scholarly journals Cardiotoxicity in patients on trastuzumab in HER2-positive breast cancer – A retrospective analysis from a center in North India

2020 ◽  
Vol 0 ◽  
pp. 1-5
Author(s):  
Anjali Aggarwal ◽  
Pratik Patil ◽  
Ranga Rao Rangaraju ◽  
Waseem Abbas ◽  
Sunny Garg
Keyword(s):  
Breast Cancer ◽  
Care Center ◽  
Tertiary Care ◽  
Left Ventricular ◽  
North India ◽  
Left Ventricular Ejection ◽  
Eligibility Criteria ◽  
Ventricular Ejection Fraction ◽  
Positive Breast Cancer

Objectives: Cardiotoxicity has been associated with trastuzumab for long and its relation with anthracyclines has also been well established. The study aims to assess the cardiotoxicity in patients on trastuzumab in human epidermal growth receptor 2-positive breast cancer. Material and Methods: This retrospective study consisting of a 3 years database of 112 patients with breast cancer from a tertiary care center in India. A total of 64 patients were scrutinized meeting the eligibility criteria. The primary eligibility criteria were availability of baseline, 3 monthly, end of treatment, and 3 months post-treatment left ventricular ejection fraction (LVEF) profile data. Results: 41/62 patients (66.1%) showed decrease in the LVEF profiles having mean reduction of 6%. Of these 41 patients, 34 (53.1%) patients exhibited a drop of 0–5%, 4 (6.2%) showed a drop of 6–10%, and 3 (4.6%) patients showed a drop of more than 10%. A significant drop (more than 10%) in the LVEF profile was observed in mean time of 6 months (8 cycles) which recovered to baseline value with the median follow-up of 3 months post-cessation of trastuzumab. Most of patients in the LVEF drop >10% group (70%) had received an anthracyclines based regimen. Conclusion: Our study demonstrated a mean drop of >10% in the LVEF profiles (4.6%) patients after mean follow-up of 6 months after starting therapy with trastuzumab and reverted back to baseline value after over a mean of 3 months post completing therapy with trastuzumab. This warrants regular and strict surveillance for the first 6 months and thereafter also after starting therapy with trastuzumab.

Long-Term Cardiac Follow-Up in Relapse-Free Patients After Six Courses of Fluorouracil, Epirubicin, and Cyclophosphamide, With Either 50 or 100 mg of Epirubicin, As Adjuvant Therapy for Node-Positive Breast Cancer: French Adjuvant Study Group

2004 ◽  
Vol 22 (15) ◽  
pp. 3070-3079 ◽  
Author(s):  
Jacques Bonneterre ◽  
Henri Roché ◽  
Pierre Kerbrat ◽  
Pierre Fumoleau ◽  
Marie-Josèphe Goudier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Study Group ◽  
Concomitant Disease ◽  
Ventricular Ejection Fraction ◽  
Node Positive ◽  
Positive Breast Cancer

Purpose To evaluate long-term cardiac function in patients without disease who had received six cycles of fluorouracil 500 mg/m2, epirubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 (FEC 50) or the same regimen with epirubicin 100 mg/m2 (FEC 100) as adjuvant chemotherapy for node-positive breast cancer in the French Adjuvant Study Group–05 trial. Patients and Methods One hundred fifty patients (FEC 50, n = 65; FEC 100, n = 85) who were without disease and who gave their informed consent were enrolled for long-term cardiac assessment. The assessment included cardiac events occurring after the end of chemotherapy, vital signs, concomitant disease, ECG, isotopic left ventricular ejection fraction (LVEF), and echographic parameters. Abnormal files were blindly reviewed by cardiologists and oncologists. Results The median follow-up time was 102 months. After FEC 100, LVEF was less than 50% in five patients (radioisotopic method), and two patients experienced congestive heart failure (CHF) that was possibly related to treatment. Asymptomatic left ventricular dysfunction (LVD) was experienced in 18 patients after FEC 100 and in one patient after FEC 50. In these patients, treatment causality was probable in eight patients. Two additional years after this assessment, all 18 patients were still asymptomatic. Conclusion After more than 8 years of follow-up, the cardiac toxicity observed after adjuvant treatment with FEC 100 comprised two cases of well-controlled CHF and 18 cases of asymptomatic LVD. In the majority of women with primary breast cancer, the benefits of treatment with FEC 100 in terms of disease-free and overall survival outweigh the risks, and cardiac risk factors should be carefully evaluated in patient selection.

scholarly journals CBR3 V244M is associated with LVEF reduction in breast cancer patients treated with doxorubicin

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jennifer K. Lang ◽  
Badri Karthikeyan ◽  
Adolfo Quiñones-Lombraña ◽  
Rachael Hageman Blair ◽  
Amy P. Early ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Care Center ◽  
Left Ventricular ◽  
The Body ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Echocardiographic Parameters ◽  
The Impact

Abstract Background The CBR3 V244M single nucleotide polymorphism has been linked to the risk of anthracycline-related cardiomyopathy in survivors of childhood cancer. There have been limited prospective studies examining the impact of CBR3 V244M on the risk for anthracycline-related cardiotoxicity in adult cohorts. Objectives This study evaluated the presence of associations between CBR3 V244M genotype status and changes in echocardiographic parameters in breast cancer patients undergoing doxorubicin treatment. Methods We recruited 155 patients with breast cancer receiving treatment with doxorubicin (DOX) at Roswell Park Comprehensive Care Center (Buffalo, NY) to a prospective single arm observational pharmacogenetic study. Patients were genotyped for the CBR3 V244M variant. 92 patients received an echocardiogram at baseline (t0 month) and at 6 months (t6 months) of follow up after DOX treatment. Apical two-chamber and four-chamber echocardiographic images were used to calculate volumes and left ventricular ejection fraction (LVEF) using Simpson’s biplane rule by investigators blinded to all patient data. Volumetric indices were evaluated by normalizing the cardiac volumes to the body surface area (BSA). Results Breast cancer patients with CBR3 GG and AG genotypes both experienced a statistically significant reduction in LVEF at 6 months following initiation of DOX treatment for breast cancer compared with their pre-DOX baseline study. Patients homozygous for the CBR3 V244M G allele (CBR3 V244) exhibited a further statistically significant decrease in LVEF at 6 months following DOX therapy in comparison with patients with heterozygous AG genotype. We found no differences in age, pre-existing cardiac diseases associated with myocardial injury, cumulative DOX dose, or concurrent use of cardioprotective medication between CBR3 genotype groups. Conclusions CBR3 V244M genotype status is associated with changes in echocardiographic parameters suggestive of early anthracycline-related cardiomyopathy in subjects undergoing chemotherapy for breast cancer.

P6237Clinical utility of echocardiographic left-ventricular ejection fraction monitoring for cardiotoxicity risk assessment in patients with HER2+ early breast cancer undergoing trastuzumab-based therapy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
F Posch ◽  
T Glantschnig ◽  
S Firla ◽  
M Smolle ◽  
M Balic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
One Year ◽  
Over Time

Abstract Background Monitoring left-ventricular ejection fraction (LVEF) is a routinely-practiced strategy to survey patients with breast cancer (BC) towards cardiotoxic treatment effects. However, whether the LVEF as a single measurement or as a trajectory over time is truly sufficient to identify patients at high risk for cardiotoxicity is currently debated. Purpose To quantify the prognostic impact of LVEF and its change over time for predicting cardiotoxicity in women with HER2+ early BC. Methods We analyzed 1,136 echocardiography reports from 185 HER2+ early BC patients treated with trastuzumab ± chemoimmunoendocrine therapy in the neoadjuvant/adjuvant setting (Table 1). Cardiotoxicity was defined as a 10% decline in LVEF below 50%. Results Median baseline LVEF was 64% (25th-75th percentile: 60–69). Nineteen patients (10%) experienced cardiotoxicity (asymptomatic n=12, symptomatic n=7, during treatment n=19, treatment modification/termination n=14), Median time to cardiotoxicity was 6.7 months, and median LVEF decline in patients with cardiotoxicity was 18%. One-year cardiotoxicity risk was 7.6% in the 35 patients with a baseline LVEF≥60% and 24.5% in the 150 patients with a baseline LVEF<60% (Hazard Ratio (HR)=3.45, 95% CI: 1.35–8.75, Figure 1). During treatment, LVEF declined significantly faster in patients who developed cardiotoxicity than in patients without cardiotoxicity (1.3%/month vs. 0.1%/month, p<0.0001). A higher rate of LVEF decrease predicted for higher cardiotoxicity risk (HR per 0.1%/month higher LVEF decrease/month=2.50, 95% CI: 1.31–4.76, p=0.005), and cardiotoxicity risk increased by a factor of 1.7 per 5% absolute LVEF decline from baseline to first follow-up (HR=1.70, 95% CI: 1.30–2.38, p<0.0001). Thirty-six patients (19%) developed an LVEF decline of at least 5% from baseline to first follow-up (“early LVEF decline”). One-year cardiotoxicity risk was 6.8% in those without early LVEF decline and a baseline LVEF≥60% (n=117), 15.7% in those without an early LVEF decline and a baseline LVEF<60% (n=65), and 66.7% in those with an early LVEF decline and a baseline LVEF<60% (n=3), respectively (log-rank p<0.0001). Table 1. Baseline characteristics Age (years, median [IQR]) 55 [49–65] Estrogen receptor positive (n, %) 124 (67%) Neoadjuvant setting (n, %) 103 (56%) Figure 1. Risk of Cardiotoxicity. Conclusion Both a single LVEF measurement and the rate of LVEF decrease strongly predict cardiotoxicity in early BC patients undergoing HER2-targeted therapy. Routine LVEF monitoring identifies individuals at high risk of cardiotoxicity that may benefit from more sensitive screening techniques such as strain imaging.

P3118CMR Fast-SENC intramyocardial LV & RV segmental strain detects cardiotoxicity during oncology treatment and impact of cardioprotection therapy before echocardiography

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Steen ◽  
M Montenbruck ◽  
P Wuelfing ◽  
S Esch ◽  
A K Schwarz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Lower Sensitivity ◽  
Pharmacological Agents ◽  
Ventricular Ejection Fraction ◽  
The Impact

Abstract Background The incidence of cardiotoxicity during cancer therapy is underestimated due to limitations of current diagnostic tests. Current biomarkers (BNP, NT-pro-BNP, hs-Troponin, etc.) and imaging calculations (e.g. echocardiography) such as left ventricular ejection fraction (LVEF) are currently included in the guidelines to designate cardiotoxicity during cancer therapy. Unfortunately, these diagnostics identify systemic damage in symptomatic patients after the heart is unable to compensate for regional dysfunction. Fast-SENC segmental intramyocardial strain (fSENC) is a unique cardiac magnetic resonance imaging (CMR) test that regionally detects subclinical intramyocardial dysfunction in 1 heartbeat. Methods This single center, prospective Prefect Study was used to evaluate cardiotoxicity and the impact of cardioprotective therapy in Breast Cancer and Lymphoma patients (NCT03543228). fSENC was acquired with a 1.5T MRI and processed with the software to quantify intramyocardial strain. Segmental strain was measured in three short axis scans (basal, midventricular, apical) with 16 LV/6 RV longitudinal segments & three long axis scans (2-, 3-, 4-chamber) with 21 LV/5 RV circumferential segments. fSENC CMR was performed before chemotherapy, during and after anthracycline/taxane therapy, at 1 year follow-up, and as needed in between designated follow-up periods. Cardioprotective therapy was offered to patients meeting the definition of cardiotoxicity by the ESC Guidelines on Cardiotoxicity and/or ESMO Clinical Practice Guidelines or those observing a substantial decline in cardiac function. Results Two hundred eight (208) CMRs were performed in fifty-two (52) patients (44 female). Patients had an average (± stdev) age of 53 (15) yrs, BMI of 26 (5) kg/m2; 77% had breast cancer, 23% had Lymphoma. fSENC CMRs required 11 (2) min total exam time. The % of normal fSENC (segmental stain <−17%) with a threshold of 65% showed a sensitivity of 87% and specificity of 89% in detecting cardiotoxicity while echocardiography GLS with a threshold of −17% observed a sensitivity of 20% and specificity of 88%. Figure 1 shows receiver operating characteristic curves for fSENC based on the percent of normal myocardium, and echocardiography global longitudinal strain (GLS) respectively. Global fSENC had substantially lower sensitivity than segmental fSENC despite having higher accuracy than the other global metrics. Figure 1 Conclusion Segmental fSENC intramyocardial strain detects subclinical dysfunction due to cardiotoxic response of chemotherapy before other biomarkers and imaging modalities. The ability to detect the subclinical cardiotoxicity of chemotherapy agents, or other pharmacological agents that cause or worsen heart failure, enables proactive prescription of cardioprotective medications to avoid tissue remodeling that precedes systemic cardiac dysfunction and worsening of global measures such as LVEF and current biomarkers.

Cardiac safety of pegylated liposomal doxorubicin (PLD) in combination with trastuzumab (T) in patients with metastatic breast cancer (MBC): Results from a multicenter phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1106-1106 ◽  
Author(s):  
E. Stickeler ◽  
D. O. Watermann ◽  
J. Woll ◽  
M. Foeldi ◽  
G. Gitsch
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cardiac Safety ◽  
Ventricular Ejection Fraction ◽  
Cardiac Side Effects

1106 Background: Combination therapy of doxorubicin and trastuzumab is highly effective for Her2 positive MBC but characterized by frequent cardiac toxicity (CT). PLD can significantly reduce CT compared to conventional doxorubicin. Patients and Methods: 15 patients were enrolled in a phase II trial to evaluate cardiac safety of T (4 mg/Kg loading dose day 2, followed by weekly 2 mg/Kg) in combination with PLD (40 mg/m2 IV bolus day 1, q 28 d). 75% of pts. presented with more than 1 metastatic site and 40% for second line treatment. PLD was administered for 6 or 9 cycles, respectively, T until disease progression. To assess CT, all pts were evaluated with electrocardiogram (ECG) and echocardiograms (E) for Left Ventricular Ejection Fraction (LVEF) at baseline, every cycle during PLD and T, and every three months during T therapy alone. CT was defined as appearance of signs/ symptoms of congestive heart failure and/or an absolute decrease in LVEF > 10 units (below 50%) or decrease in LVEF > 15 units (above 50%). Results: Four pts. received 6 cycles, 4 pts. received 9 cycles of PLD, 4 pts discontinued treatment due to PD, 3 pts. due to toxicity. After a median follow up time of 15.4 months, 6 pts. (42.9%) demonstrated a clinical benefit and median OS was 16.2 months. Non cardiac side effects were mild with only 3 CTC Grade 3 events of 247 treatment cycles (1.2%). Three pts. developed minor ECG changes without pathological significance and 5 pts. had minor changes in their E with slight diastolic (n=3) or systolic (n=2) dysfunction. During follow-up, 3 pts. were diagnosed with pathological E findings, including 1 slight decrease of LVEF, one diffuse hypokinesia and one strong decrease in LVEF.The median LVEF in the study cohort was 66.1% at baseline, 62.7% after 6 cycles of therapy, 64.4% at the first follow up and did not change significantly until the 5 th examination. Conclusions: This study supports the combination of PLD and H in pts. with HER2 overexpressing metastatic breast cancer as a safe and feasible therapy. Due to the promising clinical response rates in this prognostically unfavorable group, this combination should be evaluated in larger studies as a potential regimen for adjuvant treatment of breast cancer. No significant financial relationships to disclose.

A correlative study of cardiac biomarkers and left ventricular ejection fraction (LVEF) from N9831, a phase III randomized trial of chemotherapy and trastuzumab as adjuvant therapy for HER2-positive breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 579-579 ◽  
Author(s):  
L. A. Kutteh ◽  
T. Hobday ◽  
A. Jaffe ◽  
B. LaPlant ◽  
D. Hillman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Troponin T ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Tnf Alpha ◽  
Ventricular Ejection Fraction ◽  
Pre Treatment ◽  
Positive Breast Cancer

579 Background: N9831 and other clinical trials have demonstrated the additive survival benefit of trastuzumab (H) therapy with chemotherapy for patients with resected HER-2 positive breast cancer. Cardiac toxicity (CTox) is increased by this strategy. Prediction of or early detection of CTox is important. Methods: 95 patients provided informed consent. Brain natriuretic peptide (BNP), C-reactive protein (CRP), troponin T (TnT) and I (TnI), TNF-alpha, IL-1b, and IL-6 were to be drawn at baseline, after initiation of doxorubicin/cyclophosphamide (AC), after initiation of paclitaxel (T), and after the initiation of H (may have been given concurrently with T). 67 patients with at least a baseline sample, a post-treatment sample, and a baseline and subsequent evaluation of LVEF were studied. No patient in this group had a grade 3 decline in LVEF. Only 3 of these patients did not receive H. Values above the 99th percentile were considered abnormal for troponin. 40 ng/ml was considered elevated for BNP. Results: Values of CRP, TNF-alpha, IL- 6 and IL1b changed in very few patients and without a discernible pattern. For further evaluation of BNP, TnI, and TnT, 2 definitions of CTox were tested: 1. a >10% drop in LVEF from baseline (n=27) and 2. a drop in LVEF of 10–15% to less than the institutional lower limit of normal (LLN) OR a >15% decline in LVEF (n=14). No pre-treatment marker appeared to predict a > 10% decline in LVEF (definition 1). For patients fulfilling definition 2, pre-treatment BNP > 40 was seen in 21% of patients vs 8% of normals (nls) (p= 0.18) and an abnormal TnI (>0.04) was seen in 21% vs 6% of nls (p=0.10). Only doubling of BNP appeared promising as a serial marker of CTox using definition 2 (27% vs 7% for nls (p = 0.09). Conclusions: Baseline BNP and TnI and serial measures of BNP may be promising for further investigation for the prediction and detection of treatment-related CTox. Due to limitations of the study including the small numbers of patients analyzed, the difficulty in defining CTox, and the variation in the timing of sample procurement and assessment, these data are considered exploratory. Supported by CA-25224, CA-2115, CA 38926, CA31946. No significant financial relationships to disclose.

Anthracycline-based preoperative chemotherapy plus lapatinib and trastuzumab or both in HER2-positive breast cancer: Preliminary cardiac safety report of the CHER LOB trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 573-573
Author(s):  
V. Guarneri ◽  
A. Frassoldati ◽  
A. Bottini ◽  
K. Cagossi ◽  
L. Cavanna ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Preoperative Chemotherapy ◽  
Treatment Plan ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Cardiac Safety ◽  
Ventricular Ejection Fraction ◽  
Her 2 ◽  
Positive Breast Cancer

573 Background: The combination of anthracyclines and anti-HER-2 agents is highly active in HER-2 positive breast cancer, but its use is limited by an enhanced risk of cardiac toxicity. We are running a randomized phase II trial of combined preoperative chemotherapy (CT) with anthracycline plus trastuzumab, lapatinib, or both in HER-2 positive stage II-IIIA breast cancer patients. Aims of the study are the percentage of pathological complete response (pCR = breast + axillary nodes) and cardiac safety. We report the updated cardiac safety and activity data following the IDMC recommendation to continue study accrual. Methods: CT consists of sequential paclitaxel (P) 80 mg/m2 weekly for 12 weeks followed by 4 courses of FE75C administered every 3 weeks. Arm A is CT + trastuzumab 2 mg/kg weekly; arm B is CT + lapatinib 1500 mg po daily; arm C is CT + trastuzumab 2 mg/kg weekly + lapatinib 1,000 mg po daily. Both trastuzumab and lapatinib are started concomitantly with the first P administration, and are administered throughout the duration of CT. Left ventricular ejection fraction (LVEF) is evaluated at baseline, before the start of FE75C, and at the completion of treatment. The planned sample size is 120 patients, and has been calculated according to the two steps Simon's design. Results: 53 out of the 120 planned patients have been randomized: 16 in arm A, 17 in arm B, and 20 in arm C. Median age is 48 years (range 27–66). The mean LVEF was 63% (range 54–77%) at baseline, 61% (50–78%) at the completion of weekly P + trastuzumab, lapatinib, or trastuzumab + lapatinib, and 60.3% (54–74%) at the completion of the whole treatment plan. Thirty patients underwent surgery: 19 patients (63%) received breast conserving surgery; 13 patients (43%) achieved a pCR. Conclusions Following the updated interim analysis, the combination of T, L or both with an anthracycline-containing regimen is feasible, with very interesting level of activity. The next planned analysis will be performed when 60 patients will be evaluable and will be presented at the Meeting. [Table: see text]

Trastuzumab-Related Cardiotoxicity: Calling Into Question the Concept of Reversibility

2007 ◽  
Vol 25 (23) ◽  
pp. 3525-3533 ◽  
Author(s):  
Melinda L. Telli ◽  
Sharon A. Hunt ◽  
Robert W. Carlson ◽  
Alice E. Guardino
Keyword(s):  
Breast Cancer ◽  
Left Ventricular ◽  
Stopping Rules ◽  
Left Ventricular Ejection ◽  
Adjuvant Trastuzumab ◽  
Ventricular Ejection Fraction ◽  
International Research Group ◽  
Number Of Patients ◽  
B 31

Purpose To assess the spectrum and reversibility of the cardiotoxicity observed in the adjuvant trastuzumab trials. Design The design and efficacy of the major adjuvant trastuzumab trials was assessed, including the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31, North Central Cancer Treatment Group N9831, Herceptin Adjuvant, Breast Cancer International Research Group 006, and Finland Herceptin trials. The cardiotoxicity data were evaluated with a focus on the follow-up cardiac evaluations of women who were diagnosed with cardiotoxicity. Proposed mechanisms of trastuzumab-related cardiotoxicity were considered. The natural history of congestive heart failure (CHF) was reviewed with the goal of placing the trastuzumab experience in context. Results Up to 4% of patients enrolled onto the adjuvant trastuzumab trials experienced severe CHF during treatment. In these trials, early stopping rules that identified an unacceptable level of cardiotoxicity were never reached. Despite this, a large number of patients on these trials experienced some form of cardiotoxicity that ultimately required discontinuation of trastuzumab. Approximately 14% of patients in the NSABP B-31 trial discontinued trastuzumab because of asymptomatic decreases in left ventricular ejection fraction (LVEF). Results of follow-up cardiac evaluations of patients diagnosed with any degree of cardiotoxicity in the NSABP B-31 trial document that a clinically significant proportion of patients have sustained decrements in their LVEF to less than 50%. Conclusion Adjuvant trastuzumab provides substantial benefits to patients with human epidermal growth factor receptor 2–positive breast cancer, however, competing immediate and long-term cardiovascular risks are a great concern. Continued cardiac follow-up of these women is of critical importance.

Fluorouracil, Epirubicin, and Cyclophosphamide With Either Docetaxel or Vinorelbine, With or Without Trastuzumab, As Adjuvant Treatments of Breast Cancer: Final Results of the FinHer Trial

2009 ◽  
Vol 27 (34) ◽  
pp. 5685-5692 ◽  
Author(s):  
Heikki Joensuu ◽  
Petri Bono ◽  
Vesa Kataja ◽  
Tuomo Alanko ◽  
Riitta Kokko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Treatment ◽  
Disease Free Survival ◽  
Left Ventricular ◽  
Axillary Node ◽  
Left Ventricular Ejection ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Ventricular Ejection Fraction

Purpose Docetaxel has not been compared with vinorelbine as adjuvant treatment of early breast cancer. Efficacy and long-term safety of a short course of adjuvant trastuzumab administered concomitantly with chemotherapy for human epidermal growth factor receptor 2 (HER2) –positive cancer are unknown. Patients and Methods One thousand ten women with axillary node–positive or high-risk node-negative breast cancer were randomly assigned to receive three cycles of docetaxel or vinorelbine, followed in both groups by three cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC). Women with HER2-positive cancer (n = 232) were further assigned to either receive or not receive trastuzumab for 9 weeks with docetaxel or vinorelbine. The median follow-up time was 62 months after random assignment. Results Women assigned to docetaxel had better distant disease–free survival (DDFS) than those assigned to vinorelbine (hazard ratio [HR] = 0.66; 95% CI, 0.49 to 0.91; P = .010). In the subgroup of HER2-positive disease, patients treated with trastuzumab tended to have better DDFS than those treated with chemotherapy only (HR = 0.65; 95% CI, 0.38 to 1.12; P = .12; with adjustment for presence of axillary nodal metastases, HR = 0.57; P = .047). In exploratory analyses, docetaxel, trastuzumab, and FEC improved DDFS compared with docetaxel plus FEC (HR = 0.32; P = .029) and vinorelbine, trastuzumab, and FEC (HR = 0.31; P = .020). The median left ventricular ejection fraction of trastuzumab-treated patients remained unaltered during the 5-year follow-up; only one woman treated with trastuzumab was diagnosed with a heart failure. Conclusion Adjuvant treatment with docetaxel improves DDFS compared with vinorelbine. A brief course of trastuzumab administered concomitantly with docetaxel is safe and effective and warrants further evaluation.

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