Recurrent mutations of BRCA1, BRCA2 and PALB2 in the population of breast and ovarian cancer patients in Southern Poland.

BACKGROUND: Mutations in the BRCA1, BRCA2 and PALB2 genes are well-established risk factors for the development of breast and/or ovarian cancer. The frequency and spectrum of mutations in these genes has not yet been examined in the population of Southern Poland. METHODS: We examined the entire coding sequences of the BRCA1 and BRCA2 genes and genotyped a recurrent mutation of the PALB2 gene (c.509_510delGA) in 121 women with familial and/or early-onset breast or ovarian cancer from Southern Poland. RESULTS: A BRCA1 mutation was identified in 11 of 121 patients (9.1 %) and a BRCA2 mutation was identified in 10 of 121 patients (8.3 %). Two founder mutations of BRCA1 accounted for 91 % of all BRCA1 mutation carriers (c.5266dupC was identified in six patients and c.181 T > G was identified in four patients). Three of the seven different BRCA2 mutations were detected in two patients each (c.9371A > T, c.9403delC and c.1310_1313delAAGA). Three mutations have not been previously reported in the Polish population (BRCA1 c.3531delT, BRCA2 c.1310_1313delAAGA and BRCA2 c.9027delT). The recurrent PALB2 mutation c.509_510delGA was identified in two patients (1.7 %). CONCLUSIONS: The standard panel of BRCA1 founder mutations is sufficiently sensitive for the identification of BRCA1 mutation carriers in Southern Poland. The BRCA2 mutations c.9371A > T and c.9403delC as well as the PALB2 mutation c.509_510delGA should be included in the testing panel for this population.

Distant metastases from invasive lobular breast carcinoma classic type - treatment and prognosis.

INTRODUCTION: Invasive lobular carcinoma (ILC) comprises 4-15% of all malignant neoplasms of the breast. The "classical variant of ILC" (C-ILC) constitutes some 60-80% of this cancer. The main cause of treatment failures is dissemination observed in 8-38% patients The disant metastases (DM) are frequently localized in: bones, gastrointestinal tract, uterus, leptomeninges, and ovaries. The aim of this study was to present the methods and results of the treatment of patients with DM from the classical variant of ILC (C-ILC) at a single institution in Poland. MATERIALS AND METHODS: Between January 1983 and December 2004, 210 women with C-ILC of the breast were primarily treated surgically (mastectomy in 182 (86.7%) patients and breast conserving therapy in 28 (13.3%) patients). Then adjuvant therapy (radiotherapy, chemotherapy, and hormonotherapy) was applied according to presence of clinical indications. RESULTS: The present study focused on a group of 41 patients with a median age of 59 that died with DM from C-ILC during the ten-year follow-up. This failure developed on average 65 months (3-186) after surgery of ILC. The most frequently DM developed: bones (39.1%), GI (small bowell, stomach, colon, rectum) - 31.8%, and reproductive organs (ovary, uterus) - 19.1%. In therapy of DM, different configuration surgery, radiotherapy, and chemo-hormonotherapy were used. The median survival after the diagnosis of DM was connected with localization of distant metastases. CONCLUSION: Patients with classic variant of infiltrate lobular cancer of breast should be regularly follow-up, which could permit early diagnosis of distant metastases and improve treatment results.

Toxicity of concurrent chemoradiotherapy for locally advanced cervical cancer.

AIM OF THE STUDY: The analysis of acute and late toxicity of concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC) based on review of 120 patients treated in Centre of Oncology in Krakow between 2001 and 2007. MATERIALS AND METHODS: Medium age of the patients was 52 years (43-66). Overall, 12 patients (10.0%) were in Stage IB2, 54 (45.0%) in Stage II, 43 (35.8%) in Stage III, and 11 (9.2%) in Stage IVA. Squamous cell carcinoma was present in 114 (95.0%) patients. Well-differentiated (grade 1) tumour was found in 39 (32.5%) patients, moderately differentiated (grade 2) in 41 (34.2%), and poorly differentiated (grade 3) in 40 (33.3%). Karnofsky performance status score was 70 in 72 (60.0%) patients, and 80-90 in 48 (40%). External radiation therapy was delivered with high-energy six to 15 MV photon beams using four-field brick technique. The total dose of 50 Gy was given in 25 fractions within five weeks using standard fractionation. Concurrently with external radiotherapy, six cycles of chemotherapy were administered to all the patients as an intravenous infusion of once-weekly cisplatin 40 mg/m2. On completion of external beam radiotherapy, low-dose rate brachytherapy with tandem and two colpostats was performed to deliver the dose of 40 Gy to point A in two 20 Gy insertions at weekly intervals. RESULTS: Of the 120 patients in the investigated group, 78 (65%) were disease-free for five years. Symptoms of acute treatment-related toxicity grade 3 or 4 (WHO) occurred in 21.6% of patients including leucopoenia in 7.5%. anaemia in 5.0%, nausea and vomiting in 3.3%, diarrhea in 5.0%, and urinary tract infection in 0.8%. Full planned treatment (teleradiotherapy + chemotherapy + brachytherapy) completed 78.3% of the group; full planned radiotherapy without full chemotherapy completed 20% of the patients. Late treatment complications of grade 3 or 4 were observed in two (1.6%) patients (narrowing of large intestine requiring surgery and recto-vaginal fistula). CONCLUSIONS: In patients with LACC treated with CCRT, the most frequent acute toxic effects include: haematological disorders (leucopoenia, anaemia), gastrointestinal disorders (nausea and vomiting, diarrhea), vulvo-vaginal disorders, and urinary tract infection. The most frequent late toxic effects included: rectal bleeding, bowel complications requiring surgery, stenosis or recto-vaginal fistula, and haematuria.

Validation of the Polish version of the EORTC QLQ-CX24 module for the assessment of health-related quality of life in women with cervical cancer.

The aim of our study was to undertake a prospective validation study of the Polish version of the EORTC cervical cancer (EORTC QLQ-CX24) module used alongside the EORTC core measure. The translated module was pilot-tested according to the established EORTC guidelines. Patients with histological confirmation of cervical cancer were eligible for the study. All patients filled out the Polish version of the EORTC QLQ-CX24 module in addition to EORTC QLQ-C30 and a demographic questionnaire. Standardised validity and reliability analyses were performed. One hundred and seventy-one patients were enrolled into the study, mean age ± SD: 52.1 ± 9.6. Cronbach alpha coefficients, range 0.81-0.88, showed positive internal consistency. Re-test was undertaken with 40 patients (23.4%). Interclass correlations for the EORTC QLQ-CX24 ranged from 0.85 to 0.89 and proved appropriate test-retest reliability. Satisfactory convergent and discriminant validity in multi-trait scaling analyses was seen. Concluding, the Polish version of the EORTC QLQ-CX24 module is a reliable and valid tool for measuring HRQoL in patients with cervical cancer. It can be fully recommended for use in clinical and epidemiological settings in the Polish population.

Clinical picture of infiltrating lobular carcinoma of the breast: an analysis of 96 patients.

OBJECTIVE: The aim of this study was to present the clinical picture of infiltrating lobular carcinoma (ILC) of the breast. MATERIALS AND METHODS: A detailed analysis was performed for the group of 96 ILC patients subject to initial surgical treatment in the Krakow Branch of Centre of Oncology between 1983 and 1996. The investigated group was selected out of 2,347 breast cancer patients treated during that period, based on re-examination of histologic specimens of the initial patient group. RESULTS: The following distinctive demographic and clinical features of ILC were found: average age of patients: 59 years (37 - 83); average duration of pathological symptoms: five months; most frequent site of primary tumor: upper outer quadrant (54.2%); primary tumor Stage: I/II0 (64.6%), III0A (35.4%); tumor size in breast: up to five cm (69.8%), larger than five cm (30.2%); no axillary lymph nodes involvement in 51% of patients; multifocality of lesions in 10% of patients; contralateral disease occurrence in eight percent of patients; atypical pattern of distant metastases, e.g. gastrointestinal system, gynaecologic organs, and cerebral meninges. CONCLUSIONS: Based on this analysis as well as on literature reports, it was found that the fundamental differences between ILC and infiltrating ductal carcinoma (IDC) included demographic and clinical features as patient age, primary tumor size at diagnosis, incidence of multifocality and contralateral disease, sites of distant metastases, and histopathological status of axillary lymph nodes.

Radiotherapy for carcinoma of the vagina. Immunocytochemical and cytofluorometric analysis of prognostic factors.

BACKGROUND AND PURPOSE: The aim of this study was to assess the potential prognostic factors in patients with primary invasive vaginal carcinoma (PIVC) treated with radical irradiation. PATIENTS AND METHODS: The analysis was performed on 77 patients with PIVC treated between 1985 and 2005 in the Maria Sklodowska-Curie Memorial Institute of Oncology, Cancer Center in Krakow. A total of 36 patients (46.8 %) survived 5 years with no evidence of disease (NED). The following groups of factors were assessed for potential prognostic value: population-based (age), clinical (Karnofsky Performance Score [KPS], hemoglobin level, primary location of the vaginal lesion, macroscopic type, length of the involved vaginal wall, FIGO stage), microscopic (microscopic type, grade, mitotic index, presence of atypical mitoses, lymphatic vessels invasion, lymphocytes/plasmocytes infiltration, focal necrosis, VAIN-3), immunohistochemical (protein p53 expression, MIB-1 index), cytofluorometric (ploidity, index DI, S-phase fraction, proliferation index SG2M) factors. RESULTS: Significantly better 5-year NED was observed in patients: < 60 years, KPS ≥ 80, FIGO stage I and II, grade G1-2, MIB-1 index < 70, S-phase fraction < 10, and proliferation index < 25. Independent factors for better prognosis in the multivariate Cox analysis were age < 60 years, FIGO stage I or II, and MIB-1 index < 70. CONCLUSION: Independent prognostic factors in the radically irradiated PIVC patients were as follows: age, FIGO stage, MIB-1 index.

Effectiveness of radiotherapy in patients with primary invasive vaginal carcinoma.

INTRODUCTION: The aim of the study was to present an institutional experience in radiation therapy of primary invasive vaginal carcinoma (PIVC) patients treated in the Krakow Branch of Centre of Oncology, with special regard to treatment effectiveness and failure causes. MATERIALS AND METHODS: Between February 1967 and January 2007, 162 PIVC patients were treated with radical radiotherapy in the Krakow Branch of Centre of Oncology, Maria Sklodowska-Curie Memorial Institute. Twenty-seven (16.7%) patients in Stage I(0) were treated with intracavitary brachytherapy alone; for 127 (78.4%) patients in Stage I(0)- IV(0) intracavitary brachytherapy was combined with external radiation therapy; and eight (4.9%) patients in Stage IVA(0) were given only external radiotherapy. RESULTS: In the investigated group of 162 patients, five-year disease-free survival was observed in 46.3% of the cases. Patient age and FIGO Stage of neoplastic disease were independent prognostic factors. Five-year disease-free survival was observed in 64.9% of the patients < 60 years of age and only in 30.7% > or = 60 years of age; and in 62.3% of PIVC patients in Stages I and II(0) as compared to 19.7% of Stages III(0) and IV(0) cases. Among 78 patients who died of PIVC, in 60 (76.9%) cases the cause of death was locoregional failure; in six (7.7%), locoregional failure and distant metastasis; and in 12 (15.4%), distant metastasis. CONCLUSIONS: Radiotherapy is effective treatment for PIVC patients. Age below 60 years and non-advanced neoplastic disease were independent favourable prognostic factors in the investigated group of patients. The primary cause of treatment failure was failure to achieve locoregional disease control.

[The role of teleradiotherapy in treatment of thyroid cancer]. / Miejsce teleradioterapii w leczeniu raka tarczycy.

The role of teleradiotherapy in the treatment of patients with thyroid cancer is presented. The indications for external irradiation include patients with: primary inoperable disease or inoperable recurrence, microscopic or gross residual disease after surgery, high risk of local regional failure, and metastatic thyroid cancer, especially with skeletal, brain and mediastinal metastases.

Male breast cancer. Does the prognosis differ compared to female?

Due to the low incidence of breast cancer in males there are not many reports in the literature. In this study we analyzed results of treatment in 65 breast cancer males, who had been treated in one institution. Radical surgery was performed in 45 patients. Lymph node metastases were found in 25 patients (55.5%), the tumor was usually moderately differentiated (21 pts - 46.7%). Median survival after radical surgery was 73 months compared to 38 months for nonsurgical patients (p < 0.0001). In the group of males after radical surgery the results of 5-, 10- and 15-year survival rates were 69.8, 59.7 and 31.3% respectively. Comparable analysis of two subgroups of patients with favorable (T1 or T2, N0, grade I or II) and unfavorable (T3 or N+ or grade III) prognostic factors was also performed. In the first subgroup the 5-, 10- and 15-year survival rates were 90, 77.4 and 62%, compared to 61.8, 23.1 and 23. 1% for the second subgroup. The multivariate analysis showed grading and node status as the strongest parameters influencing survival. Relative risk of death was over 3 times higher for nodal metastases and near 3 times higher for high grade carcinomas (p < 0.01), compared to patients without metastases and low grade of tumor. Similar analysis was performed when 45 males were compared to 500 selected women, with similar clinical parameters (age, node status, grading). Again, data indicated grading and lymph node status as the strongest prognostic factors. It was not unlikely, that gender had some influence on prognosis, when relative risk of death for males was over 1.5 times higher than for females, but this result was not clearly significant (p < 0.1 ). The question, whether male breast cancer prognosis is worse then in female remains open. Multiinstitutional prospective studies are needed in this area.

[Adenoid cystic carcinoma of the breast. Analysis of 7 patients]. / Rak gruczolowo-torbielowaty gruczolu sutkowego. Analiza 7 chorych.

A retrospective analysis of 7 patients with adenoid cystic carcinoma of the breast operated at Center of Oncology in Kraków is presented. Ten years without evidence of disease survived 6 (85.7%) patients. One patient only, with poorly differentiated carcinoma, presented axillary metastases and died of metastases to the lungs and hepar.

[Infiltrating lobular carcinoma of the breast. Clinical picture, treatment and prognosis]. / Naciekajacy rak zrazikowy sutka. Obraz kliniczny, leczenie i rokowanie.

An analysis of 80 patients with infiltrating lobular carcinoma of the breast treated at Center of Oncology in Kraków is presented. All patients underwent radical mastectomy. The evaluation of treatment results showed stage, pathological tumor size, and involvement of axillary nodes as the prognostic factors. The ten-year survival rate NED in all group was 38.8%; for stage I, II, and III it was 62.5%, 48.8%, and 19.4% respectively.

[20-year survival in women with breast cancer]. / 20-letnie przezycia kobiet chorych na raka sutka.

We analysed 170 women with carcinoma of the breast who survived 20 years after local or loco-regional therapy, without adjuvant chemo-hormonotherapy. Patients with axillary lymph nodes metastases constitute thirty-six percent of this group.