Nadine Graham

An International Survey of Health Care Providers Involved in the Management of Cancer Patients Exposed to Cardiotoxic Therapy.

Cardiotoxicity is the second leading cause of morbidity and mortality in cancer survivors. The objective of this international cardiac oncology survey was to gain a better understanding of current knowledge and practice patterns among HCPs involved in the management of cancer patients exposed to potentially cardiotoxic drugs. Between 2012 and 2013, we conducted an email-based survey of HCPs involved in the management of cardiac disease in cancer patients. 393 survey responses were received, of which 77 were from Canadian respondents. The majority of respondents were cardiologists (47%), followed closely by medical oncologists. The majority of respondents agreed that cardiac issues are important to cancer patients (97%). However, only 36% of total respondents agreed with an accepted definition of cardiotoxicity. While 78% of respondents felt that cardiac medications are protective during active cancer treatment, only 51% would consider prescribing these medications up-front in cancer patients. Although results confirm a high level of concern for cardiac safety, there continues to be a lack of consensus on the definition of cardiotoxicity and a discrepancy in clinical practice between cardiologists and oncologists. These differences in opinion require resolution through more effective research collaboration and formulation of evidence-based guidelines.

The Experience of a Multidisciplinary Clinic in the Management of Early-Stage Breast Cancer Patients Receiving Trastuzumab Therapy: An Observational Study

Background. We established a dedicated cardiac oncology clinic in 2008 for the rapid diagnosis and treatment of cardiotoxicity related to cancer therapy. In this retrospective observational study, we report on clinical outcomes in women with early-stage breast cancer (EBC) referred to this clinic. Methods. Patients with EBC treated with chemotherapy/trastuzumab and referred between October 2008 and December 2010. Data included patient demographics, staging, cancer treatment/completion, dose delays, left ventricular ejection fraction (LVEF) and cardiac treatment. Results. Forty eight patients: median age 55.5 years, stage I/II disease (77%) and HER-2 positive (98%). The majority of women (n = 32) were referred for decreases in LVEF (from baseline). Overall, 37 (77%) patients experienced at least one drop in LVEF while on treatment, of which 22 patients (59%) experienced a ≥10 percentage point drop. The majority of patients (30/37; 81%) experienced declines in LVEF while on trastuzumab. Interventions included trastuzumab delays (n = 16/48; 33%) and cardiac medication (12/48: 25%). A total of 81% of patients completed ≥90% of trastuzumab therapy and 15% of patients discontinued therapy due to cardiotoxicity. Conclusion. The majority of patients referred to our clinic completed therapy. Further studies are needed to determine the impact of this multidisciplinary approach on treatment completion and cardiac outcomes.

Clinical Experience of Patients Referred to a Multidisciplinary Cardiac Oncology Clinic: An Observational Study

Cardiotoxicity is the second leading cause of long-term morbidity and mortality among cancer survivors. The purpose of this retrospective observational study is to report on the clinical and cardiac outcomes in patients with early stage and advanced cancer who were referred to our multidisciplinary cardiac oncology clinic (COC). A total of 428 patients were referred to the COC between October 2008 and January 2013. The median age of patients at time of cancer diagnosis was 60. Almost half of patients who received cancer therapy received first-line chemotherapy alone (169, 41.7%), of which 84 (49.7%) were exposed to anthracyclines. The most common reasons for referral to the cardiac oncology clinic were decreased LVEF (34.6%), prechemotherapy assessment (11.9%), and arrhythmia (8.4%). A total of 175 (40.9%) patients referred to the COC were treated with cardiac medications. The majority (331, 77.3%) of patients were alive as of January 2013, and 93 (21.7%) patients were deceased. Through regular review of cardiac oncology clinic referral patterns, management plans, and patient outcomes, we aim to continuously improve delivery of cardiac care to our patient population and optimize cardiac health.

Treatment outcomes for male breast cancer: a single-centre retrospective case-control study.

BACKGROUND Male breast cancer (bc) is a rare disease, and the availability of information on treatment outcomes is limited compared with that for female bc. The objective of the present study was to compare disease-free (dfs) and overall survival (os) for men compared with women having early-stage bc. METHODS This retrospective case-control study compared men and women treated for stage 0-iiib bc at a single institution between 1981 and 2009. Matching was based on age at diagnosis, year of diagnosis, and stage. Treatment, recurrence, and survival data were collected. Kaplan-Meier analysis was used to calculate os and dfs. RESULTS For the 144 eligible patients (72 men, 72 women), median age at diagnosis was 66.5 years. Treatments included mastectomy (72 men, 38 women), radiation (29 men, 44 women), chemotherapy (23 men, 20 women), and endocrine therapy (57 men, 57 women). Mean dfs was 127 months for women compared with 93 months for men (p = 0.62). Mean os was 117 months for women compared with 124 months for men (p = 0.35). In multivariate analysis, the only parameter that affected both dfs and os was stage at diagnosis. CONCLUSIONS This case-control study is one of the largest to report treatment outcomes in early-stage male bc patients treated in a non-trial setting. Male patients received systemic therapy that was comparable to that received by their female counterparts, and they had similar os and dfs. These results add to current evidence from population studies that male sex is not a poor prognostic factor in early-stage breast cancer.

Clinical outcomes of women with metastatic breast cancer treated with nab-paclitaxel: experience from a single academic cancer centre

BACKGROUND Nab-paclitaxel is a solvent-free, taxane-based chemotherapy approved for the treatment of metastatic breast cancer (mbc). This study reports clinical benefit and toxicities experienced by women with mbc treated with nab-paclitaxel at the Ottawa Hospital Cancer Centre. METHODS Women with mbc treated with single-agent nab-paclitaxel between June 2006 and December 2010 were included in this analysis. Retrospective data obtained included demographics, disease characteristics, prior chemotherapy, nab-paclitaxel treatment, toxicity, and survival. Clinical benefit was defined as partial or complete response or stable disease (by clinical or radiologic evaluation, or both) at 6 months or more. RESULTS Of 43 women (mean age: 57.0 years; range: 34-74 years), most had disease positive for estrogen or progesterone receptor (72.1%, 58.1%), or both. Nab-paclitaxel was administered weekly (qw: 44.2%), every 3 weeks (q3w: 46.5%), q3w switched to qw (7.0%), or qw switched to q3w (2.3%). Median duration of therapy was 5.1 months (qw) and 3.0 months (q3w). Sensory neuropathy was the primary toxicity (45.4% qw, 38.1% q3w; p = 0.62). Clinical benefit was observed in most women (76.2% qw, 57.1% q3w; p = 0.20). Women receiving nab-paclitaxel had a median overall survival of 13.6 months qw (range: 8.1-28.3 months) and 10.8 months q3w (range: 5.9-17.9 months; p = 0.03). Regardless of dosing schedule, women experiencing clinical benefit lived significantly longer than those not experiencing a benefit (17.3 months vs. 7.7 months; hazard ratio: 0.14; 95% confidence interval: 0.06 to 0.33). CONCLUSIONS Our clinical experience demonstrates that most women treated with nab-paclitaxel experienced some clinical benefit. Patients achieving clinical benefit lived significantly longer than those who did not. Nab-paclitaxel was well tolerated, with the primary toxicity being mild sensory neuropathy. Nab-paclitaxel represents another treatment option, with a favourable toxicity profile, for women with mbc.

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.

300PDATA-DRIVEN TIMING OF OPTIMAL LVEF ASSESSMENT IN BREAST CANCER PATIENTS EXPOSED TO TRASTUZUMAB

ABSTRACT Aim: While adjuvant trastuzumab has improved outcomes in patients with HER2/neu positive breast cancer, this treatment has also been associated with decreased left ventricular ejection fraction (LVEF). No data-driven schedule exists to inform clinicians of the optimal timing for serial measurements of LVEF following initiation of trastuzumab therapy. We conducted a hypothesis-generating pooled trend analysis to identify a timeline for monitoring LVEF changes secondary to trastuzumab therapy in patients with breast cancer. Methods: An English language search of Medline, Cochrane, ASCO Library, and an extensive bibliography search from January 1999 to April 2014 were performed. Inclusion and exclusion criteria were met by 35 clinical trials (n = 9,936). Primary outcome was interval reduction in percent LVEF following trastuzumab versus baseline (post-anthracycline). Results: A quadratic trend was identified between LVEF and trastuzumab across time. Decline in LVEF with trastuzumab occurred significantly early (2 months), peaked (7 to 15 months), and recovered (post 30 months) (Friedman ANOVA; F = 19.9, p 0.05). Conclusions: This pooled trend analysis reveals that LVEF assessment and potential cardiac intervention should be concentrated within the early months of trastuzumab therapy, consistent with current clinical and research protocols. Further research is required to define an optimal LVEF monitoring schedule once trastuzumab therapy is complete. Disclosure: All authors have declared no conflicts of interest.

Vascular toxicities of endocrine therapy in early-stage breast cancer: Encouraging observations in a nontrial setting.

68 Background: Endocrine therapy (ET) is the standard of care for postmenopausal (PM) women with early stage breast cancer (EBC). Studies suggest higher risk of vascular toxicities (VT) on aromatase inhibitor (AI) therapy. We report incidence/discontinuation rates of VTs in a cardiac clinic. METHODS PM women with hormone receptor positive EBC treated with ET (tamoxifen (T) ± AI) at Ottawa Hospital Cancer Center 01/99-2/06. Data included: demographics, vascular co-morbidities (VCM), ET, duration, VTs. RESULTS 626 pts, median age 59 years (r: 30-92), median follow-up 98 months (m), stage: I (196 pts), II (341 pts) III (89 pts) EBC. Majority (52.5%) pts had VCM at ET initiation; hypertension (HTN) (36%), hyperlipidemia (HYLP) (17%), coronary disease (12%), thrombosis (9%), angina (6%) TIA (6%). Treatment discontinued due to VT 3x more with T vs. AI. Most common VTs: edema, arrhythmias (ARR), cardiovascular (CVS) event, and HYLP. With Letrozole and T, previous VCM significantly increased risk of developing VT (chi-square: P=0.022 and 0.009). Time to develop VT shortest for T and exemestane. Previous VCM did not affect this interval. Longer exposure to T correlated with higher VT rate (t-test: p=0.046) not seen with AIs. Exposure to multiple AIs associated with higher VT rate (t-test: p=0.009). CONCLUSIONS This cohort study reports similar VT rates with AI therapy as reported in the literature. T was associated with higher discontinuation rates (10.5%) due to VTs compared to AIs (2.8-3.3%). Longer duration of AI therapy was not associated with increased risk of VTs. These encouraging results reflect the real-life experience of women exposed to ET. [Table: see text].