Her2neu Positivity Research Articles

HER2-neu Positivity Prognosticates for Poor Disease Control in Asian Women with Small, Node Negative Breast Cancer Treated with Conservation Therapy

HER2-neu Positivity Prognosticates for Poor Disease Control in Asian Women with Small, Node Negative Breast Cancer Treated with Conservation Therapy

HER2-neu status as a predictor of survival in patients with brain metastases from primary breast adenocarcinoma

1016 Background: Recent data suggests that Her2-neu positivity predicts for development of brain metastases in patients with breast cancer. However, there now exists a targeted agent, trastuzumab, that provides excellent systemic control of Her2-positive (Her2 +) disease. We therefore explore the course of this disease as a function of Her2 status in patients with primary breast cancer who have developed brain metastases. Method: We retrospectively analyzed data from 50 consecutive patients with primary breast cancer who subsequently developed brain metastases. Factors evaluated included Her2-neu, ER/PR, T stage, nodal stage, use of whole brain radiotherapy (WBRT) as initial management of CNS disease, initial number of metastases, hormonal therapy, use of trastuzumab, and Karnofsky Performance Status (KPS). Overall survival (OS) was modeled using Cox proportional hazard. Kaplan-Meier analysis was used for significant predictors. Results: Median age was 49 years (28–78 y). Fifty-four percent of patients were Her2 +, whereas only 15% were ER +. All but one Her2 + patient received trastuzumab. Seventy-two percent were node positive, and only 5 patients were metastatic at time of diagnosis. T stage was as follows: T1 = 24%, T2 = 36%, T3 = 8%, and T4 = 16%. Adjuvant chemotherapy was administered to 90% of the sample, and 94% underwent radiation to the primary site. Sixty-six percent had <= 3 initial brain metastases, and 38% underwent WBRT as part of their initial CNS management. Median followup was 55 weeks. A Cox multivariate model of OS yielded two independent predictors. Her2 positivity (p = 0.007) and <= 3 initial brain metastases (p = 0.003) were associated independently with OS from time of initial diagnosis of CNS disease. Median survival and actuarial one year survival for Her2 + patients were 65 weeks and 87%, respectively, versus 33 weeks and 44% for Her2 negative patients (Mantel Cox p = 0.025). Conclusions: Although Her2 + patients appear to have a greater risk of developing brain metastases, overall survival from time of initial diagnosis of brain metastasis appears to be better in this cohort. This may be a function of the improved extracranial control provided by trastuzumab in patients with Her2+ disease. No significant financial relationships to disclose.

Impact of Her-2 Neu Overexpression on Outcome of Elderly Women Treated With Wide Local Excision and Breast Irradiation for Early Stage Breast Cancer

The purpose of this study was to investigate the prognostic significance of Her-2 neu status in elderly patients managed with breast conservation strategy for stage I-II breast cancer. We conducted an IRB approved retrospective review of 153 women age 70 and older with stage I-II breast cancer, managed with wide local excision and breast radiation between January 1997 and December 2002. The subset of 106 patients had a known Her-2 neu status and was analyzed for primary patient and tumor characteristics. These characteristics were correlated with cause specific survival (CSS), overall survival (OS), and combined nodal and distant failure (NDF). Her-2 neu positivity was confirmed with FISH HercepTestTM. Statistical tests included Cox regression, contingency table and Kaplan-Meier analysis. Median follow-up was 55 months and patient's median age was 76. Twenty two percent of patients were Her-2 neu positive and 78% were Her-2 neu negative. Her-2 neu positivity was significantly associated with high histologic grade (P = 0.008), T2 stage (P = 0.001) and positive axillary lymph nodes (P = 0.02) among 73 patients who had surgical assessment of axilla. Overall, only 15 patients (14%) received chemotherapy. There were no recurrences in the breast. Her-2 neu positivity predicted for NDF and CSS on multivariate analysis. Projected 5-year freedom from NDF was 70% for Her-2 neu positive and 97% for Her-2 neu negative patients (P < 0.01, log-rank). CSS was 86% for Her-2 neu positive and 98% for Her-2 neu negative patients (P < 0.01, log-rank). OS was no different between Her-2 neu positive and Her-2 neu negative patients (80% versus 85%, P = 0.25). Her-2 neu amplification predicts development of NDF and negatively influences CSS, but not local control or OS in elderly patients treated with breast conservation. Similar to the trend in younger patients, Her-2 neu positivity may be used in the future to consider more aggressive treatment strategies in elderly patients.

Her2-Neu overexpression does not increase the risk of local-regional recurrence for patients treated with neoadjuvant doxorubicin-based chemotherapy, mastectomy, and radiation

Purpose/Objective: Preclinical data suggest that overexpression of Her2-Neu confers cellular radioresistance. We studied whether breast cancer patients with tumors that overexpressed Her2-Neu were more likely to develop local-regional recurrence (LRR) after postmastectomy radiation than patients whose tumors did not overexpress Her2-Neu. Materials/Methods: Data from 337 patients treated on 4 institutional prospective clinical trials with neoadjuvant chemotherapy, mastectomy, and radiation were reviewed. Of these, 108 (32%) patients had tumors that were tested for Her2-Neu expression. Six of these patients had Her2-Neu testing performed at the time of disease recurrence and the reminder were tested either at the time of diagnosis or for the purpose of a study assessing biomarkers and chemotherapy response. Her2-Neu was considered positive if there was 3+ protein staining by immunohistochemistry (IHC) or gene amplification detected by fluorescent in-situ hybridization (FISH). FISH testing was routinely performed on tumors with 2+ IHC staining. Eighty-nine percent of the patients had 1988 AJCC Stage III disease or involvement of supraclavicular lymph nodes without systemic metastases. All patients received a neoadjuvant combination chemotherapy regimen that included doxorubicin, with 53% also receiving a taxane. The median number of recovered axillary lymph nodes from the mastectomy was 14. Radiation treatment was delivered to the chest wall and draining lymphatics (median dose of 50Gy) followed by a chest wall boost (median dose of 10Gy). Results: Thirty-two patients had tumors with Her2-Neu overexpression and 76 patients had tumors in which the Her2-Neu test was considered normal. The Her2-Neu positive tumors were associated with a higher rate of estrogen receptor-negative disease (72% vs. 49% respectively, P=0.03) and a higher number of median positive lymph nodes after chemotherapy (n= 6 vs. n=3, P=0.002). Patients with Her2-positive tumors also had more advanced clinical stage (P=0.09) but this differences was not statistically significant. Despite these adverse features, the actuarial overall LRR rate was roughly equivalent for the patients with Her2-Neu overexpression versus those with tumors normal for Her2-Neu (5-year: 17.5% ± 7.3 vs. 13.9% ± 4.1, respectively, 10-year: 17.5% ± 7.3 vs. 18.9% ± 6.2%, respectively, P=0.76). On Cox regression analysis of LRR that adjusted for stage, the hazard ratio for Her2-Neu positivity was 1.02 (95% CI 0.61–1.84). Conclusions: Her2-Neu overexpression does not appear to predispose to LRR after neoadjuvant doxorubicin-based chemotherapy, mastectomy, and radiation.