Xinni Song

A pilot study of prospective memory functioning in early breast cancer survivors

AIMS To evaluate prospective memory (PM) functioning in early breast cancer (BC) survivors and its association with fatigue and depression. METHODS The Memory for Intention Screening Test, the Center for Epidemiologic Studies Depression Scale and the Functional Assessment of Cancer Therapy-Fatigue subscale were administered to 80 patients and 80 aged-matched healthy controls. RESULTS Patients performed more poorly than controls on the memory test (p < 0.001) and had a higher rate of impairment (odds ratio = 5.5, p < 0.01). Fatigue mediated the relationship between Group membership and PM performance. CONCLUSIONS BC survivors exhibited a clear pattern of PM deficit and fatigue was a major contributor to this deficit. This suggests that a common mechanism may be involved in fatigue symptoms and memory disturbances experienced by patients. Further research is needed to evaluate the role of adjuvant therapy in PM deficits and to explore whether interventions targeted at improving fatigue may also improve memory functioning in BC survivors.

Risk Model–Guided Antiemetic Prophylaxis vs Physician’s Choice in Patients Receiving Chemotherapy for Early-Stage Breast Cancer: A Randomized Clinical Trial

IMPORTANCE Despite multiple patient-centered factors being associated with the risk of chemotherapy-induced nausea and vomiting (CINV), these factors are rarely considered when making antiemetic recommendations. OBJECTIVE To compare risk model-guided (RMG) antiemetic prophylaxis with physicians choice (PC) in patients receiving chemotherapy for early-stage breast cancer. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial of 324 patients with early-stage breast cancer undergoing chemotherapy (cyclophosphamide and an anthracycline) for the first time at 2 specialty cancer care centers in Ottawa from April 10, 2012, to September 2, 2014. Patients were randomized to either the RMG arm (n = 154) or the PC control arm (n = 170). Prior to each cycle of chemotherapy patients in the RMG group were categorized as low or high risk for CINV, and their antiemetic treatments were adjusted accordingly. INTERVENTIONS Patients considered to be at low risk received standard dexamethasone and a 5-HT3 antagonist, while those at high risk also received aprepitant with or without olanzapine, based on their risk level. The PC control group received antiemetic agents according to the treating physicians discretion. MAIN OUTCOMES AND MEASURES The primary end points were control of both nausea and vomiting in the acute posttreatment period (first 24 hours after therapy) and in the delayed posttreatment period (days 2-5 after therapy). RESULTS The total numbers of chemotherapy cycles delivered in the RMG and PC control groups were 497 and 551 respectively. In the acute period, significantly more patients in the RMG group reported no nausea (53.7% [95% CI, 49.2%-58.1%] vs 41.6% [95% CI, 37.4%-45.3%]; P < .001) and no vomiting (91.8% [95% CI, 89.0%-94.0%] vs 82.2% [95% CI, 78.8%-85.3%]; P < .001) compared with the PC control group. Similarly, significantly more patients in the RMG group reported no nausea (39.6% [95% CI, 35.3%-44.1%] vs 30.7% [95% CI, 26.8%-34.7%]; P = .01) and no vomiting (87.1% [95% CI, 83.8%-90.0%) vs 78.0% [95% CI, 74.3%-81.4%]; P < .001) in the delayed period respectively. CONCLUSIONS AND RELEVANCE In this trial, the RMG antiemetic prophylaxis led to improved control of acute and delayed CINV compared with physicians choice of therapy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01913990.

Prospective memory impairment in chemotherapy-exposed early breast cancer survivors: Preliminary evidence from a clinical test

ABSTRACT We report the results of a secondary analysis of a cross-sectional study (Paquet et al., 2013) to evaluate the cognitive operations involved in prospective memory (PM) deficits exhibited by chemotherapy-exposed breast cancer (BC) survivors. PM was assessed with the memory for intentions screening test administered to 80 patients and 80 healthy controls. Patients performed worse than controls on the PM tasks and had more “omission” errors (indices of the prospective component of the tasks) than the controls. No group differences emerged on a recognition test. Although further studies will be needed to disentangle the multiple cognitive operations involved in PM, these findings are consistent with the notion that self-initiated retrieval processes rather than encoding are implicated in PM impairment among BC survivors.

Abstract CT131: A randomized (RCT) phase II study of oncolytic reovirus (pelareorep ) plus standard weekly paclitaxel (P) as therapy for metastatic breast cancer (mBC)

Background: Pelareorep is a Dearing strain of reovirus serotype 3, with demonstrated in vitro and in vivo activity in many cancers and synergistic cytotoxic activity with microtubule targeting agents, including taxanes. This study was designed to determine the efficacy and safety of pelareorep + P compared to P alone in mBC. Materials and Methods: This randomized, open-label, phase II study enrolled subjects who had mBC previously exposed to chemotherapy (CT). Subjects were randomized 1:1 between Arm A (P 80 mg/m2 day 1, 8 and 15 q 28 days plus pelareorep 3 x 1010 TCID50 day 1,2,8,9,15,16 q 28 days) and Arm B (P 80 mg/m2 day 1, 8 and 15 q 28 days). Treatment was continued until disease progression (PD) or unacceptable toxicity. Objective response was assessed every 8 weeks. Primary endpoint was progression free survival (PFS). The study had 90% power to detect an improvement of PFS from 4 to 7.5 months (HR 0.5, two-sided α=0.2). All p-values are two-sided. Results: Between July 2012 and April 2016, 81 subjects were accrued: 7 to the safety run-in for arm A, 36 to Arm A and 38 to Arm B. All had received prior CT, 59 as adjuvant treatment and 48 for mBC. Patients in Arm A had more favorable prognostic features, including lower LDH and less prior therapy. The median cumulative dose of P was 960 mg/m2 for arm A vs. 828 mg/m2 for arm B. Similar numbers of subjects in both arms required dose reductions, predominantly for myelosuppression. The median duration of treatment was 16.1 weeks for pelareorep and P in arm A and 14.1 weeks for P in arm B. With a median follow-up of 29.5 months, the median PFS was 3.78 mo for arm A and 3.38 mo for arm B (HR 1.04, 80% CI 0.76-1.43, p=0.87). Median OS was 17.4 mo for arm A and 10.4 mo for arm B (HR 0.65, 80% CI 0.46-0.91, p=0.1). Response rates (RR) were 25% for arm A and 23.7% for arm B (p=0.87). Pre-specified subset analysis found statistically significant differences in OS in patients with ECOG 1 or 2, aged Citation Format: Vanessa Bernstein, Susan Ellard, Susan F. Dent, Karen A. Gelmon, Sukhbinder K. Dhesy-Thind, Mihaela Mates, Muhammed Salim, Lawrence Panasci, Xinni Song, Mark Clemons, Dongsheng Tu, Linda J. Hagerman, Lesley Seymour. A randomized (RCT) phase II study of oncolytic reovirus (pelareorep ) plus standard weekly paclitaxel (P) as therapy for metastatic breast cancer (mBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT131. doi:10.1158/1538-7445.AM2017-CT131

Factors influencing Oncotype DX use in the management of early breast cancer: A single centre experience

BACKGROUND Oncotype DX recurrence score is a multi-gene assay which quantifies the risk of distant recurrence in patients with hormone receptor-positive (HR+) early breast cancer (EBC) treated with tamoxifen, and predicts the magnitude of clinical benefit of adjuvant chemotherapy. This retrospective study examined factors that were associated with use of Oncotype DX assay at a tertiary care cancer centre in Ottawa, Canada. METHODS One hundred consecutive patients (pts) diagnosed with HR+, HER2/neu negative EBC (stage I-II), who underwent Oncotype DX testing (Test Group) between 1st April 2010, and 30th June 2011 were included in the study. A second cohort of 100 randomly selected patients with HR+, HER2/neu negative EBC diagnosed from the same time period who did not receive Oncotype DX testing were used as the control group (Control Group). Demographic and clinicopathologic data were obtained from review of charts. Logistic regression was performed to identify variables associated with Oncotype DX usage. FINDINGS Median age was 58 years (r: 26-77) in Test Group and 63 years (r: 30-81) in Control Group. Sixty-two patients in the Test Group had T1 tumours, compared with 71 in the Control Group. The median 10-year recurrence risks from Adjuvant! Online were 19% and 12% in the Test Group and Control Group, respectively. Factors significantly associated with the utilisation of Oncotype DX assay on multivariate analysis include age 50-64 (p=0.049), tumour size 10.1-20mm (p=0.008) and grade 2 histological grade (p=0.004). INTERPRETATION Usage of Oncotype DX assay is associated with several clinicopathological factors. These factors reflect the clinical uncertainty of benefit from chemotherapy in these subpopulations of patients and suggest how Oncotype DX assay could complement clinicopathological factors in helping clinicians on treatment selection.

A randomized, double-blind trial evaluating the palliative benefit of either continuing pamidronate or switching to zoledronate in patients with high-risk bone metastases from breast cancer (The Odyssey Study).

155 Background: Questions remain around the optimal use of bone-targeted agents (BTA) in patients with bone metastases (BM) from breast cancer (BC). In Canada pamidronate (PAM) is the most commonly used BTA in BC.We explored whether a switch to a more potent BTA, like zoledronic acid (ZA), in patients who remain at high risk of skeletal related events (SREs) despite PAM use is associated with significant palliative benefit. METHODS BC patients with high risk BM (prior SRE, bone progression, bone pain or levels of bone turnover marker serum C-telopeptide (sCTX) >400ng/L) despite >3 months of PAM use were eligible. Patients were randomized in a double-blind manner to either switch to ZA or continue on PAM every 4 weeks for 12 weeks. Primary outcome was the proportion of patients achieving a fall in sCTX at 12 weeks. Secondary outcomes were pain control (BPI and FACT-BP) and toxicity. Results 73 patients completed the study. Median age 61 years (range 37 - 87), prior duration of PAM use 10 months (range 3 - 118). sCTX levels for all patients at baseline, 372+/- 471, week 12, 209 +/-290. Proportion of patients achieving a fall in sCTX from week 0 to week 12, 26/31 (84%) in ZA arm, 17/30 (57%) in PA arm, p=0.0262. Two patients were unable to complete the study due to deterioration in renal function (both receiving PAM), four due to progressive disease (two receiving ZA, two PAM), two patients chose to discontinue the study before completion (both receiving ZA). Four patients (5%) had SREs during the study, two receiving ZA, two receiving PAM. Quality of life and pain analysis shows no difference between week 0 and week 12 scores in either arm. Toxicity was predominantly grade 1 and 2, numerically there were more adverse effects in the ZA arm than PAM. Conclusion Switching patients with high risk BM from PAM to ZA leads to a reduction in sCTX levels but may be associated with more toxicity. Quality of life and pain scores were similar between the two treatments. While the literature suggests that a reduction in sCTX may correlate with reduced rate of SREs, given the lack of symptom improvement a switching strategy cannot be recommended. NCT01907880 Clinical trial information: NCT01907880.

Abstract P3-13-05: Evaluating efficacy of de-escalated bisphosphonate therapy in metastatic breast cancer patients at low-risk of skeletal related events. TRIUMPH: A pragmatic multicentre trial.

Background: Optimal bisphosphonate (BP) dosing intervals for breast cancer patients (pts) with bone metastases (BM) remain unknown. BP are usually prescribed q3-4 wk regardless of individual pt risk for skeletal related events (SREs). Recent evidence (Amadori J Clin Oncol, 2012 suppl; abstr 9005) shows that q12 wk BP is as effective as q4 wk in pts previously treated with >9 cycles of q4 wk therapy. Hence, further evaluation of modified BP dosing strategies is warranted. The objective of the current study was to show in women with biochemically defined low-risk bone disease that IV BP use every q12 wk for 1 year is sufficient to maintain stability of the bone turnover [measured by serum c-telopeptide (CTx) or bone specific alkaline phosphatase (BSAP)]. Methods: Eligible pts with BM, who had received >3 months of q3-4 wk IV BP and no systemic treatment change within 4 wks of study entry were enrolled. Low risk was defined as serum CTx 600 ng/L at baseline, weeks 6, 12, 24, 36 or 48. Evaluation of palliative benefit of 12-wk IV BP therapy was measured by SREs, analgesic use, and self-reported pain (BPI and FACT-BP). Results: Between Oct. 2010-Sept. 2011, 85 pts consented to screening, with 13 found ineligible. In the 71 accrued pts baseline characteristics were: mean age 60 (SD 13), median time from breast cancer diagnosis to development of bone metastases 4 months (IQR 82), median duration of prior BP therapy 14 months (IQR 19), and mean number of SREs/yr prior to entering study 0.35 (SD 0.76). Baseline median CTx was 120 ng/L (IQR 240) and BSAP 9.2 IU/L (IQR 3). To date: 26/71 pts (36%) remain on study. Reasons for coming off study include; study completion (18), elevation of CTx >600ng/L (10), or on study SRE (3). An elevation of CTx between baseline and wk 6 was significantly associated with coming off study early (p = 0.008). For pts who had had an SRE before study entry the odds ratios for coming off study early due to an on study SRE or elevated CTx was 1.005 (CI 1.002–1.009; p = 0.007) and for coming off early for an SRE was 0.0245 (CI 0.061–0.094; p = 0.046) respectively. Of the 8/13 pts who were ineligible due to baseline CTx >600ng/L, 6 had an SRE within 1 year of screening. Conclusion: De-escalating BP therapy to 12 weekly in low risk pts has advantages for both the pt and the health care system. Individual risk of SREs is highly variable, however baseline serum CTx levels Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-13-05.

Abstract P3-04-11: Systemic treatment decision making for patients with stage I and II, hormone receptor positive, her2/neu negative breast cancer

Background: Oncotype DX is a clinically validated risk stratification tool that can predict the risk of recurrence and the benefit of adjuvant chemotherapy in women with hormone receptor positive (HR+), HER2/neu negative early stage breast cancer (EBC). This tool has been available to oncologists in Ontario since April 2010 at significant cost, yet no guidelines exist regarding their use. This retrospective chart review examined the factors that were associated with use of Oncotype DX at a tertiary care cancer centre. Materials and methods: One hundred patients (pts) diagnosed with HR+, HER2/neu negative EBC (stage I-II), who underwent Oncotype DX testing between April 1, 2010, and June 30, 2011 were included in the study. A second control group of 100 patients with similar disease characteristics but who did not receive Oncotype DX testing were randomly selected. Data collection included demographics, tumor grade and stage, and Adjuvant! Online recurrence risk scores. The distribution of patients in each category was compared using the chi-square test to detect statistically significant differences between distributions. Results: Median age in the Oncotype DX group was 58 years (r: 26–77) and 63 years (r: 30–81) in the control group. 20 patients in the Oncotype DX group were aged 35–49, 57 patients were aged 50–64, and 23 patients were aged 65 or older, while the control group had 16, 43, and 41 patients, respectively (p = 0.02). The Oncotype DX group had 72 pre- and perimenopausal pts and 28 postmenopausal patients, while the control group had 81 and 19 patients, respectively (p = 0.13). 20, 56, and 24 pts in the Oncotype DX group had grade 1, 2, and 3 histology, respectively, vs. 44, 44, and 12, respectively in the control group (p 25, respectively, vs. 62, 33, and 5 in the control group (p Conclusions: This single-centre series is aimed at identifying potential clinical and pathological factors which can influence physicians9 decision to request Oncotype DX testing for pts with EBC. Physicians were more likely to request Oncotype DX testing for patients that were younger, had larger and higher grade tumors, and higher Adjuvant! Online recurrence risk scores. These results will be used to design a prospective study evaluating these factors and how Oncotype DX testing may influence treatment decision making. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-04-11.

PD04-04: Sexual Dysfunction in Women with Early Stage Breast Cancer on Endocrine Therapy: Encouraging Results from a Prospective Study.

Background: While the side effects of endocrine therapy (ET) for early stage breast cancer (EBC) have been extensively studied, the link between ET and sexual dysfunction (SD) remains a contentious issue. Most studies have focused on documenting only the presence of problems in specific domains of endocrine symptoms (ES) (e.g. hot flushes, vaginal dryness) and sexual functioning (SF) (interest, satisfaction, arousal, lubrication) without also taking sexual distress into account. To our knowledge, there have been no prospective longitudinal studies evaluating SF and SD before the onset of ET and after treatment initiation. We report the initial 6 month results of this study of SD in women initiating ET for EBC. Methods: Hormone receptor positive EBC post-menopausal women were approached for a larger study of SF aimed at comparing the prevalence of SD across endocrine agents (tamoxifen vs aromatase inhibitor) and at evaluating the impact of anxious predisposition and ES on SD. Here we report on changes in ES, SF and SD after 6 months of ET. SF was evaluated with the Female Sexual Function Index (FSFI) while sexual distress was assessed with the Female Sexual Distress Scale. ES were measured with FACT-B ES subscale. Participants completed questionnaires prior to initiation (T0) of ET and at 6 months (T1). SD was assessed using the APA classification. Results: Between January 2009 and May 2011, 118 EBC patients entered the study and 83 have completed both assessments (mean age 62; 30% received chemotherapy). Over time, the levels of ES increased (p 2 , p >.5) Importantly, women classified as experiencing SD at T0 were more likely to also experience SD at T1 (OR=4.5, 95% CI=2.162 to 9.366) than women who had no SD at T0. Discussion: This is the first prospective case cohort study evaluating ES, SF and SD in women with EBC on ET. The good news for women is that although ES increased during ET (p 6 months). The impact of specific types of ET on ES, and SD will also be evaluated. Of interest, the high uptake and high completion rate (>80%) of questionnaires, indicate this is a matter of relevance and importance to women taking adjuvant ET and merits acknowledgement and sensitive discussion. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD04-04.

P4-15-01: High Prevalence of Prospective Memory (PM) Impairment in Early Breast Cancer (EBC) Survivors within 1 Year of Adjuvant Chemotherapy Completion: Novel Findings Concerning Post Chemotherapy Cognitive Effects.

Background Numerous studies have demonstrated that EBC survivors report more memory problems than healthy controls. However, evidence of impairment on objective tests of memory remains inconclusive. Past research has focussed exclusively on retrospective memory (remembering information from the past when asked to do so), but the complaints of EBC patients appear better described as “prospective memory” failures defined as forgetting to carry out in the future previously formed intentions. The effective performance of many day-to-day activities relies on PM and its impairment has negative consequences in everyday life. Despite its high ecological relevance, no study has evaluated PM functioning in EBC survivors. Consequently, we assessed the prevalence of PM impairment among EBC survivors in the year following completion of chemotherapy. Methods We undertook a cross sectional quantitative case-control study aiming to recruit 80 patients from the Ottawa Hospital Regional Cancer Centre and 80 matched healthy controls from the community. Patients were within 1 year of having completed a first course of chemotherapy. A standardized test of prospective memory (Memory for Intention Screening Test) was administered to both groups. Following the International Cognition and Cancer Task Force recommendation (2008), impairment was defined as a score that fell one standard deviation below the mean performance of the control group. Standardized measures of depression (CESD), anxiety (STAI) and fatigue (Fact-F) were also completed. Results Data are available on 36 patients and 18 controls. Age was well balanced between the groups (case-control mean age 54y vs. 51y, respectively, p=.204). Overall PM impairment was observed in 41% of the participants. More importantly, the rate of PM impairment was significantly higher in the EBC group than controls (53% vs 17%; p Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-15-01.