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Factors Influencing Adjuvant Chemotherapy and Trastuzumab Choice in Older Human Epidermal Growth Factor Receptor 2-positive Breast Cancer Patients.

ABSTRACT: Objectives: This study aims to evaluate influence factors for adjuvant chemotherapy regimen choice on the basis of trastuzumab in older human epidermal growth factor receptor 2 (HER2)-positive breast cancer under multi-disciplinary team (MDT) modality. Materials and Methods: HER2-positive breast cancer patients aged ? 60 years who received breast cancer surgery between April 2013 and December 2017 in Shanghai Ruijin Hospital were retrospectively enrolled. Clinical and pathological features, MDT recommendations, administration of adjuvant treatment, cardiotoxicity, and disease outcome information were reviewed and analyzed. Results: A total of 222 older HER2-positive breast cancer patients were included and recommended to receive adjuvant chemotherapy plus trastuzumab therapy. Paclitaxel plus trastuzumab (PH, 41/222, 18.5%), docetaxel plus carboplatin and trastuzumab (TCH, 62/222, 27.9%), and antharcyclines plus cyclophosphamide followed by taxanes and trastuzumab (AC-TH, 119/222, 53.6%) were the three main regimens. Patients with T1a-b (P<0.001), grade 1-2 (P=0.008), node-negative (P<0.001), stage I (P<0.001), low Ki-67 level (P<0.001) disease, with cardiovascular comorbidities (P=0.011), and aged ? 70 years (P<0.001) were more likely to be recommended to PH regimen. Among the 178 patients who finally received adjuvant chemotherapy plus one-year trastuzumab treatment, only four patients (4/117, 3.4%) were recorded to have asymptomatic LVEF declining ? 10% but remaining ? 50% within one-year trastuzumab treatment. Conclusions: Clinical factors, including age, tumor size, node status, and cardiovascular comorbidity influenced the recommendation of trastuzumab with chemotherapy for older HER2-positive breast cancer patients. Low risk older HER2-positive breast cancer patients treated with PH had favorable outcome and good cardiac safety, which needed further clinical validation.

SUBMITTER: Fang Y

PROVIDER: S-EPMC7066021 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Factors Influencing Adjuvant Chemotherapy and Trastuzumab Choice in Older Human Epidermal Growth Factor Receptor 2-positive Breast Cancer Patients.

Fang Yan Y Wang Zheng Z Wu Jiayi J Huang Ou O He Jianrong J Zhu Li L Chen Weiguo W Li Yafen Y Chen Xiaosong X Shen Kunwei K

Journal of Cancer 20200214 9

<b>Objectives</b>: This study aims to evaluate influence factors for adjuvant chemotherapy regimen choice on the basis of trastuzumab in older human epidermal growth factor receptor 2 (HER2)-positive breast cancer under multi-disciplinary team (MDT) modality. <b>Materials and Methods</b>: HER2-positive breast cancer patients aged ≥ 60 years who received breast cancer surgery between April 2013 and December 2017 in Shanghai Ruijin Hospital were retrospectively enrolled. Clinical and pathological ...[more]

PMID: 32201530

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Project description:PurposePatients treated with adjuvant trastuzumab require adequate cardiac monitoring. We describe the patterns of cardiac monitoring and evaluate factors associated with adequate monitoring in a large population-based study of older patients with breast cancer.Patients and methodsPatients age 66 years or older with full Medicare coverage, diagnosed with stage I to III breast cancer between 2005 and 2009, and treated with adjuvant trastuzumab-based chemotherapy were identified in the SEER-Medicare and the Texas Cancer Registry-Medicare databases. The adequacy of cardiac monitoring was determined. Chemotherapy, trastuzumab use, cardiac monitoring, and comorbidities were identified by using International Classification of Diseases, 9th revision and Healthcare Common Procedure Coding System codes. Prescribing physician characteristics were also evaluated. Analyses included descriptive statistics and multilevel logistic regression models.ResultsIn all, 2,203 patients were identified; median age was 72 years. Adequate monitoring was identified in only 36.0% of the patients (n = 793). In the multivariable model, factors associated with optimal cardiac monitoring included a more recent year of diagnosis (hazard ratio [HR], 1.83; 95% CI, 1.32 to 2.54), anthracycline use (HR, 1.39; 95% CI, 1.14 to 1.71), female prescribing physician (HR, 1.37; 95% CI, 1.10 to 1.70), and physician graduating after 1990 (HR, 1.66; 95% CI, 1.29 to 2.12). The presence of cardiac comorbidities was not a determinant for cardiac monitoring. Of the variance in the adequacy of cardiac monitoring, 15.3% was attributable to physician factors and 5.2% to measured patient factors.ConclusionA large proportion of patients had suboptimal cardiac monitoring. Physician characteristics had more influence than measured patient-level factors in the adequacy of cardiac monitoring. Because trastuzumab-related cardiotoxicity is reversible, efforts to improve the adequacy of cardiac monitoring are needed, particularly in vulnerable populations.

Project description:PURPOSE:The Adjuvant Paclitaxel and Trastuzumab trial was designed to address treatment of patients with small human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The primary analysis of the Adjuvant Paclitaxel and Trastuzumab trial demonstrated a 3-year disease-free survival (DFS) of 98.7%. In this planned secondary analysis, we report longer-term outcomes and exploratory results to characterize the biology of small HER2-positive tumors and genetic factors that may predispose to paclitaxel-induced peripheral neuropathy (TIPN). PATIENTS AND METHODS:In this phase II study, patients with HER2-positive breast cancer with tumors 3 cm or smaller and negative nodes received paclitaxel (80 mg/m2) with trastuzumab for 12 weeks, followed by trastuzumab for 9 months. The primary end point was DFS. Recurrence-free interval (RFI), breast cancer-specific survival, and overall survival (OS) were also analyzed. In an exploratory analysis, intrinsic subtyping by PAM50 (Prosigna) and calculation of the risk of recurrence score were performed on the nCounter analysis system on archival tissue. Genotyping was performed to investigate TIPN. RESULTS:A total of 410 patients were enrolled from October 2007 to September 2010. After a median follow-up of 6.5 years, there were 23 DFS events. The 7-year DFS was 93% (95% CI, 90.4 to 96.2) with four (1.0%) distant recurrences, 7-year OS was 95% (95% CI, 92.4 to 97.7), and 7-year RFI was 97.5% (95% CI, 95.9 to 99.1). PAM50 analyses (n = 278) showed that most tumors were HER2-enriched (66%), followed by luminal B (14%), luminal A (13%), and basal-like (8%). Genotyping (n = 230) identified one single-nucleotide polymorphism, rs3012437, associated with an increased risk of TIPN in patients with grade 2 or greater TIPN (10.4%). CONCLUSION:With longer follow-up, adjuvant paclitaxel and trastuzumab is associated with excellent long-term outcomes. Distribution of PAM50 intrinsic subtypes in small HER2-positive tumors is similar to that previously reported for larger tumors.

Dataset Information

Factors Influencing Adjuvant Chemotherapy and Trastuzumab Choice in Older Human Epidermal Growth Factor Receptor 2-positive Breast Cancer Patients.

Publications

Factors Influencing Adjuvant Chemotherapy and Trastuzumab Choice in Older Human Epidermal Growth Factor Receptor 2-positive Breast Cancer Patients.

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