Annals of Oncology Advance Access originally published online on March 15, 2008
Annals of Oncology 2008 19(6):1110-1116; doi:10.1093/annonc/mdn029
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
breast cancer |
Concurrent trastuzumab with adjuvant radiotherapy in HER2-positive breast cancer patients: acute toxicity analyses from the French multicentric study
1 Department of Radiation Oncology, CLCC Oscar Lambret Anti-Cancer Center
2 University of Lille II, Lille
3 Department of Medical Oncology APHP Tenon, Cancer Est, Paris, France
4 Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois
5 University of Lausanne, Lausanne, Switzerland
6 Department of Radiation Oncology, Institut Gustave Roussy, Villejuif, France
7 Florence University, Florence, Italy
8 Department of Radiation Oncology, Institut Claudius Regaud, Toulouse
9 Department of Radiation Oncology, Institut Bergonié, Bordeaux
10 Clairval Clinic, Marseille
11 Hartmann Clinic, Neuilly sur Seine
12 Courlancy Polyclinic, Reims
13 Department of Medical Oncology, Centre Azuréen de Cancérologie, Mougins
14 Department of Radiation Oncology, Institut National de la Santé et de la Recherche Médicale, Montpellier, France
* Correspondence to: Dr Y. Belkacémi, Department of Radiation Oncology, CLCC Oscar Lambret Anti-Cancer Center, 3 rue Frédéric Combemale, Lille 59020, France. Tel: +33-3-20-29-59-59; Fax: +33-3-20-29-59-72; E-mail: y-belkacemi{at}o-lambret.fr
 |
Abstract |
|---|
 Top Abstract introductionpatients and methodsresultsdiscussionconclusionfundingAcknowledgementsReferences |
|---|
Background: Trastuzumab (T) combined with chemotherapy has been recently shown to improve outcome in HER2-positive breast cancer (BC). The aim of this study was to evaluate the toxic effects of concurrent radiation therapy (RT) and T administration in the adjuvant setting.
Patients and methods: Data of 146 patients with stages II–III HER2-positive BC were recorded. Median age was 46 years. In all, 32 (23%) and 114 (77%) patients received a weekly and a 3-week T schedule, respectively. A median dose of 50 Gy was delivered after surgery. Internal mammary chain (IMC) was irradiated in 103 (71%) patients.
Results: Grade >2 dermatitis and esophagitis were noted in 51% and 12%, respectively. According to the Common Toxicity Criteria v3.0 scale and HERA (HERceptin Adjuvant) trial criteria, respectively, 10% and 6% of the patients had a grade 
2 of left ventricular ejection fraction (LVEF) decrease after RT. Multivariate analyses revealed two independent prognostic factors: weekly T administration (for LVEF decrease) and menopausal status (for dermatitis). Higher level of T cumulative dose (>1600 mg) was only borderline of statistical significance for acute esophagitis toxicity.
Conclusion: We showed that weekly concurrent T and RT are feasible in daily clinical practice with, however, a decrease of LVEF. Cardiac volume sparing and patient selections for IMC irradiation are highly recommended. Longer follow-up is warranted to evaluate late toxic effects.
Key words: acute toxicity, breast cancer, LVEF, radiation therapy, targeted therapies, trastuzumab
|
introduction |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionconclusionfundingAcknowledgementsReferences |
|---|
The rate of breast cancers (BCs) overexpressing HER2 is
20% [1]. Before the targeted treatment era, HER2 BC was associated with an increasing risk of disease progression and poorer prognosis [2]. Trastuzumab (T) is a humanized recombinant mAb that binds with high affinity to the extracellular domain of the HER2 receptor [2]. Its impact on disease-free survival (DFS) and overall survival has been shown recently when given as adjuvant therapy for HER2-positive early BC [3–7]. Nevertheless, the best sequence for adjuvant T administration regarding timing of chemotherapy (CT) and radiation therapy (RT) is still unclear. In the metastatic setting, randomized trials have indicated a synergistic effect of T and taxane combination leading to better survival compared with CT alone [8, 9]. The principal adverse event associated with T therapy among patients with prior or concurrent exposure to anthracycline was cardiac dysfunction [10].
In an experimental model of MCF-7 cell lines overexpressing HER2 and in xenograft tumors, Pietras et al. [11] reported a significant radiosensibilization of combined T and radiation exposure compared with T or radiation alone.
The risk of toxicity of combined T and RT on normal tissues has not yet been evaluated in detail. Thus, we investigated the risk of cardiac, skin, and esophagus toxic effects following concurrent administration of adjuvant T and locoregional radiotherapy in patients with HER2-positive BC.
|
patients and methods |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionconclusionfundingAcknowledgementsReferences |
|---|
This study was designed in July 2005. As there was no particular recommendation at that time for T-timing administration in France, sequential or concomitant T–radiotherapy was delivered according to each center’s policy. Nine centers evaluated their patients according to a Common Toxicity Criteria (CTC) list. Each local institutional review board approved the registration.
patients
All registered patients had completely excised ductal or lobular carcinoma of the breast with HER2 overexpression or proven HER2 amplification. All patients received T and adjuvant RT.
At the time of this analysis, all patients have completed their treatment since at least 3 months. Median age was 46 years (range: 23–82 years). Ninety patients of 146 (62%) were nonmenopausal, and half of the patients were treated for left BC. The majority of the patients (98%) had grade II or III tumors, and half of them had nodal involvement (54%), or were hormone receptor positive (HR+) (53%). Patients’ characteristics are detailed in Table 1.
|
treatment modalities
T was started before and after surgery in 71 (49%) and 75 patients (51%), respectively. In all, 78 (53%) and 68 (47%) patients had total mastectomy and conservative surgery, respectively. In all cases, T was planned for 1 year, radiotherapy was delivered concurrently with T. CT consisted of a sequential combination of anthracyclines and taxanes.
In all, 32 (23%) and 114 (77%) of the 146 patients received a weekly and a 3-weekly T schedule, respectively. The median dose of T before RT was 1600 mg (range: 0–4312 mg). Endocrine therapy was administered in 74 HR+ patients. It consisted of tamoxifen [with or without luteinizing hormone-releasing hormone (LH-RH) agonists] and aromatase inhibitors in 34 (46%) and 40 (54%) patients, respectively.
The median dose delivered to the whole breast or the chest wall was 50 Gy (range: 40–50 Gy) in 25 fractions. A 10- to 16-Gy boost in five to eight fractions was delivered to the tumor bed in 68 patients using mainly electron beams (61 of 68, 90%).
Internal mammary chain (IMC) nodes were irradiated in 103 of 146 patients (71%). The median dose was 50 Gy (range: 15–50.4 Gy) in 25 (range: 7–28) fractions delivered mainly by a mixed photon–electron technique (93 of 103, 90%). Supraclavicular nodes were irradiated in 122 of 146 patients (84%). The median dose was 46 Gy (range: 30–50 Gy) in 23 (range: 10–25) fractions delivered following mixed photon–electron beams, electrons alone, or using teletherapy unit in 77 (63%), 35 (29%), and 1 (8%) patients, respectively. Treatment modalities are detailed in Table 2.
|
statistical analyses
Toxicity assessment of the skin and esophagus was implemented according to the CTC v3.0 scale [12]. Cardiac toxicity was assessed according to the left ventricular ejection fraction (LVEF) decrease before and after RT completion. Acute toxicity (grade
2) was defined using both CTC v3.0 scale [12] and the HERA trial criteria [6] (decrease in the ejection fraction of 10 points from baseline to LVEF of <50% at any time).
Actuarial rates of toxic effects were calculated using the product-limit method [13]. The event was grade 2 toxicity at different observation times from the date of RT completion. Differences between groups were assessed using the log-rank test [14]. Multivariate analyses were implemented using the logistic regression analysis [15]. A stepwise backward procedure was used to construct a set of independent predictors of each end point. All predictors achieving a P value <0.10 were considered and sequentially removed if the P value in the multiple models was >0.05. All tests were two-sided. No P value corrections were made for multiple testing.
|
results |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionconclusionfundingAcknowledgementsReferences |
|---|
acute toxic effects and outcome
Acute toxic effects are detailed in Table 3. Among 135 patients who had clinical evaluation during and after the RT period, 66 (51%) developed grade
2 dermatitis. Grade 2 esophagitis was observed in 16 of 136 patients (12%). RT was suspended in three patients for 5–10 days but all of them completed the initial planned treatment.
|
LVEF decreased after RT ranged between 0 and 24 points (median: 6). According to the CTC v3.0 scale and HERA trial criteria, 9 of 92 patients (10%) and 6 of 111 patients (6%), respectively, had a grade
2 of LVEF decrease. After a median follow-up of 16 months (range: 4–30 months), all patients were alive. Five of 146 (3%) developed distant metastases [brain (n = 2) and liver (n = 3)]. None of the patients had local or locoregional recurrence or contralateral BC.
univariate and multivariate analyses
Univariate analyses are shown in Tables 4 and 5. In terms of skin acute toxicity, 38% of the nonmenopausal patients developed grade 2 dermatitis versus 65% of the menopausal patients (P = 0.002). There was a trend for statistical significance between patients younger than 46 years compared with those 46 years or older (56% versus 40%; P = 0.063). In patients who received a cumulative dose of T 1600 mg and concurrent RT including IMC, grade 2 esophagitis was higher (17%) than those who received <1600 mg of T (6%) with border statistical difference (P = 0.05). A higher rate was also observed after total mastectomy compared with conservative surgery; however, the limit of statistical significance was not reached (P = 0.08). In terms of LVEF decrease after RT, either using CTC v3.0 scale or HERA criteria, we found a significant impact of menopausal status (P = 0.0006 and 0.001, respectively), age (P = 0.004 and 0.001, respectively), and weekly T schedule (P = 0.0018 and 0.005, respectively).
|
|
Multivariate analysis revealed three unfavorable prognostic factors: weekly T administration (for the risk of LVEF decrease; P = 0.004 and 0.04, according to HERA and CTC v3.0 criteria, respectively), menopausal status (for grade >2 dermatitis; P = 0.002). The limit of statistical significance was only borderline (P = 0.05) for the impact of higher T cumulative dose on esophagitis.
|
discussion |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionconclusionfundingAcknowledgementsReferences |
|---|
This study was undertaken to examine whether there was an association between the use of T concurrently with RT for HER2-overexpressing BC patients in the adjuvant setting.
In the North American [3] and HERA [4, 5] phase III trials, using 1-year T schedule, the absolute DFS benefit was 12% at 3 years and 18% at 4 years, respectively. The HERA trial has recently reported a benefit of 2.7% in overall survival in patients treated by T in adjuvant setting [5]. In FinHer trial [6] with only a 9-week administration of T, the DFS benefit was 42% at 38 months. This increase of survival was associated with acceptable toxicity in particular cardiac toxicity, which was mostly reversible. Conversely, the best sequence regarding timing of RT could not be determined from these trials. Thus, it remains unclear whether concurrent administration of T and RT could alter normal cardiac, skin, and oesophageal tissues. Even if these acute reactions could be reversible, their impact on late sequelae is still not predictable.
Pietras et al. [11] have indicated a synergistic effect of T and ionizing radiation in experimental models. They showed in an in vitro model of MCF-7 HER2-positive cells a significant inhibition of DNA repair after concomitant X-ray and T exposure compared with T or irradiation alone. Their results were confirmed in vivo in xenografts using MCF-7 HER2-positive cells.
In humans, the synergistic antitumor effect of T in combination with RT has been investigated recently in HER2-positive high-risk (n = 15) and chemoresistant (n = 7) BC [16]. The schedule consisted of hypofractionated and accelerated irradiation combined to 4 mg/kg every 2 weeks of T. CT consisted of doxorubicin (25 mg/m2 every 2 weeks) or docetaxel (40 mg/m2 every 2 weeks). With the addition of a cytoprotectant (Amifostine, Ethyol®; Schering Plough Laboratories), this schedule was well tolerated. After 3–26 months of follow-up there was no recurrence. A complete response was observed in 5 of 7 patients with locally advanced or chemoresistant disease.
The concern of our study was the potential synergistic effect of concurrent T–RT on normal tissues involved in the radiation field.
The overall incidence of grade 2 or more acute skin reactions was 51%. The follow-up in our study remains short and render impossible to predict the outcome of skin reactions and particularly the probability of late breast fibrosis. In the Dana Farber experience [17], using a weekly concurrent T (2 mg/m2; n = 21) or a 3-weekly schedule (6 mg/m2; n = 5), the grades 2 and 3 skin toxicity rates were 48% and 8%, respectively. The median follow-up period of 26 months is still short to allow relevant evaluation of late skin sequelea. In this series two patients (8%) developed interstitial pneumonitis. In our experience, among the patients who received supraclavicular RT (84%), none developed lung toxicity clinically after a 16-month median follow-up period. In addition, it is important to point out that none of these preliminary reports have taken into account age and the breast volume variation for skin toxicity evaluation.
Halyard et al. [18] reported a retrospective comparison of irradiated (n = 908) versus nonirradiated patients (n = 308) from the North Central Cancer Treatment Group phase III trial. After an 18-month median follow-up, concurrent T and RT administration did not increase skin toxicity (P = 0.78), interstitial pneumonitis (P = 0.78), dyspnea (P = 0.87), or esophagitis (P = 0.26). The results regarding esophagus and cardiac toxic effects have to be interpreted cautiously as the authors reported that among the 41 patients (3%) who had IMC irradiation the heart was shielded using blocks. In such cases, the pertinence of esophagus and cardiac toxicity analysis has to be questioned regarding the very low doses delivered to these tissues.
In the current report and according to the widely known impact of cumulative dose of anthracyclines on cardiac toxicity, we analyzed the influence of cumulative dose of T on acute toxic effects. In contrast to the anthracyclines data on heart and skin radiosensibilization, cumulative dose of T did not modify radiation-induced acute toxic effects of these tissues. Among 71% of the patients who received a median dose of 50 Gy to the IMC, the rate of grade 2 or more esophagitis was 12% during RT but remained reversible in the majority of the cases (11%) at 3 months after treatment. This has to be interpreted cautiously as there are no available data in the literature supporting this finding for the moment. In addition, the limit of statistical significance was not reached in the multivariate analysis for T cumulative dose impact on esophagitis (Table 6). Further studies and long-term follow-up are warranted to evaluate late sequelea. In the meta-analysis, the risk of secondary esophagus malignancy after BC treatment before T era was significantly increased by RT (relative risk = 2.06; P = 0.05) [19].
|
There are two options to reduce the risk of radiation-induced toxicity of the mediastinal organs. The first option may consist in a high selection of patients who will really benefit from IMC irradiation, such as patients having total mastectomy and significant axillary node involvement (
4 nodes) [20]. In a comparison between IMC irradiation practice in Europe and in the United States, Taghian et al. [21] reported a significant difference between the French and American practice for both subgroups of patients who had total mastectomy for intermediate-risk (1–3 nodes; 59% versus 15%) or high-risk (4 nodes; 64% versus 24%) BC. This difference in practice should be taken into account for interpreting results in future studies involving patients receiving T and RT. The second option may consist in the use of intensity-modulated radiation therapy (IMRT) and gating, which could allow a highly conformal dose distribution to the breast (or chest wall) and elective nodes. In the William Beaumont Hospital experience on 25 patients, the mean cardiac volume receiving 30 Gy was decreased from 2.6% to 0.6% using IMRT and gating compared with other techniques. In this series, the cardiac volume was totally excluded from the irradiation field in 15 of 25 patients [22]. Furthermore, another report from the same group has recently indicated a significant dose reduction via active breathing control during irradiation for left-sided BC. This was demonstrated using image fusion from magnetic resonance imaging and computed tomography scans [23].
Even if no difference in terms of cardiac toxicity was observed between patients treated for left or right side [24], irradiated heart volume, previous cumulative dose of anthracyclines, and T administration are highly suspected to be involved in the cardiac injury. In addition, it is impossible to predict whether the reversible decrease of LVEF during T therapy will impact the late cardiac toxicity in the context-additive effect of anthracyclines and RT. In the metastatic setting, a recent report from MD Anderson [25] showed that the two main prognostic factors for long-term cardiac tolerability of T were baseline LVEF and time from last anthracycline administration. In our study, the analyses took into account the last LVEF value measured before RT as the reference value. This baseline value was compared with the lowest value observed at any time of follow-up following RT.
The recent retrospective data analysis of the INTERGROUP randomized trial [18] did not show any difference according to the breast side following T and RT. However, the number of patients who received an IMC RT was low and the follow-up in this report is still too short to conclude. In a recent report with longer follow-up after RT alone, Harris et al. [26] reported an increased cumulative hazard risk of cardiac death in patients treated for right BC (2.9% at 15 years and 3.6% at 20 years) compared with the left side (4.4% at 15 years and 6.4% at 20 years). In addition, myocardial infarction rate was significantly higher in left-side BC patients (15% versus 5%; P = 0.006). In another recent report, the risk of myocardial infraction following RT for BC was related to anatomic sites of RT, such as left breast, anterior left breast boost field, and anterior IMC field [27]. Indeed, when IMC RT is delivered using only anterior beam’s photons, the cardiac dose may increase significantly which can lead to an increased risk of toxicity.
In the present study, the decrease of LVEF according to HERA and CTC v3.0 criteria have evaluated only acute cardiac toxicity after a 16-month median follow-up. Multivariate analysis using both criteria showed that weekly T schedule was the only unfavorable factor for LVEF decrease. In our study, 23% and 77% of the patients had weekly and a 3-week schedule, respectively. The timing and extent of LVEF reduction after RT alone, however, have to be discussed. Following left breast RT alone or combined to doxorubicin, the cardiac perfusion defects detected using single-photon emission computed tomography are not associated with changes in regional wall motion or LVEF. To date, there is no report on evaluating this issue after combined T–RT [28, 29].
Suspending T during RT may not be useful to prevent cardiac toxicity. Indeed, in practice, such suspension may be useless because of the half-life of T (4–6 weeks). Besides, there is a pharmacological similarity between daily and 3-weekly administration of T [30]. In HER2-overexpressing BC, however, the impact of late outset and/or suspension of T for 5–7 weeks of irradiation is still unknown. In the case of concomitant administration of T and RT, the issue lies in the potential interaction between T set on cardiac tissue structures and ionizing radiation. Whereas for anthracyclines and ionizing radiation the physiopathology is on the basis of the production of free radicals, cell events are less known for T. Indeed, one limit of preclinical studies is that the antibody’s humanized variable part is unable to recognize and thus bind to HER2 receptor in nonsyngeneic animal models. Moreover, in humans, HER2 expression on myocardiac cells is low. On myocardiac cells, however, we noticed HER2/HER4 heterodimers showing the dimerization of HER receptors as well as the involvement of mitogen-activated protein kinase/extracellular signal-regulated kinase and AKT pathways [31, 32]. Such pathways may also be involved in explaining doxorubicin/T-induced additive toxicity on myocardiac cells. The doxorubicin-induced apoptotic phenomena might increase with the addition of T, inhibiting AKT and extracellular signal-regulated kinase signal transduction [33]. In addition, interaction between ionizing radiation and these pathways is known.
|
conclusion |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionconclusionfundingAcknowledgementsReferences |
|---|
To our knowledge this is the first study evaluating acute toxicity of concurrent administration of T and RT. We found that weekly concurrent T and RT decreased LVEF. The acute skin and esophagus toxic effects have been resolved at 3 months following RT. Longer follow-up is warranted to evaluate whether acute reversible reactions could be predictors of significant sequelea, in particular cardiac late toxicity in the setting of anthracycline administration and aromatase inhibitors era.
At the moment, it is recommended to balance the role of each therapeutic agent and their potential toxic effects when used concurrently. It is important to spare the maximum of heart volume during RT and select the patients who will really benefit from IMC irradiation.
|
funding |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionconclusionfundingAcknowledgementsReferences |
|---|
Roche-France (1500-123-390).
|
Acknowledgements |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionconclusionfundingAcknowledgementsReferences |
|---|
The authors would like to thank Ms Frances Godson for her excellent assistance in editing the manuscript. This paper was presented at the Annual Meeting of the American Society of Therapeutic Radiology and Oncology, November 2006 (Atlanta, GA), and at the 29th Annual San Antonio Breast Symposium, San Antonio, TX, USA, December 2006. Conflict of interest statement: The authors confirm that there is no conflict of interest in connection with their authorship of this scientific paper and its content.
Received for publication August 29, 2007. Revision received January 14, 2008. Accepted for publication January 15, 2008.
|
References |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionconclusionfundingAcknowledgementsReferences |
|---|
1. Jensen OM, Esteve J, Moller H, et al. Cancer in the European Community and its member states. Eur J Cancer (1990) 26:1167–1256.[Web of Science][Medline]
2. Nahta R, Esteva FJ. HER-2-targeted therapy: lessons learned and future directions. Clin Cancer Res (2003) 9:5078–5084.
3. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med (2005) 353:1673–1684.
4. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med (2005) 353:1659–1672.
5. Smith I, Procter M, Gelber RD, et al. Two-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet (2007) 369:29–36.[CrossRef][Medline]
6. Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med (2006) 354:809–820.
7. Slamon D, Eiermann W, Robert N, et al. BCIRG 06: 2nd interim analysis phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC-T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC-TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2 positive breast cancer patients. 29th Annual San Antonio Breast Cancer Symposium (SABCS). Breast Cancer Res Treat (2006) 95(Suppl 1). (Abstr 52).
8. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med (2001) 344:783–792.
9. Marty M, Cognetti F, Maraninchi D, et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol (2005) 23:4265–4274.
10. Seidman A, Hudis C, Pierri MK, et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol (2002) 20:1215–1221.
11. Pietras RJ, Poen JC, Gallardo D, et al. Monoclonal antibody to HER2/neureceptor modulates repair of radiation-induced DNA damage and enhances radiosensitivity of human breast cancer cells overexpressing this oncogene. Cancer Res (1999) 59:1347–1355.
12. Trotti A, Colevas D, Setser A, et al. CTCAE v3.0: development of a comprehensive grading for the adverse effects of cancer treatment. Semin Radiat Oncol (2003) 13:176–181.[CrossRef][Web of Science][Medline]
13. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc (1958) 53:457–481.[CrossRef][Web of Science]
14. Peto P, Pike MC, Armitage P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient: part II. Analysis and examples. Br J Cancer (1977) 35:1–39.[Web of Science][Medline]
15. Harrell FE Jr, Lee KL, Pollock BG. Regression models in clinical studies: determining relationships between predictors and response. J Natl Cancer Inst (1988) 80:1198–1202.
16. Koukourakis MI, Manavis J, Simopoulos C, et al. Hypofractionated accelerated radiotherapy with cytoprotection combined with trastuzumab, liposomal doxorubicin, and docetaxel in c-erbB-2-positive breast cancer. Am J Clin Oncol (2005) 28:495–500.[CrossRef][Web of Science][Medline]
17. Bellon JR, Gover MT, Burstein HJ, et al. Concurrent trastuzumab and radiation therapy (RT) in the adjuvant treatment of breast cancer. Int J Radiat Oncol Biol Phys (2005) 63. (Abstr 91).
18. Halyard MY, Pisansky TM, Solin LJ, et al. Adjuvant radiotherapy (RT) and trastuzumab in stage I-IIA breast cancer: toxicity data from North Central Cancer Treatment Group Phase III trial N9831. J Clin Oncol (2006) 24. (Abstr 523).
19. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet (2005) 365:1687–717.[CrossRef][Web of Science][Medline]
20. Nielsen HM, Overgaard M, Grau C, et al. Study of failure pattern among high-risk breast cancer patients with or without postmastectomy radiotherapy in addition to adjuvant systemic therapy: long-term results from the Danish Breast Cancer Cooperative Group DBCG 82 b and c randomized studies. J Clin Oncol (2006) 24:2268–2275.
21. Taghian A, Jagsi R, Makris A, et al. Results of a survey regarding irradiation of internal mammary chain in patients with breast cancer: practice is culture driven rather than evidence based. Int J Radiat Oncol Biol Phys (2004) 60:706–714.[CrossRef][Web of Science][Medline]
22. Remouchamps VM, Letts N, Vicini FA, et al. Initial clinical experience with moderate deep-inspiration breath hold using an active breathing control device in the treatment of patients with left-sided breast cancer using external beam radiation therapy. Int J Radiat Oncol Biol Phys (2003) 56:704–715.[CrossRef][Web of Science][Medline]
23. Krauss DJ, Kestin LL, Raff G. MRI-based volumetric assessment of cardiac anatomy and dose reduction via active breathing control during irradiation for left-sided breast cancer. Int J Radiat Oncol Biol Phys (2005) 61:1243–1250.[CrossRef][Web of Science][Medline]
24. Perez EA, Romond EH, Suman VJ, Davidson N, et al. Updated results of the combined analysis of NCCTG N9831 and NSABP B-31 adjuvant chemotherapy with/without trastuzumab in patients with HER2-positive breast cancer. J Clin Oncol (2007) 25. (Abstr 512).
25. Guarneri V, Lenihan DJ, Valero V, et al. Long-term cardiac tolerability of trastuzumab in metastatic breast cancer. The M.D. Anderson Cancer Center experience. J Clin Oncol (2006) 24:1–8.
26. Harris ER, Correa C, Huang W-T, et al. Late cardiac mortality and morbidity in early-stage breast cancer patients after breast-conservation treatment. J Clin Oncol (2006) 24:4100–4106.
27. Paszat LF, Vallis KA, Benk V, et al. A population-based case-cohort study of the risk of myocardial infarction following radiation therapy for breast cancer. Radiother Oncol (2007) 82:294–300.[CrossRef][Web of Science][Medline]
28. Hardenbergh PH, Munley MT, Bentel GC, et al. Cardiac perfusion changes in patients treated for breast cancer with radiation therapy and doxorubicin: preliminary results. Int J Radiat Oncol Biol Phys (2001) 49:1023–1028.[CrossRef][Web of Science][Medline]
29. Prosnitz RG, Hubbs JL, Evans ES, et al. Prospective assessment of radiotherapy-associated cardiac toxicity in breast cancer patients: analysis of data 3 to 6 years after treatment. Cancer (2007) 110:1840–1850.[Medline]
30. Baselga J, Carbonell X, Castaneda-Soto NJ, et al. Phase II study of efficacy, safety, and pharmacokinetics of trastuzumab monotherapy administered on a 3-weekly schedule. J Clin Oncol (2005) 23:2162–2171.
31. Sawyer DB, Zuppinger C, Miller TA, et al. Modulation of anthracyclines-induced myofibrillar disarray in rat ventricular myocytes by neuroglin 1-beta and anti-erb2: potential mechanism for trastuzumab-induced cardiotoxicity. Circulation (2002) 105:1551–1554.
32. Schneider JW, Chang AW, Rocco TP. Cardiotoxicity in signal transduction therapeutics: erb2 antibodies and the heart. Semin Oncol (2001) 28:18–26.[Web of Science][Medline]
33. Chien KR. Myocyte survival pathways and cardiomyopathy: implications for trastuzumab cardiotoxicity. Semin Oncol (2001) 27:9–14.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Y. Halyard, T. M. Pisansky, A. C. Dueck, V. Suman, L. Pierce, L. Solin, L. Marks, N. Davidson, S. Martino, P. Kaufman, et al. Radiotherapy and Adjuvant Trastuzumab in Operable Breast Cancer: Tolerability and Adverse Event Data From the NCCTG Phase III Trial N9831 J. Clin. Oncol., June 1, 2009; 27(16): 2638 - 2644. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||