bluuebunny/crossref_metadata_2025 huggingface dataset:
ARN-509 in men with high-risk nonmetastatic castration-resistant prostate cancer (CRPC).
Authors: Smith Matthew Raymond , Antonarakis Emmanuel S. , Ryan Charles J. , Berry William R. , Shore Neal , Liu Glenn , Alumkal Joshi J. , Higano Celestia S. , Maneval Edna Chow , Rathkopf Dana E.
Published: February 2017

7

Background: ARN-509 is a novel second-generation anti-androgen that binds directly to the ligand-binding domain of the androgen receptor, impairing nuclear translocation and DNA binding. The Phase II portion of a multicenter Phase I/II study is evaluating the activity of ARN-509 in 3 distinct patient populations of men with CRPC (high risk non-metastatic CRPC, metastatic treatment-naïve CRPC, and progressive disease after abiraterone acetate). Preliminary results for the cohort of patients with high-risk non-metastatic CRPC are presented here. Methods: All patients had CRPC, no radiographic evidence of metastases (pelvic lymph nodes <3 cm below the iliac bifurcation were allowed), and high risk for disease progression based on PSA value ≥ 8 ng/mL within 3 months of enrollment and/or PSA doubling time ≤ 10 months. Patients received ARN-509 at the recommended Phase II dose of 240 mg/day, previously established in Phase I (Rathkopf et al, GU ASCO 2012). The primary endpoint was PSA response rate at 12 weeks according to the Prostate Cancer Working Group 2 Criteria. Secondary endpoints included safety, time to PSA progression and 1-year metastasis-free survival. PSA assessments were collected every 4 weeks and tumor scans were performed every 16 weeks. Results: Forty-seven patients were enrolled between November 2011 and May 2012. The median age was 71 years (range 51 to 88) and at baseline, patients presented with ECOG performance status 0 (77%), Gleason Score 8-10 (32%), and median PSA of 10.7 ng/mL. All patients received prior treatment with a LHRH analog with or without a first-generation anti-androgen. At a median treatment duration of 20 weeks, three patients discontinued the study. The most common treatment-related adverse events (AE) were fatigue (30%), diarrhea (28%), nausea (17%), rash (13%), and abdominal pain (11%). The incidence of Grade 3 AEs was 6.4%, and no seizures have been observed to date. The 12-week PSA response was 91% and the time to PSA progression has not been reached. Conclusions: In men with high-risk non-metastatic CRPC, ARN-509 is safe and well tolerated with promising preliminary activity based on high PSA response rates. Clinical trial information: NCT01171898.
Population-based impact on overall survival (OS) after the introduction of docetaxel as standard therapy for metastatic castration resistant prostate cancer (CRPC).
Authors: Zielinski Robert Richard , Tyldesley Scott , Chi Kim N.
Published: February 2017

77

Background: Docetaxel (DOC) was the first systemic therapy to improve OS (Hazard Ratio (HR) = 0.79) for patients (pts) with CRPC and a standard therapy since 2004. Because of the potential for severe toxicity with DOC, its use has been subject to pt selection. Even with this selective use, we sought to determine whether the introduction of docetaxel has improved OS at a population level. Methods: We performed aretrospective review of all CRPC pts treated with palliative radiotherapy (PRT) to bone metastases in the province of British Columbia, Canada. The pre-docetaxel cohort (pre-D) received PRT from 1998-2001. The docetaxel-era cohort (post-D)received PRT from 2006-2009. Time of first PRT to bone was used to select pts at a similar point in their disease state (i.e., onset of bone pain). Mortality and cause of death was attained from public registries. OS was calculated from time of first PRT using the Kaplan-Meier method and compared using the log-rank test. Results: Comparative baseline characteristics for the 1876 patients split into the pre-D (n=919) and post-D (n=957) eras were: metastatic at diagnosis 30% vs. 33% (p = 0.09), median age at PRT 75.5 vs. 76.7 years (p=0.04), time from diagnosis to PRT 3.9 vs. 3.1 years (p = 0.31), received DOC 7% vs. 37% (p < 0.0001). Median OS from time of first PRT was 7.5 months (m) vs. 10.3 m (HR: 0.79, 95% Confidence Interval 0.70 – 0.89, p < 0.0001) in the pre-D and post-D cohorts respectively. Within the post-D cohort, the median OS from time of RT was longer in pts receiving DOC at 13.9 m vs. 7.4 m for pts not receiving DOC (p=0.004). Conclusions: In this population based analysis, the introduction of DOC as a standard of care was associated with a significant improvement in OS even though DOC penetrance was <50%. This demonstrates for the first time the generalizability of the TAX-327 study results to the population at large. Even as the therapeutic landscape for CRPC evolves with the introduction of new agents that improve OS with favourable toxicity profiles, these data support the continued use of DOC in appropriately selected patients.
Sequencing of cabazitaxel and abiraterone acetate following docetaxel in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Schnadig Ian D. , Bhor Menaka , Vogelzang Nicholas J. , Hennessy Daniel , Nicacio Leonardo V. , Berry William R. , Hutson Thomas E. , Fleming Mark T. , Cowey C. Lance , Saravanan Shanmugapriya , Dhanda Rahul , Sonpavde Guru
Published: February 2017

79

Background: Following docetaxel (D), treatment options for mCRPC include cabazitaxel (CBZ), abiraterone acetate (AA), and enzalutamide. With the introduction of new agents, optimal sequencing is undefined. We evaluated the prevalence of sequencing of AA and CBZ following D in a large community-based cohort to develop a hypothesis for the most optimal sequence. Methods: A retrospective analysis of treatment patterns using the MSH iKnowMed EHR was conducted. Post-D mCRPC patients receiving CBZ and/or AA at full EHR sites with ≥2 visits were included; clinical trial patients excluded. CBZ utilization between Jun’10 and May’12 and sequencing of CBZ or/and AA from Apr’11 and May’12 (when both drugs were available) were examined. OS, time to treatment failure (TTF), and demographics analyses are ongoing. Results: 667 evaluable patients were identified. Overall CBZ (n=359 pts/2 y) utilization declined between Jun’10-May’11 (n=232) and Jun’11-May’12 (n=127). From Apr’11 to May’12: overall AA (n=465 pts/y) utilization increased between Mar-May’11 (n=73) to Jun-Aug’11 (n=164) and subsequently decreased (n=57) from Mar-May’12. Between Apr’11-May’12, 130 patients received both CBZ and AA. More men (P<0.001) received D→CBZ→AA (n=88, 67.7%) compared with D→AA→CBZ (n=42, 32.3%). Median age of patients receiving both CBZ and AA was 67 (44-89) y and their median baseline PSA (111 evaluable) was 84.3 (0.4-7672.2) ng/mL. Conclusions: AA was administered more frequently than CBZ in post-D mCRPC patients. However, the sequence of D→CBZ→AA was more prevalent than D→AA→CBZ in this large community-based cohort. Until predictive biomarkers and outcomes with respective sequences are identified, delivery of all active agents according to patient-specific clinical factors should probably be considered. [Table: see text]
Age, comorbidity, and the risk of death in men with PSA failure following radiation therapy.
Authors: Martin Neil E. , Chen Ming-Hui , Beard Clair , Nguyen Paul Linh , Loffredo Marian , Renshaw Andrew A. , Kantoff Philip W. , D'Amico Anthony Victor
Published: February 2017

82

Background: Life expectancy data based on age and comorbidity may identify men with favorable post-radiation prostate-specific antigen (PSA) failure kinetics unlikely to experience metastasis despite withholding androgen deprivation therapy (ADT). Methods: Of 206 men with unfavorable-risk prostate cancer (PC) enrolled on a randomized trial of radiation vs. radiation + ADT, 108 had a PSA failure and 53 who did not receive slavage ADT because the PSA had not meet a pre-specified criteria of 10 ng/mL (n=41) or had significant comorbidity (n=12) and were followed with q1 year (yr) bone scan and q6 month (mo) PSA formed the study cohort. Comorbidity, age and established prognostic factors were evaluated with Cox regression to determine factors associated with death after PSA failure. Results: Median age at and interval to PSA failure and PSA doubling time were 76.6 yr (interquartile range [IQR] 71.8-79.3), 49.1 mo (IQR: 37.7 – 87.4), and 25 mo (IQR: 13.1 – 42.8) respectively. After a median follow up of 4.0 yr (IQR: 2.0 – 12.5) post PSA failure, 24 (45%) men died, none from PC and no one developed metastases. The median last follow up PSA was 3.6 ng/mL (IQR: 1.8 - 8.3). Increasing age at PSA failure (adjusted hazard ratio [AHR]: 1.14; 95% CI: 1.03 – 1.25; p=0.008) and the presence of moderate to severe comorbidity (AHR: 12.5; 95% CI: 3.81 – 41.0; p<0.001) were significantly associated with an increased risk of death on multivariate analysis. At 4 yr, 86% above the median age at PSA failure and with moderate or severe comorbidity had died compared to 16% whose age was at the median or less and with no or minimal comorbidity (p< 0.001). Conclusions: Men over age 76 with significant comorbidity and a PSA doubling time > 2 yr following post-radiation PSA failure appear to be good candidates for surveillance. [Table: see text]
Long-term efficacy of stereotactic body radiotherapy for localized prostate cancer: A multi-institutional pooled analysis.
Authors: Kupelian Patrick , Katz Alan J. , Freeman Debra , Kaplan Irving D. , Fuller Donald B. , Bolzicco Giampaolo , Collins Sean P. , Meier Robert , Wang Jason , King Christopher R.
Published: February 2017

9

Background: The purpose of this study is to report biochemical relapse-free survival (bRFS) rates for a group of localized prostate cancer patients from a pooled multi-institutional dataset with at least 5 years follow-up after stereotactic body radiotherapy (SBRT). Methods: The outcome data from 1101 patients treated with SBRT between 2003 and 2011 were pooled from 8 institutions. A subset of 135 cases had a minimum 5 years follow-up. All 135 cases had clinical stage T1 or T2A disease. The distribution by Gleason score (GS) was <6 in 80% and 7 in 20%. The median pretreatment PSA (iPSA) level was 5.1 ng/ml (range: 0.1-27.8). The distribution by risk was 77% low, 21% intermediate, and 2% high risk. The median dose was 36.25 Gy (35-40 Gy range) delivered either with 4 or 5 fractions. The prescribed dose groups were as follows: 35 Gy in 42%, 36.25 Gy in 47%, and >38 Gy in 11%. Androgen deprivation therapy was given to 21% of patients. Biochemical relapse, defined as a rise > 2 ng/ml above nadir, was determined in a total of 4 failures. Results: The median follow-up for all 135 cases was 60 months (range 60 to 72). For all patients, the bRFS rate at 5 years was 97%. The 5-year actuarial bRFS rates for GS < 6, and Gleason score 7 were 98%, and 92%, respectively (p=0.15). The 5-year actuarial bRFS rates for low versus intermediate/high-risk patients were 99% and 93%, respectively (p=0.11). The 5-year actuarial bRFS rates for patients receiving 35 Gy versus >36.25 Gy were 93% and 100%. No difference in bRFS was observed with the use of androgen deprivation (p=0.78). Multivariate analysis showed only GS to be an independent predictor of relapse (p=0.03); iPSA (p=0.10) and radiation dose (0.97) were not. Conclusions: In a relatively large cohort of localized prostate cancer patients treated with SBRT, long follow-up period (>5 years), excellent efficacy was demonstrated with 97% of patients being free from relapse. For low and intermediate risk cases, these results compare favorably with other modalities with similar follow-up periods. Although a trend for worse outcome was seen with total radiation doses of 35 Gy, this was not confirmed on multivariate analysis.
Benefits of immediate versus delayed palliative care to informal family caregivers of persons with advanced cancer: Outcomes from the ENABLE III randomized clinical trial.
Authors: Dionne-Odom J Nicholas , Azuero Andres , Lyons Kathleen , Li Zhongze , Tosteson Tor , Li Zhigang , Hull Jay , Frost Jennifer , Hegel Mark , Dragnev Konstantin H. , Akyar Imatullah , Bakitas Marie
Published: February 2017

LBA9513

Background: Family caregivers of individuals with advanced cancer experience significant burden and diminished QOL; few interventions have been found to reduce these outcomes. Methods: Randomized clinical trial conducted from 10/11/2010 to 9/5/2013 of immediate versus delayed (initiated 12 weeks after randomization) entry patients (n=207) and caregivers (n=122) into ENABLE (Educate, Nurture, Advise, Before Life Ends), a phone-based concurrent oncology palliative care intervention. QOL (Caregiver Quality of Life-Cancer, lower scores=better QOL), depression (Center for Epidemiological Study-Depression) and burden (Montgomery Borgatta Caregiver Burden Scale; subjective burden [SB], objective burden [OB]; demand burden [DB]) measures were collected at baseline, 6, 12, 18, and 24 weeks, and every 12 weeks until patient death or study completion. Results: Estimated treatment effects (immediate minus delayed) for caregivers from randomization to 12 weeks were (mean [SE]): -3.1 [2.3] for QOL (P=.17), -4.1 [1.3] for depression (P=.003), -1.0 [0.4] for SB (P=.02), 0.3 [0.6] for OB (P=.60), and -0.5 [0.6] for DB (P=.39). Estimated treatment effects (immediate minus delayed) from intervention initiation to 12 weeks were (mean [SE]): -6.4 [3.4] for QOL (P=.06), -7.4 [2] for depression (P<.001), -1.0 [0.6] for SB (P=.08), -0.6 [0.7] for OB (P=.44), and -0.5 [0.8] for DB (P=.50). Estimated treatment effects (immediate minus delayed) measured backwards from the time of patient’s death were (mean [SE]): of -4.9 [2.6] for QOL (P=.07), -3.8 [1.5] for depression (P=.02), -1.1 [0.4] for SB (P=.01), -0.6 [0.6] for OB (P=.26), and -0.7 [0.6] for DB (P=.22). Conclusions: Caregivers in the immediate group had lower depression, SB, and trends towards better QOL in comparisons up to 12 weeks, following initiation of the intervention in both groups, and in the terminal decline analysis. These results suggest that concurrent oncology palliative care should be initiated as early as possible to maximize benefit to caregivers. Clinical trial information: NCT01245621.
Improving screening mammography return rates in overdue women: A randomized study of signed reminder letters from family physicians.
Authors: Chan Elisa K. , Wilson Christine , Tyldesley Scott , Lai Anky , Sam Janette , Harry Ritinder , Nichol Alan
Published: February 2017

1

Background: For asymptomatic women aged 50 to 74 with an average risk for developing breast cancer, screening mammography (SM) is recommended every 2 years in British Columbia (BC). The Screening Mammography Program of BC (SMP) uses a schedule of multiple postcard reminders, which achieves an on-time (within 30 months) participation rate of 54% among those aged 50 to 69. The purpose of this study was to determine whether the SM return rate of overdue women could be improved by a reminder letter signed by their family physicians. Methods: Eligible women met the following criteria: prior normal SM, age 52 to 74, overdue by 30 to 48 months from their last SM and had agreed to being contacted for research by the SMP. All family physicians in BC were invited to participate. Consenting physicians signed the study letters, which encouraged SM, for all of the overdue women in their practice. Women were randomized to receive a postcard reminder or a postcard reminder and the signed family physician reminder letter. Six months after the mailing, the SMP database was queried to determine the SM return rate. Results: In BC, 822 physicians participated in the study and 5,385 women with signed letters were randomized. SMP sent a postcard to 2,689 women and a postcard and letter to 2,696 women. The age, number of prior SMs and time overdue were not statistically different between the arms. Within 6 months, 600 women (22.3%) in the postcard arm returned, while 894 women (33.2%) in the postcard and letter arm returned (odds ratio 1.7, p < 0.0001). The maximum difference between the SM return rates was observed at 4 months. On multivariable analysis, women who had >1 previous SM were more likely to return compared to those who only had 1 previous SM (odds ratio 2.2, p < 0.0001). Women who were 30 to 36 months overdue were more likely to return compared to those who were 42 to 48 months overdue (odds ratio 2.4, p < 0.0001). Conclusions: A signed family physician reminder letter is a simple and effective intervention to improve screening mammography return rates in overdue women.
BRCA 1 and BRCA 2 mutations in Saudi breast cancer patients (single institution).
Authors: Abulkhair Omalkhair A. M.
Published: February 2017

10

Background: Breast cancer is the commonest malignancy among Saudi females accounting for 25% of all female cancers with a median age at diagnosis of 47 years (1,2). In Saudi, breast cancer showed an increased incidence attributed to many factors such as different lifestyles, reproductive pattern, family history, which was reported to account for 59%, dietary or cultural practice of Saudi women (2,3,4,5). The multifunctional and highly penetrant BRCA 1 and BRCA 2 are the two major breast cancer pre-disposition genes, accounting for about 20% of breast cancer families (6,7). To our knowledge, the prevalence of BRCA 1 and BRCA 2 mutations in native Saudi population is sparse (8,9). Our aim is to describe the findings of BRCA mutation testing in native Saudi patients with breast cancer in a large Ministry of National Guard Health Affairs (NGHA) community-based teaching hospital. Methods: In this study, 75 out of 516 patients with breast cancer who were clinically and histopathologically diagnosed at NGHA from October 2010 to April 2014 were included. Selection criteria: aged ≤ 40 years bilateral breast cancer, triple-negative breast cancer, strongly first degree family history at young age and male breast cancer. Molecular alterations were performed by direct gene sequencing, multiple ligation – dependent probe amplification (MLPA) at Bioscentia human genetic testing in Germany. Results: 75 native Saudi were enrolled and test performed for them. 18 patients (24%) were found to have mutation of which 10 in BRCA One and six in BRCA 2. Two have both BRCA 1 and BRCA 2. Seven patients have the same with deleterious mutations in BRCA 1 gene. Two of them are mother and daughter and other five are unrelated. The mean age of breast cancer diagnosis in the mutation carriers was 38 years. Triple negative breast cancer (TNBC) diagnosed in six patients, bilateral breast cancer diagnosed in one, first-degree family history in eight and second degree in 10 patients and four with no family history. Conclusions: BRCA 1 and BRCA 2 mutations are an important contributor to the etiology of breast cancer in Saudi women. A mutation in BRCA 1, C 1648 > C p, Asn550His in exon 10 has been reported as disease causing (11) and it is found in our study in seven patients. Such mutation might be specific for Saudi, so further studies are highly recommended.
Androgen receptor (AR) and phospho-AR protein levels in invasive breast cancers and survival outcomes: Indication of a new prognostic marker.
Authors: Iwase Hirotaka , Takeshita Takashi , Omoto Yoko , Ibusuki Mutsuko , Yamamoto Yutaka
Published: February 2017

11

Background: Androgen receptor (AR) in breast cancer may serve as a useful prognostic and predictive marker. We examined the expression patterns of AR and AR phosphorylated at serine-213/210 (pAR213/210) in breast cancer by immunohistochemistry, and evaluated their association with clinicopathological parameters and prognoses. Methods: The levels of AR nuclear protein expression were determined in tissue samples of 379 consecutive female patients with invasive breast cancer. In samples that showed detectable AR, the levels of pAR213/210nuclear and cytoplasmic expression were determined. All samples were scored semiquantitatively using a histoscore. Results: Nuclear staining of AR was observed in 76% of the samples. Elevated AR protein expression correlated with non-aggressive parameters and longer relapse-free survival (RFS) (p < .0001) and breast cancer-specific survival (BCSS) (p < .0001). Nuclear and cytoplasmic pAR213/210 were observed in 72.4% and 11.9%, respectively, of the tested samples. Although no statistically significant relationship between pAR213/210 nuclear expression and clinicopathological parameters was observed, increased expression of cytoplasmic pAR213/210 was associated with high nuclear grade (p = .026), estrogen receptor (ER) α-negative (p = .023), progesterone receptor (PgR)-negative (p = .034), human epidermal growth factor receptor 2 (HER2)-positive (p = .043), and Ki-67-positive (p = .026) tumors. Conversely, nuclear pAR213/210 expression correlated with longer RFS (p = .027) and BCSS (p = .0031), but cytoplasmic pAR213/210expression was not related with RFS and BCSS. Conclusions: AR and its phosphorylation at serine-213/210 are significant in breast cancer progression and prognosis. The expression levels of pAR213/210 could have potential as a new prognostic marker of breast cancer.
State of the research on breast cancer in young women.
Authors: Esser Michelle , Rowe Jean , McCann Megan , Lewis Stacy
Published: February 2017

117

Background: Young Survival Coalition (YSC) is the premier global organization dedicated to the critical issues unique to young women and breast cancer. In May, 2014, YSC released its Research Agenda which identified the most pressing research questions that must be answered in order to improve the quantity and quality of life for young women affected by breast cancer. Methods: This Research Agenda arose out of an almost two-year-long process created and facilitated by YSC, called the Research Think Tank (RTT). YSC assembled doctors, researchers and advocates to focus on six areas of particular importance to its young constituents: risk factors; treatment; metastasis; quality of life; fertility; and pregnancy. Results: Through the work of the RTT, YSC assessed the current state of knowledge as well as existing gaps in each of the six identified areas. While work is needed in all areas, there have been recent updates and progress regarding treatment and fertility. Additionally, quality of life studies examine the uniqueness of breast cancer in young women, although application of this knowledge through tested interventions, decision aids, or guidelines and tools for physicians are still lacking. Aspects of pregnancy during breast cancer and after breast cancer have been studied but many open questions remain. There has been little progress in understanding why so many breast cancers are diagnosed in the postpartum period, why they tend to be more aggressive, and what can be done to prevent or treat it. Research examining metastasis in young women is rare. Most research focuses on postmenopausal patients, and many studies set criteria that specifically exclude younger women. This is the topic area most in need of work and priority. Similarly, little research focuses on the specific risk factors for early onset breast cancer. These are likely distinct from the risk factors associated with postmenopausal breast cancer yet they are rarely separately examined. Conclusions: Compared to older women, young women generally face more aggressive cancers, lower survival rates, and unique psychosocial concerns. Breast cancer in young women is an area in need of additional work and clarification in order to increase their quantity and quality of life.
Modulation of insulin-like growth factors (IGF I-II) and IGF binding-protein 3 (IGFBP-3) through exercise training in women with breast cancer: A systematic review and meta-analysis.
Authors: Meneses-Echavez Jose F , Ramirez-Velez Robinson , Gonzalez-Jimenez Emilio , Schmidt Rio-Valle Jacqueline , Sanchez Perez Maria Jose , Molina Montes Esther
Published: February 2017

120

Background: Epidemiological data suggest that Insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) are associated with breast cancer risk, apoptosis and other carcinogenic mechanisms. This metaanalysis evaluates the effects of exercise interventions in controlling serum concentrations of Insulin-like growth factors (IGF1-IGF2) and IGFBP-3 in women with breast cancer. Methods: We incorporated the PRISMA statement. Databases of MEDLINE, Ovid, EMBASE and Cochrane Central Registers were searched to identify randomized controlled trials until March 2014, reporting effect estimates for IGF-1, IGF-2, IGFBP-3 and other secondary outcomes such as insulin, glucose and waist circumference as a body composition measure. An Inverse of variance (IV) with Mantel–Haenszel method was selected for analysis, and a random-effects models were used to assess the pooled estimates in addition to sensitivity analyses, whilst heterogeneity was evaluated using the Chi2 test (P<0.10) and I2 statistics (I2>50%).STATA 12.0 was used for metaanalysis procedures. Results: Six studies were included in the pooled analysis involving 321 patients. Effect estimates showed that exercise training improved IGF-1 (MD= -12.9, 95CI% -16.73 to -9.14, P<0.001), IGF-2 (MD= -43.4, 95CI% -58.5 to -28.3, P<0.001), IGFBP-3 (MD= -0.61, 95CI% -0.69 to -0.53, P<0.001) and waist circumference (MD= -1.133, 95CI% -2.20 to -0.05, P=0.03) in women with breast cancer. Conversely, non-significant differences were observed for Insulin (MD= 0.046, 95CI% -0.24 to 0.34, P=0.7), Glucose (MD=0.22, 95CI% -0.32 to 0.78, P=0.419) and Insulin Resistance (MD= 0.64, 95CI% -0.006 to 1.29, P= 0.06). There was no evidence of publication bias. Conclusions: Exercise is an effective and safe intervention in improving the serum concentrations of insulin like growth factors (IGF1-IGF2) and IGFBP-3 in women with breast cancer, strengthening the physiological effects of exercise in regulating cellular proliferation and apoptosis in breast cancer. Further evidences are encouraged.
Building the case for expanded support services to young breast cancer survivors: An evaluation of a cooperative agreement.
Authors: O'Dell Sarah , House Marnie , Hall Mary Ann , Moore Angela , Fairley Temeika
Published: February 2017

127

Background: To determine effective and appropriate communication interventions to address the psychosocial needs of young breast cancer survivors (YBCS), the Centers for Disease Control and Prevention (CDC) established a cooperative agreement with seven organizations offering tailored support and education services to YBCS. The process evaluation of this cooperative agreement aims to document program implementation and the extent to which the cooperative agreement relationship (funding, subject matter expert support, technical assistance, and training) facilitates organizations’ delivery of programs. An additional five organizations were studied for comparison to gain a broader perspective on programmatic offerings for YBCS across the United States. Methods: The evaluation utilizes a multiple case study design, entailing document review, site visits, program observation, and in-depth interviews with program staff to describe program implementation and perceptions related to program effectiveness. Thematic analysis is being utilized to analyze all qualitative data collected. Results: Organizations offer a range of services, including psychosocial support and education to YBCS, YBCS caregivers and health care providers. Services offered cover the cancer care continuum, ranging from the provision of community outreach and education via multiple platforms (e.g., partnership development, online resource compilations, social media) to structured support services offered (e.g., patient navigation, structured support plans, tailored support groups for survivors and caregivers) to relevant YBCS audiences. Specifically, grantee program staff members report that cooperative agreement funding helped to expand and strengthen organizations' YBCS-focused efforts; all organizations offer lessons learned for communication with YBCS. Conclusions: Findings from this evaluation demonstrate the utility of federal funds to help organizations augment existing or create new resources and services for YBCS. Further, findings from this evaluation support the use of tailored interventions as a promising strategy to improve YBCS communication and education efforts.
Can Twitter social media be an effective tool for breast cancer survivor support and education?
Authors: Attai Deanna J. , Landercasper Jeffrey , Schoger Jody M , Staley Alicia C , Cowher Michael S
Published: February 2017

130

Background: Despite reported benefits, approximately 60% of women do not attend breast cancer support groups. Many online resources for support exist, but information regarding the effects of participation is lacking. We report the results of a Twitter breast cancer support community participant survey. Methods: The Breast Cancer Social Media (#BCSM) Twitter support community began in July 2011. IRB approval with waiver of informed consent was obtained for a de-identified survey which was posted for two weeks on Twitter and on the #BCSM blog and Facebook page. Results: There were 206 respondents, with a median age of 45-54 and 93% being female. 74% were from the United States. 92% were Caucasian. 83% completed a 4-year college degree. 69% had been treated for breast cancer. 14% reported living with metastatic breast cancer. 72% became aware of #BCSM through Twitter. 45% had been participating in the chats for > 12 months. 81% of respondents reported increased overall knowledge about breast cancer. Increased knowledge through #BCSM was reported in all the following specific domains: 86% survivorship, 80% metastatic breast cancer, 70% cancer types and biology, 66% clinical trials and research, 56% treatment options, 56% breast imaging, 54% genetic testing and risk assessment, and 43% radiotherapy. 31% reported that participation led them to seek a second opinion or bring additional information to the attention of their treatment team. 73% percent reported plans to increase their outreach and advocacy efforts as a result of participation. Levels of reported anxiety before and after participation were analyzed. 29 of 43 patients (67%) who initially reported “high or extreme” anxiety reported “low or no” anxiety after participation (p < 0.001). Also, no patients initially reporting “low or no” anxiety prior to participation reported an increase to “high or extreme anxiety” after participation. Conclusions: While many online breast cancer patient resources exist, data documenting patient educational benefits of participation are lacking. This study demonstrates that breast cancer patients’ perceived knowledge can be increased and that their anxiety can be decreased by participation in a Twitter social media support group.
Clinical effects of prior trastuzumab on combination eribulin mesylate plus trastuzumab as first-line treatment for HER2+ locally recurrent or metastatic breast cancer (MBC): Results from a phase 2, single-arm, multicenter study.
Authors: O'Shaughnessy Joyce , Huggins-Puhalla Shannon Leigh , Wilks Sharon , Brufsky Adam , Schwartzberg Lee Steven , Berrak Erhan , Song James X. , Cox David , Vahdat Linda T.
Published: February 2017

139

Background: Eribulin mesylate, a novel nontaxane microtubule dynamics inhibitor in the halichondrin class of antineoplastic drugs, is indicated for women with MBC who previously received ≥ 2 chemotherapy regimens in the metastatic setting. Primary data from a phase 2 trial on first-line combination eribulin + trastuzumab (TRAS) in HER2+ patients (pts) showed a 71% objective response rate (ORR) and tolerability consistent with the known profile of these agents. Here we present prespecified endpoint data for this study by prior TRAS use. Methods: Pts with HER2+ MBC who had not received prior chemotherapy for MBC received eribulin mesylate 1.4 mg/m2 IV on days 1 and 8 of each 21-day cycle and initial TRAS (8 mg/kg IV/day 1), followed by 6 mg/kg/day 1 of each subsequent cycle. Response, progression-free survival (PFS), and tolerability were assessed in patients who had and had not received prior TRAS treatment. Results: The 52 pts (median age, 59.5 years) received combination eribulin + TRAS, for a median treatment duration of ~30 weeks; 40% (n=21) were previously treated with TRAS in the neo-adjuvant/adjuvant setting. There was median of 23 months since completion of adjuvant treatment prior to retreatment with eribulin + TRAS for first-line MBC.Efficacy, assessed by ORR, clinical benefit rate (CBR), PFS, and duration of response (DOR), was largely consistent in pts who received prior TRAS relative to pts who had not received prior TRAS (see table). Overall, grade (G) 3-5 adverse events (AEs), treatment-related AEs (TRAEs), and discontinuations (d/c) were similar between groups (Table). Conclusions: In this phase 2 single-arm trial in pts with HER2+ MBC, eribulin + TRAS demonstrated activity and was well tolerated as first-line treatment, irrespective of prior (neo) adjuvant TRAS treatment. Clinical trial information: NCT01269346. [Table: see text]
Overall survival (OS) in metastatic breast cancer (MBC): Are we using the right endpoint in the right way?
Authors: Raphael Jacques , Verma Sunil
Published: February 2017

142

Background: OS has been historically considered the most important clinical endpoint in MBC trials; however survival could be influenced by treatment after progression in an era of effective subsequent-line agents. Methods: We conducted a search strategy using PubMed for randomized phase 3 trials published in the last 2 decades (1994-2014) evaluating survival outcome in MBC. We investigated the frequency of trials reporting post progression outcome and response/resistance to treatment beyond progression. Results: 110 trials met our eligibility criteria: 69 (63%) evaluated chemotherapy regimens (group A), 27 (25%) evaluated targeted therapy (group B) and 14 (13%) focused on endocrine treatment (group C). The majority of the trials had OS as a primary or secondary endpoint (97% (66/69), 100% (27/27) and 86% (12/14) of the trials in group A, B and C respectively). An OS benefit was demonstrated in approximately 22% of the trials in each group. Post progression survival (PPS) and its effect on OS was reported and discussed in only 1% (1/69), 4% (1/27) and 7% (1/14) of the trials for group A, B and C respectively. Less than 10% of the trials in group A and B reported response data and duration of response after progression on trial therapy. In addition, post progression treatment resistance was only reported in group A in 3% (2/69) of the trials. Furthermore, the number of lines of treatment used post progression was reported in only 14% (10/69), 11% (3/27) and 14% (2/14) of the trials in group A, B and C respectively. Conclusions: A clear paucity of post progression treatment information is noted in the majority of the phase 3 trials for MBC. We do know that OS is directly affected by treatments used after progression. In order to assess the true clinical benefit of a new drug and a complete evaluation of overall survival outcome, a detailed collection of post progression treatment information is required and should be mandated in MBC clinical studies.
Obesity and guideline-concordant systemic therapy for locoregional breast cancer.
Authors: Moore Hollis , Trentham-Dietz Amy , Greenberg Caprice Christian , Vanness David J. , Hampton John M , Wu Xiao-cheng , Anderson Roger T. , Lipscomb Joseph , Kimmick Gretchen Genevieve , Cress Rosemary Donaldson , Fleming Steven , Wilson J. Frank
Published: February 2017

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Background: Obese breast cancer patients tend to have higher mortality than non-obese patients. Hypothesizing that differences in receipt of adequate treatment may contribute to this mortality differential, we examined whether breast cancer patients with higher body mass index (BMI) received systemic adjuvant treatment consistent with National Comprehensive Cancer Network guidelines. Methods: Female adult stage I-III breast cancer cases diagnosed in 2004 were identified from population-based cancer registries in 7 states and supplemented with abstracted medical records. Differences in receipt of concordant treatment according to BMI were investigated using logistic regression models adjusted for age and other covariates. Results: Among all women, 57% (2,174 of 3,828) received overall guideline-concordant (GC) adjuvant systemic treatment, meaning treatment adherent in each of 3 defined domains: chemotherapy, chemotherapy regimen, and hormonal therapy. Within the domains, 82% of women received GC chemotherapy, and 93% of those received a GC regimen, and 80% received GC hormonal therapy. Women with higher BMI had greater odds of receiving GC systemic therapy (odds ratio for each 5 kg/m2 increase in BMI 1.07, 95% CI 1.01 to 1.14; p value for trend = 0.04). No significant differences in guideline treatment according to BMI were found in the individual therapy domains (adjuvant chemotherapy, p = 0.18; chemotherapy regimen, p = 0.26), although a borderline significant, nonlinear pattern was seen for hormonal therapy, in which the highest odds of GC treatment were found in the lowest and highest BMI ranges (p = 0.07 from χ2 test). Conclusions: Contrary to our hypothesis, odds of guideline concordant systemic therapy increased with higher BMI, and no significant differences were found within any specific treatment domain. Further research describing how multiple factors including treatment patterns influence outcomes for obese breast cancer patients may identify areas where changes in practice can reduce disease burden and mortality. Our research also suggests further investigation into patterns of care for underweight patients.
Peripheral neuropathy (PN) in patients (pts) with metastatic breast cancer treated with eribulin: Resolution and association with efficacy.
Authors: Kaufman Peter , Olivo Martin , He Yi , McCutcheon Susan , Vahdat Linda
Published: February 2017

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Background: PN is a known adverse effect of various antimicrotubule agents, including eribulin. We report here the incidence and resolution of PN in breast cancer pts treated with eribulin in completed phase 2 and 3 studies, and the efficacy of eribulin in pts with PN in the phase 3 EMBRACE and 301 studies. Methods: In EMBRACE, women had received 2-5 lines of chemotherapy for advanced disease. In this ≥ 3rd-line setting, pts randomized to eribulin mesylate received it at 1.4 mg/m2 iv, days 1 and 8 every 21 days. The dosing schedule was the same in study 301, which involved pts who had received 0-2 prior chemotherapies for advanced disease. Overall survival (OS) and progression-free survival (PFS) were analyzed by stratified log-rank test. Data from EMBRACE and 301 were pooled with data from 2 phase 2 studies to assess time to improvement (a decrease of ≥ 1 grade) and resolution (decrease in grade to 0, 1 or baseline) of grade 3 or 4 PN. Results: In the pooled safety analysis, 7.7% (116/1503) of pts treated with eribulin had grade 3 or 4 PN; 63.8% of these experienced improvement in PN and 50% had resolution. Median time to improvement was 2.1 weeks and to resolution was 7.7 weeks. Characteristics were similar in pts with or without PN in EMBRACE and 301. Those with PN had longer exposure to eribulin vs pts without PN (median exposure [months], study 301: 4.9 vs 3.2; EMBRACE: 4.8 vs 2.9). OS and PFS were significantly longer in pts with PN (Table). Conclusions: Pts who had a favourable therapeutic response to eribulin, received a longer course of treatment and thus had a greater risk of PN. Severity of PN improved in most pts within a short period. Regarding PN, the risk–benefit ratio for eribulin supports treatment. Clinical trial information: NCT00337103, NCT00388726. [Table: see text]
A phase 1 study of dinaciclib (SCH 727965) in combination with epirubicinin patients with metastatic triple-negative breast cancer.
Authors: Mitri Zahi , Karakas Kansu , Ibrahim Nuhad K. , Alvarez Ricardo H. , Murray James L. , Briones Brian , Simmons Holly , Keyomarsi Khandan , Moulder Stacy L.
Published: February 2017

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Background: Low molecular weight cyclin E (LMW-E) isoforms are overexpressed in a majority (~70%) of triple-negative breast cancers (TNBC). LMW-E isoforms have a role in tumorigenesis, likely mediated through binding and activation of CDK2. The combination of CDK1/CDK2 inhibitors, such as dinaciclib, with an anthracycline was found to be synergistic in decreasing viability of TNBC cell lines. Based on this data, we conducted a phase 1 study aimed to determine the maximum tolerated dose of dinaciclib in combination with epirubicin in patients with metastatic TNBC. Methods: Cohorts of at least 2 patients were treated with escalating doses of dinaciclib (20-50 mg/m2) given on day 1 followed by standard dose of epirubicin (75 mg/m2) given on day 2 of a 21 day cycle. All patients received pegfilagrastim 24-48 hours after chemotherapy. No intra-patient dose escalation was allowed. An adaptive accrual design based upon toxicity during cycle 1 determined entry into therapy cohorts. The target acceptable dose limiting toxicity (DLT) to advance to the next treatment level was 30%. Results: Between 9/18/2012 and 7/18/2013, 9 patients were enrolled and treated at MD Anderson Cancer Center. Patient characteristics are included in the Table. One patient was taken off treatment after 1 cycle due to toxicity. DLTs included febrile neutropenia (grade 3, n=2), syncope (grade 3, n=2) and vomiting (grade 3, n=1). Dose escalation did not proceed past the second cohort due to toxicity. After further accrual, the first dose level was found to be too toxic. Eight patients had disease progression, median number of cycles was 1 (range 1-4), and median time to progression was 1 month (range 1-3). No treatment responses were noted and it was decided to stop accrual rather than explore lower dose levels. Associated with significant toxicities. Conclusions: The combination of dinaciclib and epirubicin does not appear to be an effective treatment option for TNBC, and is associated with significant toxicities. Clinical trial information: NCT01624441. [Table: see text]
Rates of appropriate genetic testing referral for breast cancer patients treated in a multidisciplinary cancer care setting.
Authors: Gomez Caitlin Laurel , Dawson Nicole Ann , Dvorak Robyn Lynn , Foster Nova , Hoyt Anne , Hurvitz Sara A. , Kusske Amy , Tseng Charles Y. , McCloskey Susan Ann
Published: February 2017

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Background: Approximately 5% to 10% of women diagnosed with breast cancer have a genetic predisposition, which can affect management recommendations. The National Comprehensive Cancer Network (NCCN) has established guidelines for genetics referral and testing, however recent publications have indicated low rates of family history documentation and appropriate genetics referral. We sought to assess the impact of standardized family history documentation on rates of appropriate genetics referral in a multidisciplinary breast clinic (MDC) setting. Methods: In advance of MDC consultation, women with newly diagnosed breast cancer complete an intake questionnaire which includes documentation of Ashkenazi Jewish ancestry along with a thorough family history. We retrospectively analyzed family history documentation to inform eligibility for genetic testing and rates of appropriate genetics referral. Results: Between June 2012 and April 2014, 202 women with newly diagnosed, nonmetastatic breast cancer were seen in MDC. We noted 100% compliance with family history documentation. Per NCCN Guidelines, genetic testing was indicated in 52% (106 patients), of which 77% were appropriately referred to a genetic counselor for evaluation. All patients who met criteria based on personal history factors including age ≤ 45, triple-negative disease under age 60, or two or more breast primaries under age 50 were appropriately referred. Patients who were eligible but not referred ranged in age from 46 to 93 and were eligible for testing based on Ashkenzi Jewish ancestry (3 patients) or family history factors including a relative with ovarian cancer (3 patients), ≥2 relatives with breast cancer (5 patients), or a relative with breast cancer < age 50 (7 patients). Conclusions: Compared with recently published national averages, rates of appropriate family history documentation and genetic testing referrals are significantly higher in our MDC setting. However, this analysis has identified significant opportunity for improvement via identification of overlooked referral indications. Initiatives are underway to improve future compliance.
Evaluation of the BRCA1 and BRCA2 mutation prediction models in Japanese patients with breast cancer.
Authors: Yoshida Reiko , Yotsumoto Junko , Watanabe Chie , Nakamura Seigo
Published: February 2017

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Background: The breast cancer genetic risk models for predicting BRCA1/2 mutation are widely used before genetic testing. BRCAPRO and Myriad II are common in Europe and America, and KOHBRA BRCA risk calculator (KOHCal) is utilized in the Asian model. However, it is unknown whether these mutation prediction models are useful in Japanese. In this study, we evaluated the accuracy of BRCAPRO, Myriad II and KOHCal in Japanese patients with breast cancer. Methods: We compared sensitivity and specificity with the 10% cut off value in 131 patients with breast cancer who underwent comprehensive BRCA1/2 genetic testing at Showa University Hospital between 2011 to 2014. All patients met the genetic testing criteria of NCCN Guidelines (Genetic/Familial High-Risk Assessment: Breast and Ovarian ver.1 2014) and were received counseling before genetic testing. We assessed validity of each model by constructing receiver operating characteristic (ROC) curves, and evaluating the area under each ROC curve (AUC). The carrier probabilities of BRCA1/2 with Myriad II were calculated using BRCA risk calculator from the Myriad company1), with BRCAPRO using the CancerGene software program (version 6.0) from the University of Texas South-western Medical Cernter2), and with KOHCal using KOHBRA BRCA risk calculator from the KOHBRA Study website (www.kohbra.kr)3). Results: DNA analysis identified 31 deleterious mutations (23.7%) and 10 unclassified variants (7.6%). The sensitivity of KOHcal (87.1%) was higher than BRCAPRO 67.7%) and Myriad II (72.2%) . BRCAPRO (AUC=0.882) had higher diagnostic accuracy than KOHCal (AUC=0.810) and Myriad II (AUC=0.763). KOHCal might be most suitable model to pick up patients for further genetic testing because it’s sensitivity was higher than Myriad II and BRCAPRO, although it had lower specificity than the other. Conclusion: Our results suggest that BRCAPRO and KOHCal are useful in Japanese patients with breast cancer for decision making for further genetic testing for BRCA1/2 mutations.