Search

Background. Trastuzumab and pertuzumab are approved for the neoadjuvant treatment of human epidermal growth receptor 2 (HER2)-positive breast cancer, but cardiac safety data is limited. We report the cardiac safety of dose-dense doxorubicin and cyclophosphamide (AC) followed by paclitaxel, trastuzumab, and pertuzumab (THP) in the neoadjuvant setting followed by adjuvant trastuzumab-based therapy. i T3 e b Methods. Fifty-seven patients treated with neoadjuvant dose-dense AC-THP followed by adjuvant trastuzumab-based therapy between September 1, 2013, and March 1, 2015, were identified. The primary outcome was cardiac event rate, defined by heart failure (New York Heart Association [NYHA] class III/IV) or cardiac death. Patients underwent left ventricular ejection fraction (LVEF) monitoring at baseline, after AC, and serially during 1 year of anti-HER2 therapy. Results .The median age was 46 years (range 26-68).Two (3.5%) patients developed NYHA class III/IV heart failure 5 and 9 months after initiation of trastuzumab-based therapy, leading to permanent discontinuation of anti-HER2 treatment. Seven (12.3%) patients developed a significant LVEF decline (without NYHA class III/IV symptoms). The median LVEF was 65% (range 55%-75%) at baseline and 64% (range 53%-72%) after AC, and decreased to 60% (range 35%-70%), 60% (range 23%-73%), 61% (range 25%-73%), and 58% (range 28%-66%) after 3, 6, 9, and 12 months (± 6 weeks) of trastuzumab-based therapy. Conclusion. The incidence of NYHA class III/IV heart failure after neoadjuvant AC-THP (followed by adjuvant trastuzumab-based therapy) is comparable to rates reported in trials of sequential doxorubicin and trastuzumab. Our findings do not suggest an increased risk of cardiotoxicity from trastuzumab plus pertuzumab following a doxorubicin-based regimen. [ABSTRACT FROM AUTHOR]

Introduction. Myocardial strain imaging and blood biomarkers have been proposed as adjuncts to left ventricular ejection fraction (LVEF) monitoring for the early detection of cardiotoxicity during cancertherapy.We report the results of a preplanned cardiac safety analysis of global longitudinal strain (GLS), and troponin-I (TnI) and brain natriuretic peptide (BNP) levels in the phase II study of paclitaxel, trastuzumab, and pertuzumab (THP) for metastatic HER2-positive breast cancer. Patients and Methods. Patients with 0-1 lines of prior therapy were treated with weekly paclitaxel (80 mg/m²) plus trastuzumab (8 mg/kg loading dose followed by 6 mg/kg) and pertuzumab (840 mg loading dose followed by 420 mg) every 3 weeks. Exploratory endpoints were GLS measured with speckle-tracking echocardiography every 3 months and TnI and BNP levels measured every 6 weeks (immediately pre- and postchemotherapy infusion) at 6 time points. Results. Sixty-seven of 69 enrolled patients were treated with THP: 19 (28%) had hypertension, 8 (12%) had diabetes, 11 (16%) had hyperlipidemia, and 26 (38%) had smoking history. After a median follow-up of 21 months (range: 3-38 months), no patients developed symptomatic heart failure. Two patients (3.0%) experienced asymptomatic LVEF decline (grade 2). The mean GLS (6SD) was 19% ± 2% (baseline), 19% ± 2% (month 6), and 19% ± 3% (month 12). Detectable TnI (>0.06 ng/mL) and elevated BNP (>100 pg/mL) levels were observed in 3 (4.3%) and 2 (3.0%) patients, respectively, but were not associated with LVEF decline. Conclusion. The absence of any significant changes in GLS and cardiac biomarkers (TnI and BNP) further support the cardiac safety of THP in patients with metastatic HER2-positive breast cancer. [ABSTRACT FROM AUTHOR]

The author reflects on adjuvant hormonal therapy for treating premenopausal women with breast cancer. Topics include the prevalence of breast cancer cases in the U.S. in 2014 according to the American Cancer Society, the challenge of treating this type of cancer with tamoxifen and the role of aromatase inhibitors. Also discussed is chemotherapy induced amenorrhea.

Background. Adjuvant trastuzumab is a highly effective targeted treatment that improves survival for patients with HER2-positive breast cancer. However, trastuzumab interruption is recommended for patients who develop treatment-induced cardiotoxicity (i.e., decline in left ventricular ejection fraction [LVEF], with or without symptoms) and can lead to an incomplete course of treatment. We studied the cardiac safety of continuous trastuzumab therapy among patients with asymptomatic declines in LVEF. Methods. We retrospectively evaluated patients with HER2-positive breast cancer treated with adjuvant trastuzumab at our institution between 2005 and 2010. Treatment-induced cardiotoxicity was defined by an absolute decrease in LVEF of ≥10% to below 55% or an absolute decrease of ≥16%. Logistic regression was used to determine the association between candidate risk factors and treatment-induced cardiotoxicity. Results. Among 573 patients, 92 (16%) developed treatment-induced cardiotoxicity. Trastuzumab was continued without interruption in 31 of 92 patients with treatment-induced cardiotoxicity--all were asymptomatic with LVEF of ≥50% at cardiotoxicity diagnosis with median LVEF of 53% (range, 50%-63%), and none developed heart failure during follow-up. Risk factors associated with treatment-induced cardiotoxicity included age (p = .011), anthracycline chemotherapy (p 5 .002), and lower pretrastuzumab LVEF (p < .001). Conclusion. Among patients who develop asymptomatic treatment-induced cardiotoxicity with LVEF of ≥50%, continuous trastuzumab therapy appears to be safe. [ABSTRACT FROM AUTHOR]