A B S T R A C T PurposeThe 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 MethodsTwo 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. ResultsOne 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] ϭ 0.56; 95% CI, 0.45 to 0.69; P Ͻ .0001). This HR varied with time and was significant for the first 24 months and not significant after 24 months. ConclusionOur results show that women with HER2/neu-positive disease who received trastuzumab had improved prognosis compared with women with HER2/neu-negative disease. J Clin

The goal of these guidelines, based on an expert consensus after careful review of published data, is to help the clinical diagnosis of this rare disease and to standardize management of IBC among treating physicians in both the academic and community settings.

Purpose: Androgen receptor (AR) is commonly expressed in breast cancers. However, the association between tumor AR status and breast cancer survival is uncertain. Hence, we examined the association between AR status and breast cancer survival in the Nurses' Health Study (NHS).Experimental Design: It was a prospective study of postmenopausal women enrolled in the Nurses' Health Study with stage I to III breast cancer diagnosed between 1976 and 1997 and followed from the date of diagnosis until January 1, 2008 or death. Analyses were conducted using Kaplan-Meier methods and Cox proportional hazard models, to determine the association of AR status with survival outcomes adjusting for covariates.Results: Among 1467 breast cancers, 78.7% were AR-positive (ARþ). Among 1,164 estrogen receptor (ER)-positive cases, 88.0% were ARþ. AR positivity was associated with a significant reduction in breast cancer mortality (HR, 0.68; 95% CI, 0.47-0.99) and overall mortality (HR, 0.70; 95% CI, 0.53-0.91) after adjustment for covariates. In contrast, among women with ER-negative tumors (303 cases), 42.9% were ARþ. There was a nonsignificant association between AR status and breast cancer death (HR, 1.59; 95% CI, 0.94-2.68).Conclusions: The association of AR status and breast cancer survival is dependent on ER status. In particular, AR expression was associated with a more favorable prognosis among women with ER-positive tumors. Thus, determination of AR status may provide additional information on prognosis for postmenopausal women with breast cancer, and provide novel opportunities for targeted therapy.

This large cohort study provides further insight into the natural history of relapsed and de novo stage IV breast cancer. DFI plays an important role in the prognosis for patients with relapsed breast cancer.

Purpose: To evaluate HER2 status in residual tumor identified at the time of surgery in patients not achieving a pathologic complete response (pCR) and to determine the effect of alterations in HER2 status on recurrence-free survival (RFS). Experimental Design: Clinicopathologic data for patients with HER2-overexpressing breast cancer receiving neoadjuvant therapy with a taxane, anthracycline, and concomitant trastuzumab between 2004 and 2007 were reviewed. Surgical specimens for patients achieving less than a pCR were assessed to determine if there was enough residual tissue to evaluate posttreatment HER2 status. RFS was determined using the Kaplan-Meier method and compared by the log-rank statistic. Results: A pCR was achieved in 72 of the 142 (50.7%) patients. Residual tumor was sufficient to assess posttreatment HER2 status in 25 patients. Fluorescence in situ hybridization done on pretreatment specimens confirmed HER2 amplification before beginning therapy. Eight (32.0%) posttreatment tumors were found to be HER2-negative by fluorescence in situ hybridization. At a median follow-up of 37 months (range, 8-56 months), the RFS was significantly better for patients with tumors that retained HER2 amplification (87.5% versus 50%, P = 0.04). Conclusion: High pCR rates are achieved in patients with HER2-positive breast cancer treated with neoadjuvant trastuzumab in combination with anthracyclines and taxanes. One third of patients with significant residual disease loses HER2 amplification, and this change is associated with poor RFS. Residual tumor identified at the time of surgery should be reassessed for HER2 status, and novel adjuvant therapy strategies need to be studied in this population. ( The HER2/neu (HER2) gene is amplified in ∼25% of breast cancers (1). Gene amplification results in overexpression of the HER2 protein, which is associated with an aggressive clinical course to include a shorter disease-free interval after adjuvant therapy and decreased overall survival (OS; refs. 2-4). The natural history of HER2-overexpressing breast cancer has been altered, however, by the routine use of trastuzumab, a monoclonal antibody targeting the extracellular domain of the HER2 protein. Trastuzumab has been shown to improve survival in patients with metastatic HER2-positive breast cancer (5, 6) as well as in patients with earlier stage disease. Several large, multicenter adjuvant therapy trials showed that the addition of trastuzumab to systemic chemotherapy reduces recurrence by ∼50% and improves OS by 30% (7, 8). Trastuzumab has also been shown to be efficacious when given in the neoadjuvant setting with pathologic complete response (pCR) rates ranging from 7% to as high as 65% in patients with both early and locally advanced breast cancer (9)(10)(11)(12)(13)(14). Despite these successes with trastuzumab therapy, not all HER2-positive tumors respond and some patients whose tumors do respond will experience disease recurrence. Investigators from our group recently reported a case of a patient with HER2-p...

MRI was the most accurate imaging technique in detecting a primary BPL in IBC patients. Sonography can be useful in diagnosing regional nodal disease. PET/CT provides additional information on distant metastasis, and it should be considered in the initial staging of IBC.

In our cohort of patients with breast cancer and CNS metastases, patients with HER2-positive disease treated with trastuzumab had longer times to development of and better survival from CNS metastases compared with patients with HER2-positive disease who had never received trastuzumab and patients with HER2-negative breast cancer.

Doxorubicin is an effective anti-tumor agent with a cumulative dose-dependent cardiotoxicity. In addition to its principal toxic mechanisms involving iron and redox reactions, recent studies have described new mechanisms of doxorubicin-induced cell death, including abnormal protein processing, hyper-activated innate immune responses, inhibition of neuregulin-1 (NRG1)/ErbB(HER) signalling, impaired progenitor cell renewal/cardiac repair, and decreased vasculogenesis. Although multiple mechanisms involved in doxorubicin cardiotoxicity have been studied, there is presently no clinically proven treatment established for doxorubicin cardiomyopathy. Iron chelator dexrazoxane, angiotensin converting enzyme (ACE) inhibitors, and β-blockade have been proposed as potential preventive strategies for doxorubicin cardiotoxicity. Novel approaches such as anti-miR-146 or recombinant NRG1 to increase cardiomyocyte resistance to toxicity may be of interest in the future.