Received Trastuzumab Treatment Research Articles

Echocardiographic signs of right ventricle changes after Trastuzumab treatment in breast cancer patients with erb-2 overexpression.

Objective:Left ventricular (LV) dysfunction after trastuzumab treatment in erb-2 breast cancer cases has been fully investigated. However, there is not enough data about the effect of trastuzumab treatment on right ventricular (RV) functions. This study is designed to evaluate the right heart changes by performing echocardiography after trastuzumab treatment in patients with erb-2 breast cancer.Methods:Forty-two consecutive breast cancer patients with erb-2 overexpression mean age 50.4±11.6 years who were decided to receive trastuzumab treatment were enrolled. Echocardiographic examinations including 2-D, spectral, and tissue Doppler measurements were performed at the baseline (T1) and repeated after 6 months (T2).Results:Tricuspid annular plane systolic excursion (TAPSE) was decreased, RV myocardial performance index (RVMPI) and tricuspid E/e’ ratio was increased after trastuzumab treatment (1.84 vs. 2.14; p<0.01) (0.46 vs. 0.56, p<0.01) (4.4±1.07 vs. 5.08±1.46; p=0.04). Median serum NT-ProBNP levels, troponin I, and hs-CRP levels were similar between the groups. LVEF and TAPSE were negatively correlated with dosage of trastuzumab (r=-0.392, p=0.04; r=-0.522, p=0.006). There was a stepwise decrease in LVEF when trastuzumab used with anthracyclines however this not reached statically significant (62.4±2, 60±4.5; p=0.06).Conclusion:In our study; we observed a trend of RV deterioration after trastuzumab treatment. These preliminary RV changes were demonstrated by using TAPSE, RV tissue Doppler imaging derived MPI and E/e’ ratio parameters by echocardiography and these parameters could also use as markers of trastuzumab toxicity in this population.

HER2-positive patients receiving trastuzumab treatment have a comparable prognosis with HER2-negative advanced gastric cancer patients: A prospective cohort observation

The monoclonal antibody trastuzumab has brought survival benefit to patients with advanced gastric cancer (AGC) that have human epidermal growth factor receptor 2 (HER2) over expression or amplification. This study was designed to compare the clinical outcomes of HER2-negative and HER2-positive AGC patients with or without trastuzumab treatment. There were three groups of patients enrolled for analysis. Group A was 51 HER2-positive AGC patients treated with trastuzumab and chemotherapy; group B was a matched control group of 47 HER2-positive patients who received chemotherapy only; group C was a matched group of 251 HER2-negative patients who received chemotherapy. All the patients were enrolled at Sun Yat-sen University Cancer Center or Zhongshan Hospital, Fudan University between January 2010 and December 2012. The primary endpoint was overall survival (OS). The Kaplan-Meier method and log-rank test were used for survival analysis. The median duration of follow-up was 13.5 months (range 5-18.6 months). The median OS of these three groups of patients was 14.8 months, 11.3 months and 14.4 months respectively (p < 0.001). The survival difference between group A and B was significant, p < 0.001. Similarly, there was significant difference between group B and C, p < 0.001. Moreover the survival between group A and C was comparable, p = 0.281. The median progression-free survival for these three groups was 7.4, 6.0 and 7.2 months. Multivariate analysis confirmed that trastuzumab treatment was an independent prognostic factor in group A and B patients (p = 0.017). HER2 positive was an independent adverse prognostic factor in group B and C patients (p = 0.013).

Assessing the potential cost‐effectiveness of retesting IHC0, IHC1+, or FISH‐negative early stage breast cancer patients for HER2 status

Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) tests are commonly used to assess human epidermal growth factor 2 (HER2) status of tumors in patients with breast cancer. This analysis evaluates the likely cost-effectiveness of expanded retesting to assess HER2 tumor status in women with early stage breast cancer. We developed a decision-analytic model to estimate the incremental cost-effectiveness ratio (ICER) of expanded reflex testing from a US payer perspective. Expanded reflex testing is defined as retesting tumor specimens from patients whose tumors are IHC0, IHC1+, or FISH-negative on their first test. In the base case, we assumed that 80% of patient tumors are initially IHC-tested and 20% are FISH-tested. Testing outcomes for IHC and FISH with and without retesting were based on published meta-analyses. The cost of tests and treatment and the long-term health outcomes were obtained from the literature. In the base case, we estimated that 2.27% of women who received expanded reflex testing would be HER2-positive and receive trastuzumab treatment: the projected ICER was $36,721 per life year or $39,745 per quality-adjusted life year (QALY). This varied between $47,100 per QALY and $35,500 per QALY if we assumed that 1%-8% of patients retested were then HER2+, respectively. The results of deterministic and probabilistic sensitivity analysis were robust. This strategy would result in 4700 (2000-17,000) patients being eligible to receive trastuzumab treatment annually. Retesting patients who are IHC0, IHC1+, or FISH-negative is projected to be a cost-effective clinical strategy.

Adverse prognostic impact of intratumor heterogeneous HER2 gene amplification in patients with breast cancer.

617 Background: There is increasing recognition of the existence of intratumoral heterogeneity of the human epidermal growth factor receptor (HER2), which affects interpretation of HER2 positivity in clinical practice and may have implications for patient prognosis and treatment. Only patients (pts) with HER2 positivity - defined as 3+ by IHC or FISH amplified defined as a HER2 gene to chromosome 17 (HER2/CEP17) ratio ≥ 2.0 - are eligible to receive trastuzumab treatment. Limited information is available on the prognosis of pts with HER2 2+ or FISH test with a HER2/CEP17 ratio &lt; 2.0. Methods: We retrospectively analyzed data from 455 consecutive early BC pts with HER 2+ and HER2/CEP17 ratio &lt; 2.0 who underwent surgery after 2007. The association between HER2/CEP17 ratio and other known prognostic factors was evaluated with multivariable linear regression models. The role of HER2/CEP17 ratio on recurrence free survival was assessed with multivariable Cox regression models. Results: Fifty-one percent of the evaluated pts were node negative, 51% were postmenopausal, 93% had ER positive BC and 85% had Ki-67 ≥14%. The mean HER2/CEP17 ratio was 1.27 (SD=0.3). A significant positive relationship between HER2/CEP17 ratio and Ki-67 was observed (p&lt;0.01). During a median follow-up time of 2.7 years, 40 recurrences were observed (15 locoregional events and 25 distant metastases). Overall, the association between HER2/CEP17 and the risk of recurrence was not significant. From subgroup analysis, a significant interaction between HER2/CEP17 ratio and nodal involvement emerged (p=0.02). Among pts with node-negative disease, pts with HER2/CEP17 ratio ≥1.27 were at higher risk of recurrence with respect to pts with HER2/CEP17 ratio &lt; 1.27 (adjusted HR 4.0, 95% CI 1.01-15.9). Conclusions: Among pts with BC and HER2 intratumoral heterogeneity, HER2/CEP17 ratio ≥1.27 could have a strong prognostic role in node negative HER2 2+ BC, thus suggesting potential future therapeutic approaches in this setting of pts.

HER2-positive breast cancer patients receiving trastuzumab treatment obtain prognosis comparable with that of HER2-negative breast cancer patients

PurposeThe efficacy of trastuzumab in Chinese breast cancer (BC) patients has rarely been reported. This study was designed to compare the clinical outcomes of HER2-positive BC patients receiving or not receiving trastuzumab treatment and HER2-negative BC patients.Patients and methodsThis study involved three groups of patients. The first group was 115 human epidermal growth factor receptor 2 (HER2)-positive BC patients treated with trastuzumab who were enrolled at Sun Yat-sen University Cancer Center between January 2002 and July 2010; the second group was a matched control group of 115 HER2-positive patients who did not receive trastuzumab treatment; the third group was a matched group of 115 HER2-negative patients who received conventional therapy in the adjuvant setting. The primary endpoint was 3-year and 5-year disease-free survival (3-DFS and 5-DFS, respectively). The Kaplan–Meier method, log-rank test, and multivariate Cox proportional hazard regression model were used for survival analysis. The differences in survival rates among the three groups were also analyzed according to two different periods: 2002–2006 and 2007–2010.ResultsThe median duration of follow-up was 36 months (range, 12–111 months). The 3-DFS rates in the HER2-negative group, the HER2-positive group who received trastuzumab treatment, and the HER2-positive group who did not receive trastuzumab treatment were 82.6%, 89.6%, and 67.0%, respectively. The 3-DFS rate for the total study population was statistically significant (P < 0.001). Further analysis indicated a statistically significant difference in 3-DFS between either of the first two groups and the third group (P < 0.01), but the difference between the first two groups was not statistically significant (P = 0.157). Among the three groups, the 3-DFS rates during 2002–2006 did not have a significant difference compared with that during 2007–2010.ConclusionThis study has further confirmed the efficacy of trastuzumab for HER2-positive operable BC in Chinese patients. It has also demonstrated that the 3-DFS and 5-DFS rates between HER2-positive patients receiving trastuzumab treatment and HER2-negative patients are comparable.

Management of Patients with Brain Metastases Receiving Trastuzumab Treatment for Metastatic Breast Cancer

Background: With the more effective control of visceral metastases in patients with metastatic breast cancer (MBC), an increasing number of patients face brain metastases (BM). The aim of this retrospective analysis was to investigate the incidence and factors affecting the prognosis of patients with BM under trastuzumab treatment for MBC. Patients and Methods: A total of 75 HER2positive patients treated with trastuzumab for MBC were included. Results are discussed in the context of the current literature. Results: Patients who developed BM (n = 29) had longer median progression-free survival (PFS) during first-line chemotherapy and longer overall survival (OS) after diagnosis of MBC than 46 patients without BM (PFS: 27 vs. 14 months, p = 0.039; OS: 46 vs. 18 months, p = 0.067). Median survival of patients with continuation of trastuzumab after diagnosis of BM was longer than survival of patients with discontinuation of trastuzumab treatment after BM (18 vs. 3 months, p = 0.006). Survival of patients who were treated with surgery and radiotherapy for BM was better compared with radiotherapy alone (9 vs. 5 months, p = not significant) or best supportive care (9 vs. 2 months, p = 0.049). Conclusions: Continuation of trastuzumab treatment as well as resection of BM seem to give further benefit in the treatment of patients with HER2-overexpressing MBC.

HER2 Evaluation and Its Impact on Breast Cancer Treatment Decisions

Background: Eighteen to twenty percent of breast cancer tumors show abnormal amplification of the Human Epidermal growth factor Receptor 2 (HER2) gene and increased expression of the associated protein. HER2 amplification is associated with rapid tumor proliferation and shorter disease-free and overall survival. Because women with HER2 amplification are more likely to benefit from treatment with the drug trastuzumab, testing for HER2 is recommended to guide therapy. However, little is known about use of HER2 testing in real-world settings. This study examined uptake, use, appropriateness of HER2 testing, and the relationship between HER2 test results and treatment decisions. Methods: We assessed electronic data from 3,634 patients with invasive breast cancer diagnosed from 1998 to 2007 in a large integrated health system. We collected data on patient and tumor characteristics, HER2 testing status, test results, and trastuzumab treatment. Results:From 1998 to 2000, the percent of patients who underwent HER2 evaluation increased from 12 to 94%; <3% of women with ductal carcinoma in situ, for whom HER2 testing is not recommended, were tested. Trastuzumab use increased 5-fold after 2004, when guidelines expanded to include recommending adjuvant treatment for early-stage breast cancer in addition to metastatic treatment. Ninety-five percent of women receiving trastuzumab had a positive HER2 result. After 2004, 55% of women with invasive breast cancer and overexpression of HER2 received trastuzumab treatment; this ranged from 44% of women with localized breast cancer to 80% of women with distant metastatic disease. Conclusions:These findings illustrate appropriate and effective implementation of a HER2 testing strategy in a managed care setting.

Abstract P3-12-12: HER2 Evaluation in Relation to Breast Cancer Treatment Decisions in a Managed Care Plan

Abstract Background: In 18-20% of breast cancer tumors, the human epidermal growth factor receptor 2 (HER2) gene is abnormally amplified with increased expression of the associated protein. HER2 amplification is associated with rapid tumor proliferation, shorter disease-free survival, and poorer overall survival. Because women with HER2 amplification are more likely to benefit from treatment with the drug trastuzumab, testing for HER2 is recommended to guide therapy. However, little is known about HER2 testing practices and associated treatment in real-world settings. This study examined uptake, use, and appropriateness of HER2 testing, and the relationship between HER2 test results and treatment decisions in a large integrated health system. Methods: We identified 3,634 patients with primary breast cancer diagnosed from 1998-2007 who were members of the Kaiser Permanente Northwest health plan. We collected data on patient and tumor characteristics, HER2 testing status, test results, and trastuzumab treatment from tumor registry and pharmacy datasets. We defined women as evaluated for HER2 if they received HER2 testing by immunohistochemistry (IHC) and/or fluorescent in-situ hybridization (FISH). We manually abstracted medical charts for a subset of patients to verify findings and investigate anomalies. We compared testing and treatment results to professional guidelines. Results: From 1998-2000, the percentage of patients with invasive breast cancer who underwent HER2 evaluation increased from 12% to 94%; from 2000-2007, 94% (2304/2461) received HER2 testing over all years combined. In most cases, an equivocal or positive IHC test was followed by FISH. Only 2.4% of women with ductal carcinoma in situ (13/538), for whom HER2 testing is not recommended, were tested, and the proportion remained consistently low over the entire study period. Trastuzumab use increased five-fold after 2004, when guidelines expanded to include recommending adjuvant treatment for early-stage breast cancer in addition to metastatic treatment. Ninety-five percent of women receiving trastuzumab had a positive HER2 result, while the remainder had equivocal HER2 results or received treatment outside thedelivery system. After 2004, 55% of women with invasive breast cancer and overexpression of HER2 received trastuzumab treatment; this ranged from 44% of women with localized breast cancer to 80% of women with distant metastatic disease. We estimate that, after correcting for errors in the datasets, professional guidelines were followed for over 97% of patients diagnosed since 2000. Conclusions: Kaiser Permanente Northwest is systematically performing HER2 evaluation on patients with invasive breast cancer, and the information is used to make appropriate treatment decisions. This information should be gathered in other health care settings for comparison. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-12-12.

Prognosis of Women With Metastatic Breast Cancer by HER2 Status and Trastuzumab Treatment: An Institutional-Based Review

PURPOSE The purpose of this study was to determine whether trastuzumab improves prognosis of women with metastatic human epidermal growth factor receptor 2 (HER2)/neu -positive breast cancer beyond that of women with HER2/neu-negative disease. PATIENTS AND METHODS Two thousand ninety-one women with metastatic breast cancer diagnosed from 1991 to 2007, with known HER2/neu status and who had not received trastuzumab in the adjuvant setting, were identified. Disease was classified into the following three groups: HER2/neu negative, HER2/neu positive without first-line trastuzumab treatment, and HER2/neu positive with first-line trastuzumab treatment. Overall survival (OS) was estimated using the Kaplan-Meier product-limit method and compared between groups with the log-rank test. Cox proportional hazards models were used to determine associations between OS and HER2/neu status after controlling for patient characteristics. Results One hundred eighteen patients (5.6%) had HER2/neu-positive disease without trastuzumab treatment, 191 (9.1%) had HER2/neu-positive disease and received trastuzumab treatment, and 1,782 (85.3%) had HER2/neu-negative disease. Median-follow-up was 16.9 months. One-year survival rates among patients with HER2/neu-negative disease, HER2/neu-positive disease and trastuzumab treatment, and HER2/neu-positive disease and no trastuzumab treatment were 75.1% (95% CI, 72.9% to 77.2%), 86.6% (95% CI, 80.8% to 90.8%), and 70.2% (95% CI, 60.3% to 78.1%), respectively. In a multivariable model, women with HER2/neu-positive disease who received trastuzumab had a 44% reduction in the risk of death compared with women with HER2/neu-negative disease (hazard ratio [HR] = 0.56; 95% CI, 0.45 to 0.69; P < .0001). This HR varied with time and was significant for the first 24 months and not significant after 24 months. CONCLUSION Our results show that women with HER2/neu-positive disease who received trastuzumab had improved prognosis compared with women with HER2/neu-negative disease.

The use of innovative oncology drugs in Europe

16020 Background: A number of new innovative cancer drugs have recently been approved or are in the process of being approved. Rapid patient access to new innovative drugs is important as it may lead to improved survival. Methods: We have analysed the access and uptake of new oncology drugs in 19 European countries over a 15 year period based on sales data provided by IMS Health. In the study we focus on select, “targeted” drugs that have been introduced over the last 10 years: rituximab, trastuzumab and imatinib. We have also analysed data to assess the composition of the drug “arsenal” used in the selected countries based on % of total sales for cancer drugs introduced before 1993; between1993–1998 and after 1999. Results: We see different patterns of uptake in countries studied, both with respect to speed and level of usage, in relation to use per person dying of the specific cancers.. Fast uptake is seen in Austria, Switzerland and Spain, and slow uptake as well as low usage is seen in Poland, Hungary, Norway and the UK. For example, trastuzumab uptake indicates that countries with the fastest uptake treat the majority of HER2 over expressing metastatic breast cancer patients within 2–3 years after introduction while countries with slow uptake still after 5 years seem to have a large proportion of patients not receiving trastuzumab treatment. On the other hand, for a drug like imatinib the uptake has been more rapid and uniform in most countries. The composition of the cancer drug “arsenal” used also differs significantly in between countries. Conclusions: Patient access to innovative cancer drugs varies significantly between European countries. [Table: see text]