Therapy For Early-stage Breast Cancer Research Articles

Evaluating Optimal Timing of Endocrine Therapy and Radiation Therapy in Early-stage Breast Cancer (REaCT-RETT)

Evaluating Optimal Timing of Endocrine Therapy and Radiation Therapy in Early-stage Breast Cancer (REaCT-RETT)

Optimizing HER2-Directed Therapy in Early-Stage Breast Cancer

HER2-positive early breast cancer has been revolutionized by the development of HER2-directed therapy, which has significantly reduced breast cancer recurrence risk and improved overall survival. Here, we review the available treatment options for this patient population and discuss how we might individualize therapy in the future to optimize the balance of efficacy and toxicity. The addition of pertuzumab to a trastuzumab-based adjuvant regimen improves pathologic complete response rates and invasive disease-free survival (DFS). Addition of neratinib for patients with high-risk disease also contributes to improved DFS. Current data supports use of dual HER2-directed therapy in combination with chemotherapy, as well as extended HER2-directed therapy (beyond 1 year), in those with high-risk HER2-positive early breast cancer. Ongoing studies aim to identify biomarkers of response and resistance to standard approaches, as well as identify those who might benefit from a chemotherapy-free treatment paradigm.

Predicting the response to neoadjuvant therapy for early-stage breast cancer: tumor-, blood-, and imaging-related biomarkers.

Neoadjuvant therapy (NAT) has been used increasingly in patients with locally advanced or early-stage breast cancer. However, the accurate evaluation and prediction of response to NAT remain the great challenge. Biomarkers could prove useful to identify responders or nonresponders, or even to distinguish between early and delayed responses. These biomarkers could include markers from the tumor itself, such as versatile proteins, genes, and ribonucleic acids, various biological factors or peripheral blood cells, and clinical and pathological features. Possible predictive markers could also include multiple features from functional imaging, such as standard uptake values in positron emission tomography, apparent diffusion coefficient in magnetic resonance, or radiomics imaging biomarkers. In addition, cells that indirectly present the immune status of tumor cells and/or their host could also potentially be used as biomarkers, eg, tumor-infiltrating lymphocytes, tumor-associated macrophages, and myeloid-derived suppressor cells. Though numerous biomarkers have been widely investigated, only estrogen and/or progesterone receptors and human epidermal growth factor receptor have been proven to be reliable biomarkers to predict the response to NAT. They are the only biomarkers recommended in several international guidelines. The other aforementioned biomarkers warrant further validation studies. Some multigene profiling assays that are commercially available, eg, Oncotype DX and MammaPrint, should be used with caution when extrapolated to NAT settings. A panel of combined multilevel biomarkers might be able to predict the response to NAT more robustly than individual biomarkers. To establish such a panel and its prediction model, reliable methods and extensive clinical validation are warranted.

An Update on Breast Cancer Multigene Prognostic Tests—Emergent Clinical Biomarkers

Multigene signatures generate crucial prognostic information particularly useful for cancer patients where clinical parameters and traditional immunohistochemical markers alone lead to equivocal prognosis. Clinicians are now provided with molecular tools that assist in the outline of adjuvant therapies, namely helping decide on the extension of adjuvant endocrine therapy or on suppressing adjuvant chemotherapy in patients were toxic effects are particularly deleterious or when this treatment is fundamentally not needed. The importance of cancer multigene prognostic signatures is well elucidated in the guidelines for adjuvant systemic therapy in early-stage breast cancer and the guidelines on disease staging that are progressively integrating gene expression assays as classification biomarkers. In addition to the predictive and prognostic value, some genetic tests provide intrinsic subtyping classification. Herewith, we compare the molecular tests OncotypeDX, MammaPrint, Prosigna, EndoPredict, Breast Cancer Index, Mammostrat, and IHC4 and report the eligibility of each one in the suitable setting. Through to now, there is not a commercially available multigene test that makes recommendations regarding adjuvant treatment for HER-2 and triple negative breast cancers. Thus, these patients still receive adjuvant chemotherapy. Importantly, triple negative carcinomas are very heterogeneous regarding prognosis and new molecular signatures that decipher this very heterogeneous subgroup of breast cancer may improve the clinical management of the disease.

Perceptions of vascular access for intravenous systemic therapy and risk factors for lymphedema in early-stage breast cancer-a patient survey.

The choice of vascular access for systemic therapy administration in breast cancer remains an area of clinical equipoise, and patient preference is not consistently acknowledged. Using a patient survey, we evaluated the patient experience with vascular access during treatment for early-stage breast cancer and explored perceived risk factors for lymphedema. Patients who had received systemic therapy for early-stage breast cancer were surveyed at 2 Canadian cancer centres. Responses were received from 187 patients (94%). The route of vascular access was peripheral intravenous line (IV) in 24%, a peripherally inserted central catheter (picc) in 42%, and a surgically inserted central catheter (port) in 34%. Anthracycline-based regimens were associated with a greater use of central vascular access devices (cvads- that is, a picc or port; 86/97, 89%). Trastuzumab use was associated with greater use of ports (49/64, 77%). Although few patients (7%) reported being involved in the decisions about vascular access, most were satisfied or very satisfied (88%) with their access type. Patient preference centred mainly on avoiding delays in the initiation of chemotherapy. Self-reported rates of complications (183 evaluable responses) were infiltration with peripheral IVs (9/44, 20%), local skin infections with piccs (7/77, 9%), and thrombosis with ports (4/62, 6%). Perceived risk factors for lymphedema included use of the surgical arm for blood draws (117/156, 75%) and blood pressure measurement (115/156, 74%). Most patients reported being satisfied with the vascular access used for their treatment. Improved education and understanding about the evidence-based requirements for vascular access are needed. Perceived risk factors for lymphedema remain variable and are not evidence-based.

Hypofractionation with concomitant boost using intensity-modulated radiation therapy in early-stage breast cancer in Mexico.

To evaluate whether hypofractionation with integrated boost to the tumour bed using intensity-modulated radiation therapy is an acceptable option and to determine whether this treatment compromises local control, toxicity and cosmesis. Retrospective studies have demonstrated that patients who are treated with HF and integrated boost experience adequate local control, a dosimetric benefit, decreased toxicity and acceptable cosmesis compared with conventional fractionation. A retrospective, observational and longitudinal study was conducted from January 2008 to June 2015 and included 34 patients with breast cancer (stage 0-II) who were undergoing conservative surgery.The prescribed doses were 45 Gy in 20 fractions (2.25 Gy/fraction) to the breast and 56 Gy in 20 fractions (2.8 Gy/fraction) to the tumour bed. Thirty-four patients were included. The mean follow-up was 49.29 months, and the mean age was 52 years. The mean percentage of PTV from the mammary region that received 100% of the prescribed dose was 97.89% (range 95-100), and the mean PTV percentage of the tumour bed that received 100% of the dose was 98% (95-100).The local control and the overall survival were 100%, and the cosmesis was good in 82% of the patients. Grade 1 acute toxicity was present in 16 patients (47%), and grade 1 chronic toxicity occurred in 6 cases (18%). The results of the present study demonstrate that hypofractionation with integrated boost using intensity-modulated radiation therapy is an acceptable option that provides excellent local control and low toxicity.

Risk-Imaging Mismatch in Cardiac Imaging Practices for Women Receiving Systemic Therapy for Early-Stage Breast Cancer: A Population-Based Cohort Study.

To assess prechemotherapy cardiac imaging practices in relation to patients' heart failure (HF) risk. We performed a population-based retrospective cohort study of women receiving chemotherapy for early-stage breast cancer in Ontario between 2007 and 2012. We surveyed for baseline cardiac imaging 6 months before chemotherapy or within 30 days thereafter. The proportion of patients who underwent imaging and cumulative incidence of major adverse cardiac event (MACE) rates was determined based on chemotherapy regimen and HF risk factors. Logistic regression was used to assess predictors of pretreatment cardiac imaging. We studied 18,444 women who had been treated with chemotherapy (median age, 55 years). There was near-universal imaging of women treated with trastuzumab-containing regimens, including those without additional HF risk factors. Women who received anthracyclines without trastuzumab underwent imaging more frequently if they had additional HF risk factors (73.3% v 62.6%; P < .001). The 5-year incidence of MACE was two to six times higher in patients with HF risk factors across all treatment regimens. Patients with HF risk factors who received anthracyclines without trastuzumab had a higher 5-year incidence of MACE (4.5%) than patients without HF risk factors who received trastuzumab without anthracyclines (2.6%). However, cardiac imaging was less frequent in the former group (73.3% v 93.6%; P < .001). Logistic regression indicated that most variation in baseline imaging was related to chemotherapy, followed by physician-level factors. The odds of imaging were doubled with female physicians. Patient-specific factors, including HF risk factors, made minimal contribution to variation in imaging. Baseline cardiac imaging was driven by chemotherapy regimen rather than HF risk. This risk-imaging mismatch is an impetus to reconsider current cardiac imaging practices in patients who receive chemotherapy for breast cancer.

238 (PB-033) - Radiofrequency ablation therapy for early-stage breast cancer: Results from 5 years of follow-up in a prospective multicenter study

238 (PB-033) - Radiofrequency ablation therapy for early-stage breast cancer: Results from 5 years of follow-up in a prospective multicenter study

Effectiveness of trastuzumab as adjuvant therapy in patients with early stage breast cancer: A systematic review and meta-analysis.

Background: Trastuzumab in combination with chemotherapy has long been established as a standard treatment for HER2-positive patients in early stage breast cancer (BC). The present study aimed at assessing the effectiveness of trastuzumab adjuvant therapy in early stage BC in overall survival (OS) and disease-free survival (DFS). Methods: A systematic review and meta-analysis was performed to evaluate the effectiveness of trastuzumab adjuvant therapy. PubMed, Cochrane library, Scopus, Web of Science, and Embase databases were searched for relevant RCTs from the beginning to February 2017. Quality assessment of studies was conducted using the Cochrane Risk of Bias Tool. The desired outcomes were OS and DFS. Results: A total of 1818 articles were identified first, however, only 11 studies were eligible to be included in this study. Our findings and meta-analysis results revealed that trastuzumab is effective in increasing OS (OS hazard ratio: -0.286 ± 0.049, 95%CI (-0.381, - 0.191)) and improving DFS (DFS hazard ratio: -0.419± 0.077, 95%CI (-0.569, -0.269)). The most serious but negligible side effect of trastuzumab is congestive heart failure. Conclusion: Adding trastuzumab as adjuvant therapy in early stages of BC in HER2 positive patients could increase OS and DFS of the patients effectively.

Assessing the Clinical Benefit of Systemic Adjuvant Therapies for Early Breast Cancer.

Oncologic therapy is currently undergoing significant changes. A number of innovative targeted medications currently in clinical development have raised high expectations. With that in mind, discussions about terms such as “clinical benefit” and “clinical relevance” are highly topical. This also applies to further developments in the field of adjuvant systemic therapies for early-stage breast cancer. As the treatment aim is curative, assessment of the clinical benefit of adjuvant therapies must be largely based on efficacy outcomes. The focus must be on improving disease-free survival rates and lowering the risk of recurrence. Because of the current low mortality rates, statements about overall survival rates are only possible after very long observation periods. Consequently, new drugs in adjuvant therapies should be considered as offering a clinical benefit, if they reduce the risk of recurrence below current low levels of risk. The evidence for established adjuvant therapy standards in early-stage breast cancer can be used as objective criteria for comparison. This review article considers the requirements for clinical benefit of new adjuvant therapies for early breast cancer, based on examples from adjuvant endocrine therapy, adjuvant polychemotherapy and adjuvant anti-HER2 therapy.

Gene Expression Profiling in Breast Cancer and Its Effect on Therapy Selection in Early-Stage Breast Cancer.

Breast cancer is a heterogeneous disease. The purpose of adjuvant therapy for early-stage breast cancer is to provide maximum benefit with minimum side effects and not to under-treat or over-treat. The clinical progresses of patients with the same clinical and pathological characteristics who are given similar treatments may show major differences. This fact indicates that the prognostic and predictive factors that we have used until recent years for therapy selection are not really sufficient, we need new markers, every disease and every individual are unique and that treatment should be individualized. The gene expression profiling, which has come into clinical use in recent years, is beneficial in therapy selection for luminal breast cancer cases. A differentiation can be made among patients for whom only endocrine treatment would be adequate and those who should also receive chemotherapy in addition to endocrine treatment. Several new gene expression analysis studies targeted at gaining the ability to determine drug selection in chemotherapy, endocrine treatment and neo-adjuvant therapy are also currently ongoing. The staging system for new breast cancer that is to be published in the year 2018 also includes gene expression analyses within the prognostic panel and the stage changes depending on the result. The statement 'Treat the patient, not the disease.' is becoming increasingly entrenched in our clinical practice. This article briefly summarizes the gene expression profiles, which are validated and used in the selection of therapy for early-stage breast cancer.

Preoperative indication for systemic therapy extended to patients with early-stage breast cancer using multiparametric 7-tesla breast MRI.

PurposeTo establish a preoperative decision model for accurate indication of systemic therapy in early-stage breast cancer using multiparametric MRI at 7-tesla field strength.Materials and methodsPatients eligible for breast-conserving therapy were consecutively included. Patients underwent conventional diagnostic workup and one preoperative multiparametric 7-tesla breast MRI. The postoperative (gold standard) indication for systemic therapy was established from resected tumor and lymph-node tissue, based on 10-year risk-estimates of breast cancer mortality and relapse using Adjuvant! Online. Preoperative indication was estimated using similar guidelines, but from conventional diagnostic workup. Agreement was established between preoperative and postoperative indication, and MRI-characteristics used to improve agreement. MRI-characteristics included phospomonoester/phosphodiester (PME/PDE) ratio on 31-phosphorus spectroscopy (31P-MRS), apparent diffusion coefficients on diffusion-weighted imaging, and tumor size on dynamic contrast-enhanced (DCE)-MRI. A decision model was built to estimate the postoperative indication from preoperatively available data.ResultsWe included 46 women (age: 43-74yrs) with 48 invasive carcinomas. Postoperatively, 20 patients (43%) had positive, and 26 patients (57%) negative indication for systemic therapy. Using conventional workup, positive preoperative indication agreed excellently with positive postoperative indication (N = 8/8; 100%). Negative preoperative indication was correct in only 26/38 (68%) patients. However, 31P-MRS score (p = 0.030) and tumor size (p = 0.002) were associated with the postoperative indication. The decision model shows that negative indication is correct in 21/22 (96%) patients when exempting tumors larger than 2.0cm on DCE-MRI or with PME>PDE ratios at 31P-MRS.ConclusionsPreoperatively, positive indication for systemic therapy is highly accurate. Negative indication is highly accurate (96%) for tumors sized ≤2,0cm on DCE-MRI and with PME≤PDE ratios on 31P-MRS.

Stereotactic Body Radiation Therapy for Early-Stage Breast Cancer Using a Robotic Linear Accelerator

Stereotactic Body Radiation Therapy for Early-Stage Breast Cancer Using a Robotic Linear Accelerator

Setting Quality Improvement Priorities for Women Receiving Systemic Therapy for Early-Stage Breast Cancer by Using Population-Level Administrative Data.

Purpose Routine evaluation of quality measures (QMs) can drive improvement in cancer systems by highlighting gaps in care. Targeting quality improvement at QMs that demonstrate substantial variation has the potential to make the largest impact at the population level. We developed an approach that uses both variation in performance and number of patients affected by the QM to set priorities for improving the quality of systemic therapy for women with early-stage breast cancer (EBC). Patients and Methods Patients with EBC diagnosed from 2006 to 2010 in Ontario, Canada, were identified in the Ontario Cancer Registry and linked deterministically to multiple health care databases. Individual QMs within a panel of 15 QMs previously developed to assess the quality of systemic therapy across four domains (access, treatment delivery, toxicity, and safety) were ranked on interinstitutional variation in performance (using interquartile range) and the number of patients who were affected; then the two rankings were averaged for a summative priority ranking. Results We identified 28,427 patients with EBC who were treated at 84 institutions. The use of computerized physician electronic order entry for chemotherapy, emergency room visits or hospitalizations during chemotherapy, and timely receipt of chemotherapy were identified as the QMs that had the largest potential to improve quality of care at a system level within this cohort. Conclusion A simple ranking system based on interinstitutional variation in performance and patient volume can be used to identify high-priority areas for quality improvement from a population perspective. This approach is generalizable to other health care systems that use QMs to drive improvement.

The impact of mild left ventricular dysfunction on trastuzumab use and oncologic outcomes in early stage breast cancer therapy.

e18148 Background: Trastuzumab (T) significantly reduces the risk of breast cancer recurrence, but may be associated with an increased incidence of heart failure. The intention of this study was to assess how T therapy was managed after the development of mild left ventricular ejection fraction (LVEF) drop in a non-trial setting and to evaluate the cardiovascular and oncologic outcomes. Methods: Patients (pts) who received adjuvant T therapy in British Columbia for breast cancer between September 2005 and December 2013 were identified. Pts were eligible if they had a drop in LVEF to 40-49% after starting T. Charts were reviewed for demographic information. Pts were divided into 2 cohorts: those who continued T without interruption, and those who had any interruption or discontinuation. Breast cancer outcomes and cardiac outcomes were compared in each of these groups. Results: Of the 2401 pts who were screened, 261 (10.9%) pts had a drop in LVEF to 40-49%. Of these, 229 (87.7%) had an interruption in T, while 32 (12.3%) did not have an interruption in therapy. The number of pts who experienced a cancer relapse in the T interruption and continuous groups were 38 (16.6%) and 2 (6.25%), respectively (P = 0.19). Even amongst those who received a full 17 cycles of therapy, there was a 11.25% absolute increase in the risk of breast cancer recurrence (17.5% vs 6.25%) in those who had an interruption in their course of treatment compared to those who did not have an interruption (p = 0.15). Cardiac outcomes (subsequent LVEF drop &lt; 40% or CHF) were higher in the group of pts who had treatment interrupted compared to those who had continuation of T (14.8% vs 0%). Conclusions: Interrupting T after the development of mild left ventricular dysfunction was associated with a 10.35% (p = 0.19) absolute increase in breast cancer recurrence. Continuing T was not associated with an increased risk of long term cardiovascular events. While these results are not statistically significant, they are concerning and warrant further investigation.

Initiation of Trastuzumab by Women Younger Than 64 Years for Adjuvant Treatment of Stage I-III Breast Cancer.

Purpose: Studies have reported disparities by age and race in the initiation of adjuvant trastuzumab for the initial treatment of older women with early-stage breast cancer, but less is known about its initiation in younger patients. Therefore, we assessed temporal trends and clinical and demographic factors associated with trastuzumab initiation in a large, population-based cohort of patients aged <64 years in 5 states. Methods: Using a cancer registry and claims-linked data set of 13,398 women with incident invasive breast cancer from 2006 to 2011, we identified 934 patients aged <64 years with HER2-positive stage I-III breast cancer. We assessed trastuzumab initiation within the first 9 months after diagnosis and conducted logistic regression analyses to assess sociodemographic and clinical factors associated with trastuzumab initiation. Results: From 2006 to 2011, trastuzumab initiation steadily increased in patients with node-positive (from 65% to 91%) and node-negative (from 39% to 75%) breast cancers. Several tumor-related factors were associated with trastuzumab initiation, including high histologic grades (adjusted odds ratio [aOR], 6.43; 95% CI, 3.27-12.65; and aOR, 3.25; 95% CI, 1.66-6.36, for grades 3 and 2, respectively), node-positive status (aOR, 1.88; 95% CI, 1.28-2.78; P=.001), tumor size >2 cm (aOR, 1.50; 95% CI, 1.04-2.16; P=.03), and hormone receptor-negative status (aOR, 1.51; 95% CI, 1.01-2.26; P=.04). We found a null effect of race. Conclusions: Adjuvant trastuzumab therapy for early-stage breast cancer has been widely disseminated among women aged <64 years. The initiation of this targeted therapy was associated with higher-risk features, consistent with practice guidelines.

Intensity-modulated radiation therapy for early-stage breast cancer: is it ready for prime time?

Whole breast external beam radiotherapy (WBEBRT) is commonly used as an essential arm in the treatment management of women with early-stage breast cancer. Dosimetry planning for conventional WBEBRT typically involves a pair of tangential fields. Advancement in radiation technology and techniques has the potential to improve treatment outcomes with clinically meaningful long-term benefits. However, this advancement must be balanced with safety and improved efficacy. Intensity-modulated radiation therapy (IMRT) is an advanced technique that shows promise in improving the planning process and radiation delivery. Early data on utilizing IMRT for WBEBRT demonstrate more homogenous dose distribution with reduction in organs at risk doses. This translates to toxicities reduction. The two common descriptors for IMRT are forward-planning “fields in field” and inverse planning. Unlike IMRT for other organs, the aim of IMRT for breast planning is to achieve dose homogeneity and not organ conformality. The aim of this paper was to evaluate whether IMRT is ready for prime time based on these three points: 1) workload impact, 2) the clinical impact on the patient’s quality of life, and 3) the appropriateness and applicability to clinical practice.

Information Needs of Older Women With Early-Stage Breast Cancer When Making Radiation Therapy Decisions

To identify the information older women with early-stage breast cancer need when making radiation therapy decisions, and who patients identify as the main decisionmaker. We surveyed (through face-to-face interview, telephone, or mail) women aged ≥65years who received lumpectomy and were considering or receiving adjuvant radiation therapy for early-stage breast cancer. The survey instrument was constructed with input from patient and professional advisory committees, including breast cancer survivors, advocates of breast cancer care and aging, clinicians, and researchers. Participants rated the importance (on a 4-point scale) of 24 statements describing the benefits, side effects, impact on daily life, and other issues of radiation therapy in relation to radiation therapy decision making. Participants also designated who was considered the key decision maker. The response rate was 56.4% (93 of 165). Mean age was 72.5years, ranging from 65 to 93years. More than 96% of participants indicated they were the main decision maker on receiving radiation therapy. There was wide variation in information needs regarding radiation therapy decision making. Participants rated a mean of 18 (range, 3-24) items as "essential." Participants rated items related to benefits highest, followed by side effects. Participants who were older than 75years rated 13.9 questions as essential, whereas participants aged ≤74years rated 18.7 as essential (P=.018). Older women desire information and have more agency and input in the decision-making process than prior literature would suggest. The variation in information needs indicates that future decision support tools should provide options to select what information would be of interest to the participants.

Understanding Women's Choice of Mastectomy Versus Breast Conserving Therapy in Early-Stage Breast Cancer.

Objective:To identify factors that influence Saskatchewan women’s choice between breast conserving therapy (BCT) and mastectomy in early-stage breast cancer (ESBC) and to compare and contrast underlying reasons behind choice of BCT versus mastectomy.Methods:Interpretive description methods guided this practice-based qualitative study. Data were analyzed using thematic analysis and presented in thematic maps.Results:Women who chose mastectomy described 1 of the 3 main themes: worry about cancer recurrence, perceived consequences of BCT treatment, or breast-tumor size perception. In contrast, women chose BCT because of 3 different themes: mastectomy being too radical, surgeon influence, and feminine identity.Conclusions:Although individual reasons for choosing mastectomy versus BCT have been discussed in the literature before, different rationale underlying each choice has not been previously described. These results are novel in identifying interdependent subthemes and secondary reasons for each choice. This is important for increased understanding of factors influencing a complicated decision-making process.

Comparison of two care schedules for monitoring of cardiotoxicity in patients receiving trastuzumab-based therapy for early-stage breast cancer: study protocol for a randomized controlled non-inferiority trial

Background: Cardiotoxicity is a toxic side effect of trastuzumab-based therapy. Current guidelines for cardiac monitoring (every 3 months) in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving trastuzumab-based therapy have been dictated by the increased risk of cardiotoxicity observed in clinical trials. However, the majority of these patients are at a low risk of cardiac complications and may not require such frequent monitoring. Objective: This randomized controlled clinical trial will be performed to demonstrate that cardiac monitoring (echocardiography (ECHO)/multiple gated acquisition scan (MUGA) every 4 months is not inferior to every 3 months in the detection of cardiac dysfunction (decrease in left ventricular ejection fraction (LVEF)) in patients receiving trastuzumab-based therapy for early-stage HER2-positive breast cancer. Study period: From June 2016 to December 2018. Study location: The Ottawa Hospital Cancer Centre. Principal investigator: Dr. Olexiy Aseyev and Dr. Susan Dent at Department of Medicine, Division of Medical Oncology, The Ottawa Hospital, University of Ottawa, Canada. Study design: A prospective, single-center, randomized controlled non-inferiority clinical trial. Study population: A total of 200 patients with early-stage HER2-positive breast cancer (n = 100 in each group) receiving trastuzumab-based therapy will be enrolled. Inclusion criteria: Patients with histologically confirmed early-stage HER2-positive breast cancer receiving trastuzumab-based therapy, who are over 18 years of age, have a normal baseline LVEF (> 53%) and are able to provide verbal consent will be included in this study. Exclusion criteria: Patients will be excluded if they have any contraindication to transthoracic echocardiography or MUGA. Randomization: Eligible and consented patients will be randomized using a permuted block design to receive cardiac evaluation (by either transthoracic echocardiography or MUGA) every 3 months, or every 4 months while on treatment, 100 patients for each type of cardiac evaluation. Primary outcome measure: The rate of changes in LVEF diagnosed by ECHO or MUGA throughout trastuzumab-based therapy in both groups. Secondary outcome measures: Rates of trastuzumab delay/discontinuation, referral to cardiology, rate of cardiac events. Human specimen collection: Not involved. Ethical approval: This study was approved by the Ottawa Health Science Network Research Ethics Board. Trial registration: ClinicalTrials.gov identifier: NCT02696707 on February 18, 2016. Study status: This study is currently recruiting participants. Study enrolment is expected to be completed by July 2018 and analysis of primary outcome measure will be completed by October 2018 and the study will be completed by December 2018. Discussion: This study will present data on the cardiac safety of less frequent cardiac monitoring in patients with early-stage HER2-positive breast cancer. Future trials will explore cardiac monitoring strategies using composite data including baseline cardiac risk factors, baseline cardiac imaging and cardiac biomarkers. Health care economics will be explored.