Low frequency of the CHEK2*1100delC mutation among breast cancer probands from three regions of Poland.

The 1100delC germline mutation of the CHEK2 gene appears to contribute significantly to the overall breast cancer incidence in some West and North European countries, but seems to be much less frequent among breast cancer patients from other regions of Europe. In the present study we found, respectively, 3/487, 1/296 and 0/279 carriers of this mutation among breast cancer patients from the East-Central, South-East and West-Central regions of Poland. Two carriers of the 1100delC mutation were found among 120 patients with bilateral breast cancer, but only one had a previous family incidence of breast cancer. We found no carriers among 182 patients with unilateral breast cancer with family history of this tumor and among 64 patients with breast cancer and a second primary tumor at an other site. We conclude that the 1100delC mutation of the CHEK2 gene contributes little to the overall breast cancer burden in Poland, including familial cases of this malignancy. Further studies are still needed to evaluate the contribution of this mutation to the development of bilateral breast tumors.

BRCA1 and BRCA2 mutations as prognostic factors in bilateral breast cancer patients.

BACKGROUND: Incidence of primary bilateral breast cancer (BC) is rare and does not exceed 5%. BRCA1/2 mutation carriers diagnosed with breast cancer have a strong life time risk of developing contralateral breast cancer (53% versus 2%). PATIENTS AND METHODS: A group of 108 patients with bilateral breast cancer, who reported at our Cancer Centres from 2000 to 2002, were subjected to genetic testing. Similarities and differences between BRCA1/2 carriers and non-carriers were analysed in terms of family history, pathology of tumour, age of diagnosis, developing contralateral BC and second primary cancer. RESULTS: BRCA1/2 mutations were detected in 32 of 108 patients. Family history of BC was identified in 46.9% of these patients compared with 22.4% of non-carriers (P <0.05). Synchronous BC was diagnosed significantly rarer [4 of 32 (12.5%)] in BRCA1/2 carriers than in the non-carrier group [26 of 76 (34.2%)]. In addition, patients with BRCA mutations were younger when they were diagnosed than non-carriers. BRCA1/2 carriers had a significantly higher incidence of medullary BC (13.6% versus 1.7%) and developed ovarian cancer significantly more frequently than non-carriers (12 of 32 and 1 of 72 patients, respectively). CONCLUSIONS: Patients with bilateral BC having BRCA mutations are significantly younger than non-carriers. They also have a significantly higher family history of BC and an increased risk of developing ovarian cancer. The differences in clinical aspects of BRCA carriers with bilateral BC should be considered in clinical management.

Frequent disease progression and early recurrence in patients with familial ovarian cancer primarily treated with paclitaxel and cis- or carboplatin (preliminary report).

PURPOSE: To evaluate frequencies of early disease progressions and recurrences in patients with familial vs sporadic ovarian cancers following primary paclitaxel/cis- or carboplatin chemotherapy. METHODS: The frequencies of disease progression up to six months following primary paclitaxel/cis- or carboplatin and of early disease recurrences were analysed in 18 Stage III patients with familial ovarian cancers, both carriers and non-carriers of 5382 insC BRCA1 mutation, and in 35 patients with Stage III sporadic ovarian tumors. RESULTS: Progressive disease within first six months following chemotherapy developed in 5/18 patients with familial cancers vs. 5/35 patients with sporadic tumors. Early disease recurrences (up to 6 months after treatment) occurred in 3/18 patients with familial vs. 2/35 patients with sporadic tumors. Recurrences after 7-12 months following treatment occurred, respectively, in 3/13 and 3/31 patients from these groups. CONCLUSION: The results of this preliminary report may suggest that patients with familial ovarian tumors respond less favourably to paclitaxel/cis- or carboplatin treatment than patients with sporadic ovarian tumors. These findings should be however confirmed in a prospective study on a larger group of patients.

Prognostic value of serial serum interleukin-6 level estimation in patients with lung cancer: a preliminary report.

In the present report, we serially measured the levels of interleukin-6 (IL-6) and some acute-phase proteins (APP) in 61 lung cancer patients undergoing radiotherapy in order to investigate the relationship between the response to the treatment and the changes in parameters of systemic inflammatory response. The patients were divided into two groups depending on the response to the treatment. The first group (referred to as responders) comprised 32 patients with stable disease, partial remission or total remission. Twenty-nine patients with progression of the disease were included to the second group (referred to as non-responders). Six patients died due to the lung cancer during the study. We showed a decrease in IL-6 serum level and C-reactive protein (CRP) level in responders but not in non-responders. However, the most interesting results were obtained after retrospective analysis of the data of six deceased patients. In these patients we observed an elevation of IL-6 and CRP before the patients' deaths. Following the changes in acute-phase response and interleukin-6 serum levels in lung cancer patients seems to be helpful in prognosis of the outcome of the disease. Based on our data, we conclude that an elevation in IL-6 and/or CRP level in patients with lung cancer may serve as an adverse prognostic factor.

Serum levels of interleukin-10 and interleukin-6 in patients with lung cancer.

Since the enhanced production of IL-10 by human bronchogenic carcinoma has already been documented, in the present study serum levels of IL-10 were measured serially in patients with lung cancer undergoing radiotherapy. Thirty-one full diagnosed cancer patients underwent the radiotherapy procedures. The interleukin-10 (IL-10) and interleukin-6 (IL-6) serum levels were measured before therapy and after 3, 6 and 12 months after therapy. The interleukins concentrations were evaluated using a solid phase sandwich Enzyme-Linked-Immuno-Sorbent-Assay (ELISA). In all patients the serum levels of IL-10 have been found elevated. Due to the treatment they progressively declined to almost normal ranges in responders, while they remained elevated in non-responders. Serum levels of interleukin-6 have been elevated in the majority of our patients. After 12 months observation they also decreased, mainly in patients responding to the treatment. No correlation between serum IL-10 and IL-6 level has been found. The importance of serum IL-6 determination in lung cancer patients monitoring has already been established. The present study shows, that in spite of still unclear role of IL-10 in the process of carcinogenesis, it may be considered as a prognostic factor in lung cancer.