bluuebunny/crossref_metadata_2025 huggingface dataset:
Should palpable DCIS be treated as IDC? A retrospective audit.
Authors: Nair N. S. , Pandey N. , Vanmali V. , Shet T. , Hawaldar R. , Parmar V. , Badwe R. A.
Published: February 2017

146

Background: Ductal carcinoma in situ (DCIS) identified by screening mammography accounts for 20% of breast cancer diagnoses, and microinvasion (DCIS-M) is found in 5%-10%. There are no defined treatment guidelines for palpable DCIS or DCIS-M. In the developing world wherein screening mammography is controversial due to a predominantly premenopausal population, most women with DCIS present with a palpable lump in the breast. The objective of this study was to evaluate whether disease in these patients with palpable DCIS have been treated differently from screen detected DCIS.

Methods: Annually we register 3,000 new cases of breast cancer of which DCIS constitute a small fraction. Over a period of 12 years (1998-2010) we registered 71 cases of DCIS for treatment. A retrospective analysis of these was performed.

Results: Of the 71 patients reviewed, 35 (49.2%) had foci of microinvasion. The median age of presentation was 49 years and mean tumor size was 2.3 cm; all presented with palpable breast lumps. Of the 36 women with DCIS alone Tsize was > 2 cm in 26 (72.2%), 14 (38.9%) had presence of comedo necrosis and 1 (2.7%) had positive lymph nodes on histopathology. Adjuvant chemotherapy was given to 4 (11.11%). Of the 35 women with DCIS-M Tsize was > 2 cm in 23 (66%), 10 (29%) had comedo necrosis (compared to 38.9% in pure DCIS p=0.45), 3 (8.5%) had positive lymph nodes, and 17 (48.6%) received chemotherapy. We compared this data to that of women treated for invasive ductal carcinoma with pTsize <2cm, at a median follow-up of 60 months, DFS for the women with DCIS was 82% (95% CI 0. 67- 0.98), for DCIS-M was 78% (95% CI 0. 59 -0.98), and that for IDC < 2cm was 83% (95% CI 0.70-0.95).

Conclusions: DCIS presenting in these palpable lesions poses a clinical dilemma for the use of adjuvant therapy. Over 49.2% of the palpable DCIS showed evidence of microinvasion. We thus need to consider the role of adjuvant chemotherapy when treating women with palpable DCIS.
Treatment patterns of breast cancer patients in Georgia Medicaid: Are patterns different for BCCPTA women?
Authors: Adams E. K. , Gabram S. G. A. , Chien L.
Published: February 2017

153

Background: The Breast and Cervical Cancer Prevention and Treatment Act (BCCPTA) of 2000 allowed states to cover women diagnosed with breast, cervical, or pre-cancerous cervical conditions under Medicaid upon diagnosis and while “under treatment”. We investigate breast cancer treatment of patients enrolled under BCCPTA in Georgia.

Methods: Georgia Comprehensive Cancer Registry were linked to Medicaid enrollment files to identify 2,048 enrollees with a primary cancer of breast, of whom 1,046 were BCCPTA, 674 were disabled, and 328 were in ‘other’ Medicaid eligibility groups. Logistic regressions were used to estimate the odds of receiving: (1) lumpectomy, (2) mastectomy, and (3) other surgery in addition to (4) any drug regimen (hormonal or chemotherapy) and (5) radiation.

Results: Using descriptive data and after controlling for covariates, BCCPTA women are more likely to receive any treatment (OR = 4.71, [CI] = 2.48, 8.96), any drug regimen (OR = 3.58, [CI] =2.32, 5.51), any radiation (OR = 1.61, [CI] = 1.15, 2.24), and any ‘definitive’ surgery (OR = 2.52, [CI] = 1.74, 3.66) than the ‘other’ eligibility group. There are no significant differences in the receipt of a lumpectomy versus a mastectomy by eligibility group but BCCPTA women are more likely to receive more adjuvant follow-up.

Conclusions: The BCCPTA program in Georgia appears to create a quicker pathway for previously low-income uninsured women with breast cancer to access services and in turn, receive more treatment than women enrolled in more traditional, Medicaid eligibility groups. Yet, the overall rate of adjuvant therapy, whether radiation or hormonal/chemotherapy, appears to fall short of national criteria.

[Table: see text]
The effect of molecular subtype on survival in a racially diverse cohort of patients with high-risk breast cancer receiving trimodality therapy.
Authors: Wright J. L. , Takita C. , Panoff J. E. , Reis I. M. , Zhao W. , Sujoy V. , Fernandez C. G. , Jorda M. , Franceschi D. , Hurley J.
Published: February 2017

156

Background: To understand the origins of racial disparities in breast cancer outcomes, the relative importance of race must be examined in the context of molecular subtype. We assessed racial differences in progression-free survival (PFS) and overall survival (OS) in relation to subtype in a cohort of uniformly treated stage II-III breast cancer patients.

Methods: We reviewed records of 582 consecutive patients receiving post-mastectomy radiation (PMRT) between 1/1999 and 12/2009 and evaluated the effect of demographic, tumor, and treatment characteristics on PFS and OS.

Results: Median follow-up 44.7 months. Patients: 24% black, 76% white, 55% pre/peri-menopausal. Disease: stage II 30%, stage III 70%. Treatment: all had mastectomy and PMRT; 98% had chemotherapy. All ER+ patients received endocrine therapy. Black and non-black patients were similar in age, menopause status, stage, and completion of trimodality therapy. Black patients were more likely to be ER- (56% vs 38%, p=0.0001), PR- (69% vs 54%, p=0.002), and triple negative (TN) (46% vs 24%, p<.0001). Among ER+, there were no differences in menopause or PR status by race. Black patients had worse PFS (60.6% vs 78.3%, p=.001) and OS (72.8% vs 87.7%, p<.0001). There was no racial difference in PFS (p=0.229 and 0.273 respectively) or OS (p=0.113 and 0.097 respectively) among ER- or TN. Among ER+, black patients had worse PFS (55% vs 81%, p<.001) and OS (73% vs 91%, p<.0001). The difference in PFS was seen in the ER+/PR+/HER2- (“luminal A”) subgroup (p=.002) but not ER+/PR-/HER2- (“luminal B”) (p=0.129), and in the post-menopausal ER+/HER2- subgroup (p=.004) but not pre/perimenopausal ER+/HER2- (p=.150). On multivariate analysis, racial differences in PFS (p=.055) and OS (p=.052) were maintained in the luminal A postmenopausal subgroup.

Conclusions: In a cohort of breast cancer patients black women had worse survival. This disparity was driven by (1) a higher proportion of ER- and TN tumors in the black women and (2) worse outcome of similarly treated post-menopausal black women with luminal A breast cancer. The efficacy of various types of endocrine therapy must be examined in the setting of racial diversity.
Identifying women at increased risk of breast cancer: Can we use genotyping at low penetrance loci?
Authors: Merrick C. , Dunlop J. , Baker L. , Gellatly E. , Martin A. , Quinlan P. , Tavendale R. , Thompson A. M. , Palmer C. , Reis M. , Berg J. N.
Published: February 2017

162

Background: Most inherited predisposition to breast cancer is attributable to low penetrance susceptibility loci, a number of which have been identified through genome-wide association studies. Although individually each locus has a small effect, combining data from multiple loci would be expected to provide more risk information. We investigated the size of risk determination that can be achieved using genotyping at 18 loci. We then calculated its effect when combined with risk estimated from family history alone in terms of management under UK guidelines, where a woman who has a 10 year risk of 3% or greater requires additional breast screening from a younger age.

Methods: Genotyping for 18 loci was carried out in 253 women at increased risk of breast cancer due to a positive family history and 118 matched controls. The relative risks conferred by genotype at the 18 loci were combined under a log-additive model and transformed into a log-polygenic risk. The BOADICEA risk estimation tool was used to calculate breast cancer risk due to family history.

Results: Both the increased risk and control groups demonstrated a normal distribution of log-polygenic risk with similar variance. There was a significantly higher mean in the increased risk compared to the control group (mean = 0.1313 and 0.0874 respectively, p = 0.007). No significant correlation was found between polygenic risk calculated from genotype data and the family history risk estimated using BOADICEA. When polygenic risk was combined with family history risk there was significant reclassification of risk for those with a family history. 36.76% moved into a higher risk category while 3.68% moved into a lower risk category.

Conclusions: Our data suggests that genotyping will be clinically relevant for estimating breast cancer risk. Individuals with a family history overall have a higher genotype risk than the population. The lack of correlation of genotype risk with BOADICEA risk suggests that the two risk estimates can be considered independently. By combining genotype with family history data, we demonstrated a significant reclassification of risk for individuals with a family history, with better identification of women in this group requiring intervention.
Treatment-related changes in neurobehavioral symptoms.
Authors: Patel S. K. , Beier E. , Davtyan A. , Meier A. , Palomares M. R. , Hurria A. , Bhatia S.
Published: February 2017

167

Background: Neurobehavioral outcomes, such as fatigue and neurocognitive dysfunction, are disabling side effects in a subgroup of breast cancer (BC) patients. Longitudinal studies with appropriate controls to dissociate treatment-related effects from those experienced by healthy post-menopausal women are sparse, and virtually all define “pre-treatment” baseline as prior to adjuvant therapy, but following surgery. Given the phenomenon of “postoperative cognitive dysfunction” reported in older patients undergoing major surgery, we are evaluating treatment-related impact using pre-surgery assessment as the baseline.

Methods: Eligible post-menopausal BC patients are assessed prior to any local or systemic treatment and one month after completion of treatment (surgery, radiation and/or chemotherapy). Healthy controls (HC) are age-matched 1:2-3 and tested at similar time intervals. Currently 130 BC and 60 HC are enrolled; results for 80 BC and 30 HC who have reached Time 2 are available (Mean time between assessments = 143 days, SD = 93).

Results: Interim analyses using repeated measures ANOVA, controlling for age and education differences, show that the BC group declined in verbal memory functioning post-treatment relative to baseline, while the HC group improved due to practice effects (F(1, 102) = 3.43, p = .061). A similar interaction effect is observed for executive functioning, where the BC group failed to benefit from practice effects to the same degree as did HC (F(1, 102) = 6.04, p = .016). Anxiety but not depression was significantly elevated at baseline and decreased post treatment in BC patients treated with and without chemotherapy (F (1, 102) = 6.85, p = .010). Fatigue did not significantly change for the BC group; however, it was significantly higher than HC at baseline (t =2.77, p = .01) and remained high at the post-treatment measurement.

Conclusions: Significant declines in neurocognitive functioning soon after completion of BC treatment were observed compared to healthy post-menopausal women. This observation did not appear to be due to mood disturbance, as anxiety and depression decreased following treatment. Our data also suggest that fatigue is present even prior to any cancer treatment.
Factors associated with mortality after breast cancer metastasis.
Authors: Jung S. Y. , Rosenzweig M. Q. , Sereika S. M. , Linkov F. , Brufsky A. , Weissfeld J. L.
Published: February 2017

174

Background: It is generally accepted that patients with breast cancer metastases have poor survival. Metastatic breast cancer patients can be considered a heterogeneous population with a varied clinical course, which underscores the need for accurate prediction of survival based on prognostic factors. The purpose of the present study was to identify factors related to survival in breast cancer patients after diagnosis with metastatic disease.

Methods: A total of 557 patients with breast cancer metastasis diagnosis seen at one large urban practice have been followed up between January 1, 1999 and June 30, 2008. Demographic, tumor characteristics, clinical factors as predictors of survival were analyzed using Cox regression model.

Results: The median survival length was 40 months (range 1-114 months) with 269 (48.3%) alive and 288 (51.7%) dead. This study demonstrated that hypertension, estrogen receptor (ER) and/or progesterone receptor (PR) status, human epidermal growth factor receptor-2 (HER2) status, number of metastatic sites, and body mass index (BMI) at diagnosis with metastatic breast cancer were the most relevant prognostic factors for survival after metastasis.

Conclusions: Findings of this study may form a foundation for the corpus of knowledge explaining the outcome differences in treatment of patients with metastatic breast cancer, potentially helping to create tailored counseling and personalized treatment approaches for this vulnerable group.

[Table: see text]
Alcohol consumption: The single most important behavioral risk factor in breast cancer?
Authors: Lautenschlaeger T. , Dedousi-Huebner V. , Chakravarti A.
Published: February 2017

176

Background: Breast cancer research has identified certain risk factors over the years, which influence a woman's chance of getting the disease. While factors such as personal history of breast abnormalities, age and the occurrence of breast cancer among first-degree relatives have been identified as estimation factors for breast cancer risk, other factors are less conclusive. Increasingly, obesity is being analyzed as a significant risk factor for many cancers and, after tobacco use, may be one of the most modifiable behavioral cancer risk factors. Interestingly when comparing the incidence rate of breast cancer to the obesity rate nationwide many states show a disparity in the two. It may be that other behavioral risk factors are of greater importance.

Methods: The US States Mississippi and West Virginia display the highest rates of obesity (over 29.4% of their population display a BMI over 30.0) and the lowest rates in breast cancer incidence nationwide (under 113.9 and 113.5 people per 100.00. residents are diagnosed with cancer each year respectively). We set out to look at various behavioral risk factors to possibly detect an underlying pattern for breast cancer. Using selected metropolitan/micropolitan area risk trend data from the Behavioral Risk Factor Surveillance System from the CDC, we compared median percentages of the following risk factors: health status, exercise, diabetes, flu vaccination, current smoking, binge drinking and obesity.

Results: Both states displayed higher percentages in all risk factors compared to the national average except for one in which they were below the national average: binge drinking. Rhode Island and Connecticut, the two states with the highest incidence rates in breast cancer, in turn displayed slightly higher rates of binge drinking compared to the national average.

Conclusions: It appears that binge drinking might weigh more than other behavioral factors in terms of risk associated to breast cancer. Future research will need to analyze the interplay and patterns of the various risk factors as well as evaluate the association of mammographic density and alcohol drinking to further investigate the role of alcohol and binge drinking in the development of breast cancer.
May axillary dissection be avoided after micro metastases in sentinel lymph node analyzed by OSNA method?
Authors: Velasco A. , Morales S. , Panades M. J. , Gonzalez S. , Vilardell F. , Canosa C. , Iglesias E.
Published: February 2017

18

Background: The study of the sentinel node biopsy is a common method to assess axillary involvement before surgical resection. The OSNA assay based on reverse transcriptase loop mediated amplification (RT-LAMP) and quantification of cytokeratin 19 (CK19) mRNA allows a rapid intra-operative detection of the metastases in the sentinel lymph node in breast cancer patients. Pathologists considered micro metastases when the size of the node involvement was between 0.2 and 2 mm and the OSNA method assess micro metastases when the copy number of CK19 is between 250 and 5000.

Methods: From a total of 341 patients in which sentinel node had been analyzed, we studied a series of 32 patients whose sentinel nodes had micro metastases assessed by OSNA and who underwent subsequent axillary dissection. Median breast tumour size was 1.6 cm, 10 patients (31%) had less than 1 cm in size and only 6 patients (19%) had >2 cm. 78% of patients shown positive oestrogen receptor and 14 patients (44%) had low Ki67 (<14%). The CK19 mRNA was quantified in all patients (32) resulting in a median value of 540 (210-4800).

Results: The median value of the nodes removed by axillary dissection was 14 (9-19). We found tumor invasion in none of them by histopathological conventional study.

Conclusions: Since we have found no axillary involvement when the sentinel node have micro metastases analyzed by the OSNA method it seems that quantitative measure of CK19 by OSNA may be a useful procedure in order to avoid axillary dissection, although it would be necessary to perform larger studies to demonstrate this effect.
Predictors and prevalence of germ-line BRCA mutations in high-risk patients among different ethnicities.
Authors: Riaz S. S. , Ahsan S. , Bloom R. E.
Published: February 2017

190

Background: Germ-line mutations in tumor suppressor genes, BRCA1 and BRCA2, confer high risks of breast and ovarian cancer in affected individuals. Genetic testing for these pathogenic mutations has potentially important health implications for judicious counseling and screening of high risk individuals.

Methods: A retrospective analysis was conducted of all the patients seen at our oncology/genetics clinic from 2000 to 2010. A population of over 500 patients was identified, out of whom 310 subjects underwent risk factor assessment. BRCA testing was performed on 231 of these subjects whereas 79 subjects were not tested secondary to lack of insurance/follow up, or patient/physician preference. Various ethnic groups were identified which included 138 Caucasian, 41 African American, 28 Ashkenazi Jewish, 4 Middle Eastern, 2 Asian and 2 Hispanic subjects. The ethnicity of 16 subjects was unknown secondary to lack of documentation.

Results: BRCA mutation testing was completed on 231 subjects out of whom 34 were identified as carriers, comprising 31 female and 3 male individuals. 25 subjects carried BRCA1 and 11 subjects carried BRCA2 mutations, whereas 2 subjects carried both mutations simultaneously. In terms of racial prevalence, the population screened was divided into 4 main groups. Using the Maximum Likelihood Ratio Chi-Square Test, a p-value of 0.96 (p=0.9633) was obtained which indicated that the proportion of mutation did not differ for the races among the population screened.

Conclusions: The estimated ethnicity prevalence of BRCA mutations was found to be the highest in African American followed by Caucasian and Ashkenazi Jewish subjects in the population screened at our facility. Overall, BRCA mutations are more common in the Jewish population on which most of the research has been focused. Our study is one of the few to indicate the possibility of high prevalence of mutations in the under-studied and less reported high risk kindred, that is, the African Americans.

[Table: see text]
In vitro assessment of the inflammatory breast cancer cell line SUM 149: Discovery of two single nucleotide polymorphisms in the RNase L gene.
Authors: Nokes B. T. , Cunliffe H. , Brown A. R. , Sheth G. R. , Stopeck A. , Livingston R. B. , Futscher B. W. , Lang J. E.
Published: February 2017

196

Background: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer, accounting for 5% of breast cancers diagnosed annually in the United States. Understanding the distinct biology of IBC could help provide novel treatment targets. We sought to evaluate whether or not the IBC cell lines SUM 149 and SUM 190 demonstrated evidence of viral infection.

Methods: We performed single nucleotide polymorphism (SNP) genotyping for 2 variants of the ribonuclease (RNase) L gene that have been correlated with the risk of prostate cancer due to a possible viral etiology. We also performed proliferation assays; developed dose response curves to assess the treatment effect of interferon-alpha (IFN-a); and assayed for evidence of the putative human mammary tumor virus (HMTV, which has been implicated but not definitively associated with IBC,) in the DNA and RNA of SUM 149 cells.

Results: According to our allelic discrimination SNP assay, 2/2 IBC cell lines were homozygous for the 462 and 541 variants, whereas 0/10 non-IBC cell lines were homozygous positive for the 462 variant (p = 0.015) and 2/10 non-IBC cell lines contained homozygous alleles for the 541 variant (p = 0.52). We also found a dose and time-dependent decrease in the proliferation of SUM 149 IBC cells treated with IFN-a. In contrast, non-IBC cell lines did not show a dose-response decrease in cell proliferation. Our reverse transcriptase polymerase chain reaction (RT-PCR) and Southern blot analysis for the env/LTR and late LTR sequences of the putative HMTV revealed no evidence of the putative viral genome.

Conclusions: We discovered 2 SNPs, in the 462 and 541 variants of the RNase L gene, that were homozygously mutated in IBC cell lines but the 462 variant was absent in non-IBC lines. Our discovery of these mutated SNPs present in IBC cell lines suggests a possible genetic risk factor for IBC. In our study, the IBC cell line SUM 149 demonstrated a direct and specific response to treatment with IFN-a, an antiviral agent. We noted no evidence of HMTV infection in that cell line. Further studies of the prevalence and significance of the RNase L 462 and 541 variants in human IBC tissue specimens are warranted to validate our in vitro findings.
The effects of clinical trials on improving breast cancer care at a single institution.
Authors: Dooley W. C. , Parker J. , Bong J.
Published: February 2017

198

Background: We reported in 2011 at the Society of Surgical Oncology a 19 year retrospective at a single academic institution which identified practice differences between surgical oncologists and general surgeons which were associated with a significant survival advantage. Clinical trial participation was much higher amongst patients treated by a surgical oncologist.

Methods: This is an IRB approved, retrospective review of all breast cancer patients receiving primary treatment at a single institution from 1/1/2001 to 12/31/2008. Details of pathology, surgical therapy, chemotherapy, hormonal therapy and radiation therapy were compared between patients participating in clinical trials and those not participating. The specific trials were segregated as to type (tissue banking, therapeutic, prevention, etc.) to understand differential effects if any between type of trial participation.

Results: During the time period, there were 1220 patients who received primary breast cancer treatment at this institution. The mean age was 55.6 and mean follow-up >40 months. Stage distribution was stage 0 - 16.8%, Stage 1 - 26.6%, Stage 2 - 33.1%, Stage 3 - 15.9%, and Stage 4 - 6.1%. Patients participating in any clinical trial numbered 468 and 752 participated in no clinical trials. Overall survival (clinical trial 98.8% vs. not in clinical trial 75.7%; p<0.0001). Overall the use of breast conservation was more likely in clinical trial participants (54.3% vs. 44.4%; p<0.0001). The completion of chemotherapy was more likely in clinical trial participants (52.4% vs. 49.5%; p=0.02).The successful completion of systemic therapies (chemo and hormonal) was more likely also (71.4% vs. 64.0%; p=0.009). The type of trial (tissue banking vs. therapeutic) had no effect on improved outcomes. Overall the best predictor of better outcomes was to be treated by a high volume clinical trial enrolling physician.

Conclusions: High volume clinical trial enrollment is associated with the best overall treatment outcomes in breast cancer whether trials are directly related to therapeutic changes or not. Each individual in the breast center treating team can have dramatic effect on outcomes by improving their clinical trial enrollment and participation.
Prediction of late recurrences by breast cancer index in the NCIC CTG MA.17 cohort.
Authors: Sgroi D. , Carney E. , Richardson E. , Steffel L. , Binns S. N. , Finkelstein D. M. , Shepherd L. E. , Kesty N. C. , Schnabel C. , Erlander M. G. , Ingle J. N. , Porter P. , Paik S. , Muss H. B. , Pritchard K. I. , Tu D. , Goss P. E.
Published: February 2017

2

Background: The MA.17 trial demonstrated that extended adjuvant endocrine therapy with letrozole after 5-y of tamoxifen markedly reduced the risk of recurrence in women with ER+ early stage breast cancer. This trial provides an opportunity to assess the ability of biomarkers to predict late recurrences in ER+ breast cancer. The Breast Cancer Index (BCI), a continuous risk index based on the combination of HOXB13:IL17BR (H:I) and the molecular grade index (MGI), estimates the individual risk of recurrence in ER+ breast cancer patients. In this study, the prognostic utility of BCI to predict late recurrences was examined.

Methods: FFPE tumor blocks were collected from patients who experienced a breast cancer recurrence up to unblinding of MA.17. Controls were matched 2:1 for age, tumor size, nodal status and prior chemotherapy, and were disease free for longer than cases. All cases were reviewed for standard histopathology and evaluated using the real-time RT-PCR BCI assay.

Results: Patient characteristics for the case-control study were similar to that from the overall study. Characteristics for cases (N=83) and controls (N=166) were not significantly different except for treatment. A higher percentage of controls compared to cases tended to be categorized as low risk by BCI (58% vs 43%), while a lower percentage of controls than cases tended to be categorized as high risk by BCI (34% vs 24%). In univariate analysis, treatment, BCI, H:I and HOXB13, but not tumor grade or MGI, were significant predictors of late recurrence. After adjusting for standard variables (age, tumor grade and treatment), BCI (OR 2.37; P=0.03), H:I (OR 2.55; P=0.04) and HOXB13 (OR 1.35; P=0.02) remained significant predictors of recurrence. HOXB13 expression at diagnosis predicted patient benefit from extended endocrine therapy with letrozole.

Conclusions: In this case-controlled study, the data demonstrate that BCI is a significant predictor of late recurrences in ER+ patients following 5-y of tamoxifen. The prognostic performance of BCI to predict late recurrences was largely dependent on HOXB13 expression. The integration of H:I and MGI within BCI provides prognostic utility for both early and late recurrences.
Quality assurance review center: Role in multi-institutional breast cancer trials.
Authors: Moni J. , Le-Petross H. T. , Boughey J. C. , Laurie F. , Hanusik R. , Howley S. , Logan D. G. , Bishop-Jodoin M. , Simmons R. M. , Ellis M. J. , Hunt K. , Cicchetti M. G. , Sioshansi S. , Quinlan R. M. , Whalen G. F. , Fitzgerald T. J.
Published: February 2017

205

Background: Central review is an important trial management and validation tool. Multisite trials require data systems to accommodate diverse image acquisition and review. Breast cancer is challenging as its imaging objects are not always easily shared across departments. Quality Assurance Review Center (QARC) has a diverse portfolio of facile data acquisition and powerful informatics support that meets these needs. We report on the role of QARC in three of the current breast cancer trials from the American College of Surgeons Oncology Group.

Methods: QARC data management system includes secure network infrastructure and a validated relational operating database (MAX). QARC has data acquisition/imaging re-distribution expertise for real time response reviews, response measuring tools and corresponding data archive for secondary reviews. MAX includes query ability; records link to digital information. QARC underwent systematic information systems validation process for 21 CFR Part 11. DICOM/non-DICOM files are stored in the QARC PACS. On-site/remote reviewers use MAX to retrieve, view, annotate and save images. Data extracted is securely sent to partner statistical centers.

Results: In Z1031, a neoadjuvant endocrine therapy trial, all of the mammographic exams are archived at QARC. For Z1071, a sentinel lymph node trial, pre- and post-treatment ultrasound (US) images of 321 patients were remotely reviewed. For Z1072, the cryoablation US, pre and post-cryoablation MRI for 40 of 47 cases were remotely archived, retrieved and transferred to investigator workstation for post-processing and review. The other 7 patients did not have evaluable imaging studies. In all three trials, the costs of shipping hardcopies of exams and travel to QARC for central review functions were eliminated.

Conclusions: QARC data management systems provide diverse informatics supports for multi-institutional trials, ranging from archives of images, provide remote access and download of data, and central review. The vibrant informatics supports meet the growing needs of clinical trials. Future directions include radiation field review for breast cancer trials and the incorporation of pathology microarray analysis as DICOM objects.
Multidisciplinary care of the breast cancer survivor: An innovative approach.
Authors: Morrow P. K. H. , Bevers T. B. , Zandstra F. , Russell L.
Published: February 2017

206

Background: The Institute of Medicine recognizes cancer survivorship as an integral part of cancer care and advocates for appropriate survivorship care. We will describe the development of a Multidisciplinary Breast Survivorship Clinic (MBSC) and the metrics used to assess the program’s progress.

Methods: To ensure effective integration of a MBSC into a major comprehensive cancer center, clinical leaders (in both the institution and breast leadership group) were approached and engaged in facilitating smooth transitioning of patients from the breast clinic to the survivorship domain. Eligibility criteria included: time of diagnosis ≤ 5 years and no evidence of active breast malignancy. After establishing these criteria, a multidisciplinary team (including endocrinologists, family physicians, medical oncologists, nurses, and research librarians) conducted an extensive literature review of evidence-based disease surveillance, risk reduction, screening for second cancers, and late effects of treatment modalities. These data became the basis of practice algorithms for invasive breast cancer, noninvasive breast cancer, and bone health. Treatment pathways included 4 domains of care: surveillance of the primary malignancy, risk reduction, cancer screening, and monitoring for late effects. The Passport Plan for Health (Passport) evolved from these domains.

Results: Metrics used to assess the MBSC’s progress included number of survivors seen the clinic and number receiving Passports. Each patient is seen on the day of her mammogram (if clinically appropriate) and given a Passport on the initial visit, as well as subsequent visits. Between 9/1/2009-5/16/2011, 3594 patients participated in the Breast Survivorship Clinic. Of the 3584 patients seen in the survivorship clinic, 3435 patients received a completed Passport.

Conclusions: The Passport strengths are to: facilitate communication with primary care physicians, communicate the care needs of the patient and designate the health care provider for their evaluation. Models of care such as the Multidisciplinary Breast Survivorship Clinic provide a rich environment to facilitate survivorship research aimed at assessing the optimal approach to the breast cancer survivor.
Improvement in the quality of care for patients with locally advanced breast cancer through implementation of an integrated electronic care pathway.
Authors: Hogeveen S. , Han D. , George R. L. , Sweet-Goldstein M. , Dinniwell R. E. , Muradali D. , Brezden C. B. , Haq R. , Simmons C. E.
Published: February 2017

207

Background: Locally advanced breast cancer (LABC) refers to the most advanced stage of non-metastatic tumours with an incidence of approximately 10% in newly diagnosed breast cancers. Currently, for optimal care, patients with LABC require a multidisciplinary approach including coordinated planning with medical, surgical and radiation oncologists. We created an interactive electronic care pathway and self populating quality assurance database at St. Michael’s Hospital (SMH) to facilitate multidisciplinary teams to track LABC patient histories and patient treatments in order to coordinate therapy effectively and expedite care (LABC E-PATH).

Methods: This is an observational before-and-after cohort study of patients with LABC with a retrospective review pre-implementation and prospective collection of clinical data post-implementation. The completeness of workup and the timeliness of treatment pre- and post-implementation of the LABC E-PATH in May 2010 were assessed.

Results: With the implementation of the LABC E-PATH in May 2010 at SMH, the delay between the identification of the patient as LABC and their referral to a medical oncologist for treatment for their LABC decreased from a median of 9 days pre-implementation, (range 0-780 days) to 1 day post-implementation, (range 0-52 days). The time between referral to medical oncologist and the start of their chemotherapy treatment decreased from a median of 12 days to 9 days (pre-implementation: range = 4 to 494, post-implementation: range = 0 to 39). All pre-treatment staging was completed faster post-implementation of the LABC e-path than pre-implementation, expediting time to initiation of chemotherapy. The number of referrals for LABC to the SMH program increased from < 1 patient per month to 5 patients per month post-implementation.

Conclusions: The LABC E-PATH at SMH has achieved its goal of expediting care for this patient population. It has also ensured timely and appropriate resource allocation. This unique system may also be applied to other disease sites where coordination of a multi-disciplinary team is critical for appropriate patient management.
Influence of breast cancer CME on provider knowledge and competence.
Authors: Stacy T. B. , Heintz A. A. , Dopson K. , McLane K. , Haas M. E.
Published: February 2017

214

Background: Due to the volume and pace of scientific advances within oncology, the timely dissemination of clinical trial results and discussion regarding the appropriate incorporation into therapeutic decision making is necessary to provide the highest quality patient care. Increasing awareness in the breast cancer community on similarities and differences amongst practice management strategies helps to identify practice patterns and benchmark individual knowledge and competence against one’s professional peers.

Methods: During 2010 and 2011, educational outcomes assessments were gathered during 83 independent continuing medical education (CME) activities held within community and academic institutions across the USA. Participants were asked a series of case-based questions via an audience response system to assess baseline knowledge, competence, and identify practice patterns. Assessments were repeated post a 1-hour CME certified activity, with an additional 6-week electronic follow-up. Barriers to implementing the information learned were also captured. Educational gaps were identified through documentation and comparison of current best practices versus actual participant responses.

Results: To date, a total of 1,515 healthcare providers have participated in the initiative. Number of years in practice ranged from <10 to >30. The number of breast cancer patients seen per month ranged from ≤10 to >40. Provider competency in applying recent literature to the patient care setting was both assessed and measured. Results of neoadjuvant data knowledge, adjuvant therapy selection, relapsed HER2+ disease treatment strategies, and competence in discussing efficacy and safety data from recent clinical trials will be presented. Participants reported a number of barriers to applying data learned at the activities into clinical practice. Responses included lack of reimbursement, treatment side effects, newness of treatment data, and perceived efficacy.

Conclusions: The results suggest the education of providers on the most currently available clinical trial results and expert discussion of how to optimize translation of this information into patient care increases breast cancer provider knowledge and competence.
Relationship of BTG2 expression and anastrozole resistance in breast cancer.
Authors: Nishiya S. , Jinno H. , Hayashida T. , Takahashi M. , Kitagawa Y.
Published: February 2017

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Background: The B-cell translocation gene-2 (BTG2) belongs to a class of proteins known as the Tob and BTG antiproliferative protein family. It was shown that estrogen and progesterone suppress BTG2 expression for the development of mammary gland. We demonstrated that proliferation rate of low level BTG2 expression in MCF7 was strongly inhibited by the administration of tamoxifen. In postmenopausal breast cancer patients, androgens can be converted to mitogenic estrogens by aromatase in breast cancer cells. Based on these results, we hypothesized that BTG2 expression affects the sensitivity against aromatase inhibitior.

Methods: We used tetracycline-inducible BTG2 expression model in MCF7 stably transfected with the human aromatase gene (MCF7/tet/aro) as in vitro models of aromatase-driven breast cancer. The effects of BTG2 expression and administration of anastrozole in breast cancer cells were assessed by proliferation assays.

Results: Administration of androstendion increased 79.1% of cellular proliferation, suggested that introduced aromatase gene worked well. Elevated level of BTG2 mRNA expression by tetracycline treatment was confirmed by Quantitative-RTPCR. Anastrozole treatment (100nM) reduced 37.8% of cellular proliferation ability, whereas the concomitant administration of tetracycline and anastorozole reduced 59.0% of cellular proliferation. These results suggested that the inhibitory effect of anastrozol for cellular proliferation was enhanced under the condition of BTG2 expression.

Conclusions: Our results suggested loss of BTG2 expression may be affects the sensitivity against aromatase inhibitor.
Expression (Exp) of FIP200 and Rb in breast cancer (BreastCA) metastasis (met) to the brain.
Authors: Hashemi Sadraei N. , Burgett M. , Ahluwalia M. S. , Tipps R. , Khosla D. , Weil R. , Nowaki A. , Prayson R. , Shi T. , Gladson C.
Published: February 2017

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Background: BreastCA is the 2nd leading cause of cancer deaths in women in the US. Although the outcome for BreastCA with brain met remains poor, there is significant variation in overall survival (OS). Yet, there are no markers or models to predict OS. FIP200 regulates several pathways. In the nucleus, it inhibits cell proliferation by promoting Rb-1 and p21, and in the cytoplasm it promotes cell survival by inhibiting Pyk2 and regulating autophagy. It has been reported that FIP200 gene is deleted or mutated in 20% of primary BreastCAs, and its Exp is correlated with Rb1 levels. FIP200 Exp, its cellular localization, and gene alterations have not been examined in brain met of any cancer.

Methods: Brain met tissues of 21 BreastCA patients (pts) biopsied in our institution between 8/2000 and 3/2010 were obtained and Exp of FIP200 and Rb1 were analyzed. Biopsies were selected based on tissue adequacy and prior diagnosis (Dx) of invasive intra-ductal BreastCA. Immunohistochemistry (IHC) was used to evaluate the localization and Exp levels of FIP200 and Rb1 which in turn were tested as predictors of OS. Genetic alterations in FIP200 and Rb1 were examined after DNA extraction.

Results: Median time from Dx to met was 23 (range 0-245) months (mos), and median OS from Dx was 43 (range 6-264) mos. Nuclear Exp of Rb1 in < 30% vs. ≥ 30% of cells were seen in 11 vs. 10 pts. Median OS was 39 (range 6-264) mos for Rb1 Exp < 30% and 47 (range 20-190) mo for Rb1 Exp ≥ 30%. Nuclear Exp of FIP200 in <20% vs. ≥ 20% of cells were seen in 13 vs. 8 pts. Median OS was 39 (range 6-264) mo for FIP200 nuclear Exp <20% and 45 (range 43-122) mo for FIP200 Exp ≥ 20%. DNA analysis of 11 pts for copy number variations and loss of heterozygocity (LOH) showed no deletion mutations in FIP200 or Rb1, loss of p53 in 4 of 11, ErbB2 (Her-2) amplification in 4 of 11, and no EGFR gene mutations.

Conclusions: The nuclear Exp of Rb1 in brain met from invasive intra-ductal BreastCA may be linked OS. An expanded study is underway to define whether nuclear FIP200 in >20% of cells correlates with nuclear Rb and OS in BreastCA.
A pilot study of the decision-making process of seeking medical care in women diagnosed with large breast tumors.
Authors: Eggar J. M. , Lea C. S. , Bellin L. S. , Raab R. E. , Wong J. H. , Burke L. P.
Published: February 2017

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Background: Twelve percent of women diagnosed with invasive breast cancer in eastern NC present with large tumors (≥ 4 cm). The reasons for presentation with advanced cancer are not known and may include both social factors and tumor characteristics.

Methods: The objective of this qualitative pilot study was to investigate the decision-making process of seeking medical care in women diagnosed with ≥ 4 cm breast tumors through in-depth interviews. Six female breast cancer patients treated at Brody School of Medicine completed in-depth qualitative semistructured interviews along with demographic questionnaires. The interviews, designed to uncover barriers and motivators to seeking breast cancer diagnosis and care, were recorded and transcribed verbatim.

Results: Six women (aged 44-68) completed the interview process, three African Americans and three Caucasians. Mean tumor at diagnosis size was 11.2 cm (range 4-18 cm). Three women who lived alone hid breast cancer symptoms from their family; of these, two women had fungating tumors and one had nipple drainage for more than 1 year prior to diagnosis. Four women had health insurance. Two women reported being without insurance for more than 10 years and cited this as the primary reason for delaying care. Both insured and uninsured subjects delayed care due to fear of being a burden to family, financially or support wise. One woman delayed care due to fear of chemotherapy and radiation. Three women reported regular mammograms; two presented with fast-growing tumors, one had a chest wall tumor that was missed on mammography.

Conclusions: Three of six patients presenting with locally advanced disease stated that they made a decision to delay medical care. Subjects’ lack of insurance, fear of cancer and cancer treatments, and concern for family were among reasons for delays. Qualitative approaches may be useful in studying factors that affect patient access to care. More research is needed on ways to improve access and empower women to seek care.
Determining the rate of tumor growth and decay in patients with metastatic breast cancer as an early efficacy endpoint: A study assessing ixabepilone efficacy.
Authors: Amiri-Kordestani L. , Jawed I. , Wilkerson J. , Stein W. D. , Bates S. E. , Swain S. M. , Fojo A. T.
Published: February 2017

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Background: Early efficacy assessment in drug development should help find new cancer therapies. We have developed a novel method to analyze tumor response to therapy by quantifying the rate of tumor regression (d) and growth (g). We have shown g is slower when pts are on effective therapy and that g correlates with survival (Stein et al, Oncologist 2008). We utilized this method to evaluate a phase III trial of capecitabine (CAP) ± IXA in second line therapy (Tomas et al, JCO 2007) and a three-cohort phase II trial in second and subsequent lines of therapy in pts with MBC consisting of (1) Daily X 5 IXA given to taxane (TAX)-naïve patients (Denduluri et al, JCO 2007); (2) Daily X 5 IXA in pts previously treated with TAX (Low et al, JCO 2005); and (3) Daily X 3 IXA in pts previously treated with TAX (Denduluri et al, Invest New Drug 2007).

Methods: Using tumor measurements assessed by RECIST and a two-phase mathematical equation we determined d and g.

Results: In the phase III study g was superior to PFS identifying a significant difference between the arms very early—before the 200th pt had enrolled. In an individual patient the g values could be estimated as early as the 3rd evaluation, long before tumor growth was observed clinically. IXA + CAP in second line (g = 0.0018) was more effective than CAP (g = 0.0023) at reducing g, and more effective (p=0.0085) than single agent IXA in the Phase II study (g = 0.0027). Single agent IXA was comparably effective (p=0.814) in reducing the g of tumors previously exposed to a TAX (g = 0.0032) as in reducing the g of TAX-naïve tumors (g = 0.0035), consistent with its development as an agent active in TAX-refractory disease. Unlike differences in g, the d of single agent IXA (0.118) was comparable to that of IXA+CAP (0.0074) suggesting differences were primarily driven by effect on the growth of residual tumor.

Conclusions: Unlike PFS, an incremental measure of efficacy, g is a continuous variable and can more accurately assess differences between treatments. Because calculations of g are indifferent to assessment intervals, estimating a tumor’s g allows comparison of efficacy across trials.
Defining survival for patients with breast cancer with brain metastases.
Authors: Pathe N. P. , Khalid S. , Khan C. , Atem F. D. , Trombetta M. G. , Geyer C. E.
Published: February 2017

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Background: Brain metastases account for 100,000 to 170,000 cases per year in the U.S, the bulk being from breast and lung primaries. About 10-15% of breast cancer patients develop brain metastases and historically, their survival has been poor. Introduction of novel chemotherapeutic and biologic agents and newer radiation techniques in the past decade has led to better control of systemic disease raising the possibility of increasing incidence of brain metastases as well as better control of CNS disease. The aim of this study was to determine the survival of breast cancer patients with brain metastases in our practice in the last 10 years.

Methods: This study was a retrospective chart analysis and we analyzed the charts of 18 patients with breast cancer who had developed brain metastases. The parameters analyzed included patient age at diagnosis of breast cancer and at development of brain metastases, receptor status and various treatment modalities used to control local as well as Metastatic disease.

Results: The median survival time after adjusting for age at diagnosis of breast cancer, age at diagnosis of brain metastases and the number of brain metastases was 55 months. The time to death was analyzed using Cox proportional hazard model, adjusting for age and number of brain metastases. Age at diagnosis of breast cancer was significant with a p-value of 0.007 and the number of brain metastases was not significant with a p-value of 0.55. Using the Log Rank test, median survival for Her2neu positive patients was 71 months and for Her2neu negative patients was 58 months with a non-significant p value of 0.86. Review of treatment modalities revealed that six patients underwent surgical removal of metastases and 12 patients received WBRT. Average number of systemic treatments used was 6.7 including chemotherapeutic, biological and hormonal agents.

Conclusions: In our practice, the overall survival of breast cancer patients with brain metastases was found to be 55 months after adjusting for age at diagnosis of breast cancer, age at diagnosis of brain metastases and number of brain metastases. Overall survival did not vary significantly with the number of brain metastases and Her2neu receptor status.