cancer subsequently developed metastatic disease. Baseline P1NP level ≥ 75 ng/mL predicted time to development of bone metastases in patients with stage I-III breast cancer (hazard ratio = 2.7, 95% confidence intervals = (1.2, 6.0), p = 0.031), even after adjusting for clinical factors (p = 0.019). Baseline P1NP level also correlated with OS when it was modeled as a quadratic polynomial (on the log scale) with patients with P1NP level ≥ 75 ng/mL having a worse overall survival (hazard ratio = 3.3, 95% confidence intervals = (1.5, 7.3),p = 0.0036. Conclusions: In patients with stage I-III breast cancer, serum P1NP levels >75 ng/mL prior to definitive treatment correlated with shorter time to development of bone metastases and shorter overall survival rate. Baseline serum levels of IL-6, CTX and osteocalcin did not correlate with development of bone metastases.
Funding of biomarker, imaging, quality-of-life (QOL), and cost-effectiveness analysis (CEA) studies by NCI.
Authors: Petryshyn Ray A. , Seidel Geoffrey David , Prindiville Sheila Ann
Published: February 2017

104

Background: NCI’s purpose for the Biomarker, Imaging, and QOL Studies Funding Program (BIQSFP) is to ensure that the most important, scientifically meritorious biomarker, imaging, QOL, and/or CEA studies can be initiated in a timely manner in association with NCI clinical trials. BIQSFP studies are embedded in selected large, randomized phase II treatment trial concepts with a control arm and an integral study(ies), along with integral and/or integrated studies associated with phase III treatment trials, cancer prevention trials, and primary symptom management trials. Methods: BIQSFP provides opportunities to enhance clinical outcomes by validating targets, reducing morbidity, predicting treatment effectiveness, identifying populations that may better benefit from treatment, improving clinical trial accrual and retention, and modifying standards of care. BIQSFP applications are accepted from NCI Cooperative Groups and Community Clinical Oncology Programs. Integral components must be performed in order for the trial to proceed. Integral studies have the highest funding priority. Integrated components are clearly identified as part of the clinical trial from the beginning, are intended to identify or validate (in the patient population of interest) assays/tests/QOL tools that are planned for use in future trials, are performed in real time, and include complete plans for specimen collection, laboratory measurements, and statistical analysis. Integrated studies in general should not be exploratory but rather should be designed to test a hypothesis, not simply to generate hypotheses. Results: Since 2009, 36 BIQSFP funding applications have been reviewed with most evaluations via NCI’s Scientific Steering Committees (http://ccct.cancer.gov/). Twenty studies have been approved for BIQSFP funding. Conclusions: BIQSFP information presented in the poster includes scope of activity, process for application and evaluation, and funded projects (http://biqsfp.cancer.gov/). Funded by NCI Contract No. HHSN261200800001E.
Cell-free microRNA expression profiles in malignant effusion associated with patient survival in non-small cell lung cancer.
Authors: Wang Tingting , Liu Baorui , Hou Yayi
Published: February 2017

13

Background: MicroRNAs (miRNAs) expression is altered in cancer cells, and miRNAs could serve as diagnostic and prognostic biomarker for cancer patients. This study was designed to analyze circulating miRNAs expression in the malignant pleural effusion (MPE) and their association with patient survival in non-small cell lung cancer (NSCLC). Methods: Pleural effusion from 184 patients with NSCLC and MPE were collected. MiRNA microarray and bioinformatics interpretation were used to evaluate miRNA expression profiles in 10 NSCLC patients with different survival prognosis. Associations were validated in 184 patients (randomly classified into training and validation set with equal number in each group) using quantitative RT-PCR. Risk scores were formulated based on the expression signature of miRNAs. Clinical data, such as patient survival, were collected for correlation analysis. Results: Thirty-three miRNAs were found to be altered more than two-fold by microarray in malignant effusions between longer-survival and shorter-survival groups, and levels of five miRNAs (miRNA-93, miRNA-100, miRNA-134, miRNA-151, and miRNA-345) were significantly associated with overall survival. High expression of miR-100 and low expression of miRNA-93, miRNA-134, miRNA-151, and miRNA-345 were associated with poor survival in both the training and validation cohort. Patients with high risk scores had overall poor survival compared to the patients with low risk scores. Risk score was an independent predictor of patient survival. Conclusions: Expression patterns of miRNAs are systematically altered in MPE of patient with NSCLC. The five miRNA signature from the effusion may serve as a predictor for the overall survival of patients with lung cancers.
MicroRNA in biofluids—Robust biomarkers for disease, toxicology, or injury studies: The case of minimally invasive colorectal cancer detection.
Authors: Mouritzen Peter , Nielsen Søren Jensby , Wrang Teilum Maria , Blondal Thorarinn , Andreasen Ditte , Tolstrup Niels
Published: February 2017

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Background: MicroRNAs function as post-transcriptional regulators of gene expression. Their high relative stability in common clinical source materials (FFPE blocks, plasma, serum, urine, saliva, etc.) and the ability of microRNA expression profiles to accurately classify discrete tissue types and specific disease states have positioned microRNAs as promising new biomarkers for diagnostic application. Furthermore microRNAs have been shown to be rapidly released from tissues into the circulation with the development of pathology. Methods: Thousands of biofluid samples were profiled including blood derived plasma/serum and urine using a genome-wide LNA-based microRNA qPCR platform, which has unparalleled sensitivity and robustness even in biofluids with extremely low microRNA levels. Only a single RT reaction is required to conduct full miRNome profiling thereby facilitating high-throughput profiling without the need for pre-amplification. Results: Normal reference ranges for circulating microRNAs were determined in several biofluids, allowing development of qPCR arrays containing only relevant microRNA subsets present in various biofluids together with tissue specific microRNA markers. Procedures were developed to control pre-analytical variables, for quality checking and qualifying biofluid samples in particular serum and plasma but also urine and other biofluids. An extensive QC system was implemented in order to secure technical excellence and reveal any unwanted bias in the dataset. We currently screen and validate microRNAs biomarkers for cancer with the aim of developing minimal invasive tests to be applied in early detection population screens. Conclusions: The qPCR panels support development of robust biomarkers in disease, toxicology, and injury studies. We will demonstrate how panels may be quickly and robustly applied in biomarker discovery/validation projects using the specific case early detection of colorectal cancer in blood. Close attention is required on pre-analytical parameters. Hemolysis and cellular contamination affect miRNA profiles in biofluids and control is required.
Role of M402, a novel heparan sulfate mimetic, in pancreatic cancer cell invasion and metastasis: Inhibition of the Sonic Hedgehog pathway and heparanase activity.
Authors: Galcheva-Gargova Zoya , Chu Chia Lin , Long Alison , Duffner Jay , Holte Kimberly , Schultes Birgit Corinna
Published: February 2017

25

Background: M402 is a novel heparin sulfate mimetic that binds to multiples growth factors, adhesion molecules, and cytokines to inhibit tumor angiogenesis, progression, and metastasis in nonclinical studies. We investigated if M402 could modulate tumor-stroma interactions in pancreatic cancer by inhibiting the Sonic Hedgehog (Shh) pathway as well as inhibit the activity of the extracellular matrix degrading enzyme, heparanase. Methods: Surface plasmon resonance (SPR) was used for analysis of M402 binding to Shh in vitro. A cell based Gli-1 reporter assay was implemented to assess the effect of M402 on Shh signaling. Immunohistochemistry and RT-qPCR were utilized to investigate M402’s effect on Shh activity in an orthotopic Capan-2 model in nude mice. The effect of M402 on heparanase activity in vitro and on Capan-2 tumor samples isolated from treated and untreated mice was measured using an HTRF-FRET assay. Results: There was specific binding of M402 to Shh in vitro. Additionally, Shh signaling was inhibited in the presence of M402. Immunohistochemistry and RT-qPCR of Capan-2 tumor samples from animals treated with M402 also demonstrated reduction of Shh signaling via Gli, its targeted transcription factor. The degree of inhibition of heparanase activity, as measured in the HTRF assay, was affected by the size, structure, and sulfation pattern of the different heparin sulfate mimetics evaluated. M402 was the most potent inhibitor of heparanse activity in vitro from all compounds tested. In addition, treatment with M402 inhibited heparanase activity in the pancreatic tumor lysates in a dose-dependent manner. Conclusions: M402 was shown in nonclinical studies to modulate tumor-stroma interactions involved in the metastatic, invasive, and desmoplastic pathways by simultaneously inhibiting two distinct pathways: Shh signaling and the activity of heparanase. M402 regulates a variety of polysaccharide-based binding proteins, which provides a rationale for the clinical investigation of M402 in a range of cancers.
A nanofluidic immunoassay system to develop proteomic responsive biomarkers in non-small cell lung cancer.
Authors: Chen Jin-Qiu , Lee Jih-hsiang , Herrmann Michelle , Wang Yisong , Park Kang-seo , Heldman Madeleine , Goldsmith Paul , Giaccone Giuseppe
Published: February 2017

27

Background: Molecular targeted therapy is widely used to treat non-small cell lung cancer (NSCLC). However, errors in predicting response to targeted therapies are 20-30%, based on sequencing or FISH, and patient specimen are at times not sufficient for conventional protein technologies. Developing clinically feasible proteomic biomarkers may be valuable to identify patients who may benefit from targeted therapy. Methods: NanoPro technology (ProteinSimple), is a capillary-based isoelectric-focusing (IEF) immunoassay system, which detects and quantifies multiple protein phosphorylation isoforms that are not readily assessed by traditional immunoassays. The platform only uses nanograms of protein for analysis. Results: We studied dynamic phosphoprotein activities in NSCLC cells (PC9, H827, H4006, H2122 and H322) treated with EGFR or/and MEK inhibitors. In MEK inhibitor (PD325901) treated cells, NanoPro showed that the drug efficiently inhibited Erk phosphorylation, and also revealed a complex MEK response profile which was not detectable by Western blotting, demonstrating its on-target effect. NanoPro also identified a MEK2 signature that associated with erlotinib sensitivity and distinguished erlotinib sensitive from resistant cells. This MEK2 signature was further confirmed in acquired resistant cells to erlotinib (H827R, H4006R). In a H827 xenograft study, NanoPro was able to detect and distinguish human Erk1 isoform from mouse Erk1 based on their pI difference, and clearly demonstrated that erlotinib effectively inhibited Erk phosphorylation in human xenograft cancer cells but not in surrounding mouse stromal cells. We further demonstrated that Nanopro could monitor erlotinib and AZD2644 response in a KrasG12C NSCLC patient (NCT01229150) by profiling 18 signaling molecules with as little as 4ug tumor material. Conclusions: NanoPro provides a valuable platform to monitor signaling response to targeted therapy. Nanopro assesses protein phosphorylation both qualitatively and quantitatively using small sample size, thus creates new opportunities for pharmacodynamic biomarker assessment in clinical studies.
The analytic validation of prostate-specific mRNA detection in whole blood by RT-PCR as a prognostic biomarker for patients with castration-resistant prostate cancer (CRPC).
Authors: Danila Daniel Costin , Anand Aseem , Heller Glenn , Wan Mingliang , Zehnder Matthew , Khanin Raya , Schultz Nikolaus , Fleisher Martin , Lilja Hans , Scher Howard I.
Published: February 2017

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Background: To estimate the association between molecular biomarkers and outcomes, robust assays are needed before clinical qualification. Although tumor specific transcripts detected in blood by PCR have been associated with outcome, an analytically validated platform enabling detection of CTC-associated transcripts in clinical settings remains to be identified. Here we explore the efficacy of detecting a panel of prostate specific transcripts in CRPC. Methods: Blood was collected from 97 pts with progressive CRPC in PAXgene tubes (2.5 ml) for total RNA extraction using PAXgene Blood RNA Kit. Five genes expressed in prostate but not in nucleated blood cells were analyzed by RT-PCR. We used Fluidigm Dynamic Array platform to analytically validate RT-PCR assays for KLK3, KLK2, HOXB13, GHRL2, and FOXA1 transcripts. Each PCR-reaction was run in 6 replicates, detection thresholds for each gene were chosen by ROC analysis of an independent set of 56 CRPC patients versus 51 healthy volunteers, and results were reported as transcripts present or absent. CellSearch reported CTC number/7.5 ml of blood drawn into CellSave tube. Results: Prostate specific transcripts (≥ 2 genes) were detected in 52/97 (54%, 95% CI 43-64%) of patients with progressive CRPC studied with a median survival time of 17 months (95% CI: 13.8, 23.5). 40/45 CRPC-patients with ≥ 5 CTC and 15/52 CRPC patients with < 5 CTC had transcripts present in blood. Similar to CTC enumeration, transcript detection predicted overall survival in proportional hazards models that included LDH dichotomized at above and below 300. The predictive accuracy (CPE) of PCR detection + LDH was 0.785 (SE 0.036), comparable to CTC-enumeration + LDH (0.796, SE 0.035). Conclusions: Detecting prostate specific mRNA in whole blood using validated RT-PCR assays, applicable to larger CRPC cohorts, provides prognostic biomarkers that predict overall survival. The clinical utility in monitoring treatment will be prospectively explored. [Table: see text]