Exploratory investigation of PSCA-protein expression in primary breast cancer patients reveals a link to HER2/neu overexpression.

BACKGROUND: Prostate stem cell antigen (PSCA) has been suggested as biomarker and therapeutic target for prostate cancer. Recent advances showed that PSCA is up-regulated in other cancer entities, such as bladder or pancreatic cancer. However, the clinical relevance of PSCA-expression in breast cancer patients has not yet been established and is therefore addressed by the current study. METHODS: PSCA-protein expression was assessed in 405 breast cancer patients, using immunohistochemistry (PSCA antibody MB1) and tissue microarrays. RESULTS: PSCA-expression was detected in 94/405 patients (23%) and correlated with unfavorable histopathological grade (p=0.011) and increased Ki67 proliferation index (p=0.006). We observed a strong positive correlation between PSCA-protein expression and HER2/neu receptor status (p<0.001). PSCA did not provide prognostic information in the analyzed cohort. Interestingly, the distribution of PSCA-expression among triple negative patients was comparable to the total population. CONCLUSION: We identified a subgroup of PSCA-positive breast cancer patients, which could be amenable for a PSCA-targeted therapy. Moreover, given that we found a strong positive correlation between PSCA- and HER/neu expression, targeting PSCA may provide an alternative therapeutic option in case of trastuzumab resistance.

Trastuzumab and survival of patients with metastatic breast cancer.

INTRODUCTION: Prognosis of Her2-positive breast cancer has changed since the introduction of trastuzumab for treatment in metastatic and early breast cancer. It was described to be even better compared to prognosis of Her2-negative metastatic breast cancer. The purpose of this study was to evaluate the effect of trastuzumab in our cohort. Besides the effect of adjuvant pretreatment with trastuzumab on survival of patients with metastatic Her2-positive breast cancer was analyzed. METHODS: All patients with primary breast cancer of the Regional Breast Cancer Center Dresden diagnosed during the years 2001-2013 were analyzed for treatment with or without trastuzumab in the adjuvant and in the metastatic treatment setting using Kaplan-Meier survival estimation and Cox regression. Age and tumor stage at time of first diagnosis of breast cancer as well as hormone receptor status, grading, time, and site of metastasis at first diagnosis of distant metastatic disease were analyzed. RESULTS: Of 4.481 female patients with primary breast cancer, 643 presented with metastatic disease. Her2-positive status was documented in 465 patients, including 116 patients with primary or secondary metastases. Median survival of patients with Her2-positive primary metastatic disease was 3.0 years (95% CI 2.3-4.0). After adjustment for other factors, survival was better in patients with Her2-positive breast cancer with trastuzumab therapy compared to Her2-negative metastatic disease (HR 2.10; 95% CI 1.58-2.79). Analysis of influence of adjuvant therapy with and without trastuzumab by Kaplan-Meier showed a trend for better survival in not pretreated patients. Median survival was highest in hormone receptor-positive Her2-positive (triple-positive) primary metastatic breast cancer patients with 3.3 years (95% CI 2.3-4.6). CONCLUSION: Prognosis of patients with Her2-positive metastatic breast cancer after trastuzumab treatment is more favorable than for Her2-negative breast cancer. The role of adjuvant chemotherapy with or without trastuzumab warrants further research. Survival is best in triple-positive metastatic breast cancer. This will effect counseling at the time of first diagnosis of metastatic breast cancer.

Impact of breast cancer subtypes and patterns of metastasis on outcome.

Clinical outcome of patients with stage IV breast cancer is dependent on tumor biology, extent, and localization of metastases. Routine imaging diagnostics for distant metastasis is not recommended by the national guidelines for breast cancer follow-up. In this study, we evaluated different patterns of metastases of cancer subtypes in order to generate hypotheses on individualization of follow-up after breast cancer in the adjuvant setting. Patients of the Regional Breast Cancer Center Dresden diagnosed within the years 2006-2011 were classified into the five intrinsic subtypes luminal A (ER+, Her2-, G1/2), luminal B/Her2 negative (ER+, Her2-, G3), triple positive (ER+, PR+, Her2+), Her2-enriched (ER-, Her2+), and triple negative (ER-, PR-, Her2-) and with a median follow-up of 45 months. Tumor stage at time of first diagnosis of breast cancer as well as time and site of metastasis at first diagnosis of distant metastatic disease was analyzed. Tumor specimen of 2284 female patients with primary breast cancer was classified into five subtypes. Distant recurrence-free survival at 3 years was most unfavorable in Her2-enriched (66.8 %), triple negative (75.9 %), and triple-positive breast cancer (81.7 %). The same subtypes most frequently presented with visceral metastases only at first presentation: Her2-enriched 46.9 %, triple negative 45.5 %, and triple-positive breast cancer 37.5 %. Longest median survival of 2.3 years was seen in luminal A and in Her2-enriched metastatic disease, respectively. Median survival was significantly better in the luminal A, Her2-enriched, and triple-positive subtype compared to triple-negative breast cancer (p < 0.005). Differences in time to metastatic disease, first localization of metastases, and overall survival after diagnosis of metastatic disease were shown. Considering new targeted therapies and the option of surgery of oligometastases, screening for visceral metastases might be reasonable after diagnosis of Her2-positive subtypes.

Prognostic relevance of tumour cell-associated uPAR expression in invasive ductal breast carcinoma.

AIMS: The urokinase-type plasminogen activator receptor (uPAR) is a key molecule for pericellular proteolysis in tumour cell invasion and metastasis. The aim was to evaluate the prognostic impact of uPAR in invasive breast cancer dependent on which cell types within the tumour express uPAR. METHODS AND RESULTS: uPAR expression was analysed by immunohistochemistry in 270 tumour tissue specimens of invasive ductal breast carcinomas using tissue microarrays. For evaluation of uPAR immunoexpression we used the epitope-mapped, uPAR domain II-specific monoclonal antibody IID7. High uPAR score values in both tumour cells (uPAR-Tc) and stromal cells were significantly related to high tumour grade (G3), and inversely correlated with oestrogen receptor status. On multivariate analysis, high uPAR-Tc values contributed independent prognostic information for disease-free survival (hazard ratio 1.93, P = 0.007) when adjusted for prognostically relevant clinicopathological parameters, whereas uPAR expression in stromal cells was not related to prognosis. In addition, elevated uPAR-Tc values were found to be prognostic indicators in clinically relevant subgroups of patients with invasive breast cancer. CONCLUSIONS: In invasive breast cancer uPAR expression in invasive carcinoma cells, but not in stromal cells, has a significant impact on patients' prognosis, and contributes to a more aggressive tumour phenotype.

A psychosomatic intervention in pregnant in-patient women with prenatal somatic risks.

PURPOSE: This study examined whether a short-term psychosomatic intervention during pregnancy had effects on characteristics of labour and delivery as well as on the long-term course of anxiety, depression and physical complaints in pregnant in-patient women. METHODS: All gynaecological and obstetric inpatients of a university hospital, who had either exhibited complications during their pregnancy or were considered high-risk pregnancies, were examined. Symptoms of anxiety and depression (HADS) and physical symptoms (GBB) were assessed by standardised questionnaires. Women with elevated scores on either the HADS or the GBB were randomly assigned to either a treatment group, which had received a psychosomatic intervention or an untreated control group. Of the n = 238 women who were assessed during their stay in our hospital, n = 135 were included in the follow-up 1-year later. RESULTS: More than one-third of the participants (38.7%) had elevated scores of anxiety, depression and/or physical symptoms. The psychosomatic intervention had a significant effect on anxiety scores (p = 0.006), but not on depression scores, physical complaints and characteristics of labour and delivery. CONCLUSIONS: Findings suggest that a short-term psychosomatic intervention can have a positive long-term effect on anxiety symptoms. Future studies are needed to show whether the reduction of anxiety symptoms in turn can lead to a reduction of postnatal complications and lower rates of disturbed mother-child interactions.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by vinorelbine treatment of metastatic breast cancer.

BACKGROUND: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is known as a rare adverse event with chemotherapy. We report the case of a SIADH occurring after vinorelbine treatment. CASE REPORT: In a 79-year-old woman breast cancer was first diagnosed in 2000. Three years after the first diagnosis the patient developed bone and liver metastases. Seven days after receiving the 1st course of palliative chemotherapy with vinorelbine the patient suffered from decreased mental awareness, fatigue, and physical weakness. After the diagnosis of SIADH based on laboratory findings in combination with clinical symptoms, we started therapy with balanced fluid intake and intravenous infusion of normotonic saline. CONCLUSION: The development of SIADH as a rare adverse event with vinorelbine treatment has to be taken into consideration.