PTEN loss is not associated with trastuzumab resistance in metastatic breast cancer.

PURPOSE: Although the clinical benefits of trastuzumab are well known, intrinsic or acquired resistance is a commonly encountered clinical condition. A potential resistance mechanism is aberrant downstream signal transmission due to loss of phosphatase and tensine homologue (PTEN). This study investigated the relationship between trastuzumab response and loss of PTEN in metastatic breast cancer patients. METHODS: Patients with histologically confirmed human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer, who were treated with trastuzumab were enrolled into the study. PTEN expression was immunohistochemically evaluated. RESULTS: The patient median age was 50 years. Of 38 patients, 6 (15.8%) showed PTEN loss. No statistically significant difference was found between trastuzumab response, overall survival (OS) and progression-free survival (PFS) and PTEN loss (p=0.538). CONCLUSION: The activation of phosphatidylinositol 3-kinase (PI3K) pathway resulting from PTEN loss was not found to be correlated with trastuzumab response and survival. PTEN loss should not lead to exclusion of patients from the potential to benefit from trastuzumab administration.

p95-HER2 and trastuzumab resistance in metastatic breast cancer; is immunohistochemistry appropriate?

PURPOSE: Unraveling the mechanisms underlying the resistance to trastuzumab is important for amending the prognosis of patients with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer. Experimentally, it has been shown that p95-HER2 positive breast tumors are resistant to trastuzumab. The aim of this study was to investigate the predictive and prognostic importance of p95-HER2 expression by immunohistochemistry in HER2-positive metastatic breast cancer patients treated with trastuzumab. METHODS: Only patients who had a histological diagnosis of HER2-positive metastatic breast cancer and who had received first line therapy containing trastuzumab were enrolled in the study. Immunohistochemistry was used to analyze p95-HER2 expression in the tissue blocks of the patients. RESULTS: The study was performed on 38 patients aged between 30 and 84 years. In 14 patients (36.8%), p95-HER2 was positive, whereas it was negative in the remaining 24 patients (63.2%). There was no significant correlation between p95-HER2 expression and overall survival, response to trastuzumab, and progression-free survival (PFS). CONCLUSION: Unlike previous reports, there was no correlation between the p95-HER2 expression and resistance to trastuzumab. It may be argued that an analysis using immunohistochemistry is inadequate for determining p95- HER2. In order to ascertain whether immunohistochemistry is an appropriate method, studies with larger patient groups are needed.

Clinical outcome of Turkish metastatic breast cancer patients with currently available treatment modalities--single center experience.

BACKGROUND: Breast cancer is the most common malignancy and the second leading cause of cancer-related death among women in the developed countries. Despite advances in screening, improved local therapies and adjuvant systemic treatments, median survival of metastatic breast cancer patients (MBC) is in the range of 2-3 years at most. We aimed to investigate whether the prognostic factors and therapeutic responses of our Turkish patients are similar to those in the literature. MATERIALS AND METHODS: We reviewed the medical records of MBC patients who had been treated in our institution between 1999-2009 and analyzed their clinicopathological features and survival outcomes retrospectively. RESULTS: A hundred and sixty patients were included. Median age was 47 (23-82), median follow up was 24 (2-186) months. At the time of diagnosis 59% of patients were under the age of 50 and 46% were postmenopausal. The majority (37%) had multiple sites of metastases. Forty percent received endocrine therapy and 40% chemotherapy as first line metastatic treatment. Thirty (20%) patients were treated with molecular targeting agents like trastuzumab, lapatinib and sunitinib, frequently combined with a chemotherapy agent. Five-year overall survival (OS) was 32% and median OS was 38 months for the whole group. Five year progression free survival (PFS) was 10% and median PFS was 10 months. Menopausal status, hormone receptor expression and disease free status had a significant impact on overall survival in the multivariate analysis (p 0.018, p 0.018 and p:0.003, respectively). CONCLUSIONS: All our patients were treated with the modern oncologic therapies recommended by the international guidelines. From our data, MBC patients live up to 3-4 years, indicating that further improvement beyond that requires development of new treatment modalities. The survival outcomes of our patients were consistent with the data reported in the literature.

Clinical outcome of breast cancer patients with N3a (≥10 positive lymph nodes) disease: has it changed over years?

It has been shown that breast cancer patients with N3a (10 positive lymph nodes) had a poor prognosis. We planned to investigate the clinical outcome BC patients who presented with N3a disease and had no evidence of systemic metastasis at the time of diagnosis. We made a retrospective chart review of breast cancer patients who had ≥10 positive lymph nodes and received adjuvant systemic therapy in Marmara University Hospital between 1998 and 2008. We recorded clinical, pathologic and treatment characteristics of the patients and analyzed the survival outcome. We identified 73 patients with N3a disease who were treated in Marmara University Hospital between 1998 and 2008. The median age was 52. Most (75%) of the patients had invasive ductal histology, 75% had T2/T3 tumors, 36% had grade 3 tumors. The median number of metastatic lymph nodes was 15. Estrogen and progesterone receptors were both positive in 61% and both negative in 16+ tumors. Her-2/neu status was assessed in 68% of the tumors; 18% of patients had 3+ and 50% had negative scores. Six patients had triple negative tumors. All patients except one received adjuvant chemotherapy and radiotherapy. Seventy-four percent of patients received anthracycline/taxane-based chemotherapy. Fifty-nine patients received adjuvant endocrine therapy, 42% them received aromatase inhibitors. Five of the 13 Her-2 positive patients received adjuvant trastuzumab. With a median follow-up of 47 months, 5-year disease and overall survival rates were 66 and 81%, respectively. Twenty-four patients had relapsed and 14 patients died. Her-2 status and the number of lymph nodes (<20 vs. ≥20) had significant impact on disease-free survival in the univariate analysis (P=0.03 and 0.05, respectively) and Her-2 retained its significant impact on disease-free survival in the multivariate analysis (P=0.05). The prognosis of BC patients with N3a disease has changed favorably in the past decade with the current standards of care.