Adjuvant Trastuzumab For Breast Cancer Research Articles

Significant Influence of Cardiac Radiation Dose on the Risk of Cardiotoxicity in Patients Receiving Adjuvant Trastuzumab and Radiation Therapy for Breast Cancer

PurposeThis study aimed to analyze the incidence of cancer therapy-related cardiovascular toxicity (CTRCVT) and identify the radiation dosimetric and clinical risk factors for these events in patients with HER2-positive breast cancer. Materials and methodsData from 1,378 patients who were treated with curative surgery and adjuvant trastuzumab for breast cancer were retrospectively analyzed. A total of 959 patients underwent postoperative radiation therapy (RT), while 419 patients were managed without RT (no-RT). CTRCVT were categorized according to the time of occurrence in relation to trastuzumab as follows: during trastuzumab cycles (CTRCVT-during T) or after completing trastuzumab (CTRCVT-after T). The cardiac radiation dose was extracted from the RT plan of each individual patient. The incidence of and contributing factors for CTRCVT-during T and -after T were evaluated. ResultsAfter a median follow-up of 95.8 months (range, 4.3–181.1 months), 69 patients (5.0%) had experienced CTRCVT. CTRCVT-during T was detected in 41 patients (3.0%), and the 8-year rate of CTRCVT-after T was 2.2%. Of the patients developing CTRCVT-during T, 27 (2.0%) discontinued trastuzumab. The cardiac radiation doses were significantly associated with the risk of both CTRCVT-during T (odds ratio, 1.087; P = 0.001) and -after T (hazard ratio, 1.177; P <0.001). The 8-year rates of CTRCVT-after T were not significantly different between the no-RT and RT groups (2.0% vs. 2.4%, P = 0.956). However, the rate was significantly higher in patients with heart V25Gy ≥3% compared to those with heart V25Gy <3% (5.7% vs. 1.5%, P = 0.019). Patients who received <17 cycles of trastuzumab had worse oncological outcomes than those who received ≥17 cycles. ConclusionsBoth CTRCVT-during T and -after T were associated with the cardiac radiation dose. Therefore, evaluation of the cardiac radiation dose is necessary to prevent early termination of trastuzumab treatment, which could lead to worse outcomes.

Abstract P3-14-04: Tailored duration of adjuvant trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer

Abstract Background: A number of clinical trials were conducted to assess the efficacy and toxicity of shorter durations of adjuvant trastuzumab compared with 12-month standard duration. However, the results were controversial and the reduced time varied among trials. To assess the effect of treatment time of adjuvant trastuzumab on the clinical outcomes at trial level, we performed a systematic literature search and a trial-level meta-regression analysis to figure out the appropriate time for trastuzumab treatment. Methods: A comprehensive search of (neo)adjuvant trastuzumab in breast cancer in PUBMED and EMBASE databases from Jan 2000 to June 2019 was performed. We treated the “12-month trastuzumab” as the standard. The “shorter duration” is less than 12 months, including extreme value of 0-month for no trastuzumab. The primary clinical outcome is DFS. HR with 95% confidence intervals (CIs) should be reported. Shortened treatment time (months) and DFS outcome (expressed as HRs) were extracted from each trial. Meta-regression was performed using HR of DFS and shortened time of adjuvant trastuzumab in random-effects model. The coefficient of determination (R2) and the regression coefficient (β) were calculated. We also performed sensitivity analysis by omitting each study to find the potential outliers. Results: A final set of 12 trials was included in the analysis. Five studies compared the 12-month trastuzumab with shorter duration in a non-inferiority setting and 7 studies compared with no trastuzumab in a superiority design (Table 1). The between-study variance τ2 is 0.0062 and the adjusted R2 is 63.14%, which means 63% of the variability among the effects on DFS can be explained by the shortened time of adjuvant trastuzumab, and the remaining between-study variance appears small at 0.0062. We estimated the effects of different shortened times of trastuzumab on DFS and the regression coefficients β of shortened treatment time is 0.04 (P=0.038, 95% CI, 0.0029-0.0788), indicating for each month reduced, the ln(HR) of DFS events increased 0.04. If transferred to HR, the values were 1.042 (e0.04), indicating the risk of DFS would increase 4.2% for each month trastuzumab shortened. Similarly, if 3-month reduced, the risk increased 12.7% (e0.12=1.127); 6-month reduction would increase risk of 27.1%, and 9-month, 43.3% (Table 2). Further subgroup analyses according to estrogen receptor status and lymph nodes status yielded qualitatively similar results. Conclusion: We revealed a significant linear association between shortened time of trastuzumab and the risk of DFS events. These findings suggest that a shorter duration of trastuzumab might be appropriate for patients with lower-risk disease but unacceptable for those with high-risk disease. We believe that the duration of adjuvant trastuzumab should be tailored according to the risk, as well as toxicity and cost. Table 1. Summary of included studies.IDITT numberTrial designHazard marginHR with 95% CIShortened time (month)EndpointMedian Follow-up (year)PHARE1691non-inferiority1.151.08 (0.93-1.25)6DFS7.5HORG481non-inferiority1.531.57 (0.86-2.10)6DFS3Short-HER1253non-inferiority1.291.15 (0.87-1.53)9.9DFS5.2SOLD2174non-inferiority1.31.39 (1.08-1.80)9.9DFS5.2PERSEPHONE4088non-inferiority1.291.07 (0.90-1.27)6DFS5.4E2198227superiorityNA1.18 (0.56-2.44)12DFS6.4NCCTG N98311944superiorityNA1.72 (1.52-1.92)12DFS8.4NSABP B-312102superiorityNA1.72 (1.52-1.92)12DFS8.4HERA3401superiorityNA1.45 (1.27-1.69)12DFS8BCRIG-0062147superiorityNA1.39 (1.18-1.64)12DFS10.3PACS04528superiorityNA1.16 (0.82-1.64)12DFS3.9NOAH235superiorityNA1.69 (1.11-2.63)12EFS3.2 Table 2. Shortened time of adjuvant trastuzumab and increased risk of DFSShortened Time (Month)Change in ln(HR)Increased relative risk of DFS eventsPredicted DFS in APT trial (%)Predicted DFS in N9831/B31 trials (%)10.044%937330.1213%927160.2427%916790.3643%9063120.4862%8958 Citation Format: Ke-Da Yu, Zhi-Rui Zhou, Zhi-Ming Shao. Tailored duration of adjuvant trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-14-04.

Short-course adjuvant trastuzumab in breast cancer: Experience from a tertiary cancer center in rural India

Introduction: Majority of the patients in low-to-middle income countries (LMICs) have no access to adjuvant trastuzumab due to financial constraints. Short-course (9 weeks) schedule of trastuzumab is a feasible alternative in this setting. The objective of this study was to assess the feasibility and outcomes of adjuvant short-course trastuzumab in patients with breast cancer treated at our center.Materials and Methods: This was a retrospective study conducted in a tertiary cancer center in South India. Case records of all patients who received short-course (9 weeks) adjuvant trastuzumab from June 2014 to December 2016 were reviewed. Baseline characteristics, treatment details, and outcomes were analyzed.Results: During the study, 129 patients received short-course trastuzumab. The median age was 50 years (range, 30–74 years). Majority of the patients were postmenopausal (64%). The most common histology was infiltrating ductal carcinoma; 57% had Grade 2 disease. The most common chemotherapy regimen used was doxorubicin + cyclophosphamide (AC), followed by weekly paclitaxel (n = 110, 86%) and docetaxel + cyclophosphamide (TC) (n = 17, 13%). Majority of the patients (n = 120, 93%) had T1 or T2 disease and were node-negative (n = 62, 57%). Sixty-two patients (48%) had hormone receptor-positive disease. One hundred and eight patients (84%) underwent modified radical mastectomy, and the rest had breast conservation surgery. At a median follow-up of 29 months, the 3-year overall survival (OS) was 98%; the median OS was not reached. The 3-year disease-free survival (DFS) was 97.4%; the median DFS was not reached. The regimen was well tolerated and none of the patients developed symptomatic cardiac failure.Conclusions: Our study shows that a 9-week short course of trastuzumab is a feasible strategy in a resource-limited setting and can lead to promising outcomes, especially in early breast cancer.

Early Decline in Left Ventricular Ejection Fraction Can Predict Trastuzumab-Related Cardiotoxicity in Patients with Breast Cancer: A Study Using 13 Years of Registry Data.

PurposeWhile concerns regarding trastuzumab-related cardiac dysfunction (TRCD) in patients with breast cancer are increasing, there is a lack of evidence supporting the current recommendations for TRCD monitoring. We aimed to investigate the clinical predictors of TRCD in the adjuvant setting of human epidermal growth factor receptor 2–positive breast cancer patients.Materials and MethodsFrom August 2003 to April 2016, consecutive 998 patients who were treated with adjuvant trastuzumab for breast cancer were retrospectively evaluated. TRCD was defined as a decrease ≥10% in left ventricular ejection fraction (LVEF), with a decline below the normal limit or symptomatic heart failure.ResultsAmong 787 eligible patients who had complete data sets consisting of both baseline and follow-up assessment of left ventricular systolic function by echocardiography (mean age, 49.9±9.5 years), 58 (7.4%) developed TRCD. TRCD patients had lower baseline LVEF (63% [59–66] vs. 65% [61–68], p=0.016) and more frequently administered Adriamycin (98% vs. 89%, p=0.022) than those without TRCD. On follow-up echocardiography, a drop in LVEF ≥5% within the first 3 months was more frequent in TRCD patients (78.3% vs. 38.4%, p<0.001). Regardless of baseline LVEF and Adriamycin treatment, a drop in LVEF ≥5% within the first 3 months of trastuzumab administration was strongly associated with the development of TRCD (adjusted hazard ratio, 45.1[17.0–127.6], p<0.001).ConclusionThe overall incidence of TRCD was 7.4% in Asian breast cancer patients treated with adjuvant trastuzumab. A decline in LVEF ≥5% within the first 3 months of trastuzumab initiation was strongly associated with TRCD development in patients with breast cancer.

An Attempt to Quantitate "Value" In Medical Oncologic Therapy.

ObjectiveWe wanted to examine the incremental cost-effective ratio (ICER) for a variety of Food and Drug Administration (FDA) approved oncology drugs in the adjuvant or curative setting to determine the value provided.DesignWe examined the annualized incremental drug costs of a variety of FDA approved chemotherapeutic drugs used in an adjuvant or curative setting based on National Comprehensive Cancer Network (NCCN) category 1 practice guidelines for melanoma, Her2/neu over-expressive breast cancer, renal cell carcinoma, stage IIIA non-small cell lung cancer, myeloma, B cell lymphoma, and Hodgkin lymphoma. The studies we examined were randomized clinical trials on which the NCCN guidelines are based; we solely examined the incremental cost-effectiveness of the trial drug as we assumed that the costs of the health care provided were equivalent between the two treatment arms. We used a formula to determine the incremental cost-effectiveness ratio (ICER). The ICER compares a new intervention (C new) with its alternate (C alt) divided by the quality-adjusted life-years (QALY) that results from the new intervention (QALY new) versus the alternate (QALY alt) and is expressed as ICER = (C new-C alt)/(QALY new-QALY alt). The QALY’s were derived from what was reported in the study and based on the incremental disease-free survival.ResultsDrugs such as rituximab provide high value in the curative therapy for lymphoma. Drugs such as adjuvant dabrafenib and trametinib provide intermediate value in the treatment of melanoma, and similarly with maintenance lenalidomide in myeloma and adjuvant trastuzumab in breast cancer. Oncologic drugs that provide low value include adjuvant ipilimumab in melanoma, adjuvant sunitinib in renal cell carcinoma, adjuvant neratinib in breast cancer, adjuvant durvalumab in lung cancer, and brentuximab in the curative therapy for Hodgkin’s lymphoma.ConclusionThe ICER needs to be evaluated for newly approved FDA oncology chemotherapeutic drugs before incorporating them into routine clinical practice.

Cost considerations in determining the affordability of adjuvant trastuzumab in breast cancer

Cost considerations in determining the affordability of adjuvant trastuzumab in breast cancer

Cost considerations in determining the affordability of adjuvant trastuzumab in breast cancer

Cost considerations in determining the affordability of adjuvant trastuzumab in breast cancer

Cost considerations in determining the affordability of adjuvant trastuzumab in breast cancer

Cost considerations in determining the affordability of adjuvant trastuzumab in breast cancer

Cost considerations in determining the affordability of adjuvant trastuzumab in breast cancer

Cost considerations in determining the affordability of adjuvant trastuzumab in breast cancer

Cost considerations in determining the affordability of adjuvant trastuzumab in breast cancer.

The drug cost of adjuvant trastuzumab to benefit one patient with localised human epidermal growth factor receptor 2 (HER2)-positive breast cancer depends on the baseline survival rate (BLSR) of the prognostic group of the patient. This varies from ZAR13 752900 (BLSR 90%) to ZAR4006 100 (BLSR 60%). All treated patients are exposed to potential toxicity. The value and affordability of treatments need to be considered, as there are finite resources available in our healthcare system. All patients must have access to cost-effective treatments. However, patient selection for expensive treatments is important, as expenditure on patients where the gains are relatively small will result in resources not being available for other patients. The state, healthcare institutions and the pharmaceutical industry need to work together to optimise the benefits of treatment to patients.

Heart failure in women treated with adjuvant trastuzumab for breast cancer

The amplification of the HER receptor system is present in approximately 20% of breast cancers and confers a marked malignancy and a poor prognosis. Trastuzumab, a monoclonal antibody directed against the HER2 receptor, has dramatically improved the prognosis of patients with HER2+ metastatic and early breast cancer. However, the use of trastuzumab is associated with the possible development of myocardial dysfunction and heart failure. Trastuzumab-induced cardiac injury may be reversible, and a substantial proportion of patients can complete therapy. For this reason, careful monitoring of cardiac function, an aggressive treatment of hypertension and possibly the use of non-anthracycline-containing chemotherapy protocols are required during trastuzumab treatment. Owing to the selection of patients enrolled in major randomized trials, the safety profile of trastuzumab is currently unclear in elderly women, in patients at high cardiovascular risk and in those with structural heart disease on optimal treatment. Further studies are therefore needed to determine whether this highly effective therapy in breast cancer survival can be extended to such categories of patients.

Congestive Heart Failure with Adjuvant Trastuzumab for Breast Cancer

The risk for congestive heart failure (CHF) in breast cancer patients using trastuzumab has been carefully documented. To evaluate this cardiac effect on a population level, investigators conducted a retrospective cohort study of 19,074 women identified in the Ontario Cancer Registry who received adjuvant chemotherapy for stage I–III breast cancer between 2003 and 2009. Of these patients, 15,703 (82.3%) received chemotherapy alone …

Impact of physician and center case volume on the adequacy of cardiac monitoring during adjuvant trastuzumab in breast cancer.

128 Background: A recent study suggests that cardiotoxicity from adjuvant trastuzumab (T-mab) is associated with inadequate cardiac monitoring (Ng et al. SABCS 2012). Few studies have examined the impact of centre or physician (MD) case volume (vol) on the quality of care in systemic therapy, including the adequacy of cardiac monitoring during T-mab treatment. Methods: All breast cancer patients treated with adjuvant T-mab in Ontario between 2003-2009 were identified through a provincial drug funding program. Patient demographics, hospitalizations, cardiac risk factors, cardiac imaging, comorbidities, treatment centres and MDs were ascertained. Annual case vol was calculated as the number of patients treated per year with adjuvant T-mab by each MD and centre. Cumulative case vol was calculated as the total number of patients treated with adjuvant T-mab. Centre and MD vol were divided into terciles (T1, T2 and T3) by the year of diagnosis. Inadequate cardiac monitoring was defined as per recent guidelines and per Ng et al. Hierarchical multivariable logistic regression models were constructed to examine factors associated with inadequate cardiac monitoring. Results: Our cohort consisted of 3,777 patients, 214 MDs and 68 centres. Of the total patients, 16.5% were over age 65; 30.3%, 9.4%, and 1.2% had previous diagnoses of hypertension, diabetes, and heart failure (HF), respectively; 24.3% did not receive adequate cardiac monitoring. Inadequate cardiac monitoring was associated with lower cumulative MD vol (T1: 27.9%, T2: 23.3%, T3: 20.8%, p &lt; 0.0001) and lower annual centre vol (T1: 32.5%, T2: 19.7%, T3: 20.7%, p &lt; 0.0001) in univariate analyses, and remained significant after adjusting for age, comorbidities, previous HF, socioeconomic status based on income, rural residence and calendar period. After adjusting for patient clustering at the MD, centre, and regional levels, lower cumulative MD vol (p=0.012), but not annual centre vol, remained a significant predictor for inadequate cardiac monitoring. Conclusions: Our findings suggest improved cardiac monitoring with greater MD experience, supporting the notion of centralization of systemic therapy to high vol MDs to optimize outcomes.

Impact of center case volume on cardiotoxicity during adjuvant trastuzumab in breast cancer.

6625 Background: A recent study suggested that cardiotoxicity from trastuzumab (T) was associated with regional variation and insufficient cardiac monitoring (Ng et al.SABCS 2012). Few studies have examined the impact of centre or physician (MD) case volume (vol) on outcomes in systemic therapy. Methods: All breast cancer patients who were diagnosed in 2003-2009 in Ontario and treated with adjuvant T were identified through a provincial drug funding program, and linked to administrative databases to ascertain patient demographics, hospitalizations, cardiac risk factors, cardiac imaging, comorbidities, and treating centre and MD. For each year, we calculated case vol as the number of patients treated with adjuvant T by each MD and by each centre. Cardiotoxicity was defined as receiving less than 16 out of 18 doses of T because of heart failure (HF) admission, HF diagnosis by physician claims, or discontinuation after cardiac imaging. Insufficient cardiac monitoring was defined as per recent guideline and per Ng et al. Logistic regression and mixed models were constructed to examine factors associated with cardiotoxicity. Results: Our cohort consisted of 3,777 patients, 214 MDs and 68 centres. For patients, 16.5% were over age 65; 30.3%, 9.4%, and 1.2% had previous diagnoses of hypertension, diabetes, and HF, respectively; 16.9% had cardiotoxicity. Univariate analyses found that high centre vol, but not MD vol, was associated with lower cardiotoxicity. Cardiotoxicity rates by centre vol quintiles (Q) were 23.4% (Q1-3), 18.2% (Q4), and 15.2% (Q5). Multivariable analyses found that lower cardiotoxicity was associated with higher centre vol (OR=0.85 per Q, p=0.02) and diagnosis in recent years (2008-2009 vs. before 2008; OR=0.50, p&lt;0.001), after adjusting for age, previous HF, comorbidities, regional variation, and cardiac monitoring. Accounting for clustering within centres, there remained a strong trend of lower cardiotoxicity with higher centre vol (OR=0.77 per Q, p=0.06) and recent diagnosis (OR=0.50, p&lt;0.001). Conclusions: Our findings suggest a reduction in cardiotoxicity with experience and over time, and support the notion of centralization of systemic therapy in high vol centres to optimize outcomes.

Abstract P5-18-02: Selective Crossover in Randomized Trials of Adjuvant Trastuzumab for Breast Cancer: Coping with Success

Abstract BACKGROUND: Disease-free survival (DFS) is often a primary endpoint of randomized trials of adjuvant therapies for breast cancer, but long-term follow-up of DFS and especially overall survival (OS) remain important. When the primary DFS results favor the experimental arm, patients (pts) assigned to the control group may select the option to crossover to receive the experimental treatment via protocol amendment. Such “selective crossover” disturbs the integrity of the randomized comparison for any efficacy endpoints that rely on further follow-up. Selective crossover, which is motivated by positive results having been observed in the current trial, is distinct from so-called “unplanned crossover,” which refers to non-adherence to protocol. In this abstract, we discuss the consequences of selective crossover for trials evaluating adjuvant trastuzumab, using the HERA (HERceptin Adjuvant) trial as an example, and present a variety of alternative analysis approaches. METHODS: HERA enrolled 5102 women with HER2-positive early breast cancer who had completed all surgery and (neo)adjuvant chemotherapy to compare 1 or 2 years of trastuzumab treatment vs observation. After a positive first interim analysis at 1y median follow-up (MFU) showed that 1 year of trastuzumab significantly improved DFS vs observation [MJ Piccart-Gebhart et al; NEJM 2005], event-free patients in the observation group were offered crossover to receive trastuzumab. 885 (52%) of the 1698 pts in the observation group selectively crossed over to trastuzumab. RESULTS: Previously reported intention-to-treat (ITT) analysis of HERA at 4y MFU showed a decreasing effectiveness of trastuzumab with respect to DFS compared with those at 2y MFU [L Gianni et al, Lancet Oncol 2011; I Smith et al, Lancet 2007]. In addition, the ITT analysis of OS at 4y MFU showed little effect of trastuzumab, while the analysis artificially censoring follow-up in the observation group at the time of selective crossover showed a substantial OS advantage for trastuzumab. The dependent censored analysis of OS is clearly biased in favor of trastuzumab because data for pts who remain event-free can be censored at the time of crossover, while data for the sicker pts in the observation group (those who relapsed) cannot be censored due to crossover. The issues related to the ITT and dependent censored analyses will be reviewed and discussed. Alternative analytic approaches designed to estimate the treatment effect that would have been observed had there been no selective crossover will be presented. The methods include the inverse probability of censoring weighted (IPCW) approach, and randomization-based estimators under the accelerated failure time model. HERA data to about 8y MFU (available fall 2012) will be used to illustrate approaches. CONCLUSION: Alternative methods addressing selective crossover are required to estimate the trastuzumab effect for updated analyses of DFS and OS for HERA, and for any other large randomized trial with positive interim results. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-02.

Late Cardiac Events Rare After Adjuvant Trastuzumab for Breast Cancer

Cardiac toxicity is a potential effect of trastuzumab-based therapy, particularly when the agent is combined concurrently with anthracyclines. Since an

Meta-analysis of concomitant compared to sequential adjuvant trastuzumab in breast cancer: the sooner the better

Adjuvant trastuzumab (T) significantly reduces the risk of progression and death in HER-2 positive high-risk early breast cancer. The differential benefit of T, administered either sequential or concomitant, has been calculated with 2 comparative meta-analyses of randomized trials. We have meta-analyzed sequential and concomitant arms of 6 T adjuvant trials separately and then calculated the pooled hazard ratios (HRs) for disease-free survival (DFS) and overall survival (OS) in both meta-analyses. Primary cardiac event rates have also been meta-analyzed. In the concomitant T meta-analysis, HRs for DFS and OS were 0.62 and 0.68, respectively (P < 0.0001 and <0.00001 for both endpoints). Conversely, in the sequential T meta-analysis, HRs for DFS and OS were, respectively, 0.74 and 0.87, where P is, however, significant only in the first comparison (P < 0.00001 and P = 0.09). Relative risks (RRs) for major cardiac events (severe cardiac hearth failure or death) are 2.44 (P = 0.07) in the concomitant T meta-analysis and 8.35 (P < 0.0001) in the sequential T meta-analysis. Concomitant adjuvant T therapy seems to give a significant and greater benefit than sequential administration in both DFS and OS, and the number of cases of severe cardiotoxicity does not seem to be higher in concomitant administration than in the sequential one.

Adjuvant Trastuzumab in Breast Cancer: Experience from the University of Florence

The objective of this study was to evaluate the efficacy and tolerability profile of sequential trastuzumab in the adjuvant treatment of non-metastatic breast cancer. We analyzed 94 patients with non-metastatic breast cancer who under went postoperative treatment between November2003 and December 2008 at the University of florence. All patients received one year of sequential trastuzumab after adjuvant chemotherapy. Cardiac monitoring in our study consisted of assessment of left ventricular ejection fraction (LVEF) by echocardiography at baseline, after the completion of chemotherapy, then every 3 months during trastuzumab treatment and every 6 months thereafter. 91.6% of patients were alive without evidence of distant or local relapse, while 8.4% developed disease recurrence. The cumulative incidence of cardiotoxicity was 14.5%. In our experience trastuzumab given postoperatively with adjuvant chemotherapy was well tolerated and produced optimal clinical results in terms of disease-free survival.

Cardiac toxicity and adjuvant trastuzumab for breast cancer – the Cancer Centre of Southeastern Ontario experience.

Abstract Abstract #3158 Background: In May 2005 several large randomized trials reported a significant improvement in DFS following the addition of trastuzumab (T) to adjuvant chemotherapy (CT) in early stage breast cancer (BC) such that in the summer of 2005 adjuvant T became standard of care for patients (pts) whose tumors over-expressed her2. Cardiotoxicity had been reported as the main toxicity suffered by pts exposed to T. As the generalizability of clinical trial results to the 'real world' is under increasing scrutiny from the oncology community, we undertook this study to identify and follow the population of interest and to characterize cardiac toxicity related to adjuvant T as practice changed.&amp;#x2028; Methods: We conducted a retrospective review of electronic and paper records of all pts prescribed adjuvant T for early stage BC at the Cancer Centre of Southeastern Ontario from June 2005 through January 2007; collecting demographic, disease-related, and treatment-related variables, along with serial left ventricular ejection fraction (LVEF) measurements for each pt.&amp;#x2028; Results: 54 pts prescribed adjuvant T were identified in this time period, nearly half of which were still on T at the time of this analysis. Mean age was 54.4 ± 9.5 years, 38.9% had N0 disease, and 40.7% had left sided tumors, with 42.6% being ER+ and 50% being PR+. Most pts received anthracycline based CT (53.7%) and 39% received an anthracycline/taxane combination. T was concurrently with CT in 14.8% of pts, concurrently with radiotherapy in 33.3% and sequentially in the remainder. T was initiated at a mean of 91.2 days from completion of chemotherapy (range 19-365). Our local protocol mandated LVEF assessments at baseline pre CT, upon completion of CT and/or prior to initiation of T for all pts, and while on T all pts underwent LVEF assessments at 12, 24, 36, 48 and 52 weeks, and in response to any symptoms suggesting cardiac dysfunction. Mean LVEF pre CT and post CT was 64% and 62% respectively. We saw no change in LVEF post CT and pre T. We noted a significant decline in LVEF after 12 weeks on T, from 60.5 ± 6.2% to 56.5 ± 9.5% respectively (p = 0.003), with LVEF values remaining stable thereafter. However, at the time of this analysis only approximately half the pts had completed the full year of therapy. Twelve pts (22.2%) interrupted their T therapy due to a drop in LVEF of &amp;gt;10%, only one pt experienced symptomatic cardiotoxicity requiring treatment. Of these twelve, only two pts restarted T at a later date. Follow-up of those patients still on trastuzumab is ongoing.&amp;#x2028; Discussion: Adjuvant trastuzumab in general clinical practice is associated with significant decreases in LVEF that are associated with premature discontinuation of therapy. A better understanding of factors associated with LVEF decline and the trends in LVEF over time may allow for targeted interventions for pts at risk. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3158.

Cardiac monitoring and toxicity with adjuvant trastuzumab in breast cancer: Data from clinical practice

17551 Background: Adjuvant trastuzumab, recommended for HER2-positive early stage breast cancer, is associated with asymptomatic drop in left ventricular ejection fraction (LVEF) in 10–15% of patients and symptomatic congestive heart failure in 2–4%. There are limited data on cardiac toxicity with trastuzumab in clinical practice and there is no standard cardiac follow-up during adjuvant treatment. Phase III trials (NSABP B31/NCCTG N9831/ HERA) recommended echocardiograms at baseline, after anthracyclines and every 3 to 6 months afterwards. Methods: Retrospective evaluation of all patients with HER2-positive breast cancer treated in a private clinic with adjuvant trastuzumab since its approval in 2005. Timing and frequency of echocardiograms and cardiac adverse events were reviewed. Results: Forty-seven patients received adjuvant trastuzumab until December 2007. Thirty-three (70%) finished 1-year treatment and 14 are still on treatment (median 6 months, range 3–11). Median age: 51 years (range 31–82). No patient had uncontrolled hypertension or heart failure at baseline. Adjuvant chemotherapy was an anthracycline followed by taxanes in 41 patients (87.2%), anthracycline/ cyclophosphamide in 4 (8.5%) and docetaxel/ carboplatin in 2 (4.3%). Twenty-one patients (44.7%) have not received appropriate cardiac monitoring (considering published phase III trials). Seven patients (14.9%) had to discontinue trastuzumab (6 cases of asymptomatic LVEF drop and 1 symptomatic arrhythmia). Three patients resumed trastuzumab after 1-month interval. Four patients (8.5%) required permanent discontinuation of trastuzumab (3/7/11/11 months): 3 for a significant drop in LVEF (≤ 50%) and 1 due to arrhythmia). All these patients recovered from cardiac dysfunction and LVEF returned to baseline/ normal levels after treatment interruption (1 still on medication). Conclusions: Despite the absence of standard guidelines, our results show inadequate cardiac monitoring during adjuvant trastuzumab in a private clinic. Cardiotoxicity was observed as often as in clinical trials. Severity was mild and reversible in all patients. Continued and appropriate cardiac follow-up of these women is of critical importance. No significant financial relationships to disclose.