Neutrophil gelatinase-associated lipocalin (NGAL) predicts response to neoadjuvant chemotherapy and clinical outcome in primary human breast cancer.

In our previous work we showed that NGAL, a protein involved in the regulation of proliferation and differentiation, is overexpressed in human breast cancer (BC) and predicts poor prognosis. In neoadjuvant chemotherapy (NACT) pathological complete response (pCR) is a predictor for outcome. The aim of this study was to evaluate NGAL as a predictor of response to NACT and to validate NGAL as a prognostic factor for clinical outcome in patients with primary BC. Immunohistochemistry was performed on tissue microarrays from 652 core biopsies from BC patients, who underwent NACT in the GeparTrio trial. NGAL expression and intensity was evaluated separately. NGAL was detected in 42.2% of the breast carcinomas in the cytoplasm. NGAL expression correlated with negative hormone receptor (HR) status, but not with other baseline parameters. NGAL expression did not correlate with pCR in the full population, however, NGAL expression and staining intensity were significantly associated with higher pCR rates in patients with positive HR status. In addition, strong NGAL expression correlated with higher pCR rates in node negative patients, patients with histological grade 1 or 2 tumors and a tumor size <40 mm. In univariate survival analysis, positive NGAL expression and strong staining intensity correlated with decreased disease-free survival (DFS) in the entire cohort and different subgroups, including HR positive patients. Similar correlations were found for intense staining and decreased overall survival (OS). In multivariate analysis, NGAL expression remained an independent prognostic factor for DFS. The results show that in low-risk subgroups, NGAL was found to be a predictive marker for pCR after NACT. Furthermore, NGAL could be validated as an independent prognostic factor for decreased DFS in primary human BC.

Demographic and psychosocial factors associated with risk perception for breast cancer.

The objective of this study was to investigate, in a female population-based sample, specific demographic and psychosocial predictors of perception of risk for female breast cancer. The study was a cross-sectional survey of 7135 healthy women ranging from 15 to 85 years. A questionnaire assessed the perceived risk for breast cancer in 6 German centers. Specified awareness was personal knowledge in relation to breast cancer incidence, risk factors, perception, and level of concern. An awareness score was defined and related to values of several risk factors. Generally, 78.1% of women were aware of breast cancer. However, only one-third (31.2%) of women estimated the incidence of breast cancer correctly; 52% recognized age, 33.9% recognized hormonal contraceptives, and 34.1% recognized hormonal replacement therapy as factors of breast cancer risk. The most frequent specified sources of information were gynecologists (48.4%). The awareness score of women informed by gynecologists was significantly better compared to women informed by other healthcare professionals. However, a statistically significant improvement of the awareness score was reached for women with a higher educational level, information seeking by TV, radio, printed sources, medical books and healthcare flyers. Recommendations for improvement of cancer prevention programs include targeting comprehension regarding the lifetime risk of breast cancer, age as a risk factor, survival from breast cancer and hormonal factors. According to these results, there is an urgent need to separately address the perceptions of women, depending on age, social status and educational level.

Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer.

PURPOSE: To compare the efficacy of pegylated liposomal doxorubicin (PLD) with that of a common salvage regimen (comparator) in patients with taxane-refractory advanced breast cancer. PATIENTS AND METHODS: Following failure of a first- or second-line taxane-containing regimen for metastatic disease, 301 women were randomly assigned to receive PLD (50 mg/m(2) every 28 days); or comparator-vinorelbine (30 mg/m(2) weekly) or mitomycin C (10 mg/m(2) day 1 and every 28 days) plus vinblastine (5 mg/m(2) day 1, day 14, day 28, and day 42) every 6 to 8 weeks. Patients were stratified before random assignment based on number of previous chemotherapy regimens for metastatic disease and presence of bone metastases only. RESULTS: Progression-free survival (PFS) and overall survival (OS) were similar for PLD and comparator (PFS: hazard ratio [HR], 1.26; 95% CI, 0.98 to 1.62; P =.11; median, 2.9 months [PLD] and 2.5 months [comparator]; OS: HR, 1.05; 95% CI, 0.82 to 1.33; P =.71; median, 11.0 months [PLD] and 9.0 months [comparator]). In anthracycline-naïve patients, PFS was somewhat longer with PLD, relative to the comparator (n = 44; median PFS, 5.8 v 2.1 months; HR, 2.40; 95% CI, 1.16 to 4.95; P =.01). Most frequently reported adverse events were nausea (23% to 31%), vomiting (17% to 20%), and fatigue (9% to 20%) and were similar among treatment groups. PLD-treated patients experienced more palmar-plantar erythrodysesthesia (37%; 18% grade 3, 1 patient grade 4) and stomatitis (22%; 5% grades 3/4). Neuropathy (11%), constipation (16%), and neutropenia (14%) were more common with vinorelbine. Alopecia was low in both the PLD and vinorelbine groups (3% and 5%). CONCLUSION: PLD has efficacy comparable to that of common salvage regimens in patients with taxane-refractory metastatic breast cancer, thereby representing a useful therapeutic option.

Prognostic and predictive impact of the HER-2/ neu extracellular domain (ECD) in the serum of patients treated with chemotherapy for metastatic breast cancer.

BACKGROUND: The extracellular domain of the HER-2/neu -receptor (ECD) is shed from the receptor protein and can be detected in serum. However, the clinical implication of HER-2/neu ECD measurement must be further evaluated. METHODS: In patients with metastatic breast cancer participating in a trial on first-line chemotherapy, the association of serum HER-2/neu ECD with progression-free interval, survival, and response was studied. Blood samples of patients receiving epirubicin and either cyclophosphamide (EC) or paclitaxel (ET) were collected before (n = 103) and in addition, after three courses of therapy (n = 46). RESULTS: HER-2/neu ECD levels correlate with HER-2/neu overexpression of corresponding primary tumors determined by immunohistochemistry (antibody CB11, p = 0.018) with an optimized cut-off at 15 ng/mL. Elevated serum levels of HER-2/neu ECD before chemotherapy were correlated with shorter overall survival (p = 0.0097), but not with reduced progression-free survival and response to chemotherapy. In subgroup analyses, patients with elevated pretherapeutic HER-2/neu ECD levels treated with EC showed shorter overall survival (p = 0.0092); no difference was seen in the ET group. With regard to progression-free survival, patients with elevated HER-2/neu ECD levels tended to benefit from ET (p = 0.0341), in patients with low levels no difference was observed between EC and ET. A decrease of HER-2/neu ECD levels after three courses of therapy was associated with response to therapy (p = 0.006). CONCLUSION: In our group of metastatic breast cancer patients, elevated HER-2/neu ECD levels are associated with decreased overall survival. With regard to progression-free survival, particularly patients with high HER-2/neu ECD levels seem to benefit from taxane-containing chemotherapy.