bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P3-05-05: Classification using dynamic re-discovery of the strongest prognostic features in each analysis outperforms static gene expression signatures for prognostic prediction in breast cancer
Authors: Györffy B , Karn T , Sztupinszki Z , Weltz B , Müller V , Pusztai L
Published: August 2014

Introduction: To overcome limitations of previous multigene prognostic classifiers, we propose a new dynamic predictor. Our classifier does not use a single universal training cohort and an identical list of informative genes to predict the prognosis of new cases but a case-specific predictor is developed for each test case.

Methods: We analyzed gene expression data from 3,534 breast cancers with clinical annotation including survival. For each test case we select a case-specific training subset including only molecularly similar cases and a case-specific predictor is generated. This method yields different training sets and different predictors for each new patient but preserves the independence of model building and validation. The model performance was assessed in leave-one-out validation and also in 325 independent cases.

Results: Prognostic discrimination was high for all cases (n = 3,534, HR = 3.68, p = 1.67E-56). The dynamic predictor showed higher overall accuracy (0.68) than genomic surrogates for the 21-gene predictor (0.64), the 97-gene genomic grade index (0.55) or the 70-gene prognostic signature (0.41). The dynamic predictor was also effective in triple-negative cancers (n = 427, HR = 3.08, p = 0.0093) where the above classifiers all failed. Validation in independent patients yielded similar classification power (HR = 3.57).

Discussion: We developed a new method to make personalized prognostic prediction using case-specific training cohorts. The dynamic predictors outperform static models developed from single historical training cohorts and they also predict well in triple-negative cancers. The dynamic classifier is available on line at http://www.recurrenceonline.com/?q = Re_training.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-05-05.
Abstract P3-05-09: Interlaboratory variability of Ki67 labeling index in breast cancer tissue microarrays
Authors: Focke CM , Gläser D , Finsterbusch K , Bürger H , Korsching E , Berghäuser K-H , Hinrichs B , Krause U , Lorenzen J , Packeisen J , van Diest PJ , Decker T
Published: August 2014

Objective: Assessment of tumor proliferation using the Ki67 labeling index (Ki67-LI) is increasingly recommended for prognostication and adjuvant chemotherapy decisions in breast cancer. Our aim was to investigate interlaboratory variance of Ki67-LI results using TMA and centralised assessment to exclude preanalytic influences and postanalytic variance, respectively.

Methods: Nine pathology laboratories (8 German and 1 Dutch) performed Ki67 staining of a TMA slide according to their routine in house protocol (including internal and external quality assurance). 40 samples per lab were centrally analyzed. The Ki67-LI was calculated after counting first all tumor cells and subsequently all Ki67 positive tumor cells of each sample regardless of staining intensity. For each tissue sample we evaluated the range of Ki67-LIs between different labs. Further 20 labs of the German Breast Screening Pathology Initiative will participate in 2013.

Results: The range of Ki67-LIs between the labs was: 1-5% in 4 (10%), 6-10% in 6 (15%), 11-15% in 7 (17,5%), 16-20% in 2 (5%), 21-25% in 7 (17%), 26-30% in 4 (10%), 31-35% in 1 (1%), 36-40% in 4 (10%), 41-45% in 2 (5%), 46-50 in 0 (0%) and >50% in 3 samples (7%), respectively. Thus, in 35% of results of the 9 labs (26 of the 40 TMA specimens) the Ki67-LI differed by more than 25%. The analysis of variance (ANOVA) came out with F = 4.24 which is much larger than the critical F value of 1.97 for these study results (p = 7.74902E-05). This means that the observed interlaboratory variance of 4.24 is systematic and not due to sampling error. The respective standard deviation is 33.4%.

Conclusion: In a setting strictly standardised in terms of preanalytic influences by using TMA and postanalytic variance by centralised quantification, Ki67-LI seems to be heavily influenced by laboratory-specific analytic variables. Taking this into consideration, there may be a risk of prognostic or predictive misclassification in some breast cancer patients in daily practice.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-05-09.
Abstract P3-06-05: HER2/HR positive early breast cancer patients have nowadays the highest disease-free survival: Results from the south-east of the Netherlands
Authors: Tjan-Heijnen VCG , Lobbezoo DJA , Dercksen M , Voogd AC , van den Berkmortel F , van de Wouw AJ , van Kampen RJW , Peer PGM
Published: August 2014

Background

Adjuvant systemic therapy choices in early breast cancer largely depend on human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) status. Overexpression of HER2 has been shown to be associated with a worse outcome (Slamon et al, Science, 1987). With this cohort study, we aimed to assess the outcome of early breast cancer patients per subtype based on HER2 and HR status in daily practice treated in a time period of routine use of anti-HER2 treatment.

Patients and methods

Patients diagnosed with early breast cancer during the years 2005-2007 in five participating hospitals in the South-East part of the Netherlands were included. Patients with primary metastatic breast cancer were excluded. Information regarding disease characteristics and treatment was collected. Patients were categorized in 4 subtypes based on the HER2 and HR status of the primary tumor: HER2 positive (+)/HR positive (+), HER2 negative (-)/HR+, HER2+/HR-, and triple negative (TN) (i.e. HER2- and HR-). Disease-free survival (DFS) was estimated using the Kaplan-Meier method. Cox proportional hazards model was used to determine the prognostic impact of breast cancer subtype, adjusted for possible confounders.

Results

A total of 2579 patients were included with a median follow-up of 52.6 months.

Median 5-year DFS rate was highest for the HER2+/HR+ subtype (comprising of 13% of all patients) with 78%, compared to 68% for the HER2+/HR- subtype (5% of all patients), 75% for the HER2-/HR+ subtype (70% of all patients) and 64% for the TN subtype (12% of all patients).

In multivariate analysis, subtype was confirmed to be an independent prognostic factor. Compared to the HER2+/HR+ subtype, the HER2+/HR- subtype was associated with a worse DFS (HR 2.05, 95% CI 1.21-3.46, P = 0.008) and the HER2-/HR+ was associated with a similar DFS (HR 1.09, 95% CI 0.79-1.52, P = 0.6). Furthermore, classical clinicopathological parameters were all confirmed to be of independent prognostic relevance, as well as the use of adjuvant systemic therapy. At the meeting, we will show the results according to the type of adjuvant systemic treatment used.

Conclusion

In this cohort, we noted that 13% of patients had HER2+/HR+ early breast cancer. These had the highest 5-year disease-free survival of all subtypes, significantly better than the HER2+/HR- subgroup. This may indicate a differential prognostic impact of HER2 according to HR status, with HR+ having a positive prognostic impact, irrespective of the presence of HER2 overexpression.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-05.
Abstract P3-06-14: Increase in the proportion of stage IV breast cancer amongst young women with newly diagnosed breast cancer, report from the National cancer data base, 1998-2009
Authors: Yao K , Tomasz C , Pesce C , Huo D , David WJ , David WP , Edward W
Published: August 2014

Background: A recent SEER study showed a significant increase in the incidence of advanced breast cancer in women 25 to 39 years old. We hypothesized a similar trend amongst newly diagnosed breast cancer patients treated at Commission on Cancer Accredited Cancer Centers in the United States and that such increase is greatest among minority young women.

Methods: We utilized data from the National Cancer Data Base to determine the proportion of patients <40 years old who were diagnosed with Stage IV disease from 1998-2009. Patient demographics (insurance, race, income) and tumor characteristics (size, node status, grade, estrogen receptor (ER), histology) were included to compare the risk factors associated with advanced disease between younger and older women. Statistical analyses were performed using both univariate and multivariable logistic regressions in SAS 9.3 (SAS Inc., Cary, NC).

Results: A total of 1,955,190 women with newly diagnosed breast cancer were included. The proportion of young women (<40 years old) diagnosed with stage IV breast cancer has increased by 58% between 1998 and 2009 (Table 1). This increase in young women was significantly greater than other age groups with Stage IV disease: 40-54 years old (Δ = 9%), 55-69 (Δ = 13%) and >70 years old (Δ = 17%) (all p<0.001). Amongst women with stage IV disease, women <40 years old compared to women ≥40 years old were more likely to be nonwhite (29% vs. 19%, p<.0001), have grade III tumors (70% vs. 57%, p<.0001), have an estrogen receptor (ER) negative tumor (34% vs. 28%, p<.0001), and have a ductal carcinoma (85% vs. 78%, p<.0001). In the multivariable analysis, young women (<40 yr) remained at significantly greater risk of being diagnosed with stage IV disease (OR = 1.19, 95% CI 1.14-1.24, p<.0001) compared to women ≥40 years old after adjusting for income, race/ethnicity and tumor characteristics. While the proportion of women with stage IV disease has increased between 1998 and 2009, the increasing odds was significantly greater among young women (OR = 1.54) as compared to old women (OR = 1.17) in the risk adjusted multivariable models.

Table 1. Trend in proportion of women diagnosed with Stage IV disease according to patient age, 1998 and 2009.Age19982009Age <401.973.12Age 40-541.471.61Age 55-691.591.81Age 70+1.802.11

Conclusions: The proportion of women with stage IV disease under 40 years old has increased significantly over the past decade and this trend was not seen in older age groups. Young minority women with ER negative tumors are at greatest risk to be diagnosed at a later stage.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-14.
Abstract P3-06-16: The difference of molecular subtypes and prognosis after surgery for breast cancer patients with each blood types
Authors: Kondo N , Fujita T , Sawaki M , Hattori M , Horio A , GONDO N , Idota A , Ichikawa M , Iwata H
Published: August 2014

(Introduction) ABO blood type has been associated with various malignancies, including pancreatic and stomach cancer. However the correlation between blood type and hormone receptor (ER/PR), HER2/neu, patient outcomes remains largely unexplored in patients with breast cancer.

(Methods)This study involved retrospective chart review of patients diagnosed with primary breast cancer stages I-III at Aichi Cancer Hospital between January 2004 and December 2011. Among 1944 breast cancer patients, the relationships between ABO blood type and clinicopathological findings, outcomes were analyzed. Descriptive statistics and c2 analysis were utilized for data summary and comparisons.

(Results) Of 1944 patients, 723 (37%), 577 (29%), 446 (23%), 198 (11%) were blood type A, O, B, AB respectively. This distribution is similar to that reported previously for general Japanese population. 327 (16.8%) patients were ductal carcinoma in situ and 1617 (83.2%) were invasive cancer, and there were no significant differences in this distribution based on each blood types. Among 1617 invasive breast cancer patients, we did not observe significant associations between blood type and pathological T stage or pathological N stage. However, patients with blood type O had lower rate of Luminal type (68.2%) compared blood type A, B, AB (73.5%, 75.2% and 76.0%, respectively (P = 0.03). The blood type O had higher rate of Tripe Negative type (13.7%) compared blood type A, B, AB (10.6%, 9.9% and 8.4%, respectively (P = 0.04). No other statistically significant differences in baseline characteristics among the four blood type groups were noted. No significant differences were observed in type of treatment (endcrine therapy, chemotherapy and anti-HER2 therapy) in each breast cancer subtypes among four blood type groups. Compared to women with blood type A, there was no significant difference in disease free survival among the for blood type O [hazard ratio (HR) 1.754; 95% confidence interval (CI) 0.735-2.731], blood type B (HR 0.978; 95% CI 0.724-1.542.), blood type AB (HR 1.235; 95% CI 0.694-2.864). For patients with blood type O, this difference did not reach statistical significance, although a trend toward worse prognosis of the patients with blood type O status was seen.

(Conclusion) The blood type O had lower rate of Luminal type and higher rate of Tripe Negative type compared other blood types. No significant differences were observed in disease-free survival according to ABO blood types.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-16.
Abstract P3-07-06: BRCA mutations among Hispanic breast cancer patients of Mexican origin in El Paso, TX
Authors: Nahleh ZA , Heydarian R , Saldivar JS , Castaneda K , Sanchez L
Published: August 2014

Introduction: El Paso, TX is a large American-Mexican border city of population around 900,000, 85% Hispanic of Mexican origin. Limited cancer research has been conducted in this population. The relative homogeneity of this Hispanic population lends a unique opportunity to study the prevalence of BRCA mutations among Hispanic patients of Mexican origin, to identify reported Mexican founder or recurrent mutations, and to study the breast cancer characteristics in mutation carriers. Methods: Hispanic women with a personal history of breast cancer, who presented consecutively for genetic cancer risk assessment, were enrolled in an Institutional Review Board -approved registry and underwent BRCA testing bases on NCCN guidelines. The characteristics of tumors and patients with positive BRCA mutation were analyzed. Descriptive statistics were utilized. Results: 59 patients were screened; 13 patients (22%) tested positive. Mean age was 50 years; 8 patients (62%) had stages I or II, 2 patients stage III, and 3 unknown. 10 (77%) ductal, 1 (7%) lobular and 2 undetermined; 30% had ER positive tumors versus 61% ER negative; 69% had HER2 -neu negative tumors and 23% HER2-neu positive; 62% were triple negative. Nine patients (69%) were diagnosed with breast cancer at younger than 50 years. Median BMI was 31.78. Ten patients had BRCA1 mutations and 3 BRCA2 mutations. A total of 9 unique deleterious BRCA Mutations were observed, BRCA1 R71G (330A>G);del exons 1-2;C1787S(5478T>A) and G1788D(5482 G>A); C1225X (3794 C>A); A 1708E(5242 C>A); R1751X(5370C>T; and del exons 9-12 and BRCA2 Q742X (2452 C>T); and 3492 insT Conclusion: This study confirms that breast cancer patients with BRCA mutations in the El Paso, TX present at a younger age, and have predominantly triple negative tumors. Of particular interest is 44% (4 of 9) BRCA mutations (BRCA1 exon 9-12 del; C1787S & G1788D and BRCA 2 3492insT; Q742X) identified have been reported as recurrent mutations in Hispanic individuals from Mexico as the country of origin, including BRCA1 ex9-12del, the 1st Mexican founder mutation and 100% of the BRCA2 mutations. A more cost-effective approach to initial screening of Hispanic individuals based on country of origin may be desirable and would potentially decrease the number of cases requiring complete sequencing. Increasing breast cancer awareness and encouraging genetic counseling among high risk younger patients of Mexican descent is also needed.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-07-06.
Abstract P3-07-10: Breast cancer risk-related gene polymorphisms, ESR1/6q25.1-rs2046210 and rs3757318, and clinical characteristics of breast cancer patients
Authors: Taira N , Mizoo T , Nishiyama K , Nogami T , Iwamoto T , Motoki T , Shien T , Matsuoka J , Doihara H , Ishihara S , Kawai H , Kawasaki K , Ogasawara Y , Ishibe Y
Published: August 2014

[Background] Based on the results of a case-control study performed in Japan (Okayama and Kagawa), it was revealed that gene polymorphisms of the estrogen receptor (single nucleotide polymorphisms, SNPs), ESR1/6q25.1-rs2046210 and SNPs of rs3757318 were closely related to breast cancer risk in Japanese women, and that the odds ratio per allele of individual SNPs were 1.37 [95% CI: 1.1 - 1.7] and 1.33 [1.04 - 1.7], respectively (San Antonio Breast Cancer Symposium 2012, Mizoo et al.). We analyzed the relationship of ESR1/6q25.1-rs2046210 and rs3757318 SNPs with the clinical characteristics of breast cancer patients.

[Methods] Among the patients enrolled in the case-control study, 508 breast cancer patients who underwent genotyping for ESR1/6q25.1-rs2046210 and rs3757318 were analyzed as the subjects. SNPs were analyzed using the TaqMan genotyping assay® for blood samples. To analyze the relationship of genotypes (AA/GG, GG) with age at diagnosis, height, weight, BMI, age of menarche, birth history, pathological degree of progression and estrogen receptor, t-test and chi-square test were used.

[Results] The genotypes of rs2046210 are AA (12%), AG (41%) and GG (46%), and the patients with the risk allele (AA/AG) had significantly higher height (p = 0.0015, t-test) and lower Body Mass Index (BMI) (p = 0.0022, t-test). The genotypes of rs3757318 are AA (8%), AG (39%) and GG (53%), and the patients with the risk allele (AA/AG) were characterized by significantly lower BMI (p = 0.041, t-test), no birth history (p = 0.0473, chi-square) and negative hormone receptor (p = 0.0128, chi-square). Overall, tendencies related to increased height, lower BMI and negative estrogen receptor were confirmed for the risk alleles of rs2046210 and rs3757318.

[Conclusion] It was suggested that SNPs of rs2046210 and rs3757318 might be related to the development of estrogen-receptor-negative breast cancer.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-07-10.
Abstract P3-08-10: Feasibility and promise of a self-directed walking program to reduce joint pain among older breast cancer patients on adjuvant aromatase inhibitors
Authors: Nyrop KA , Muss HB , Hackney B , Cleveland R , Callahan LF
Published: August 2014

Background: Most breast cancer cases diagnosed among postmenopausal women are hormone receptor positive (HR+); standard adjuvant endocrine treatment usually includes an aromatase inhibitor (AI). Joint pain/stiffness/achiness (arthralgia) is a common AI side-effect, and AI discontinuation due to this side-effect is an estimated 20-32%. There is a need for effective alternative or adjunctive approaches to arthralgia management that enable survivors to remain on AI therapy while optimizing as pain-free a life as possible. This pilot study investigates the feasibility of a highly scalable 6-week self-directed physical activity (PA) program – Walk With Ease (WWE) – among elderly female breast cancer survivors on AIs who report joint pain. WWE goal: minimum of 30 minutes of walking 5 days a week (150 minutes/week).

Methods: Recruitment: BC survivors age 65+ were recruited through the oncology clinic of a university-affiliated hospital. Eligibility: age 65+; Stage I-III breast cancer; currently on AI therapy; self-reported joint pain/stiffness; physician permission to engage in PA; English speaking. Measures: (1) walking – number of days per week and number of minutes per walk, (2) visual analog scales (VAS) for joint pain, fatigue and stiffness, and (3) arthritis self-efficacy (ASE) to manage joint pain and fatigue. Statistics: t-test evaluation of changes in mean values.

Results: Sample (N = 20) – mean age 71 (65-87), 85% Caucasian, 35% < high school, mean BMI 29. 63% chemotherapy, 61% radiation therapy. 90% completed the 6-week intervention. Compared to baseline, total minutes of walking per week increased from 95 (0-450) to 172 (45-700) (p<.001) and mean joint pain decreased 10% (p = 0.63), fatigue decreased 19% (p = 0.31), and joint stiffness decreased 32% (p = 0.07). Post-intervention, 71% of participants were “fairly” or “extremely” confident they would continue walking; 100% would recommend WWE to other breast cancer survivors experiencing joint pain or stiffness; 100% thought they had learned how joint pain or stiffness could be lessened by physical activity, and how to safely engage in moderate-intensity physical activity; 90% thought WWE had motivated them to become more physically active, and how to overcome physical and mental barriers to walking; and 90% were fairly to extremely confident they would continue walking.

Conclusions: A moderate-intensity self-directed walking program is feasible for older breast cancer patients on AI therapy and almost doubled the total time of walking per week over a 6 week period. Joint pain, stiffness, and fatigue decreased, and the walking program was perceived as informative and motivational. These data are promising and the WWE intervention warrants testing in a larger randomized trial of breast cancer survivors on AI therapy.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-08-10.
Abstract P3-08-11: Pregnancy after breast cancer and recurrence risk
Authors: Preusse C , Gammill H , McDougall J , Ma K , Gooley T , Li C , Gadi VK
Published: August 2014

Background: Several retrospective studies report an improved overall (and possibly disease-free) survival of women who become pregnant following breast cancer diagnosis compared to women who choose not to or are unable to become pregnant. The objective of the current study is to evaluate associations with breast cancer biologic and stage characteristics from the baseline tumor with different recurrence outcomes in women with and without a pregnancy subsequent to their cancer diagnosis.

Methods: From a population-based cohort study of all women aged 20-44 diagnosed with invasive breast cancer in the three county Seattle-Puget Sound metropolitan area, we conducted a secondary recontact interview. Recontact information included cancer recurrence and obstetric history, including all pregnancies occurring after breast cancer diagnosis. Univariate associations were evaluated using chi square. A time-to-event analysis was conducted, evaluating the relationship between pregnancy and recurrence, with consideration of stage and tumor type (triple negative tumor or not) as confounders.

Results: At this interim, an approximately 70% response rate for the re-contact study was achieved, yielding data from 458 women overall. Excluding 8 women who were pregnant at the time of their breast cancer diagnosis, 450 were available for analysis. Of these, 13 (2.9%) became pregnant at least once after their breast cancer diagnosis. Among women with complete pathologic information available (n = 274), those with a pregnancy subsequent to their cancer diagnosis had triple negative tumor types more often than those who did not have a subsequent pregnancy (4/8, 50% vs. 44/266, 17%, p = 0.03). Tumor stage did not differ between women with and without a subsequent pregnancy. Overall, 30 total cancer recurrences were captured in the re-contacted cohort; none of these occurred among women with subsequent pregnancy (0/13, 0% vs. 30/437, 6.9% among women without subsequent pregnancy), p = 0.3. For 448/450 women with complete information on timing of recurrence, a time-to-event analysis adjusting for tumor type did not show a significant association between subsequent pregnancy and recurrence risk, p = 0.14 by Likelihood Ratio test.

Conclusions: In this population, breast cancer recurrence risk was not increased among women with a pregnancy subsequent to their cancer diagnosis. Despite the more common triple negative tumor type among the group of women with subsequent pregnancy, none of these women experienced a cancer recurrence. Our study adds to a substantial literature suggesting that pregnancy after breast cancer does not appear to have a detrimental effect on disease recurrence. The relationship between tumor type and its potential influence on both decision-making regarding pregnancy and the biology of pregnancy as it relates to breast cancer recurrence merits further investigation.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-08-11.
Abstract P3-08-17: Objectively measured physical activity in breast cancer survivors
Authors: Soria A , Pagola I , Ortega MJ , Brea L , Fiuza C , Cebolla H , Palomo I , Montil M , Malón D , Guerra J , Lucia A , Ruiz A
Published: August 2014

Background: Obesity and physical inactivity are poor prognostic indicators for breast cancer (BC). Cardiorespiratory fitness (VO2max) is a good predictor of survival. Despite preserved LVEF, cardiorespiratory function is impaired in women with breast cancer after the completion of adjuvant therapy. International organizations recommend at least 150 minutes per week of moderate-vigorous physical activity (MVPA). Some studies show that a minority of cancer survivors are meeting the PA recommendations. A limitation of physical activity (PA) research has been the use of self-reported measures.

Eligibility criteria: 1) Age 18-79, 2) Able to walk a mile, 3) More than one year from diagnosis, 4) More than 3 months since the last therapy, 5) No evidence of disease.

Aims: Objective assessment of physical activity in breast cancer survivors. Adherence to international recommendations.

Material and methods: PA was evaluated through accelerometry (600 minutes per day, 5 days per week, 2 week-end days were required to consider as valid accelerometry values). Cardiorespiratory fitness was assessed through the “one-mile test”.

Results: 92 women (W) with BC history were included. 86 W were evaluable for accelerometry. 85 W were evaluable for VO2max. Age: 54.02 years (33-77), BMI: 27.89 (SD 8.89), waist perimeter: 89.74 cm (SD 17.37), median time from diagnosis 3.94 years, treatment with anthracyclines 55 W (63.9%), radiotherapy 69 W (80.23%). Accelerometry (86W): Average weekly time MVPA 351.14 min/wk (SD: 168.98). 76 (88%) met international recommendations of PA. Women previously treated with anthracyclines (47 W; 340.25 min/wk), radiotherapy (59 w; 343 min/wk) and both (48 W; 331 min/wk) exercised less than women who did not receive these therapies (8 W; 386 min/wk). This association was not statistically significant.

Average VO2max was 24.8 ml/kg/min (SD: 7.6).There was a significant effect of anthracyclines for VO2 max. Women not treated with anthracyclines had a VO2max: 26.41 whereas treated W had VO2max 22.08 ml/kg/min.

Discussion: A cohort of Spanish women met international recommendations of PA when it was objectively assessed. This cohort exhibited a poor cardiometabolic and cardiorespiratory profile. Previous exposure to anthracyclines predicted a poorer cardiorespiratory fitness. Specific research to investigate the role of exercise to mitigate that dysfunction in breast cancer survivors is warranted.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-08-17.
Abstract P3-09-14: Using lean methods to increase access to support services in younger breast cancer survivors
Authors: Mayer DK , Kinley T , Gerstel A , Jackson M , Shea T , Donald RL , Lawrence MB
Published: August 2014

Background: A variety of ‘structured support services’ (services) are available to patients (e.g. genetics, fertility, counseling, physical functioning, nutrition). Many of these services have value for breast cancer survivors (survivors) as they are often likely to face issues regarding genetic factors, fertility, parenting, relationships, work, and financial hard-ships. As part of an ongoing CDC-funded initiative, we report about barriers to services use for survivors.

Methods: We used lean techniques to analyze system complexity including: process mapping; inventorying support services, providers/staff, and referral methods; stake holder leadership events; and Kaizen events to facilitate system improvements.

Results: We identified several barriers to patients getting services which reflect the complexity of cancer care delivery in an academic cancer center including: varying care pathways, lack of standard processes; lack of staff awareness of available service (hospital staff are located in 5 different clinics and include physicians, APPs, clinic nurses, nurse navigators, and patient schedulers); numerous different contact and referral methods to services (tribal knowledge of staff necessary to make SS referrals). We initially identified 7 and found 38 services through inventorying and mapping systems.

We implemented a number of systematic and non-systematic interventions to address these barriers. Systematic implementations include assisting in the development and piloting new patient orientation binders to include services, implementation of a revised scheduling form to streamline referrals, created and disseminated a quick reference referral guide to educate staff for how to make referrals. Non-systematic interventions included hosting services fair for breast cancer providers to meet and learn about them and advertising services on waiting room TVs.

Conclusions: Patients and providers both perceive many challenges accessing support services. Applying improvements in a complex health care system is difficult and incrementally addresses identified barriers. We will now be measuring the impact of these changes on the receipt of support services in breast cancer survivors.

Funding: CDC Grant 1U58DP003414 (PI Marks, L.).

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-09-14.
Abstract P3-11-02: Women with pregnancy-associated early breast cancer achieve improved emotional well-being as a result of their cancer experience
Authors: Murthy RK , Schover LR , Theriault RL , Valero V , Woodard TL , Hodge S , Litton JK
Published: August 2014

Background: Pregnancy-associated early breast cancer (PAEBC) has increased in incidence as more women pursue childbearing at an older age. The objective of this study was to measure the impact of diagnosis and treatment on emotional health and evaluate the positive emotional outcomes in a group of women with PAEBC. Methods: Between 1989 and 2010, 81 patients were treated for PAEBC with 5-flurouracil, doxorubicin and cyclophosphamide (FAC) chemotherapy. Patients completed the Impact of Events Scale-Revised (IES-R), which is a questionnaire that measures subjective distress caused by traumatic events and the Post-traumatic Growth Inventory (PGI), which measures positive outcomes after a traumatic event. Results: Of the 81 women, 53% (43/81) completed the IES-R and 44% (36/81) also completed the PGI. The time since diagnosis ranged from 6 months to greater than 5 years. The median age of the participants was 33 years (range 26-43 years). Of the 43 patients who completed the IES-R, 91% (39/43) did not use avoidance as a primary coping strategy; they felt well equipped to deal with feelings about their diagnosis and treatment. Of patients who inadvertently thought about their diagnosis, 70% (30/43) noted that they avoided becoming upset by their thoughts. Less than 10% (9/43) of patients surveyed felt apathetic towards their diagnosis and subsequent treatment. In terms of positive outcomes, 94% (33/36) felt they were enabled to depend on others in times of crises and felt a greater appreciation for people and their kindness following their diagnosis of PAEBC. Eighty-six percent (31/36) had changed their priorities about what is important in life, felt more compassionate towards others, and felt a greater appreciation for the value of their own life. In addition, 86% (30/36) of patients indicated that they had discovered their inner strength and felt more inclined to change things in their life. Finally, 75% of patients surveyed felt they had developed a stronger religious faith because of their experience and had a better understanding of spiritual matters. The majority of patients reported improvement in interpersonal skills – placing more effort into their relationships and sharing a greater sense of closeness with others. Conclusions: Although women who experience PAEBC are thought to be at high risk for experiencing psychosocial distress, these findings suggest that most do not suffer negative emotional consequences; in fact, these data suggest that they often achieve improved emotional well-being as a result of their cancer experience. It is possible that these women have better emotional outcomes because they have successfully carried a pregnancy while facing a life-threatening illness. Comparisons to other premenopausal breast cancer survivors will be crucial in interpreting these findings.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-11-02.
Abstract P3-12-10: Feasibility of four cycles of docetaxel and cyclophosphamide every 14 days as an adjuvant regimen for breast cancer: A Wisconsin oncology network study
Authors: Wisinski KB , Burkard ME , Njiaju U , Donohue S , Hegeman R , Stella A , Mansky P , Shah V , Goggins T , Qamar R , Dietrich L , Kim K , Traynor A , Tevaarwerk A
Published: August 2014

Background: Dose-dense therapies have had a major impact on reducing toxicity and improving outcomes in breast cancer. A combination of docetaxel plus cyclophosphamide (TC) every 3 weeks has emerged as a common chemotherapy regimen used for treatment of node-negative or lower-risk node-positive breast cancer. We tested whether it is feasible to deliver TC on a dose-dense schedule.

Patients and Methods: We enrolled women with early stage breast cancer on a single-arm phase II study of adjuvant dose-dense TC (ddTC) through a regional oncology network (WON). All women completed primary surgery; subsequent therapy with TC was deemed appropriate by the treating physician. Planned treatment was docetaxel 75 mg/m2 plus cyclophosphamide 600 mg/m2 every 2 weeks for 4 cycles with subcutaneous pegfilgrastim 6 mg administered 24-48 hours after the administration of each chemotherapy cycle. The primary endpoint was feasibility of administering therapy within 10 weeks. A Simon Optimal 2-Stage design was employed for the study design.

Results: Of 42 women enrolled, 41 were evaluable by prespecified criteria. Median age was 54 (28-73). Most subjects had node negative (73%) or hormone receptor positive (71%) tumors. Of the 41 subjects, 37 (90.2%) completed therapy within 10 weeks and 34 (83%) completed therapy at 8 weeks without dose modification. Rates of grade 2 neuropathy were similar to that reported previously (15%) and there were no cases of grade 3 or higher neuropathy. The rate of neutropenic fever was low (2.5%). Rash and plantar/palmar erythrodythesia were common and reached grade 3 in four subjects (9.8%).

Conclusion: Dose-dense TC is feasible with tolerability profiles similar to standard TC and a low likelihood of neutropenic fever. This study supports further clinical development of this 8-week adjuvant chemotherapy regimen.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-12-10.
Abstract P3-12-11: Provincial variation in utilization of adjuvant chemotherapy regimens in early stage breast cancer: Data from the cancer care Ontario new drug funding program (NDFP)
Authors: Eisen A , Srikanthan A , Yeung L , Iyer R , Trudeau M
Published: August 2014

Objectives: Recent improvements in breast cancer mortality are partly due to increased utilization of appropriate systemic therapy in early stage disease. The objectives of this study were to 1. review utilization of the most effective adjuvant breast cancer regimens across Ontario, 2. identify regions where there are variations from best practices.

Methods: We used data from the Ontario NDFP to determine the utilization of 8 drug regimens approved for early stage breast cancer in each of the 14 provincial local health integration networks (LHINs). The NDFP funds the use of new and expensive cancer drugs; over 90% of all cancer treatments are funded through this mechanism. In Ontario, there were an estimated 9000 new cases of breast cancer in 2011. The analysis was restricted to patients with early stage, Her2 negative breast cancer treated in 2011-12. Data were obtained from individual cancer clinics in each LHIN. We estimate that data collection was >95% complete for these regimens.

Results: 3375 women were treated with an NDFP regimen. Across the province, the most commonly used regimen was FEC-D (43%), followed by TC (23%) and ddACT (21%). The remaining regimens (AC-Docetaxel, ACT q 3 wks, CEF, FEC and AC-weekly P) were used in less than 5% of cases. However, there was important regional variation. In LHIN A, ACT q 3 wks was used in 42% of cases, and no patients received FEC-D. In LHIN P, TC was used in 40% of cases. In LHIN R, only 6% of patients received FEC-D, whereas 63% received ddACT.

Utilization of Adjuvant Chemo Regimens n = 3375 AC-DocetaxelddACT q2wksACT q3wksAC-weekly PCEF/FECTCFEC-DLHIN K212004109241LHIN J3417101545212LHIN Q12000640104LHIN D1530732568165LHIN V57120031027LHIN R5188390104018LHIN P2246184111115LHIN B35311182795LHIN C0588002326LHIN A0132581120LHIN H2410189109LHIN T510425466038LHIN M1011318319175263LHIN S1715004728Total (%)128 (4)708 (21)156 (5)37 (1)139 (4)766 (23)1441 (43)

Conclusion: The ACT q3 wks and TC regimens are widely used. This is of concern as they are likely less effective than FEC-D or ddACT. Factors such as tumour stage, geographic distance from treatment centre and private insurance coverage for supportive care medications may also affect choice of regimen. Consensus guidelines for the adjuvant systemic therapy of breast cancer in Ontario are being developed, along with a knowledge translation strategy to disseminate the results.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-12-11.
Abstract P3-12-12: Body mass index does not influence febrile neutropenia and delivered dose intensity in adjuvant chemotherapy for breast cancer
Authors: Mayr D , Hochreiner G , Fuchs D , Fridrik MA
Published: August 2014

Background

Obese patients are often not fully dosed when receiving adjuvant chemotherapy for breast cancer, which might influence the inferior outcomes seen in this patient population. Current guidelines recommend full, weight-based dosing of chemoherapy for obese patients. The aim of the present study was to assess toxicity and deliverable dose intensity in patients treated with adjuvant chemotherapy for breast cancer.

Patients and Methods

We conducted a single-center retrospective case review on patients treated with adjuvant chemotherapy for early breast cancer at our institution from 2009 to 2012. Data were extracted from electronic patient records and side effect were graded according to CTC AE 3.0 in the source data.

Statistics: Chi-Square, Fisher's exact test, MANOVA and repeated measures ANOVA. Software: SPSS 18.

The study received approval from the local ethics comitee.

Results

We included 187 patients (185 female, 2 male) who received a total of 924 courses of chemotherapy with full eight-based dosing with either 6 courses of FEC-T (n = ,%) or TC (n = ,%). There were no differences accross BMI categories for age, gender, endocrine receptor expression, grading or her2-status.

Obese patients had more unplanned admission (p = 0.008), infections (grade 3-4, p = 0.005, all grades, p = 0.025) and diarrhoe (all grades, p = 0.033) compared to normal-weight patients. This was not the case for overweight patients (p = 0.063, 0.322, 0.199, 0.107, 0.065). Obese and overweight patients had more constipation than normal-weight patients (all grades, p = 0.025 and 0.006, respectively). There were no signficant differences across weight categories for neutropenic fever, delivered dose intensity, dose reduction and premature discontinuation of therapy.

Discussion

Obese and overweight patients can be treated with full dose intensity and do not suffer from excessive serious complications compared to normal-weight patients. However, due to partly increased toxicity seen in obese patients, adequate supportive therapy is of particular importance.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-12-12.
Abstract P3-12-13: First analysis of ASTER study AT for 3 cycles followed by CMF for 3 cycles as neo or adjuvant chemotherapy in early stage breast cancer. A single institution experience
Authors: Mariani G , Galli G , Mariani P , Bianchi GV , Capri G , Cresta S , Damian S , De Benedictis E , Valagussa P , Magazzu' D , De Braud FG , Moliterni A
Published: August 2014

Background: The ECTO study demonstrated the efficacy of concurrent doxorubicin and paclitaxel (AT) for 4 cycles followed by cyclophosphamyde/ methotrexate/fluorouracil (CMF) for 4 cycles in the neoadjuvant and adjuvant treatment of operable breast cancer (Gianni L. et al. JCO 2009). With the purpose of ameliorating the tolerability of the regimen, we designed the ASTER study to reduce both the duration and the total dose of treatment with AT followed by CMF. Herein we report on the first data of efficacy of the study and the toxicity.

Methods: A total of 345 patients with operable breast cancer were enrolled between September 2008 and November 2011. Median age was 50 years (range 23-74); 74.5% of patients presented with hormonal receptor positive (HR +) and 23,5% of patients with both hormonal receptor negative (HR-PgR-); 19% of patients presented HER2 over expression/amplification; half patients had Ki67 >14%, almost of patients had pT1 (66%) or pT2 (30%) with 27,5% of pN0. Patients were treated with Adriamycin (60 mg/mq) + Paclitaxel (200 mg/mq) q21 for 3 cycles followed by CMF i.v. 1, 8q28 for 3 cycles (73 as neo-adjuvant and 272 as adjuvant regimen). After chemotherapy in patients with HER2+ trastuzumab was delivered for 1 yr and in patients with HR+ tumors hormonal treatment was recommended for 5 yr. Breast irradiation was mandatory after conserving surgery (64% of cases).

Results: At a median follow-up of 36 months, the relapse free survival (RFS) and overall survival (OS) were 92% and 96% respectively. As expected in patients HR+/HER2- RFS were 95% and OS 99%, in patients HER2+ RFS were 90% and OS 97% and in those HR-/HER2- 83% and 79% respectively.

In the neoadjuvant subset tnpCR, defined as the absence of invasive cells in the primary tumor and in nodes, was obtained in 10% of cases. A tnpCR was achieved in 27% of patients with triple negative cancer and only in 5% of HR positive cancer.

Peripheral neuropathy toxicity was reported in 37% of cases and was essentially mild to moderate. Only 8,7% of patients experienced neutropenia G 3, 4,3% GI toxicity G3 and 2,3% mucositis G3. No cardiotoxicity was documented even in the 65 patients who received postoperative trastuzumab to date.

Conclusions: This results of Aster study AT for 3 cycles followed by CMF for 3 cycles showed similar efficacy and very favorable toxicity compared whit our previous experience of eighth cycle of sequential and non cross resistant chemotherapy in early stage breast cancer.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-12-13.
Abstract P3-13-07: A-TaXel: Multicenter phase II combination of bevacizumab (A) with weekly paclitaxel (Ta) and capecitabine (Xel) in first line treatment for patients with triple negative metastatic or locally advanced breast cancer (TNMBC), a GINECO study
Authors: Ferrero J-M , Hardy-Bessard A-C , Capitain O , Lortholary A , Salles B , Follana P , Herve R , Deblock M , Dauba J , Atlassi M , Largillier R
Published: August 2014

Background: Weekly paclitaxel and capecitabine intermittent regimen is a safe and effective combination in first line treatment of MBC including triple negative cancer (Lortholary et al, Breast Cancer Res Treat 2012). In TNMBC, the combination of A with first line Ta or Xel has been shown to improve response rate (RR) and progression-free survival (PFS) (Miller K et al., N Engl J Med 2007, Robert J et al., J Clin Oncol 2011). This phase II study is to evaluate the efficacy and safety of A-TaXel combination in TNMBC.

Methods: Patients (pts) with measurable TNMBC were treated in first line until progression with q28 cycles of Ta (80 mg/m2 D1, 8, 15) + Xel (800 mg/m2 bid D1-5, 8-12, 15-19) + A (10 mg/kg D1, 14). Primary end point was best overall RR; secondary were safety, PFS, response duration and overall survival (OS).

Results: From 04/2010 to 03/2012, 64 pts were accrued including 2 ineligible pts. Patients characteristics were: median age (56.7 yrs), ECOG PS 0 (55%), histological grade III (61%), previous adjuvant chemotherapy (74%), visceral disease (65%), > 1 metastatic sites (74%).

Patients received a median of 6 cycles (1-6), mean 5.1. Grade 3-4 neutropenia, anemia and thrombopenia were 23%, 4% and 16% respectively with febrile neutropenia in 5% of pts. G-CSF support was observed in 7% of cycles. Most frequent non hematologic toxicities were alopecia (gr2 40%), hand-foot syndrome (gr2 27%, gr3 13%), nail toxicity (gr2 40%), hypertension (gr3 35%), neuropathy (gr2 26%, gr3 6%), mucositis (gr2 16%, gr3-4 9%), fatigue (gr3 18%, gr4 2%), nausea (gr2 15%, gr3 2%) and thrombosis (gr2 3%, gr3-4 5%). Treatment interruption due to toxicity was 22%, DPD deficiency in one patient, hospitalization 23%.

RR was 77%, CR 19%, PR 58%, stable disease 14% and progressive disease 9%. Median response duration was 5.6 months. Median PFS was 7.9 months (6.7-9) and OS 19.2 months (17.3-21.1).

Conclusion: A-TaXel is an effective regimen with high RR and manageable toxicity.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-13-07.
Abstract P3-14-03: Pathological complete response after primary chemotherapy as a surrogate end point of treatment efficacy in breast cancer patients: A trial-based meta-analysis
Authors: Amoroso V , Berruti A , Gallo F , Bertaglia V , Paloja E , Simoncini EL , Generali D , Bottini A , Bruzzi P , Sormani MP
Published: August 2014

Background: The relationship between pathological complete response (pCR) and improved long-term prognosis was first reported in the landmark NSABP B-18 and B-27 trials and then validated in large cohort studies and in meta-analyses. Whether pCR, as surrogate end point, should capture the full effect of neoadjuvant chemotherapy on survival is still unproven. To assess the role of pCR as surrogate of disease-free survival (DFS) and overall survival (OS) at a trial level, we performed a trial-based meta-regression of randomized studies comparing different neoadjuvant therapies with data on both pCR rates and outcome end points.

Methods: The systematic search included electronic databases and proceeding of international meetings. No restriction regarding treatment types was set up except for endocrine therapy trials that were excluded. We did not include studies comparing neoadjuvant versus adjuvant chemotherapy. Relevant data were extracted from each selected trial: patients randomly assigned to treatment and analyzed per arm, tumor stage, type of chemotherapy and targeted therapy, cycles number, additional post-surgical treatments, number of patients achieving pCR and number of outcome events per arm. For each trial, the experimental and the control arm were defined. Treatment effects on DFS and OS were expressed as hazard ratios (HRs) and on pCR as odd ratios (ORs). A weighted regression analysis was performed on log-transformed treatment effect estimates to test the association between the treatment effects on the surrogate outcome and the treatment effects on the clinical outcome.

Results: A final set of 28 trials, 57 arms and 29 contrasts for a total of 13,738 patients was included in the analysis. As one trial had 3 arms, it contributed two contrasts to the analysis. The regression of the logHR for DFS on the logOR for pCR, using the complete set of data, demonstrated a weak but significant association between the two effects (R2 = 0.16, p-value = 0.03). Sixteen% of the variability among the effects on DFS can be explained by the observed effects on pCR. The regression of the logHR for OS on the logOR for pCR demonstrated a weak association between the two effects (R2 = 0.15, p-value = 0.04).

Conclusions: This trial-based meta-regression showed a possible role of pCR as surrogate end point for DFS and OS in breast cancer patients treated with neoadjuvant chemotherapy. The surrogacy of pCR warrants to be further evaluated in more homogeneous subsets of clinical trials in the neoadjuvant chemotherapy-based setting.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-03.