bluuebunny/crossref_metadata_2025 huggingface dataset:
Do younger women with early breast cancer have a higher recurrence risk?
Authors: Yap K. K. L. , Efiom-Ekaha D. N.
Published: February 2017

178

Background: There has been conflicting evidence in the literature regarding the association between age and breast cancer recurrence risk. Cancer Research UK reported a better survival among patients aged 50 to 69 compared to younger women. The National Cancer Institute had reported the same, but only in women with stage 1 cancer. Fox Chase Cancer Center and Lyman et al had however suggested that there is no association between breast cancer recurrence and age at diagnosis. Our objective is to investigate the association between breast cancer recurrence and age at diagnosis.

Methods: An IRB-exempted restrospective chart review of female patients at Wellspan Group who had Oncotype DX analysis in 2008 and 2009. Data collected included Oncotype DX score and age at diagnosis. Data was analyzed to determine the correlation between Oncotype DX score and age at diagnosis. The patients were divided into three groups: age less than 45 years, age 45 to 59 years, and age 60 or more. Oncotype DX score was used because it has been clinically validated as a reliable predictor of breast cancer recurrence for node-negative breast cancer.

Results: A total of 125 patients were identified. The Pearson Correlation score for Oncotype DX score and age at diagnosis was -0.064 (p = 0.478). The mean score was 18.36 for those aged less than 45 years, 22.04 for those aged 45 to 59 years, and 19.16 for those age 60 or more. The difference between these groups was not significant (p = 0.340).

Conclusions: There was neither significant correlation between breast recurrence and age, nor difference between the three age groups. Our study shows that age at diagnosis is not an independent predictor of breast cancer recurrence risk.
Features of recurrence of triple-negative (TN), non-metastatic breast cancer (NMBC) patients: A single institution study.
Authors: Alarcon-Rozas A. E. , Cueva M. R. , Galarreta J. , Torres J. , Gonzales E. , Ramirez J.
Published: February 2017

180

Background: The TN BC is the most agressive subtype. Previous studies suggested that DFS of women with TN-BC is shorter than any other subtype and they demonstrated racial differences. The behaviour of these tumours are characterised by poor prognosis affecting mostly African American young obese women. Our goal is to determine the incidence of TN in non metastatic (NM) BC, the recurrence rate (RR), the patterns of recurrence by anatomic region and the DFS.

Methods: We reviewed the medical records of patients with BC diagnosed between Jan/2000 to Dec/2005 at Almenara Hospital in Lima, Peru. There were a total of 1042 patients with BC; of them 215 were identified as TN NM BC according to IHC ER, PR, and Her2/neu negatives. We collected the clinical data including age, menopausal status, staging, hormone receptor status as well as Her2/neu status. The data were analized by statistic software SPSS v. 17.0.

Results: The incidence of TN NM BC were 20.6% (215); of them 18.6% (40) patients had recurrences. The median age of recurrence were 52.5 years (31-93); the median DFS were 27 months, with a median follow-up of 64 months. According to inicial staging the recurrences were 7.5% (3); 32.5% (13); and 60% (24) respectively for patients with stages I, II and III. Almost one third (35%) of patients with recurrences were lymphatic node negative at diagnosis after mastectomy. The most frequent involved organs were visceral (lung=12, liver=3) 37.5% (15); bone 25% (10); skin 20% (8); CNS 12.5% (5) and contralateral breast 5% (2). There were four nuliparus women two of them had skin recurrence and the others two had bone metastasis.

Conclusions: TN NM BC constitutes 20.6% of all BC in our institution; the majority of relapses were stage III (60%). The median DFS for recurrence were 27 months and the most frequent sites involved were visceral (37%) and bone (25%). 12.5% of recurrences were to CNS and one third of the patients were lymph node negatives. This is to our knowledge the first study of patterns of recurrence in TN nonmetastatic BC in a Latino population. The incidence of TN-BC which is close to African-American population (25%).
Are we seeing more obese breast cancer patients in Brooklyn?
Authors: Sultana R. , Thwin M. , Villani G. M. , Grand M. A. , Tun N. M.
Published: February 2017

182

Background: Breast cancer is the most common female cancer in the US and the second most common cause of cancer death in women. Obesity has become a significant health challenge. The prevalence of obesity among non-Hispanic black women is reported to be approximately 50% with a prevalence of Class lll obesity of 5.2%. The objective of this study was to evaluate the severity of obesity in female breast cancer patients at our facility over the last three years.

Methods: A retrospective study was conducted on 191 patients treated between January 2008 and December 2010 for breast cancer. Prevalence of obesity by class (Class I = BMI from 30 to 34.99 kg/m2, Class II = BMI from 35 to 39.99 kg/m2, Class IIl= BMI greater than 39.99 kg/m2) was calculated. Pearson chi-square statistic was used to investigate the relation between classes of obesity and stages of breast cancer (early stage = CIS to stage 2, advanced stage = stage 3 and 4).

Results: Data from 191 breast cancer patients with BMI of 30 or more were analyzed. Class I constituted 39.3%, Class II 34% and class III 26.7%. The majority (75.9%) were diagnosed at an early stage, 24.1% diagnosed with advanced stage. Severity of obesity was not associated with the stage of breast cancer at diagnosis (c2= 0.004, df = 2, n = 191, p > 0.5). African American women constituted the majority (78.5%) of our study population.

Conclusions: Our study reveals an alarming rate of class lll obesity among our breast cancer patients. It does not show a correlation among obesity and stage of disease, The majority of patients have early stage, potentially curable breast cancer. Given the fact that obesity has been associated with an increase in mortality (cardiovascular mortality is 50% greater in obese people and 90% greater in severely obese persons in comparison with that for people of average weight) our study suggests that treatment of obesity may play an equally important role in achieving long term outcomes as treatment of breast cancer itself.
Association of a common genetic variant of the IGF1 gene with clinical outcome in patients with HER2-positive breast cancer.
Authors: Lang A. , Muendlein A. , Hartmann B. L. , Drexel H. , Decker T. , Fricke H. , Hofmann W. , Mueller-Holzner E. , Marth C. , Hubalek M.
Published: February 2017

193

Background: Insulin-like growth factor 1 (IGF1) stimulates mitosis and inhibits apoptosis. Circulating IGF1 levels may be linked with an increased risk of colorectal and breast cancer. Further, IGF1 single nucleotide polymorphisms (SNPs), especially variant rs2946834, recently have been associated with a poor clinical outcome in patients with colorectal cancer. However, the influence of IGF1 SNPs on the prognosis of patients with breast cancer is unknown. Therefore, we aimed at investigating the influence of IGF1 tagging polymorphisms associated with IGF1 levels on event-free survival in patients with HER2-positive breast cancer.

Methods: The present study included 161 consecutive white patients with HER2-positive breast cancer treated between 2000 and 2010 at the Department of Gynecology and Obstetrics, Medical University of Innsbruck, Austria. Event-free survival was calculated as the time from cancer diagnosis to either relapse or death from any cause. Genomic DNA was extracted from archived formalin-fixed paraffin embedded tumor tissue samples; five IGF1 tagging polymorphisms (rs2946834, rs6220, rs1520220, rs5742694, and rs5742678) were genotyped by SNaPshot assays.

Results: Mean follow up period was 4.3 (± 2.5) years. Kaplan-Meier analysis showed a poorer clinical outcome for carriers of the rare allele of SNP rs2946834 (log-rank test, p = 0.029). Concordantly, in univariate Cox regression analyses the rare allele of SNP rs2946834 was significantly associated with a decreased event-free survival (HR = 2.87 [1.07 –7.70]; p = 0.036). Multivariate analysis adjusted for age and tumor stage confirmed this result (HR = 2.86 [1.06 –7.71]; p = 0.038). Thus, our results are in concordance with a recent report that the same SNP is associated with poorer clinical outcome in colorectal cancer patients. Other investigated genetic variants of the IGF1 gene were not significantly associated with event-free survival (all p-values > 0.05).

Conclusions: For the first time, our study investigates the influence of IGF1 tagging polymorphisms on the clinical outcome of HER2-positive breast cancer patients suggesting SNP rs2946834 as a predictor for reduced event-free survival.
Who provides ongoing care to breast cancer survivors and does it make a difference?
Authors: Sowden M. , Sanft T. B. , Chagpar A. B.
Published: February 2017

199

Background: There is a paucity of data regarding who provides ongoing care for breast cancer survivors, and the impact of this on adherence to screening guidelines. The purpose of this study was to define, in a population based cohort, with whom breast cancer survivors receive their ongoing care and the impact of provider choice on quality of care.

Methods: Data from the 2005 National Health Interview Survey were queried for provider types and screening adherence in breast cancer survivors. Statistical analyses were performed using SAS and SUDAAN software.

Results: 435 breast cancer survivors were surveyed in 2005. Their mean age was 66, and the median age at diagnosis was 57. 284 (60.9%) were more than 5 yrs out from diagnosis. Of respondents, 84.3% reported having a clinical breast exam (CBE) within the past year and 79.8% reported having had a mammogram (MMG) within the past 2 years. 429 (99%) reported whether they had seen a family physician (GP) and/or OBGYN in the preceding 12 months; specific reference to care by oncologist was unavailable. 91.8% of survivors had seen either their GP and/or OBGYN in the last year. No significant differences were seen in provider choice nor adherence to surveillance recommendations based on survivorship period (≥ or < 5 yrs). There was no significant difference in CBE and MMG between survivors who had seen their GP within the preceding 12 months and those who did not, but those who had seen their OBGYN had a significantly higher rate of having had a CBE (92.0% vs. 81.1%, p=0.01) and MMG (90.1% vs. 75.3%, p<0.01) than those who did not. Adherence to screening recommendations was superior for patients who had been seen by multiple providers than those who had not been seen by any.

Conclusions: Breast cancer survivors get their follow-up care through a variety of providers, often relying on primary care. A collaborative survivorship plan involving multiple specialties may improve adherence to screening guidelines.

[Table: see text]
The potential economic impact of the 21-gene recurrence score: Guided chemotherapy in a population-based cohort with node-negative and node-positive early-stage breast cancer.
Authors: Lamond N. W. D. , Skedgel C. , Rayson D. , Lethbridge L. , Younis T.
Published: February 2017

201

Background: The 21-gene recurrence score (Oncotype DX: RS) appears to augment clinical-pathological prognostication and predicts adjuvant chemotherapy (chemo) benefits in patients with node-negative (N-) and node-positive (N+) hormone-receptor positive early-stage breast cancer. Economic analyses suggest that RS-guided chemo is a cost-effective strategy in N- breast cancer, but no evaluations were reported for N+ disease based on pre RS chemo utilization in clinical practice. We examined the cost-utility (CU) of a RS-guided chemo strategy, compared to current practice without RS in a population based cohort, in N- and N+ early-stage breast cancer.

Methods: A generic state-transition model was developed to compute cumulative costs and quality-adjusted life years (QALY) over a 25-year horizon for patients with hormone-receptor positive early-stage breast cancer considered for chemo. We examined outcomes with and without chemo in RS-untested cohorts and in those with low, intermediate and high RS based on the reported prognostic and predictive impact of the RS. Chemo utilizations (current vs RS-guided), costs and utilities were derived from a Nova Scotia population based cohort, local resources and the literature. Sensitivity analyses were conducted for key model assumptions/parameters.

Results: RS-guided chemo strategy is associated with incremental costs and QALY gains compared to chemo with no RS testing in both N- and N+ patients. The resultant CU ratios are $17,141/QALY and $5,772/QALY for N- and N+ disease, respectively. These CU ratios are well below commonly quoted thresholds and were most sensitive to RS-distribution, upfront chemo costs, chemo utilization rates and relative benefits of chemo in various RS-strata.

Conclusions: RS-guided chemo in a population based cohort appears to be a cost-effective strategy, compared to chemo with no RS testing, in N- and N+ early-stage breast cancer.
Breast cancer (BC) care and outcomes in Latin America and the Caribbean (LAC).
Authors: Justo N. , Wilking N. E. , Jönsson B.
Published: February 2017

202

Background: The global BC Care and Outcomes Report revealed ample differences in BC care and outcomes exist across continents, exposing the need for regionally focused studies. Aim: Provide an overview of the burden of BC and of BC care and outcomes in LAC and identify the major challenges

Methods: Review of literature (PubMed, LILACS, SCIELO), public databases (Globocan 2002 and 2008, CEPALSTAT, DIRAC, PAHO, WHOSYS, etc) and conference presentations (ASCO, ISPOR). Local experts and patient organizations were surveyed. Current BC epidemiology in LAC, countries’ risk profiles and future trends, disease burden and available resources, patterns of care and treatment access (case studies), and outcomes (such as mortality-to-incidence ratios - MIRs) were analyzed and compared (Sweden as benchmark).

Results: BC exhibits the highest annual incidence (114,900 cases) and mortality (37,000 deaths) of all cancers in LAC and is expected to double by 2030. Age is the main risk factor. Heavy burden is due to younger age at diagnosis. Poor outcomes are partly due to late diagnosis. Availability of specialized surgeons, waiting times, node clearance policy and access to breast reconstruction vary widely across countries and between public and private settings. Radiotherapy equipment is insufficient, except in Uruguay, Chile, and Venezuela. All modern systemic therapies are available, but some not widely diffused due to their costs. Palliative care is developing but, despite great efforts, problems persist. BC MIRs have improved, albeit unevenly, over time.

Conclusions: Inequalities in access to diagnosis and treatment, fragmented organization and management of BC care and poor uptake of evidence-based best practices result in high morbidity and associated societal costs.

[Table: see text]
Timeliness of breast tissue pathology reports: Quality thresholds for breast centers.
Authors: Kaufman C. S. , Shockney L. D. , Landercasper J. , Rabinowitz B. , Askew J. B. , Wiggins D. , Quality Committee T.
Published: February 2017

204

Background: The National Quality Measures for Breast Centers (NQMBC) was started in 2005 to provide quality metrics for breast centers. Each center enters confidential aggregate results to questions regarding the process of breast care. Each data entry can be immediately compared with all other centers. We reviewed data regarding the timeliness of pathology reports after tissue sampling to look for variation among different types of breast centers.

Methods: We reviewed the following measures: 1) Time between needle/core biopsy and availability of pathology report; 2) Time between surgical biopsy and availability of pathology report; and 3) Time between initial cancer surgery and availability of pathology report. We looked for variation in results according to structural differences of breast centers.

Results: There were 391 center entries reviewing over 21,000 patient encounters between 2005 and 2011. Results included percentiles at 10, 25, 50, 75, and 90 and mean value. Overall, pathology reports for needle biopsy were available much sooner (mean 1.4 days) than any surgical biopsy or excision (2.1, 2.4 days). Results were not altered according to demographic characteristics (type of center, cancer volume, financial structure, size of city and geographic location).

Conclusions: The timeliness of pathology reporting of breast specimens is very consistent throughout the participating NQMBC centers, regardless of type and size of breast center. In view of the consistency of those results, a threshold level of care (10th percentile) may be identified above which all centers should be expected to perform. This minimum level of performance is called the quality threshold. Centers that do not perform above this quality threshold should be ready to explain why their performance falls below this level. Centers who surpass this quality threshold should strive for a quality goal (50th percentile). We expect that by setting both the quality threshold and the quality goal for each measurement, we will have ongoing encouragement for achievable improvement for each measure.
Time interval as a quality measure: What is our baseline prior to nurse navigator implementation?
Authors: Amin M. , Basu M. , Patterson S. G. , Pinkerton H. , Torres M. A. , Newell M. , O'Regan R. , McCarthy C. , Tarpley R. , Gabram S. G. A.
Published: February 2017

208

Background: There are various outcome measures to evaluate the quality of multidisciplinary care for breast cancer patients. The National Consortium of Breast Centers defines quality of breast cancer care as accurate evaluation and appropriate services in a timely manner. In a tertiary academic center a diverse referral pattern possibly influences time to treatment. We choose to examine two outcome measures before the start of a nurse navigator: Time from initial diagnosis to first consultation and if the pretreatment consultation for those receiving neoadjuvant chemotherapy or hormonal therapy included all subspecialists.

Methods: Electronic medical records of female patients with breast cancer seen during January-June 2010 were reviewed. Patients with stage IV breast cancer were excluded.

Results: 150 patients were divided into 4 categories: external pathology consult (B1), internally diagnosed with a primary care physician (PCP) at our institution (B2), evaluated by a surgical oncologist before the biopsy (B3), and internally diagnosed with PCP outside of the institution (B4). For B2, B3 and B4 we examined the time intervals to first surgical oncology appointment after diagnosis as shown in the table. For all patients (n=10) who received neoadjuvant therapy, 1 patient saw a surgical oncologist, medical oncologist and radiation oncologist, 9 patients saw 2 subspecialties prior to initiation of first treatment.

Conclusions: Patients are seen within an average of 2 weeks whether they are diagnosed internally (B2, B3) or externally (B4). The group seen by a surgical oncologist prior to biopsy (B3) were seen sooner. For the patients receiving neoadjuvant therapy, 10% saw all 3 specialties prior to initiation of therapy. In July 2010 a nurse navigator was added to the care team. With this new position, our goal is to decrease the time from biopsy to visit by 33% and have 100% of patients receiving neoadjuvant therapy evaluated by all 3 specialists prior to treatment. Our intent is to quantify the effect of a nurse navigator in a large academic center as a quality metric in improving care.

[Table: see text]
Training overweight/obese older women at high risk for breast cancer to use web-based weight loss tools: The HELP pilot study.
Authors: Cadmus Bertram L. A. , Pierce J. P. , Patterson R. E. , Ojeda-Fournier H. , Newman V. A. , Parker B. A.
Published: February 2017

233

Background: Excess weight is one of the few modifiable risk factors for incident breast cancer. Many programs can achieve a 7% weight loss but few can maintain it over time. Training women to use self-help resources over the internet has potential for reducing intervention costs and ensuring program maintenance.

Methods: 50 overweight/obese (BMI≥27.5 kg/m2) women at increased risk of breast cancer (Gail score≥1.7) were identified from a mammography registry and enrolled in the HELP pilot study and randomized with 2:1 probability to a 12-week lifestyle intervention or a comparison group. Twelve telephone-based coaching calls trained participants to use a free, publicly available website to set goals and track performance for dietary intake and physical activity. The comparison group received information but no training. At baseline and 12 weeks, participants were weighed, fitted with an accelerometer for physical activity pattern, and completed questionnaires.

Results: At baseline, participants were 60.9±0.79 years of age with a BMI of 33.1±0.60 kg/m2; 39% were daily internet users. Thirty-three were randomized to the intervention group with 91% completing follow-up. Fifty-four percent were able to use the website reliably and found it to be helpful, including 44% of previously nondaily internet users. At 12 weeks, intervention group participants who found the website helpful had lost 5.6±0.7 kg, or 6.7% of initial weight, intervention participants who did not find it helpful lost 0.8±0.9kg or 1.1% of initial weight and the comparison group gained 1.0±0.94 kg (89% follow-up) The between-group difference weight change was 4.2 kg (p<.0001). 74% of intervention group participants lost weight, compared to only 34% of women assigned to the comparison group.

Conclusions: A 12-session telephone coaching program to train women to use publicly available web-based weight loss programs effectively achieved a large short-term weight loss among the majority of participants. Further follow-up is needed to identify how well the initial weight loss is maintained without further intervention assistance.
A prospective, multicenter trial of complementary and alternative medicine (CAM) utilization by patients undergoing definitive breast radiotherapy.
Authors: Moran M. S. , Yang J. , Ma S. , Gaudreau B. , Higgins S. A. , Weidhaas J. B. , Wilson L. D. , Peschel R. , Fass D. , Rockwell S.
Published: February 2017

241

Background: A substantial number of breast cancer (BC) pts use complementary and alternative medicines (CAM), but there is a paucity of data on CAM specifically during radiation therapy (RT). The purpose of this study was to prospectively assess the utilization of CAM during RT for BC pts.

Methods: 456 pts w/stage 0-III BC were accrued from 5 RT centers from 9/07-2/09. Participating MDs were advised not to discuss CAM. A validated survey instrument was administered during the last week of RT under guidance of a study nurse, which included demographics, details regarding types/doses/frequency of CAM and skin assessments by pt and nurse.

Results: 360 pts were eligible for analysis (79%); median age 57 yrs; stage 0-II, 91%; white race 89%; chemotherapy 39%; hormone therapy (HT) w/ RT, 26%; > college education, 59%. CAM was reported in 54% (n = 195), of which 72% reported programs/activities (i.e., Reiki, healing touch, visualization, etc.), and 66% oral/topical CAM. Only 16% reported counseling prior to starting CAM. CAM use did not differ by ethnicity, chemotherapy or stage (all p > 0.05), but correlated significantly with higher education level (p = 0.0001) and inversely correlated w/ HT/RT (p = 0.015). There was a trend towards CAM use in younger pts (p = 0.069). On MVA, education (RC: 1.859; OR: 6.417, 95% CI: 2.023, 20.357, p = 0.002) and HT/RT (RC: -0.530, OR: 0.589, 95% CI: 0.357, 0.970, p = 0.038) independently predicted for CAM use. Rationale for oral/topical: 32% “improve their chance of cure”; 24% “provide treatment-related symptom relief”. For programs/activities: 31% “relaxation/stress reduction”; 11% “reduces treatment-related symptoms”. Despite these beliefs, there were no significant differences between the perception of the pts to nursing skin assessment score as a function of CAM use (p = 0.497).

Conclusions: To our knowledge, this is the first and largest prospective study of CAM during RT for BC pts. Given the high prevalence of undocumented CAM use during RT, questions regarding CAM should be considered during consultation and weekly tx visits. A better understanding of CAM practices during RT will facilitate evaluation of potential interactions of CAM and RT for BC.
Perforator flap breast reconstruction in thin patients.
Authors: Chen C. M. , Ahn C. , Levine J.
Published: February 2017

242

Background: Perforator flap breast reconstruction has strong appeal for many women seeking breast reconstruction, but the procedure requires adequate donor site tissue to produce realistic breasts. Thin women requesting perforator flaps are often advised that they lack sufficient donor site tissue for autologous tissue breast reconstruction, and that implants are their only option. We have expanded the reconstructive options for thin women who seek an alternative to implants with innovative new techniques.

Methods: A retrospective review was done of 223 patients who underwent 293 consecutive perforator flap breast reconstructions from April 2007-May 2011. Preoperative imaging allowed visualization of the microvascular anatomy and subcutaneous tissue. Donor sites evaluated included the abdomen, medial thigh, buttocks, and back. Complications included flap loss, hematoma, seroma, takeback, and fat necrosis. No patients were turned away for perforator flap breast reconstruction due to insufficient donor site tissue.

Results: Out of 293 perforator flap breast reconstructions, 45 perforator flap breast reconstructions (15.4%) were reported in 26 thin women with a BMI < 23 (mean BMI 20.7, range BMI 18.2-22.7). Out of 45 perforator flap breast reconstructions in thin women, donor sites included 35 hemi-abdominal flaps (77.8%), 4 medial thigh flaps (8.9%), 7 buttock flaps (15.6%), and 2 back flaps (4.4%). Of the 35 hemi-abdominal flaps, 8 hemi-abdominal flaps were combined to create 4 stacked DIEP flaps (22.9%) while the remaining 27 hemi-abdominal flaps were regular DIEP flaps (77.1%). There was one seroma (2.2%) and one takeback for postoperative pain (2.2%); there were no flap losses.

Conclusions: Even in thin women, perforator flap breast reconstruction is a safe, reliable, and consistent technique for recreating new breasts. While implant-based breast reconstruction may be acceptable to many women, there is a growing subgroup of patients who prefer autologous tissue breast reconstruction. By challenging common conceptions about the amount of donor site tissue required, we have been able to expand reconstructive options in thin women by using perforator flaps to construct natural, aesthetic breasts.
The experience of young women diagnosed with breast cancer who undergo fertility preservation (FP) consultation.
Authors: Hill K. A. , Nadler T. , Mandel R. , Burlein-Hall S. , Librach C. , Warner E.
Published: February 2017

249

Background: In recent years FP has been a growing concern for young women diagnosed with breast cancer. ASCO has recommended that such women be referred to a reproductive specialist as early as possible before beginning systemic adjuvant therapy. Aim: To gather information about young breast cancer patients’ experiences with FP referral, consultation, and decision making.

Methods: Anonymous questionnaires were mailed to consecutive breast cancer patients referred January 2005 through January 2010 from our center to the CReATe clinic in Toronto. Topics included information about demographics, cancer stage and treatment, previous fertility problems, referral source and timing, options presented and chosen, and satisfaction with the referral, consultation and decision making processes.

Results: Of the 50 women identified 26 (52%) participated. Average age of respondents was 31 (range 24-41). 17 (65%) were married or in a long-term relationship, and 9 (35%) already had 1 child. Seven (27%) were referred before surgery, 16 (62%) after surgery but before systemic therapy, 2 (8%) after starting hormone therapy, and 1 after completing chemotherapy. Only 54% opted for FP. Of the 17 (66%) who reported plans to start/add to their family prior to diagnosis of breast cancer, 53% proceeded with FP and of the 9 who did not have plans to start/add to their family 5 (55%) pursued FP. 41% had difficulty with decision making and 50% found cost to be a significant barrier. A common theme among respondents was inadequate time for decision making. Several complained about the lack of written material before and/or after their consultation. 85% felt that access to a psychosocial counselor would have been beneficial to the decision making process. 57% were satisfied or extremely satisfied overall.

Conclusions: (1) If appropriate, FP referral should be initiated by the surgeon as soon as a diagnosis of invasive cancer is made. Obtaining receptor and HER2 status on core biopsy samples may identify women who will require systemic therapy and may benefit from early FP referral. (2) Women need written materials before and after FP consultation. (3) There is a major role for a FP counselor who is able to spend additional time helping with decision making.
Usefulness of an original self-completed questionnaire for screening of cancer-related mental disorder in patients with newly diagnosed early breast cancer.
Authors: Kawaguchi K. , Tuyuki S. , Yoshitoshi E. Y. , Honda M. , Takase M. , Yoshida Y. , Kono Y.
Published: February 2017

267

Background: Cancer-related mental disorder reduces (e.g., depression and anxiety disorder) not only treatment compliance but also compromises the quality of life of the patient. However, psychiatric intervention at the cancer notification has been barely performed in Japan because Japanese people traditionally tend to have a prejudice against psychiatric consultation and about sexual activity. In order to provide more effective treatment for breast cancer patients, it is necessary to treat cancer-related mental disorder in Japan.

Methods: Based on Self-rating Depression Scale, Hamilton's Rating Scale for Depression and Beck Depression Inventory, the questionnaires were modified for Japanese patients by psychiatrists and clinical psychologists of our hospital. We asked newly diagnosed breast cancer patients an original self-completed questionnaire regarding the depression and anxiety disorder between January 2010 and March 2011. This questionnaire consists of 14 questions about depression and anxiety disorder without questions of sexual activity, which has two points each question (maximum total points were 28). We recommended the psychiatric interference by a psychiatrist and the clinical psychologist to all patients with more than 14 points in this questionnaire.

Results: We obtained data from 116 patients. No patient refused to answer the questionnaire. 23 patients had higher than 14 points in this questionnaire. Of 23 patients, 9 patients received psychiatric intervention without medication, and four patients received psychotropic medications. Based on the results, we avoided the administration of anticancer agent by intravenous infusion in three patients who had higher than 14 points in the questionnaire. Multivariate analysis revealed that unmarried status is associated with a significantly higher score (OR 16.1; p = 0.013).

Conclusions: Our data suggest that our original self-completed questionnaire is useful for the screening of the cancer-related mental disorder in order to provide appropriate therapy to newly diagnosed breast cancer patients.
Results of ENCORE 301, a randomized, phase II, double-blind, placebo-controlled study of exemestane with or without entinostat in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive (ER+) breast cancer progressing on a nonsteroidal aromatase inhibitor (AI).
Authors: Yardley D. A. , Ismail-Khan R. , Klein P.
Published: February 2017

268

Background: Hormonal therapy, including AIs, is the mainstay of ER+ breast cancer (BC) treatment; however, both acquired and intrinsic resistance limits its clinical benefit. Entinostat is a novel, oral, class I selective histone deacetylase inhibitor that has been shown to inhibit growth factor signaling pathways that mediate AI resistance. This study was designed to evaluate the impact of the addition of entinostat to exemestane therapy on progression-free survival (PFS).

Methods: Postmenopausal women with ER+ advanced BC who had progressed on a non-steroidal AI were randomized to exemestane 25 mg daily + entinostat 5 mg or placebo weekly.

Results: A total of 130 women were enrolled (66 exemestane+placebo; 64 exemestane+entinostat). All but 1 patient had Stage IV disease, and 82% had measurable disease. All patients had received prior hormonal therapy (1 prior line 42%; >1 prior line 58%), and 62% had received prior chemotherapy (33% in the advanced BC setting). Analysis of the intent-to-treat population showed that PFS was significantly (defined prospectively as p <0.10) longer with exemestane+entinostat than with exemestane+placebo (4.28 versus 2.27 months, respectively; hazard ratio [HR] = 0.73; p=0.06). Entinostat combined with exemestane was well-tolerated with the most frequent adverse events (AEs) consisting of fatigue, gastrointestinal disturbances, and hematologic abnormalities. AEs with a ≥20% higher incidence with exemestane+entinostat than with exemestane+placebo were fatigue (46% versus 26%, respectively) and uncomplicated neutropenia (25% versus 0%, respectively). The serious AE rate was similar for exemestane+entinostat (13%) and exemestane+placebo (12%).

Conclusions: Exemestane+entinostat significantly prolonged the median PFS and reduced the risk of disease progression by 27% versus exemestane+placebo (HR = 0.73). In light of these positive data, a phase III evaluation of this combination is planned.
Human papillomavirus infection and increased risk of breast cancer in north of Iran.
Authors: Naghshvar F. , Sigaroodi A. , Nadji S. A. , Janbabaei G.
Published: February 2017

28

Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer deaths among women worldwide. Human papillomaviruses have been related to the pathogenesis of breast cancer. In this study, we have analyzed the possible relevance of HPV infection for breast cancer risk among Iranian women from north part of Iran, Mazandaran province.

Methods: Polymerase chain reaction method with three different primer sets was applied for detection of HPVs in formalin-fixed paraffin-embedded breast cancer and breast fibroadema as case and control tissues, respectively. HPV genotypes were determined by phylogenetic analysis of viral genome sequences.

Results: Of the 58 women with breast cancer, 25.9% (15 isolates) had positive test results for HPV DNA in breast tumor samples in contrast to 2.4% of women (1 out of 41) with non cancer status (P + 0.002). The infection of HPV had an OR of 14.247 (95% CI 1.558-130.284; P + 0.019). The HPV genotypes in samples of breast cancer patients were 26.67% for HPV-16 (4 isolates) and HPV-18 (4 isolates), 13.3% for HPV-23 (2 isolates) and HPV-6 (2 isolates), 6.67% for HPV-11 (1 isolate), HPV-15 (1 isolate) and HPV-124 (1 isolate) and one isolate could not be genotyped compared to HPV reference sequences, while the sole detected HPV in control specimens was HPV-124.

Conclusions: Our study reveals that HPV infection and age are the risk factors in breast cancer development in the north part of Iran, Mazandaran province. The association between risk of breast cancer development and viral infection is open and deserves further investigation.
A phase II neoadjuvant trial of concurrent trastuzumab and paclitaxel without anthracycline in women with HER2-positive operable breast cancer.
Authors: Jinno H. , Hayashida T. , Takahashi M. , Hirose S. , Kitagawa Y.
Published: February 2017

283

Background: Neoadjuvant paclitaxel plus trastuzumab followed by 5-fluorouracil, epirubicin, and cyclophosphamide plus trastuzumab revealed the high pathologic complete response (pCR) rate of up to 60% in patients with HER2-positive breast cancer. However, combination of trastuzumab and anthracycline has been associated with an increased incidence of cardiac dysfunction. The objective of this study was to determine the efficacy of concurrent administration of trastuzumab and paclitaxel without anthracycline as neoadjuvant chemotherapy. Predictive factors of pCR including deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway were also investigated.

Methods: Patients with HER2-positive operable breast cancer received 12 cycles of weekly paclitaxel (80 mg/m2 IV) plus weekly trastuzumab (4mg/kg loading dose followed by 2 mg/kg IV) before surgery. PTEN status was evaluated by IHC with PTEN antibody (Thermo Scientific, CA). PTEN expression level was scored semiquantitatively based on staining intensity (0; no staining , 1+; reduced staining, and 2+; equal staining as compared to the internal control). PIK3CA mutation status was evaluated by sequencing of PIK3CA exons 9 and 20 using PCR amplification and direct sequencing. pCR was defined as no residual invasive carcinoma in the breast.

Results: Among 37 patients enrolled, ER and PgR were positive in 18 (48.6%) and 16 (43.2%) patients, respectively. The overall response rate was 86.5% (32/37) and the pCR rate was 48.6% (18/37). pCR rate was significantly correlated with PgR negativity (p=0.004) and higher Ki67 (p=0.01). PTEN loss was observed in 33.3% (8/24) of the tumor examined. PIK3CA sequence analysis of the 13 tumors identified 2 mutations in exon 20 and 2 mutations in exon 9, corresponding to a PIK3CA mutation frequency of 30.8%. PTEN loss and/or PIK3CA mutation were not significantly associated with pCR rate.

Conclusions: These data indicate that the combination of trastuzumab and paclitaxel without anthracycline is effective neoadjuvant chemotherapy with high pCR rate. PTEN loss and/or PIK3CA mutation were not useful predictors of resistance to trastuzumab.
The effect of trastuzumab on pCR in locally advanced HER2-positive breast cancer.
Authors: Lavasani S. M. , Pritchard K. I. , Kiss A. , Verma S. , Wright F. , Boileau J. , Trudeau M. E. , Czarnota G. J. , Dent R. A.
Published: February 2017

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Background: Neoadjuvant therapy (NAT) is now standard of care for locally advanced breast cancer (LABC). Evidence shows that pathological complete response (pCR) predicts for disease free and overall survival. The pCR rates for LABC vary widely in the literature but prognosis still remains poor for this group of pts. Increases in pCR have been reported in clinical trials with the addition of trastuzumab (T) but these studies have predominantly included operable pts. The aim of this study was to evaluate whether the addition of T to NAT has improved the rates of pCR in HER2+ LABC pts at our center.

Methods: Pts from the LABC prospective database at the Sunnybrook Odette Cancer Center in Toronto were included if they had confirmed HER2+ LABC [primary tumors greater than 5cm (T3) with skin or chest wall involvement (T4) or with matted axillary adenopathy (N2)]. Two cohorts of LABC pts, pre-T and post-T groups were compared for baseline characteristics and pCR. Chi square tests and p values were used for comparing proportions.

Results: 43 pts were diagnosed between Jan 2002 to Dec 31, 2006 who had HER2+ breast cancer and received NAT without T (pre-T cohort). 17 HER2+ pts were diagnosed with LABC between Jan 1, 2007 to Dec 31, 2009 who received neoadjuvant T (post-T cohort). Baseline characteristics were similar in two cohorts (Table) except more pts in pre-T cohort received neoadjuvant hormonal therapy. The rate of pCR in the pre-T cohort was 9.3% and in the post-T cohort 29% (p value=0.02).

Conclusions: The pCR rate dramatically improved in our LABC patients with the addition of T to NAT. The pCR rates still remain lower than in published clinical trials likely reflecting the more advanced nature of LABC in clinical practice.

[Table: see text]
A vaccine approach for breast cancer immunotherapy by targeting HER2/neu antigen to B cells via CD19 molecule.
Authors: Xiang D. , Ma Y. , Ding C. , Kloecker G. H. , Yan J.
Published: February 2017

287

Background: Trastuzumab has been proven to be effective in the immunotherapy for Her-2/neu-positive breast cancer. However, this adoptively transferred therapeutic Ab must be continuously given to the patient with huge financial cost. Thus, it would be desirable if tumor vaccines could elicit long-lasting trastuzumab-like Ab.

Methods: Constructing fusion protein of anti-mouse CD19 single chain variable fragment (anti-CD19-scFv) with human Her-2/neu extracellular domain P3-4 (P3-4) by extracting total RNA from Rat anti-mouse CD19 hybridoma (1D3) and first strand cDNA was synthesized accordingly. VH and VL were amplified using designed primers. Single chain Fv (VL-VH) was then synthesized by overlapping PCR. Then constructs were sequenced and cloned into pET-20b(+) vectors. Fragments P3-4 of extracellular domains of human Her-2/neu was cloned from pcDNA3.1-Her2 and then cloned into pET-20b(+)-scFv. Series of constructs were expressed and purified according to standard protocol and verified by Western Blot.

Results: Both in vitro and in vivo studies demonstrated that fusion proteins anti-CD19-scFv and anti-CD19-scFv-P3-4 but not P3-4 could specifically bind to B cells with high affinity. Mice immunized with anti-CD19-scFv-P3-4 secreted higher titers of IgG and IgM than those from controls (p<0.05). Studies also demonstrated that sera from anti-CD19-scFv-P3-4 but not anti-CD19-scFv or P3-4 immunized mice stained with Her-2/neu expressing SKOV-3 tumor cells. These Abs also competitively inhibited trastuzumab-mediated Ag binding, suggesting that trastuzumab-like Ab responses were elicited. WT mice immunized with anti-CD19-scFv-P3-4 fusion protein then challenged with D2/F2-Her-2 mammary tumor cells showed significantly reduced tumor burden compared to those immunized with control fusion proteins (p<0.05) and had enhanced median overall survival to 45 days versus 34 days in WT mice immunized with either anti-CD19-scFv or P3-4.

Conclusions: Targeting of Her-2/neu antigens to B cells stimulates Th-dependent humoral immune responses with anti tumor effect in mouse model. These findings provide a novel avenue for successful development of breast cancer vaccination strategy and help to fight for cancer.
Predicting nipple-areolar involvement using preoperative breast MRI and primary tumor characteristics.
Authors: Steen S. T. , Chung A. P. , Han S. , Vinstein A. , Yoon J. L. , Giuliano A. E.
Published: February 2017

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Background: Preoperative assessment of the nipple-areolar complex (NAC) is invaluable when considering nipple-sparing mastectomy (NSM). We hypothesized that breast MRI could predict involvement of the NAC with tumor.

Methods: We compiled clinical, pathologic and imaging data for patients who underwent preoperative breast MRI followed by mastectomy or NSM between 2006 and 2009. Blinded rereview of all MRI studies was performed by a breast MRI imager and compared to initial MRI findings. Multivariate analysis identified variables predicting NAC involvement with tumor.

Results: Of 77 breasts, 18 (23%) had tumor involving or within 1 cm of the NAC. The sensitivity of detecting pathologically confirmed NAC involvement was 61% with history and/or physical exam, and 56% with MRI. Univariate analysis identified the following variables as significant for NAC involvement: large tumors close to the nipple on preoperative MRI, node-positive disease, invasive lobular carcinoma, advanced pathologic T stage, and neoadjuvant chemotherapy. On multivariate analysis, only tumor size > 2 cm and distance to the NAC < 2 cm on MRI maintained significance. Pearson correlation coefficient for MRI size compared to pathologic size was 0.53 (p<0.0001).

Conclusions: MRI is not superior to thorough clinical evaluation for predicting tumor in or near the NAC. However, MRI-measured tumor size and distance from the NAC are correlated with increased risk of NAC involvement. Preoperative history and physical examination, tumor characteristics, plus breast MRI can aid the surgeon in planning for successful NSM.
Topoisomerase II alpha (TopoIIa) and MAPtau: Potential predictive markers of response in locally advanced breast cancer (LABC) treated with epirubicin and docetaxel (ET) in neoadjuvant setting.
Authors: Cristofano A. , Inno A. , Arena V. , Nicosia L. , Jocollè G. , Campitiello M. , Carassai P. , Pozzo C. , Numico G. , Barone C.
Published: February 2017

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Background: Neoadjuvant chemotherapy can achieve a high objective response rate in patients with LABC. This allows breast conservation surgery in those patients who are initially not suitable for this procedure. The patients who mainly benefit from neoadjuvant chemotherapy are those who achieve a pathological complete response (pCR) with no residual microscopic tumour. This occurs in only 3–16% of patients, who have substantially improved disease-free survival (DFS) and OS compared to those with pathological evidence of residual cancer. In order to identify patients most likely to achieve benefit from neoadjuvant chemotherapy, it would be useful to identify predictors of pCR. ET is a valid doublet therapy in the neoadjuvant setting; Topo-IIa and MAP-Tau are the principal targets of anthracyclines and taxanes, respectively. We evaluated a possible role of the two proteins in predicting a pathological response rate in LABC.

Methods: TopoIIa and MAPtau expression was evaluated by immunohistochemistry (IHC) in tumour biopsy from 22 women with LABC treated with ET as neoadjuvant chemotherapy, and protein levels were correlated to the outcome.

Results: TopoIIa over-expression was significantly associated with ductal histology (58.3% in ductal carcinoma vs 0% in other hystotypes, p=.038) and hormone receptors (HRs) expression (63.6% in HR+ vs 0% in HR- tumours), whereas no significant correlation was observed with HER2 expression. MAP-tau did not correlate with histology, grading, HRs and HER2 status. Pathological complete response (pCR) rate was higher in tumours with MAPtau low/normal expression compare to those over-expressing the protein (36.4% vs. 14.3%), although not significantly. Pts with TopoIIa over-expression achieved a significantly higher pCR rate than those with a low/normal expression (57.1% vs. 9.1%; p=.047). Data on the RFS are not available because of the short period of follow-up.

Conclusions: IHC evaluation of TopoIIa might be useful in identifying pts potentially responsive to neoadjuvant chemotherapy with anthracyclines and taxanes. Data on RFS will be available later.