HER2 testing in breast cancer: NCCN Task Force report and recommendations

The NCCN HER2 Testing in Breast Cancer Task Force was convened to critically evaluate the ability of the level of HER2 expression or gene amplification in breast cancer tumors to serve as a prognostic and a predictive factor in the metastatic and adjuvant settings, to assess the reliability of the methods of measuring HER2 expression or gene amplification in the laboratory, and to make recommendations regarding the interpretation of test results. The Task Force is a multidisciplinary panel of 24 experts in breast cancer representing the disciplines of medical oncology, pathology, radiation oncology, surgical oncology, epidemiology, and patient advocacy. Invited members included members of the NCCN Breast Cancer Panel and other needed experts selected solely by the NCCN. During a 2-day meeting, individual task force members provided didactic presentations critically evaluating important aspects of HER2 biology and epidemiology: HER2 as a prognostic and predictive factor; results from clinical trials in which trastuzumab was used as a targeted therapy against HER2 in the adjuvant and metastatic settings; the available testing methodologies for HER2, including sensitivity, specificity, and ability to provide prognostic and predictive information; and the principles on which HER2 testing should be based. Each task force member was charged with identifying evidence relevant to their specific expertise and presentation. Following the presentations, an evidence-based consensus approach was used to formulate recommendations relating to the pathologic and clinical application of the evidence to breast cancer patient evaluation and care. In areas of controversy, this process extended beyond the meeting to achieve consensus. The Task Force concluded that accurate assignment of the HER2 status of invasive breast cancer is essential to clinical decision making in the treatment of breast cancer in both adjuvant and metastatic settings. Formal validation and concordance testing should be performed and reported by laboratories performing HER2 testing for clinical purposes. If appropriate quality control/assurance procedures are in place, either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) methods may be used. A tumor with an IHC score of 0 or 1+, an average HER2 gene/chromosome 17 ratio of less than 1.8, or an average number of HER2 gene copies/cell of 4 or less as determined by FISH is considered to be HER2 negative. A tumor with an IHC score of 3+, an average HER2 gene/chromosome 17 ratio of greater than 2.2 by FISH, or an average number of HER2 gene copies/cell of 6 or greater is considered HER2 positive. A tumor with an IHC score of 2+ should be further tested using FISH, with HER2 status determined by the FISH result. Tumor samples with an average HER2 gene/chromosome ratio of 1.8 to 2.2 or average number of HER2 gene copies/cell in the range of greater than 4 to less than 6 are considered to be borderline, and strategies to assign the HER2 status of such samples are proposed.     

Metastatic breast cancer, version 1.2012: featured updates to the NCCN guidelines

These NCCN Guidelines Insights highlight the important updates/changes specific to the management of metastatic breast cancer in the 2012 version of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer. These changes/updates include the issue of retesting of biomarkers (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2) on recurrent disease, new information regarding first-line combination endocrine therapy for metastatic disease, a new section on monitoring of patients with metastatic disease, and new information on endocrine therapy combined with an mTOR inhibitor as a subsequent therapeutic option.     

NCCN Task Force Report: breast cancer in the older woman

Breast cancer is common in older women, and the segment of the U.S. population aged 65 years and older is growing rapidly. Consequently, awareness is increasing of the need to identify breast cancer treatment recommendations to assure optimal, individualized treatment of older women with breast cancer. However, the development of these recommendations is limited by the heterogeneous nature of this population with respect to functional status, social support, life expectancy, and the presence of comorbidities, and by the underrepresentation of older patients with breast cancer in randomized clinical trials. The NCCN Breast Cancer in the Older Woman Task Force was convened to provide a forum for framing relevant questions on topics that impact older women with early-stage, locally advanced, and metastatic breast cancer. The task force is a multidisciplinary panel of 18 experts in breast cancer representing medical oncology, radiation oncology, surgical oncology, geriatric oncology, geriatrics, plastic surgery, and patient advocacy. All task force members were from NCCN institutions and were identified and invited solely by NCCN. Members were charged with identifying evidence relevant to their specific expertise. During a 2-day meeting, individual members provided didactic presentations; these presentations were followed by extensive discussions during which areas of consensus and controversy were identified on topics such as defining the "older" breast cancer patient; geriatric assessment tools in the oncology setting; attitudes of older patients with breast cancer and their physicians; tumor biology in older versus younger women with breast cancer; implementation of specific interventions in older patients with breast cancer, such as curative surgery, surgical axillary staging, radiation therapy, reconstructive surgery, endocrine therapy, chemotherapy, HER2-directed therapy, and supportive therapies; and areas requiring future studies.     

Tamoxifen--an update on current data and where it can now be used

Over the past 30 years, data from a large number of clinical trials have confirmed the efficacy of tamoxifen in estrogen receptor (ER)-positive breast cancer, both as adjuvant therapy and for advanced disease. The 1995 Early Breast Cancer Trialists' Collaborative Group (EBCTCG) overview of randomized trials of adjuvant tamoxifen versus no tamoxifen showed that during approximately 10 years of follow-up, the proportional reductions in mortality for 1, 2 and approximately 5 years of adjuvant tamoxifen were 12, 17 and 26%, respectively. Tamoxifen is also effective for the prevention of breast cancer. In the National Surgical Adjuvant Breast and Bowel Project (NSABP) breast cancer prevention study (P-1), 5 years of tamoxifen therapy reduced the incidence of invasive and non-invasive breast cancers by 49 and 50%, respectively. In a randomized NSABP trial in women with ductal carcinoma in situ (DCIS), tamoxifen brought about a significant 47% reduction in ipsilateral invasive breast cancers and a 15% reduction in non-invasive breast cancers, compared with placebo. In trials performed by the Swedish Breast Cancer Co-operative Group and the NSABP, the optimal duration of adjuvant tamoxifen therapy appears to be 5 years, although this is equivocal and not yet conclusively defined.     

Dose modifications of ribociclib and endocrine therapy for treatment of ER+ HER2− metastatic breast cancer

Breast Cancer Research and Treatment - Treatment for estrogen receptor positive (ER+), human epidermal receptor 2 negative (HER2?) metastatic breast cancer (MBC) has improved with the...     

Tamoxifen – An Update on Current Data and Where it Can Now be Used

Over the past 30 years, data from a large number of clinical trials have confirmed the efficacy of tamoxifen in estrogen receptor (ER)-positive breast cancer, both as adjuvant therapy and for advanced disease. The 1995 Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) overview of randomized trials of adjuvant tamoxifen versus no tamoxifen showed that during approximately 10 years of follow-up, the proportional reductions in mortality for 1, 2 and ～5 years of adjuvant tamoxifen were 12, 17 and 26%, respectively. Tamoxifen is also effective for the prevention of breast cancer. In the National Surgical Adjuvant Breast and Bowel Project (NSABP) breast cancer prevention study (P-1), 5 years of tamoxifen therapy reduced the incidence of invasive and non-invasive breast cancers by 49 and 50%, respectively. In a randomized NSABP trial in women with ductal carcinoma in situ (DCIS), tamoxifen brought about a significant 47% reduction in ipsilateral invasive breast cancers and a 15% reduction in non-invasive breast cancers, compared with placebo. In trials performed by the Swedish Breast Cancer Co-operative Group and the NSABP, the optimal duration of adjuvant tamoxifen therapy appears to be 5 years, although this is equivocal and not yet conclusively defined.     

Outcomes of HER2-positive non-metastatic breast cancer patients treated with anti-HER2 therapy without chemotherapy

Breast Cancer Research and Treatment - Anti-HER2 therapy delivered in the adjuvant setting for breast cancer is given in conjunction with cytotoxic chemotherapy. For HER2-positive (HER2+) patients...     

Adjuvant systemic therapy for lymph node-negative breast cancer less than or equal to 1 cm

Routine screening mammography has increased the incidence of stage I breast cancers. Many more women are being diagnosed with lymph node-negative tumors that are less than or equal to 1 cm in greatest diameter. The National Surgical Adjuvant Breast and Bowel Project recently performed a retrospective analysis of 10,302 women participating in one of five clinical trials, including women with lymph node-negative breast cancer. Of these women, 1259 had tumors less than or equal to 1 cm. The analysis of the women with tumors less than or equal to 1 cm revealed an improved relapse-free survival (RFS) if tamoxifen was given after surgery, compared with surgery alone, for women with estrogen receptor (ER)-positive tumors; and for women with ER-negative tumors, RFS was improved by delivering chemotherapy after surgery. The authors suggested that adjuvant systemic therapy should be considered for anyone with an invasive breast cancer, regardless of the size of the tumor. This paper reviews the data presented in that important, historic article, and discusses their conclusions. Also reviewed are the most recent recommendations for treatment of primary breast cancer from the International Consensus Panel that convened at the Seventh International Conference on Adjuvant Therapy of Primary Breast Cancer in St. Gallen, Switzerland. That panel also addressed the issue of adjuvant systemic therapy in women considered to have a minimal or low risk of developing recurrent disease.     

A randomized clinical trial of adjuvant chemotherapy for radically resected locoregional relapse of breast cancer: IBCSG 27-02, BIG 1-02, and NSABP B-37

In this phase III, multinational, randomized trial, the International Breast Cancer Study Group, Breast International Group, and the National Surgical Adjuvant Breast and Bowel Project will attempt to define the effectiveness of cytotoxic therapy for patients with locoregional recurrence of breast cancer. We will evaluate whether chemotherapy prolongs disease-free survival and, secondarily, whether its use improves overall survival and systemic disease-free survival. Quality of life measurements will be monitored during the first 12 months of the study. Women who have had a previous diagnosis of invasive breast cancer treated by mastectomy or breast-conserving surgery and who have undergone complete surgical excision of all macroscopic disease but who subsequently develop isolated local and/or regional ipsilateral invasive recurrence are eligible. Patients are randomized to observation/no adjuvant chemotherapy or to adjuvant chemotherapy; all suitable patients receive radiation, hormonal, and trastuzumab therapy. Radiation therapy is recommended for patients who have not received previous adjuvant radiation therapy but is required for those with microscopically positive margins. The radiation field must encompass the tumor bed plus a surrounding margin to a dose of >or= 40 Gy. Radiation therapy will be administered before, during, or after chemotherapy. All women with estrogen receptor-positive and/or progesterone receptor-positive recurrence must receive hormonal therapy, with the agent and duration to be determined by the patient's investigator. Adjuvant trastuzumab therapy is permitted for those with HER2- positive tumors, provided that intent to treat is declared before randomization. Although multidrug regimens are preferred, the agents, doses, and use of supportive therapy are at the discretion of the investigator.     

Is Adjuvant Therapy for Older Patients with Node (+) Early Breast Cancercost-effective?*

Background: Node (+) breast cancer represents over 40% of cases in older women and currently there is a debate whether adjuvant therapy for all older women is cost-effective. Purpose: To evaluate if adjuvant treatment for early-stage (Stage I-IIIa) node (+) breast cancer with hormone therapy, chemotherapy, or combination therapy is cost-effective in older patients. Design: A decision-analysis model for 65, 75, and 85 year-old female breast cancer patients using life tables integrated the cost of treatment in dollars and impact in length and quality of life. Both estrogen receptor (ER) (-) and (+) patients were considered. The primary data sources were meta-analysis from the Early Breast Cancer Trialists’ Collaborative Group and the Red Book Average Wholesale Price for drugs. The cost of treatment in dollars and impact of quality of life was examined. Scenarios were used when treatment benefit was uncertain. The incremental cost-effectiveness of different treatment strategies were then compared and mapped graphically. Results: Adjuvant therapy is cost-effective in 65 year-old women with early breast cancer. In a 75 year-old ER (+) patient, hormone therapy is cost-effective, $10,965/quality-adjusted life years (QALY), but chemotherapy was more cost-effective, $27,406/QALY, if one assumed it was as efficacious as in a 65 year-old woman. In a 75 year-old ER (-) patient, chemotherapy was cost-effective at $42,605 with the same assumption. In an 85 year-old ER (+) patient, hormone therapy was cost-effective, $26,463/QALY, if efficacy is not age-sensitive, but chemotherapy was not as cost-effective for either ER (+) or ER (-) patients. Conclusion: Treatment decisions for older breast cancer patients suffer from the lack of sufficient clinical trial data. Decision-analytic models can help policy makers who are faced with decisions about whether to support adjuvant therapy in older breast cancer patients and also outline the important parameters that need to be considered in such a decision. *Adjuvant Therapy in Older Breast Cancer Patients Some of preliminary work and data in this paper were presented as part of a RAND Graduate School dissertation.     

Adjuvant therapy for Breast Cancer in Kyushu

BACKGROUND: There is lack of information on the present status of adjuvant therapy for breast cancer in Kyushu. Therefore, the Kyushu Breast Cancer Study Group (KBC-SG) started registering newly diagnosed breast cancer patients who were to receive adjuvant therapy. METHODS: During a period from 2001 to 2003, institutions participating in KBC-SG registered new patients who underwent curative surgical treatment for breast cancer to the registration office. One year later, the office sent them inquiries to gather any missing information. RESULTS: A total of 2284 patients were registered from 49 institutions. The mean age was 55, ranging from 30 to 93 years, and 46% had stage I disease. Estrogen and/or progesterone receptor was positive in 71% by immunoperoxidase staining, and HER2 was expressed in 297 (33%) of 906 patients. Twenty percent of the patients underwent adjuvant radiation therapy with or without antineoplastic agents. Overall, 98% received hormonal and/or cytotoxic agents. Anthracycline-containing regimens were given to 628 of 1285 (49%) patients with chemotherapy, while 360 (28%) received oral 5-fluorouracil derivatives with or without oral cyclophosphamide. CONCLUSIONS: Anthracycline combination chemotherapy was commonly used as adjuvant therapy, but there were over a quarter of patients only given oral 5-FU derivatives, which might not be recommended by worldwide consensus. Adjuvant radiation therapy was also given to only 20% of the patients in Kyushu, which might be fewer than the report by the Japanese Breast Cancer Society. Based on these data, the KBC-SG will continue cooperative studies to improve the quality of adjuvant treatment for early breast cancer.     

Real-world evidence from a University Hospital system regarding the uptake of adjuvant pertuzumab and/or neratinib before and after their FDA approval

Breast Cancer Research and Treatment - Adjuvant pertuzumab and neratinib are independently FDA-approved for treatment of early-stage HER2-positive breast cancer in combination with or following...     

Does preoperative MRI accurately stratify early-stage HER2 + breast cancer patients to upfront surgery vs neoadjuvant chemotherapy?

Breast Cancer Research and Treatment - HER2?+-?amplified breast cancer patients derive benefit from treatment with anti-HER2-targeted therapy. Though adjuvant treatment is based on...     

Use of adjuvant systemic therapy for early breast cancer among women 65 years of age and older.

BACKGROUND: The National Institutes of Health (NIH) consensus statement recommends adjuvant therapy for early breast cancer irrespective of age. However, the actual use of such therapy is not well documented among women over 65 years of age. METHODS: We studied the frequency of use of adjuvant therapy and report the receipt of this therapy among 200 women aged > or = 65 years diagnosed with early breast cancer who were identified from the New Jersey State Cancer Registry. RESULTS: In this population, 28% of patients received chemotherapy alone or in combination with hormonal therapy, whereas 42% received hormonal therapy alone. Less than half of the women with estrogen receptor-negative tumors received chemotherapy alone or in combination with hormonal treatment. Adjuvant therapy was not prescribed in 30% of patients. CONCLUSIONS: Despite NIH recommendations, the frequency of use of adjuvant therapy in New Jersey is low among women over 65 years of age, regardless of their receptor status.     

Advances in Therapeutic Approaches for Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC), defined as breast cancer lacking expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), accounts for up to 20% of all breast cancer, and it occurs at a higher frequency in younger, African American, and Hispanic women. Compared to breast cancers that are hormone receptor and/or HER2 positive, TNBC has an aggressive clinical course and worse prognosis. Because TNBC is by definition unresponsive to endocrine therapy (eg, tamoxifen, aromatase inhibitors) and HER2-directed therapies (eg, trastuzumab), chemotherapy continues to play an important role. TNBC constitutes a molecularly heterogeneous group of tumors that can vary in response to treatment, and clinical management can be challenging, particularly for the practicing community oncologist, for whom breast cancer may be only one of many tumor types encountered. In January 2020, the Breast Cancer Therapy Expert Group (BCTEG) convened a roundtable discussion on the topic of advances in the treatment of TNBC. Topics discussed included histopathologic classification/definition of TNBC, neoadjuvant strategies, adjuvant chemotherapy (with special emphasis on management of patients who do not experience a pathologic complete response), and treatment of metastatic disease. Also reviewed was the wide range of emerging pathways and therapies currently under investigation to expand TNBC treatment options, including immunotherapies and poly(ADP-ribose) polymerase (PARP) inhibitors. This article summarizes the BCTEG discussion and highlights the key opinions relating to the treatment of patients with TNBC.     

Adjuvant endocrine therapy in hormone receptor-positive postmenopausal breast cancer: evolution of NCCN, ASCO, and St Gallen recommendations

Endocrine therapy has a firm role in adjuvant treatment of women with hormone receptor-positive invasive breast cancer. Until recently, tamoxifen was the most commonly used adjuvant endocrine therapy in premenopausal and postmenopausal women. Several randomized clinical trials have studied the third-generation selective aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) as adjuvant endocrine therapy in postmenopausal women. These studies compared therapy with an AI alone versus tamoxifen alone; 2 to 3 years of tamoxifen followed by switching to an AI versus continuation of tamoxifen; or extended therapy with an AI after approximately 5 years of tamoxifen therapy. No statistically significant differences in overall survival were observed. A single trial using extended treatment with an adjuvant AI suggests a small, statistically significant survival advantage in women with axillary lymph node-positive disease while showing no statistically significant decrease in survival with the use of an AI. The toxicities of the AIs are generally acceptable, with fewer endometrial cancers, gynecologic complaints, and thromboembolic events, but more bone fractures and arthralgias compared with tamoxifen alone. Three widely disseminated treatment guidelines, the National Comprehensive Cancer Network Breast Cancer Clinical Practice Guidelines in Oncology, the American Society of Clinical Oncology Technology Assessment on the Use of Aromatase Inhibitors, and the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer, now incorporate AIs in the adjuvant therapy of postmenopausal women with estrogen receptor-positive breast cancer.     

Impact of the updated 2018 ASCO/CAP guidelines on HER2 FISH testing in invasive breast cancer: a retrospective study of HER2 fish results of 2233 cases

Breast Cancer Research and Treatment - Human epidermal growth factor receptor 2 (HER2, ERBB2) is a valuable prognostic and predictive biomarker in breast cancer. Accurate assessment of HER2 status...     

Value of epidermal growth factor receptor, HER2, p53, and steroid receptors in predicting the efficacy of tamoxifen in high-risk postmenopausal breast cancer patients.

PURPOSE: Few studies have examined the possible importance of biologic prognostic factors in breast cancer connected with differentiation and growth in predicting response to a specific adjuvant treatment. HER2, epidermal growth factor receptor (EGFR), and p53 have all been suggested as possible markers of tamoxifen resistance. The aim of this study was to investigate interactions between adjuvant treatment with tamoxifen and the content of EGFR, HER2, and p53 in steroid receptor-positive patients. PATIENTS AND METHODS: A total of 1,716 high-risk postmenopausal breast cancer patients were randomly assigned to treatment with tamoxifen (868 women) or to observation (848 women) in a prospective trial (Danish Breast Cancer Cooperative Group's 77c protocol). The content of the steroid receptors and expression of p53, EGFR, and HER2 were determined by immunohistochemical analysis of paraffin-embedded tissue. The length of follow-up was 10 years. The end point for this analysis was disease-free survival. RESULTS: Multivariate analysis demonstrated no increased risk of recurrence after treatment with tamoxifen for HER2-, EGFR-, and p53-positive, high-risk, steroid receptor-positive patients. Patients with steroid receptor-positive tumors and positive immunohistochemical staining for HER2, EGFR or p53 benefited from treatment with tamoxifen for 1 year, although the latter variable contained independent prognostic information by itself. CONCLUSION: With the statistical power of the present randomized study, we did not find support for the hypothesis that HER2/EGFR or p53 status predicts benefit from tamoxifen treatment in estrogen receptor-positive patients with early-stage breast cancer. Thus, neither HER2, EGFR, nor p53 overexpression/accumulation should be used as a contraindication for giving tamoxifen.     

Adjuvant therapy of primary breast cancer: a review of key findings from the 7th international conference, St. Gallen, February 2001

Breast cancer research has developed at a rapid pace over the last decades. Recent discoveries promise to provide individualized treatment options, increased long-term survival for women with breast cancer, and the possibility of moving toward curative intent in the treatment of advanced breast cancer. Age, race, tumor size, histological tumor type, axillary nodal status, standardized pathological grade, and hormone-receptor status are accepted as established prognostic and/or predictive factors for selection of systemic adjuvant treatment of breast cancer. The role of other promising new factors, such as p53 mutations, HER-2 status, plasminogen activator system, histological evidence of vascular invasion, and quantitative parameters of angiogenesis will be determined in ongoing prospective studies. Currently, 5 years' treatment with adjuvant tamoxifen in women with hormone-positive receptor status, is regarded as the optimal duration of treatment. Long-term follow-up on the randomized trials will determine the added benefit of treatment beyond 5 years. Ovarian ablation has shown a reduction in recurrence and death, and the exact role and extent of adjuvant chemotherapy in premenopausal women with hormone-responsive tumors is under discussion. Combination hormonal and chemo-hormonal therapies are also being evaluated. There are no convincing data on the survival impact of tamoxifen as a preventative therapy for breast cancer: longer-term follow-up is required, and the planned meta-analyses in 2005 should help shed light on this issue. Statistically significant benefits have been observed with adjuvant chemotherapy (particularly with anthracycline-containing regimens in premenopausal women) versus no adjuvant chemotherapy. The optimal length of adjuvant anthracycline/cyclophosphamide (AC) regimens needs further evaluation as do randomized comparisons of AC to cyclophosphamide/ doxorubicin/5-fluorouracil (5-FU) and cyclophosphamide/epirubicin/5-FU. Although taxanes promise to provide an additive benefit to adjuvant chemotherapy regimens, the Cancer and Leukemia Group B 9344 and the National Surgical Adjuvant Breast and Bowel Project B-28 studies evaluating paclitaxel in the adjuvant setting have not yet demonstrated statistically significant benefits on disease-free survival and overall survival. In the year 2000, all adjuvant therapy studies conducted by the Co-operative Groups in both node-negative and node-positive disease involve a taxane. High-dose chemotherapy evaluations are still ongoing. The numerous prospective adjuvant therapy trials (hormonal; selective estrogen-receptor modulators; aromatase inhibitors; chemotherapy, involving anthracyclines/taxanes/platinum/trastuzumab; biological factors; elderly women (>70 years); high-risk patients; radiotherapy in 1-3 positive lymph nodes), and neoadjuvant studies might further define the chances to enhance cure rates in the treatment of primary breast cancer.     

Efficacy and cardiac safety of adjuvant trastuzumab-based chemotherapy regimens for HER2-positive early breast cancer

BackgroundTrastuzumab-based adjuvant therapy has become the standard of care for human epidermal growth factor receptor-2 (HER2)-positive early breast cancer (EBC). Both anthracycline- and non-anthracycline-containing trastuzumab regimens are approved in the United States, but cardiotoxicity is increased with anthracycline-containing regimens.DesignThis paper reviews published and reported efficacy and cardiac safety data from the adjuvant trastuzumab trials [National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31/North Central Cancer Treatment Group (NCCTG) N9831, Breast Cancer International Research Group (BCIRG) 006, Herceptin Adjuvant (HERA), FinHer, and Programme Adjuvant Cancer Sein (PACS) 04].ResultsThe addition of trastuzumab to adjuvant chemotherapy significantly improved disease-free survival (from 24% to 58%) in five of the six trials. Overall survival was significantly improved (23%–35%) in the large trials. In NSABP B-31/ NCCTG N9831, 5.0%–6.6% of patients who received doxorubicin and cyclophosphamide (AC) were unable to receive trastuzumab. Cardiac event rate was highest in the anthracycline-containing trastuzumab arms (1.9%–3.8%) and lowest with the regimen of docetaxel, carboplatin, and trastuzumab (TCH) (0.4%).ConclusionsIncorporation of trastuzumab into anthracycline and non-anthracycline adjuvant chemotherapy regimens has substantially improved outcomes in HER2-postive EBC. The TCH regimen has the lowest rates of cardiac dysfunction, but uncertainty exists regarding the relative efficacy of TCH compared with anthracycline-containing trastuzumab regimens. Cardiac risk factor assessment can aid in selection of trastuzumab-based adjuvant therapy regimens.