bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival variation of the ER/PR/HER2 subtypes by race in a single institution.
Authors: Parise C. , Caggiano V.
Published: February 2017

183

Background: We have investigated breast cancer in California noting variation in survival among race/ethnicity, age, and the ER/PR/HER2 subtypes. The purpose of this study is to determine if similar variation exists in a single institution in California.

Methods: We indentified 994 cases of first primary invasive breast cancer between January 2004 and December 2007. Descriptive statistics were used to assess the distributions of race/ethnicity, ER/PR/HER2 subtype, age, and treatment status. Kaplan-Meier survival estimates were computed and the Log-Rank Test used to compare 5-year survival.

Results: The most common subtype was ER+/PR+/HER2- (49.6%). There were 221 cases of the HER2-positive subtype; 25% of these were the HER2 over-expressed subtype (ER-/PR-/HER2+). There were 113 cases of ER-/PR-/HER2- (14.0%) and only 3 cases of the ER-positive/PR-positive subtype. The distributions of race and subtype were similar to statewide data for this region. Of the 994 cases, 81% were White, 5.9% Black, 6.5% Asian, 6.2% Hispanic, and 0.3% were American-Indian. For all subtypes and stages combined, 5-year survival was worse for African-Americans (70%) when compared with White patients (83%) Χ2 = 15.29, p < 0.001. There were no statistically significant differences in mean age of diagnosis among the eight subtypes. Of the 113 cases of ER-/PR-/HER2-, 80 were White, 15 Black, 8 Asian, and 8 Hispanic. Only one Black patient with ER-/PR-/HER2- was younger than age 45. African-American patients with ER+/PR+/HER2+ and ER+/PR-/HER2- were more often diagnosed in stages 3 and 4. The ER-/PR-/HER2- subtype had worse 5-year survival (64%) than both the ER+/PR+/HER2+ (88%) and the ER+/PR+/HER2- (85%) subtypes (p < 0.001). There was no difference in survival by race for the ER-/PR-/HER2- subtype. For ER-positive patients, African-Americans had worse 5-year survival than whites (66% versus 86%) Χ2 = 16.18, p < 0.001 despite comparable hormonal and chemotherapy regimens.

Conclusions: The ER+/PR+/HER2+ subtype does not always mean poor survival. The triple-negative subtype has the worst survival for both Black and White patients. African-American patients with any ER-positive subtype fare poorly. Referral bias and small sample sizes are study limitations.
Learning from the lowest incidence rates in breast cancer: Health information from men, young women, and Native American/Alaskan native women.
Authors: Dedousi-Huebner V. , Chakravarti A. , Lautenschlaeger T.
Published: February 2017

185

Background: Breast cancer rates by the NCI show the lowest incidence for young women under 30, Native American/Alaskan Native women and males overall. Using the National Health Interview Survey we set out to investigate what these three very heterogeneous appearing groups seem to have in common in order to possibly detect preventive factors for breast cancer.

Methods: The NHIS is a continuous national survey of the US civilian population. The data are collected yearly through in-person computer assisted household interviews. All members of the household 17 years of age and over who are at home at the time of the interview were invited to participate and respond for themselves. Using the data from this survey provided by the Office of Analysis and Epidemiology, National Center for Health Statistics, Centers for Disease Control and Prevention, we controlled for gender, race/ethnicity, poverty level and age.

Results: Over 29.5% of all questioned Native American/Alaskan Native women responded to be in good health while only 17.8% of all white women responded the same. The difference in reported health status between white women and white men was not statistically different. For the health status of women in different age groups we found a picture that is reverse to the incidence trend of breast cancer. The older the women, the more likely they were to respond that they were in good health.

Conclusions: As can be expected from such heterogeneous groups they did not have one variable in common that might have a preventive effect on breast cancer. The higher estimate of positively reported health status in association with the low incidence of breast cancer of Native American/Alaskan Native women certainly makes it worth investigating the positive attributes associated with this group’s health behavior. Another more unsettling interpretation of the low incidence rate in this population may be attributed to health insurance coverage, 32.5%—more than double the rate of the population of Caucasian females—do not have health insurance coverage which might lead to a lower rate of reported cancer cases.
Ductal carcinoma in situ (DCIS) of the breast: Race- and treatment-adjusted specific disease-free probability.
Authors: Stark A. , Yan X. \(. , Stapp R. , Raghunathan A. , Kirchner L. , Griggs J. , Newman L. A. , Dick A. W. , Chitale D.
Published: February 2017

186

Background: Findings of DCIS outcome between African-American (AA) and White-American (WA) women are inconclusive.

Methods: We conducted a retrospective longitudinal study with the objective of comparing the risk of any second breast cancer after the first primary DCIS, adjusting for pathologic prognostic indicators, treatment, age, and the established epidemiologic risk factors. Women were diagnosed and treated in one institution between 1990-1999. Diagnostic slides were reviewed and prognostic indicators documented; demographic, clinical and method of detection, screening mammography vs. palpation, were collected from medical records. We applied Accelerated Failure Time Modeling (AFTM) to determine the variables that were best associated with the risk of a second cancer.

Results: 335 women, 29.6% (n=100) AA with mean age of 60 (±13) and 70.4% (n=235) WA with mean age of 57 (±12.4), contributed to this study. Distributions of some of the prognostic indicators and final treatment are presented. (Table) During the 10 years of follow-up 12.0% (n=12) of AA and 3.0% (n=7) WA experienced second cancer in ipsilateral breasts; 5.0% (n=5) of AA and 3.8% (n=9) WA in their contralateral breasts and 2 women, 1 AA and 1 WA, in both breasts. Results from the AFTM yielded race as the only variable associated with the risk of a second cancer but only in ipsilateral breasts (HR= 4.11, 95% CI=1.6-10.5 p=0.003).

Conclusions: No difference in the risk of a second cancer in contralateral breast between AA and WA women support the notion of equal access and equal treatment in comparable treatment outcome. Reasons for increased risk of a second cancer in ipsilateral breast in AA women are being evaluated.

[Table: see text]
Racial and ethnic disparities in presenting stage and overall survival in women treated for breast cancer.
Authors: Salner A. L. , Staff I.
Published: February 2017

187

Background: Over the past 20 years, we have recognized racial/ethnic disparities in breast cancer outcomes, and have attempted to develop outreach, screening, and care strategies to address these. This study explored changes in these disparities over twenty years in presenting stage and overall survival at a single large urban teaching and community hospital with an active cancer outreach program, a member of the NCI Community Cancer Centers Program.

Methods: Between 1990 and 2009, 9733 women were diagnosed and treated with breast cancer at our institution. 8918 women with complete race/ethnicity and clinical data were analyzed. The women were grouped into four five-year cohorts, and 3 subgroups-Caucasian, African American, and Latina. All four cohorts were compared for stage migration, while only the initial three cohorts were compared for 5 year overall survival to allow follow-up. Chi-Square tests of proportions were utilized to compare subgroups.

Results: Of the 8918 women analyzed, 91.5% are Caucasian, 4.5% African American, and 4% Latina. Over the 20 years of the study, significant stage migration occurred; the total number of women diagnosed with early stage disease(in-situ and localized) increased from 71.7% to 78.7%. Significant stage migration was found for all subgroups of women. Stronger trends were found focusing only on in-situ disease—an overall increase from 14.4% to 30.8%. Five year overall survival of the entire group improved from 78.7% to 85.4%, and also improved for each of the subgroups. Caucasian women were significantly older (60 vs. 54) but the cohort and ethnic findings remained in multivariate analysis. Significant disparities between Caucasians and Latinas for stage and between Caucasians and African American for 5 year survival gradually diminished.

Conclusions: Significant improvements are seen in earlier stage presentation and five year overall survival amongst women treated for breast cancer between 1990 and 2009, as well as in subgroups of Caucasian, African American and Latina women. Differences between subgroups diminish and in many cases disappear by the end of the study period, suggesting that strategies may have helped reduce breast cancer disparities.
Locoregional lymphatic recurrence following axillary dissection for breast cancer.
Authors: Lim S. M. L. , Lam F. L. , Remulla S. J. N.
Published: February 2017

19

Background: The risk of locoregional recurrence is of concern for women following breast cancer surgery. We report a single surgeon’s experience of locoregional lymphatic recurrence following axillary dissection (AD) in women with breast cancer.

Methods: The aim of this study is to identify risk factors for locoregional lymphatic recurrence in women who have undergone breast surgery and AD for T1, T2 tumours. 14 women were identified over 10 years with documented recurrence in the regional lymphatic basin; ipsilateral, contralateral, supraclavicular and internal mammary lymph nodes. One patient presented with bilateral breast cancer. Patient characteristics as well as the tumour grade, ER, PR, HER2 reactivity and presence of lymphovascular invasion (LVI) were analysed.

Results: Between 1996 and 2006, 756 women underwent primary surgery for breast cancer in our practice. We identified 14 women who relapsed with locoregional lymphatic recurrence and underwent further surgical management after a median follow-up of 4.5 years. 13/14 had undergone primary breast surgery at our centre, of which 73% underwent total mastectomy and AD. The median age was 48 years, 14% were nulliparous, and 50% were premenopausal. The mean tumour size was 2.48 cm and 7% had a contralateral cancer. The median axillary lymph node (LN) yield was 11.5 of which 57% (8/14) were node negative at primary surgery. In those 8 patients with negative AD, 50% recurred in the ipsilateral axillary LNs, 37.5% recurred in the ipsilateral supraclavicular LNs in the absence of axillary relapse, and 12.5% recurred in the contralateral axillary LNs in the absence of ipsilateral axillary relapse. Of the primary tumour characteristics, 13% were low grade, 43% had LVI, 57% were ER+, 64% PR+, 43% HER2+, and 14% triple negative. None of the patients had distant metastases at the time of relapse in the locoregional lymphatic basin.

Conclusions: An axillary dissection did not prevent locoregional lymphatic recurrence in 14 women in our small series. On retrospective analysis, there was no dominant risk factor which could help to identify this group at high risk of relapse, although at least 50% who relapsed locoregionally were less than 50 years, premenopausal with a high tumour grade.
Assessment of genetic predisposition to lymphedema.
Authors: Armer J. M. , Stewart B. R.
Published: February 2017

195

Background: In the United States, 203,000 women are diagnosed annually with breast cancer (BC). Currently, over 2.3 million women in the United States are breast cancer survivors. With the increased incidence and survivorship, more women are living with the long-term treatment effects such as lymphedema (LE). We are nearing completion of stage one of a three-stage research project to examine genetic factors that potentially predispose BC survivors to develop LE. In stage one, we are working to identify novel genetic polymorphisms pointing to genomic regions and genes associated with LE risk. In stage two, we will use exome sequencing to examine both rare and common genetic variants potentially associated with variation in symptom manifestations of LE in breast cancer survivors; to examine phenotypic and genotypic variation in LE emerging following cancer treatment; and to examine associations between LE phenotypes among breast cancer survivors with LE and genomic factors and non-genomic factors. In stage three, we will replicate at the genetic level the associations detected.

Methods: Institutional funding was obtained for a GWAS-design feasibility study with 96 breast cancer survivors with and without LE (48/48). Genetic material (from buccal swabs), limb volume (by perometry and circumferences), and self-reported LE-related symptoms were collected in one laboratory appointment.

Results: Ninety-five percent of survivors participating in an on-going longitudinal study consented to participate in the genetic pilot (N=96). Buccal swabs provided yield for DNA extraction (concentration average 174.94 ng/ul). An additional 96 specimens have been collected for a second pilot GWAS (N =192).

Conclusions: The pilot findings form the basis for a larger multisite proposed study to examine genetic predisposition to secondary LE. The findings of the larger study will lead to the design and timing of subsequent interventions aimed at reducing LE risk and improving overall survivorship quality of life. Findings concerning interactions among best cancer treatments and LE genetic predisposition will have the potential to guide the selection of cancer treatment to minimize complications when survival outcomes are equivalent across competing treatment approaches.
Results of a pilot study of a web-based care plan to meet the communication needs of breast cancer survivors and their primary care physicians.
Authors: Haq R. , Leung F. H. , Dastur D. , Baker N. A. , Heus L. , Li B. , Parsons J. A.
Published: February 2017

200

Background: Following treatment, breast cancer patients (BCPs) can feel “lost in transition”. Family practitioners (FP) also report feeling ill-equipped to provide follow-up care to breast cancer patients. In this 3-phase qualitative pilot study we designed, implemented and evaluated a multi-faceted care plan (MCP) to address the information/communication needs of BCPs and their FPs.

Methods: We first conducted focus groups and interviews with 35 participants from 3 stakeholder groups (BCPs, FPs and oncology team), to identify specific information and communication needs. A MCP was designed based on these findings. The MCP was then evaluated via focus groups and interviews with 26 participants. Interviews and focus groups were audiotaped, transcribed and content analysed for emergent themes and patterns.

Results: Pre-implementation, participants identified communication needs pertinent to BCPs and FPs. Patients commented that web-based, paper-based and human resources components are essential to any care plan. Patients did not focus solely on the post-treatment period, but rather spoke of evolving needs throughout their cancer journey. FPs indicated that any tools to support them must distill important information in a readily accessible and easy-to-use format. Based on this needs assessment, a MCP was designed and implemented for BCPs and FPs. This consisted of tailored websites, as well as paper-based care plans and a patient booklet. Patients provided positive feedback about the MCP, indicating that it was effective at addressing many of their needs and commented “I wish I’d had this before”. Suggestions for future improvements to the MCP included greater emphasis on health-and-wellness post-treatment. In addition, some patients voiced resistance to the terms “survivor” and “survivorship” in materials, as they did not self-identify with such terms.

Conclusions: This MCP shows promise in addressing the information/communication needs of BCPs and FPs who care for them. Next steps include tool refinement, further evaluation, and planning for more extensive implementation.
Probably benign findings, BIRADS category 3 (MR-Bi3), on magnetic resonance imaging of the breast (BrMR): Is repeated MRI an alternative to biopsy?
Authors: Janicek M. J. , Camaya V. M.
Published: February 2017

21

Background: The shift from the use of BrMR for confirmation of known abnormality to the screening mode in problematic breast is associated with higher frequency of probably benign findings. Some of them still require biopsy, with or without close BrMR follow up (f/u), some may remain on observation only. Our pilot study analyzed clinical outcomes of MR-Bi3 pts and added value of close BrMR f/u. Proportion of MR-Bi3, some after “second look ultrasound” (2ndUS) with or without biopsy could be used among other monitors of BrMR practices.

Methods: We reviewed BIRAD categories assigned to all 743 BrMRs done in period of year 2007 in our specialized breast imaging practice with dedicated BrMR (Aurora) system and full complement of diagnostic and interventional modalities. Frequency of MR-Bi3 and studies resulting in MR-Bi3 or biopsies after 2ndUS were analyzed. With benefit of 3 year clinical data, the outcome of patients on such short term f/u schedule was reviewed.

Results: MR-Bi3 was assigned to 40 (5.4%) of our BrMRs on the initial evaluation, all of them yielded benign findings on follow up. Additional 26.2% of our studies required 2ndUS. After 2ndUS, 40% of these pts were converted to Bi4+5, continued with image guided biopsy with cancer detected in 35% of those. Remaining 60% of 2ndUS yielded “probably benign findings”, MR-Bi3, which means that total of 21.6% of our BrMRs remained on close f/u schedule with MRI. There were no additional delayed findings of malignancy in this group. Single additional BrMR was sufficient to confirm benign findings only in 47% of cases, 24% of patients required multiple BrMRs at 6 month intervals, remaining patients were followed by other modalities.

Conclusions: Utilization of MR-Bi3 category reflects readers' confidence avoiding or justifying biopsies for border line findings. Targeted use of 2ndUS helps to identify patients who benefit from biopsy rather than close f/u. Proportion of repeated Bi3 and outcome of Bi3 could become valuable QA indices for monitoring of BrMR practices. Only in small proportion of cases, the use of Bi3 was not contributory, particularly in case of repeated BrMRs for the same abnormality.
Relationship between lack of patient compliance with adjuvant therapy guidelines and recurrence in early breast cancer.
Authors: Citrin D. L. , Neelam R. , Grutsch J. F. , Mortensen S. J.
Published: February 2017

215

Background: Modern treatment (Tx) of early stage breast cancer (BC) often requires a combination of surgery, radiation and adjuvant drugs (chemotherapy, hormones and/or Herceptin). Lack of patient compliance is often an issue, due to the prolonged nature of Tx and lack of perceived benefit when there is no clinically overt disease.

Methods: We retrospectively evaluated consecutive patients with recurrent BC who had primary Tx for stage I-III BC elsewhere, and were seen at MRMC over an eighteen month period by DLC or RN following relapse. Patients with stage IV or inflammatory BC at initial diagnosis were excluded. All patients in this study were therefore considered failures of primary Tx.

Results: A total of 215 patients (median age 44, range 27-74) were included in this study. Sites of recurrence were loco-regional 73, distant mets 117, both 25. 215 (60%) were found to have had inadequate Tx as per NCCN guidelines. The most common deviations from NCCN guidelines were due to patients’ refusal of chemotherapy or hormone therapy. Detailed information about nodal status was available for 208 patients (see table). The proportion of patients with 0-3 nodes positive who received inadequate primary Tx was statistically significantly greater than the proportion of patients with > 3 nodes involved (Pearson Chi Square p < 0.0001).

Conclusions: This retrospective study suggests that patient compliance is a key factor in determining efficacy of primary Tx of early BC.

[Table: see text]
Methylation RE in serum of patients with breast cancer and relation with molecular phenotype and worse prognostic factors.
Authors: Martínez-Galan J. , Torres-Torres B. , Del Moral R. , Núñez M. I. , Ríos S. , Ballesteros P. , Delgado J. R.
Published: February 2017

224

Background: To determine whether Estrogen Receptor (ESR1) (+) and ESR1(-) status relates to epigenetic changes in breast cancer-related genes and to correlate with molecular breast cancer subtypes.

Methods: Since January/02 to June/05, we quantified methylation levels ERS1 gene in serum of 92 pts breast cancer. A PCR quantitative technique was used to analyze levels of methylation gene. We also examined and correlationed the expression of ESR1 in tumors by immunohistochemistry with molecular phenotype.

Results: Median age was 58 years (32-88); 69% were postmenopausal women. Nodal involvement (N0; 63%, N1; 30%, N2; 7%), tumor size (T1; 58%, T2; 35%, T3; 4%, T4; 4%) and grade (G1; 20%, G2; 37%, G3; 30%). Of the cases, 37 pts (40%) were Luminal A (LA), 32 pts (33%) Luminal B (LB), 14 pts (15%) Triple-negative (TN) and 9pts (10%) HER2+. The methylated ESR1 in serum was significantly associated with ESR1(-) in breast tumors >80% (p=0.0179). Methylation ESR1 was preferably associated with TN (80%) and HER2+ (60%) subtype. Nevertheless unmethylation ESR1 was found more frequently in LA (71%) and LB (59%) phenotype. With a median follow up of 5 years, we found worse overall survival (OS) with more frequent ESR1 methylation gene (p>0.05), Luminal A; ESR1 Methylation OS at 5 years 81% vs 93% when was ESR1 Unmethylation. Luminal B; ESR1 Methylation 86% SG at 5 years vs 92% in Unmethylation ESR1. Triple negative; ESR1 Methylation SG at 5 years 75% vs 80% in unmethylation ESR1. HER2; ESR1 Methylation SG at 5 years was 66.7% vs 75% unmethylation ESR1.

Conclusions: Gene promoter region hypermethylation is a significant event in primary breast cancer. However, its impact on tumor progression and potential predictive implications remain relatively unknown. Our study identifies the presence of variations in global levels of methylation promoters ESR1 genes in breast cancer with different phenotype classes and shows that these differences have clinical significance. Although numerous issues remain to be resolved, quantitative measurement of circulating methylated DNA may be of significance in the assessment and search of targeted therapy resistance related to ESR1 and HER2 status by epigenetic or transcriptional cancer therapy.
SmgGDS splice variants: Potential novel targets for breast cancer therapeutics.
Authors: Bergom C. , Hauser A. , Lorimer E. L. , Li R. , Mackinnon A. C. , Williams C. L.
Published: February 2017

225

Background: Breast cancer malignancy is promoted by the small GTPases K-Ras, Rap1, RhoA, and Rac1. We recently reported that the activity of these GTPases is regulated by two splice variants of SmgGDS, named SmgGDS-558 and SmgGDS-607. SmgGDS is overexpressed in lung and prostate cancer, but its role in breast cancer is unknown. Here we examine whether SmgGDS splice variants are expressed in breast cancer and promote breast cancer malignancy.

Methods: Immunohistochemical staining for SmgGDS was performed on archival human breast tumors (N=183) and normal breast tissue (N=22). Immunoblotting was used to detect SmgGDS splice variants in human breast cancer cell lines. siRNAs that silence different SmgGDS splice variants were used to examine the effects of SmgGDS knockdown on breast cancer cell spreading, cell proliferation via [3H]thymidine uptake, anchorage-independent cell growth using soft agar colony assays, and NF-kB activation using luciferase reporter assays.

Results: SmgGDS expression was detected in >65% of DCIS and invasive lobular and ductal carcinoma, and in 100% of metastatic tumors, but was detected in only 18% of normal breast tissue specimens (p<0.01). All tested cell lines expressed both SmgGDS splice variants. Silencing SmgGDS-558 or SmgGDS-607 with siRNA significantly diminished cell proliferation (100±2.0 vs. 11.3±1.0 vs. 50.5±2.2, p<0.05) in MCF-7 cells, with similar results in MDA-MB-231 and T47D cells. MCF-7 soft agar colony formation was significantly decreased 71% and 49% when SmgGDS-558 or SmgGDS-607 was silenced. MCF-7 cell spreading was promoted by silencing SmgGDS-558, but not SmgGDS-607. NF-kB activation was also decreased by 30% in resting and TNF-α-treated MCF-7 and MDA-MB-231 cells by silencing either splice variant.

Conclusions: SmgGDS is disproportionally expressed in human breast cancers. Reduction of SmgGDS-558 and SmgGDS-607 levels dramatically reduced breast cancer cell proliferation, soft agar colony formation, and NF-kB activation. Our results indicate that SmgGDS splice variants regulate breast cancer malignancy, most likely through their regulation of small GTPases. This study identifies SmgGDS splice variants as novel therapeutic targets in breast cancer.
Metastatic breast cancer detection and therapy monitoring using folate-targeting flow cytometry.
Authors: Hong B. , Mace M. , Crowder R. , Coleman T. , He W. , Szczepanski F. , Feczko J. , Lyzak J.
Published: February 2017

23

Background: Circulating tumor cell (CTC) has emerged as a valuable surrogate tumor marker for cancer diagnosis, prognosis, therapy personalization, and drug discovery. To identify CTCs, EpCAM and/or cytokeratin have been commonly used; however, their expression may diminish for subgroups of breast cancers or during epithelial-mesenchymal transition. A unique approach by targeting folate receptor (FR) on CTCs overcomes the limitation. Cancer cells overexpress FR with high affinity (KD=0.1 nM) to internalize high levels of folate for rapid growth. FR is also found upregulated in most cancers, while at very low levels in normal tissues.

Methods: A flow cytometry based in-vitro CTC assay kit (OncoIVDx) was developed by IV Diagnostics Inc to specifically enumerate CTCs which overexpress FRs. 20 mL of 9 metastatic breast cancer (MBC) patients' peripheral blood was collected using CellSave tube before and after the treatment in midst of therapy. CTCs were tagged by fluorescently labeled folate conjugate, while leukocytes were counterstained by anti-CD45. To absolutely count the rare CTCs, a fluorescent bead was added serving internal control.

Results: Table.

Conclusions: No obvious shift in dot plots was found for patients' leucocytes compared to those in normal sample. Tumor size, histologic grade, nodal involvement and lymphovascular invasion (LVI) did not display a significant association with CTC presence, although more positive nodes with identified LVI might indicate an unfavorable increase in CTC counts. CTC presence was found associated with serum marker CA27.29. A score of 30 and less correlated with CTC response to the treatment. Chemotherapy alone or in combination with hormone therapy did not correlate with the change in CTC counts after treatment, except for hormone therapy alone. Unfavorable progression of cancers could be predicated for the patients with approximately 25 and more CTCs. We would like to thank NIH/NCI for SBIR phase I grant (1R43CA13789301A1).

[Table: see text]
Barriers to screening and treatment of breast cancer: Data analysis from Edgecombe County.
Authors: Picton M. E. , Ramirez B. , Liles D. , Sastry T. R. , Petruzziello M.
Published: February 2017

232

Background: Edgecombe County in NC was described as the 3rd highest location breast cancer mortality according to the Susan G. Komen report (2007). The major issues detected were low education, lack of healthcare providers, and large numbers of uninsured individuals. Our analysis sought to further characterize the circumstances unique to this region and measures to improve mortality.

Methods: Between October 2008 and January 2009, 493 surveys were conducted throughout the county. The surveyors randomly approached female residents of Edgecombe County who completed a questionnaire, which was analyzed for this study.

Results: Of the total population 354 women were older than age 40. In this group 82.5% had recent mammograms and 79.8% clinical breast examinations. Also, 91.7% had a Primary Physician who recommended mammograms in 85% of the cases. Only 27.1% had family history of breast cancer and, of those, 86.2% were recommended mammograms. Most were educated (58.6%), had low income (76%) and health insurance (87.4%). Nearly equal numbers of Caucasians and African Americans completed the survey (50.6% vs. 47.6%). Just 8.1% had transportation problems and 3.6% were aware of free mammograms in the health department. Statistical analysis by the Fisher’s Exact Test evaluated the relationship between the likelihood of having a screening mammogram and different variables. Women who attended church were more likely to undergo mammograms (p=0.00054), as were women with insurance (p=0.024). Family histories of breast cancer, lack of transportation, low income or deficient education were not significant determinants to obtain a mammogram. A logistical regression model demonstrated that attendance to church and insurance were the two factors statistically significant in terms of obtaining a mammogram.

Conclusions: The main issues identified by our analysis were low-income, low health care literacy and lack of awareness regarding breast cancer programs. Our results were discordant with some of the Susan Komen report data, particularly that the majority of participants had a mammogram. Transportation and religious beliefs were not barriers to screening of breast cancer.
The effect of tumor subtype on survival and the graded prognostic assessment (GPA) for patients with breast cancer and brain metastases.
Authors: Sperduto P. W. , Kased N. , Roberge D. , Shanley R. , Chao S. T. , Bhatt A. K. , Brown P. D. , Shih H. A. , Kirkpatrick J. , Gaspar L. E. ,   Graded Prognostic Assessment \(GPA\) Consortium
Published: February 2017

238

Background: The Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) was published to clarify prognosis for patients with brain metastases. This study refines the existing Breast GPA by analyzing a larger cohort and tumor subtype.

Methods: A multi-institutional retrospective database of 400 breast cancer patients treated for newly-diagnosed brain metastases was generated. Prognostic factors significant for survival were analyzed by multivariate Cox regression (MCR) and recursive partitioning analysis (RPA). Factors were weighted by magnitude of their regression coefficients to define the GPA index. A GPA score of 4.0 represents the best prognosis, 0.0, the worst.

Results: Significant prognostic factors by MCR and RPA were Karnofsky Performance Status (KPS), HER2, ER/PR status, and the interaction between ER/PR and HER2. RPA showed age was significant for patients with KPS 60-80. The median survival time (MST) overall was 13.8 months, and for GPA scores of 0-1.0, 1.5-2.0, 2.5-3.0 and 3.5-4.0 was 3.4 (n=23), 7.7 (n=104), 15.1 (n=140) and 25.3 (n=133) months, respectively (p < 0.0001). See table. Among HER2-negative patients, being ER/PR-positive improved MST from 6.4 to 9.7 months whereas in HER2-positive patients, being ER/PR-positive improved MST from 17.9 to 20.7 months. The log-rank statistic (predictive power) was 110 for the Breast-GPA versus 55 for tumor subtype.

Conclusions: The Breast-GPA documents wide variation in prognosis and shows clear separation between subgroups of patients with breast cancer and brain metastases. This tool will aid clinical decision-making and stratification of clinical trials. These data confirm the effect of tumor subtype on survival and show the Breast-GPA offers significantly more predictive power than the tumor subtype alone.

[Table: see text]
Impact of eribulin on overall survival in patients with metastatic breast cancer with visceral disease.
Authors: Vahdat L. T. , Cortes J. , Twelves C. , Wanders J. , Seegobin S. , Dutcus C. , O'Shaughnessy J.
Published: February 2017

239

Background: Visceral disease is associated with poor survival outcome in women with metastatic breast cancer (mBC). Eribulin mesylate is a nontaxane microtubule dynamics inhibitor indicated for 3rd-line monotherapy in patients (pts) with mBC previously treated with at least two chemotherapeutic regimens in the metastatic setting, including an anthracycline and a taxane.

Methods: Evidence from the global, randomized, multicenter, phase III clinical trial of eribulin in mBC (EMBRACE) demonstrated improved overall survival (OS) for eribulin-treated pts when compared to treatment of physician’s choice (TPC). In this unplanned subgroup analysis, we compare the clinical benefit of eribulin to TPC in mBC pts with visceral disease using the Independent Review database. Patients were categorized as having visceral disease if they had target or non-target lesion involvement in the adrenal gland, liver, lung, pleural, pericardial/peritoneal cavity, spleen, or thyroid. Patients with brain metastases were excluded from the trial.

Results: EMBRACE enrolled 762 pts with mBC, with single organ disease present in 120 pts (15.7%). The remaining pts had multi-organ disease. A total of 81.9% (624) of pts were classified as having visceral disease–81.3% (413) randomized to receive eribulin and 83.1% (211) to receive TPC. Metastatic tumor site was similar in eribulin and TPC arms, with liver (58.3%; 62.6%), lung (38.8%; 37.4%) and pleural (17.1%; 16.5%) involvement. Patients with visceral disease treated with eribulin demonstrated a significant benefit in OS compared to TPC (HR 0.77, p=0.02). Median OS in mBC pts with visceral disease was 12.45 months (mos) for eribulin-treated pts, with ORR=11.0% and CBR*=21.7% compared to OS=10.12 mos, ORR=5.0%, CBR*=16.6% for TPC-treated patients (*CBR defined as CR+PR+SD>6mos). No significant treatment difference was observed in the non-visceral disease patients however due to the small number of patients with non-visceral disease, no robust statistical conclusions can be made.

Conclusions: Treatment with eribulin resulted in significant improvement in overall survival for mBC pts with visceral disease compared to other commonly used chemotherapeutic agents.
Impact of reconstruction on satisfaction with contralateral prophylactic mastectomy.
Authors: Boughey J. C. , Hoskin T. L. , Hartmann L. C. , Johnson J. L. , Jacobson S. R. , Degnim A. C. , Frost M. H.
Published: February 2017

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Background: Contralateral prophylactic mastectomy (CPM) is increasingly chosen by patients with breast cancer. Satisfaction after CPM is high. However, decreased satisfaction has been associated with reoperation after reconstruction. This study’s aim was to examine the adverse aspects patients attribute to reconstruction and the subsequent effect on psychosocial consequences and satisfaction with CPM.

Methods: 487 unilateral breast cancer patients with a family history of breast cancer who underwent CPM between 1960 and 1993 were mailed a questionnaire evaluating QOL and satisfaction with CPM.

Results: Of 269 respondents, 210 (78%) underwent reconstruction and 59 (22%) did not. Mean age at CPM was 46 and 50 years respectively (p=0.01). Mean follow-up was 20.2 years. Reconstruction was immediate in 96%, 98% with implants and 2% with tissue flap. Reconstruction was associated with lower satisfaction with CPM (p=0.03), but still only 7% (vs 2% in those without reconstruction) said they were dissatisfied. Most (83%) of those with reconstruction said they would choose reconstruction again while 7% were unsure and 10% said they would not. In those who did not undergo reconstruction, 18% said they would choose reconstruction if able to make the choice again while 5% were unsure and 77% said they still would not. 95 patients (45%) of those that underwent reconstruction required one or more reoperations for complications. Those with reoperation reported poorer responses for satisfaction with CPM (p=0.04), choice to have CPM again (p=0.008), and choice to have reconstruction again (p=0.004) when compared to patients with reconstruction and no reoperation. Those with and without reconstruction did not differ significantly with respect to femininity, sexual relationships or emotional stability, but those without reconstruction reported significantly poorer effects related to self esteem (p=0.04) and body appearance (p=0.002).

Conclusions: In patients who undergo CPM, many years after surgery satisfaction with CPM is higher in those choosing not to have reconstruction than those with reconstruction although it was high in both groups. Reoperation is common after reconstruction and is associated with lower satisfaction.
Pregnancy-associated breast cancer: Review of the literature.
Authors: Bjelic-Radisic V. , Retussnig C. P. N.
Published: February 2017

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Background: Overall, 0.2%-3.8% of all breast cancer cases are diagnosed during the pregnancy. It is to be expected that the incidences of pregnancy-associated breast cancer (PABCS) will likely increase. Therapy of PABCS is the challenge and requests team play of different experts in this area. The aim of this study was to review the actual therapy of PABCS.

Methods: Publications relevant to PABCS and their therapy were identified by searching Pubmed database for the period between 1960 and 2010. We used the keywords “cancer”, “pregnancy”, “chemotherapy”, and “systemic treatment”. Search results were adjusted by references from relevant articles. 221 relevant articles and abstracts were found. Articles describing the same patient cohort and articles without data of the kind of drug, trimester of application and without size of patient cohort were excluded from analyses. 79 articles matched the search criteria and were included in analyses.

Results: The use of anthracycline-based chemotherapy has been documented in 320 cases, congenital malformation (CM) occurred in 3.75% of the reported cases (similar to the standard population). 14 publications described a methotrexate-containing therapy during pregnancy, CM occurred in 6.67%. Use of taxanes has been documented in 29 cases, CMs were observed in 3.45%. 9 articles (20 cases) published the effects of vinca alkaloids-containing treatment, in 1 cases occur missed abortion. Tamoxifen use during pregnancy is described in 9 publications, 30% of the exposed newborns showed CM. The application of target-agent-trastuzumab during pregnancy is described in 16 case reports with developing of oligo- or anhydramnion, IUGR, pulmonal hypoplasia.

Conclusions: Anthracyclines are regarded the safest chemotherapeutic agents during pregnancy and can be given with minimal fetal risk after the first trimester. The routine use of newer agents like taxanes or vinca alkaloids are with high possibility safe in 2. And 3. Trimenom, but because of limited data are not recommended so far. Methotrexate should be avoided during pregnancy. Tamoxifen, aromatase inhibitor and target agents are contraindicated during the pregnancy. Target agents can not be recommended for the use in the pregnancy.
Male breast cancer: An institution’s 25-year experience.
Authors: Scow J. S. , Degnim A. C. , Jakub J. W. , Shah S. , Jimenez R. E. , Boughey J. C.
Published: February 2017

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Background: There are no prospective and few large retrospective studies of male breast cancer (MBC). This study’s aim was to describe our institutional experience with MBC and evaluate the ability of the AJCC staging system to stratify survival.

Methods: All MBC cases were identified from our institution’s cancer registry from 1984-2008. Data collected included tumor characteristics, lymph node status, treatment, age, and survival.

Results: During the study period 166 MBC cases were identified. Median age at diagnosis was 62 years (range 27-87). Most common presentation was a palpable breast mass (77%). Stage at diagnosis was stage 0 (6%), stage 1 (27%), stage 2 (36%), stage 3 (17%), stage 4 (5%), and unknown (9%). Procedure performed was mastectomy in 148 patients (89%), lumpectomy in 10 patients (6%) and unknown in 8 patients (5%). Median tumor size was 2.0 cm (range 0.2-11.0 cm). Most common histology was invasive ductal carcinoma (91%). Estrogen and progesterone receptor status assessed at diagnosis was positive in 93% and 86% of cases tested respectively. HER2/neu status was positive in 6 of 47 cases tested (13%). Nodal staging was performed by axillary dissection (AD) (70%), sentinel node biopsy (SN) alone (11%), SN and AD (11%) and no axillary staging (8%); 43% were node positive, 47% node negative and 10% unknown. Adjuvant chemotherapy was given to 40 patients (24%), adjuvant hormonal therapy to 42 patients (25%) and adjuvant radiation therapy was used in 33 cases (20%). With a median follow-up of 5.5 years, 86 patients (52%) have died: 44 due to breast cancer, 23 due to causes unrelated to breast cancer, and in 19 the cause of death is unknown. Median overall survival was 9.3 years. Median cancer-specific survival was 16.0 years. For patients initially diagnosed at stage 2, 3, and 4 median cancer-specific survival was 12.9, 7.2, and 0.8 years respectively. Median cancer-specific survival was significantly different for stages 2 vs. 3 (p = 0.03) and 3 vs. 4 (p = 0.0006).

Conclusions: MBC most commonly presents as a palpable mass, is hormone responsive, and is most commonly treated with mastectomy. The TNM system appropriately stratifies men with MBC by duration of survival.
Tolerance of docetaxel: Is obesity a risk factor for toxicity? A pilot study.
Authors: Parent D. , Rallet A. , Jovenin N. , Yazbek G. , Cure H. , Rey J.
Published: February 2017

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Background: Few data are available in the literature regarding chemotherapy dosage adjustment in obese patients. Docetaxel is a lipophilic substance, highly bound to albumin; obesity might result in an accumulation and may lead to a higher rate of toxicity. The objective of this study was to assess the tolerance to docetaxel in obese and non obese patients, according to their body mass index (BMI).

Methods: A retrospective study was performed. Patients were divided according to their BMI, considering a limit of 30 kg/m2. All patients received docetaxel (100 mg/m2) as a part of adjuvant chemotherapy for breast carcinoma. Toxicity of docetaxel such as neutropenia, hand-foot syndrome (HFS), mucositis, and neuropathy were assessed in both groups. The included patients received docetaxel alone or in association with trastuzumab or bevacizumab. Qualitative data analysis was performed using Fisher's exact test. Quantitative data were studied using the Student test.

Results: Among the 49 patients, 18 (37%) presented with a BMI greater than 30 kg/m2. The median age was 53 years in the group BMI greater than 30 and 55 years in the group BMI less than 30 (p = 0.9383). The median value for albumin was 75 g/L (59-86 g/L) in the BMI greater than 30 and 71 g/L (56-79 g/L) in the BMI less than 30 (p = 0.122). Toxicity in both groups is shown in the table below. No neuropathy was observed.

Conclusions: Obese patients (BMI > 30 kg/m2) presented with more toxicities (p = 0.013). Hypoalbuminemia did not represent a risk factor for toxicity in this study. Obesity is a risk factor for toxicity in patients treated with docetaxel. Dosage calculation according to body surface area is not suitable for these patients. Toxicity in the group BMI < 30 seems to demonstrate greater susceptibility to the molecule for these patients. Further studies will try to identify the different mechanisms of toxicity of docetaxel involved obese patients, including the interaction between docetaxel and fats. Measures have also to be taken to obtain a favorable effectiveness/toxicity balance in obese patients.

[Table: see text]
Breast cancer survivors’ motivation to perform preventive health behaviors: An application of the protection motivation theory.
Authors: Mohamed I. , Jordan T. , Coman M.
Published: February 2017

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Background: Little is known about what motivates breast cancer survivors to engage in preventive health behaviors to prevent recurrence of breast cancer. The primary objective was to assess how survivors’ fear of recurrence, spirituality, and perceptions of risk and coping appraisal were associated with their motivation to perform healthy lifestyle and cancer screening behaviors.

Methods: A reliable and valid questionnaire was developed. An a priori power analysis indicated that a minimum of 386 completed surveys were needed for adequate statistical power. Based on an estimated 50% return rate, the investigators randomly selected a state-wide sample of 800 survivors from Ohio. A 3-wave mailing was used to increase response rate.

Results: 559 surveys were completed (72%). Respondents with higher perceived risks of recurrence were more motivated to perform healthy lifestyle behaviors than those with lower perceived risks (t=2.51, df=521, p=.039). Most (>70%) agreed that healthy lifestyle behaviors such as regular exercise reduce one’s risk of recurrence. Only 43% exercised regularly. Only 54% reported their doctor discussed how to reduce the risk of recurrence. Survivors who were satisfied with their physician’s communication exercised more regularly than those who were not satisfied (chi-square =13.09, p=.016, df=5). Cancer survivors with a high level of motivation and high level of behavioral intentions were more likely to be engaging in preventive health and cancer screening behaviors. Higher levels of spirituality were positively correlated with a higher level of motivation to engage in preventive health behaviors (r=.345, n=468, p<0.001).

Conclusions: This study provides strong evidence that the Protection-Motivation Theory (PMT) helps to explain certain factors that impact survivors’ motivation and behavioral intentions to engage in healthy lifestyle behaviors and follow up screening tests. When developing programs for breast cancer survivors, health professionals should consider incorporating spirituality, fear of recurrence, and the constructs of the PMT.