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The aim of the study was to analyze the frequency and magnitude of association of 21 recurrent founder germline mutations in BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 genes with ovarian cancer risk among unselected patients in Poland. We genotyped 21 recurrent germline mutations in BRCA1 (9 mutations), BRCA2 (4 mutations), RAD51C (3 mutations), PALB2 (2 mutations), and CHEK2 (3 mutations) among 2270 Polish ovarian cancer patients and 1743 healthy controls, and assessed the odds ratios (OR) for developing ovarian cancer for each gene. Mutations were detected in 369 out of 2095 (17.6%) unselected ovarian cancer cases and 117 out of 1743 (6.7%) unaffected controls. The ovarian cancer risk was associated with mutations in BRCA1 (OR = 40.79, 95% CI: 18.67–114.78, p = 0.29 × 10−15), in BRCA2 (OR = 25.98, 95% CI: 1.55–434.8, p = 0.001), in RAD51C (OR = 6.28, 95% CI 1.77–39.9, p = 0.02), and in PALB2 (OR 3.34, 95% CI: 1.06–14.68, p = 0.06). There was no association found for CHEK2. We found that pathogenic mutations in BRCA1, BRCA2, RAD51C or PALB2 are responsible for 12.5% of unselected cases of ovarian cancer. We recommend that all women with ovarian cancer in Poland and first-degree female relatives should be tested for this panel of 18 mutations.

Objectives: Numerous reports suggest that the clinical course of ovarian cancer (OC) in BRCA , including BRCA1 , mutation carriers ( BRCA1 -OC) is different than in patients with sporadic ovarian cancer (SOC). Most of the authors indicate more fa­vourable treatment results in patients with BRCA1 -OC. The aim of the study was to compare the effectiveness of treatment of patients with advanced-stage (FIGO III/IV) SOC and BRCA1 -OC. Material and methods: Between 2004 and 2009, 957 OC patients were treated in Cracow Branch of Cancer Center, M. Sklodowska-Curie Memorial Institute, Poland. Germline BRCA1 mutation was found in 66 patients. To compare the effective­ness of treatment, the group of 47 advanced-stage BRCA1 -OC patients was matched with the group of 47 advanced-stage SOC patients. Pairs of patients were matched in terms of the most important prognostic factors, i.e. stages according to FIGO, primary cytoreduction extent, tumour histologic subtype and grade, as well as year of diagnosis and treatment. Results: The 5-year overall survival rate was 42.9% for BRCA1 -OC patients and 34.3% for SOC patients (p = 0.354). Mean time to progression was 22.7 and 14.5 months for BRCA1 -OC and SOC group, respectively (p = 0.05). Complete response to pri­mary surgery and first line chemotherapy was obtained in 42.5% and 37.9% of cases, respectively; the difference, however, did not reach the statistical significance. Conclusions: Results of combined treatment in the group of BRCA1 -related OC patients seem to be better than in the group of sporadic ovarian cancer patients.

The prognosis for patients with melanoma who have brain metastases is poor, a median survival does not exceed 4-6 months. There are no uniform standards of treatment for patients with melanoma brain metastases (MBMs). The most preferred treatment approaches include local therapy - surgical resection and/or stereotactic radiosurgery (SRS). The role of whole brain radiotherapy (WBRT) as an adjuvant to local therapy is controversial. WBRT remains a palliative approach for those patients who have multiple MBMs with contraindications for surgery or SRS, or/and poor performance status, or/and very widespread extracranial metastases. Corticosteroids have been used in palliative treatment of MBMs as relief from symptoms related to intracranial pressure and edema. In recent years, the development of new systemic therapeutic strategies has been observed. Various modalities of systemic treatment include chemotherapy, immunotherapy and targeted therapy. Also, multimodality management in different combinations is a common strategy. Decisions regarding the use of specific treatment modalities are dependent on patient's performance status, and the extent of both intracranial and extracranial disease. This review summarizes current treatment options, indications and outcomes in patients with brain metastases from melanoma.

Within the past years the proportion of cervical adenocarcinomas has increased, however, there is a shortage of data regarding immunohistochemical and molecular features and their prognostic relevance in early-stage cervical adenocarcinoma (esCAC). Aim of the present study was to evaluate molecular prognostic factors in esCAC patients treated with primary surgery. Analyses of surgical specimens in 59 patients with esCAC were performed on fixed paraffin-embedded sections of tumour tissue. Tumour tissue sections were routinely stained with hematoxylin and eosin followed by microscopic examination. Immunohistochemical analyses (IHC) were performed on paraffin-embedded section. Flow cytometry (FCM) analysis of paraffin-embedded tumor tissue was performed using flow cytometer FACSCalibur equipped with argon laser. DNA histogram analysis was performed with ModFit application. Treatment effectiveness was evaluated using overall 5-year survival. Survival probability was estimated using the Kaplan-Meier method. Overall survival rate estimated using Kaplan-Meier method was 74.6%. Among the IHC and FCM features univariate analysis showed statistical significance of nm23-H1 gene expression and total S-phase fraction ≤ 11.9% (S-TOT). In multi- variate analysis LVSI and parametrial involvement had significant, negative impact on survival (HR = 8.04, p < 0.003 and HR = 4.03, p < 0.017, respectively). However, none of the tested IHC and FCM features had any influence on overall 5-year survival.

Summary Objective The evaluation of efficacy of palliative thoracic radiotherapy (PTR) in patients with advanced non-small cell lung cancer (NSCLC) and to compare it with efficacy of supportive care (SC) alone. Materials and methods Between 2000 and 2012, 235 patients with advanced NSCLC (IIIB and IV) and Karnofsky Performance Status accounted 40–30, were qualified to PTR. In fact, 125 (53.2%) out of them were treated with PTR, and 110 (46.8%)—with SC alone, in accordance with patients expectations. There were no differences between PTR and SC group with respect to patient and tumor characteristics as well as with respect to the type and incidence of symptoms related to the local growth of NSCLC. In all 125 PTR patients the delivered tumor dose was 20Gy given in five daily fractions over five treatment days. All 110 patients who refused PTR were treated with SC in another hospital (28.2%), in a hospice (21.8%) or by general practitioners at home (50.0%). Results The 90-day overall survival rate in the group of PTR patients was 20.0%, and in the group of SC patients it was 18.2%. Median survival amounted 58 and 59 days, respectively. The efficacy of PTR and SC, relative to the symptoms associated with the local growth of NSCLC, was comparable. Tolerance of PTR was poor and early toxicity—significant. Moreover 41.6% of irradiated patients received PTR within the last 30 days of their lives and 16.0% of these patients—within the last 15 days prior to death. Conclusion The life expectancy of patients with advanced NSCLC and poor performance status (Karnofsky 40–30), who presenting moderate or severe symptoms related to the local growth of cancer, is measured in days or weeks. The effective method of treatment for these patients is modern supportive care rather than PTR.

Background The main goal of this study was to compare contrast-enhanced spectral mammography (CESM) and breast magnetic resonance imaging (MRI) with histopathological results and to compare the sensitivity, accuracy, and positive and negative predictive values for both imaging modalities. Material/Methods After ethics approval, CESM and MRI examinations were performed in 102 patients who had suspicious lesions described in conventional mammography. All visible lesions were evaluated independently by 2 experienced radiologists using BI-RADS classifications (scale 1–5). Dimensions of lesions measured with each modality were compared to postoperative histopathology results. Results There were 102 patients entered into CESM/MRI studies and 118 lesions were identified by the combination of CESM and breast MRI. Histopathology confirmed that 81 of 118 lesions were malignant and 37 were benign. Of the 81 malignant lesions, 72 were invasive cancers and 9 were in situ cancers. Sensitivity was 100% with CESM and 93% with breast MRI. Accuracy was 79% with CESM and 73% with breast MRI. ROC curve areas based on BI-RADS were 0.83 for CESM and 0.84 for breast MRI. Lesion size estimates on CESM and breast MRI were similar, both slightly larger than those from histopathology. Conclusions Our results indicate that CESM has the potential to be a valuable diagnostic method that enables accurate detection of malignant breast lesions, has high negative predictive value, and a false-positive rate similar to that of breast MRI.

Mucinous breast carcinoma (MBC) carcinoma represents approximately 1-6% of all malignant breast carcinoma and is divided into pure (PMBC) and mixed (MMBC) subtypes. This study presents the comparison of clinical characteristics and treatment results in 70 patients with PMBC and 40 patients with MMBC, treated at a single institution during 25 years. Performed analyses showed that only nodal status was different in both subtypes. Patients with MMBC showed a significantly higher incidence of axillary nodal metastases in comparison to PMBC (25% versus 10%, respectively). Instead, the 10-year disease-free survival rate was significant higher in PMBC than MMBC (85.7% versus 65%, p < 0.02, test log rank). Authors own observations and data from literature proved that MMBC should be considered as subtypes of mucinous breast cancer.

Citation Mach P, Blecharz P, Basta P, Marianowski P, Skret-Magierlo J, Kojs Z, Grabiec M, Wicherek L. Differences in the soluble HLA-G blood serum concentration levels in patients with ovarian cancer and ovarian and deep endometriosis. Am J Reprod Immunol 2010 Problem The relationship between endometriosis and cancer has been widely discussed in the literature but is still not well clarified. Perhaps significantly, soluble human leukocyte antigen-G (sHLA-G) has been identified in the microenvironment of both ovarian cancer and endometrioma. The aim of this study has been to evaluate the sHLA-G levels in the blood sera of women with deep endometriosis and ovarian endometrioma over the course of the menstrual cycle and to compare to the levels of sHLA-G in the blood sera of women with ovarian cancer. Method of study In our study, we examined the blood sera obtained from 123 patients operated on because of ovarian cancer (65 cases), ovarian endometrioma (30 cases), and deep endometriosis (28 cases). We decided to compare the levels of sHLA-G in patients with endometriosis to those found in patients with ovarian cancer with respect to the menstrual cycle phases. The sHLA-G concentration level was measured by enzyme-linked immunosorbent assay kit. Results The level of sHLA-G concentration in the blood serum of patients with deep endometriosis fluctuates over the course of the menstrual cycle, and during the proliferative and secretory phases, it remains at a high level comparable to that found in patients with ovarian cancer. By contrast, the level of sHLA-G concentration in the blood serum of patients with ovarian endometrioma fluctuates minimally over the course of the different menstrual cycle phases and, as in patients with ovarian cancer, it remains at high level during the proliferative phase. Conclusion sHLA-G blood serum concentration levels would seem to provide important information regarding the degree of immune system regulation disturbance in both ectopic endometrial cells and the cancer cell suppressive microenvironment.

Problem Alterations in RCAS1 (a receptor-binding cancer antigen expressed on SiSo cells) expression in the placenta and decidua may be related to the regulation of the process of maternal immune tolerance against fetal antigens. Moreover, it has been demonstrated that the occurrence of the spontaneous beginning of stillbirth is related to a decrease in the placental expression of RCAS1. There are no data currently available on the immune processes in decidua during stillbirth. The aim of this study was to evaluate the RCAS1 immunoreactivity level in decidua and to identify the cytotoxic immune cells present during labor, induced after intrauterine fetal death either with a combination of oxytocin (OT) and prostaglandins or with OT alone; a further objective was to assess the potential impact of these molecular alterations on the effectiveness of stillbirth induction. Methods The immunoreactivity of RCAS1, CD3, CD56, CD69, and CD25 was assessed by immunohistochemistry in 31 decidual samples derived from patients in whom the stillbirth occurred before the onset of labor. Results The RCAS1 immunoreactivity level was higher in a statistically significant manner in decidual tissue samples derived from patients in whom OT alone proved insufficient to induce labor after the diagnosis of intrauterine fetal death but required additionally the use of prostaglandins when compared with samples from women in whom stillbirth was induced successfully with OT alone. However, we did not observe any differences either in CD56 and CD3 positive cell presence or in CD25 and CD69 antigen immunoreactivity in the respective decidua of these two groups of patients. Conclusion The level of RCAS1 in decidua seems to influence the effectiveness of stillbirth induction.

Background: Treatment outcomes appear to be better for ovarian cancer (OC) patients carrying the BRCA1/2 germline mutation than for patients with sporadic OC. However, most published data are for North American, British and Jewish populations. There have been very few studies on treatment outcomes in Central and Eastern European patients with OC. The aim of this study was to analyse prognostic factors in Polish patients with BRCA1-dependent OC (BRCA1-OC). Methods: The records of patients with OC treated with surgery and chemotherapy at the Centre of Oncology in Kraków, Poland, between 2004 and 2009 were reviewed. Based on family history, a group of 249 consecutive patients fulfilling the criteria for risk of hereditary OC were selected and tested for the germline BRCA1 mutation. Response to combination therapy (surgery and chemotherapy) in the BRCA1-OC group was assessed based on clinical examination, imaging and serum CA125. Results: Germline BRCA1 mutations were detected in 69 of the 249 patients, but three of these patients failed to complete the study. Finally, 66 patients with BRCA1-OC were included in the study group. The median age of the study patients was 49.5 years. All had undergone primary or interval cytoreductive surgery and chemotherapy. Progression occurred in 48 (72.7 %) of the 66 patients and median time to progression was 20 months. The 5-year overall survival rate in was 43.9 % and median survival time was 32.3 months. On multivariate analysis, the endometrial subtype of OC and serum CA125 < 12.5 U/ml at the end of treatment were independent, positive prognostic factors for 5-year overall survival. Conclusion: Prognostic factors for favourable treatment outcomes in Polish patients with BRCA1-OC do not appear to differ from those in patients with sporadic OC. The incidence of the endometrial subtype of OC was relatively high (34.9 %) among women in the study. This was unexpected and has not been reported previously. This subtype of OC was an independent prognostic factor for favourable treatment outcomes.

This article presents methods and results of surgical treatment and radiation therapy of brain metastases in breast cancer patients (brain metastases from breast cancer BMF-BC). Based on the literature data, it was shown that patients with single BMF-BC, aged less than 65 years, with Karnofsky score (KPS) of 70 or more and with cured or controlled extracranial disease are the best candidates to surgical treatment. Irrespective of the extracranial disease control status, there are indications for surgery in patients with symptomatic mass effect (tumour diameter larger than 3 cm) and patients with obstructive hydrocephalus from their BMF-BC. Stereotactic radiosurgery (SRS) has some advantages over surgery, with similar effectiveness: it may be used in the treatment of lesions inaccessible to surgery, the number of lesion is not a limiting factor if each lesion is small (< 3) and adequate doses can be delivered, it is not contraindicated in patients with active extracranial disease, it does not interfere with ongoing systemic treatment, and it does not require general anaesthesia or hospitalisation. A disadvantage of SRS, as compared to whole brain radiotherapy (WBRT), in patients with BMF-BC is the possibility of subsequent development of new lesion in the non-irradiated field. Thus the majority of the BMF-BC patients are not good candidates to surgery or SRS; WBRT alone or combined with a systemic treatment still plays a major role in the treatment of these patients.

In the systemic treatment of brain metastases from non-small cell lung cancer (BMF-NSCLC) chemo- and targeted therapy are used. Response rates after platinum-based chemotherapy, range from 23% to 45%. Development of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs): gefitinib or erlotinib, was an improvement in treatment of advanced NSCLC patients. EGFR mutations are present in 10-25% of NSCLC (mostly adenocarcinoma), and up to 55% in never-smoking women of East Asian descent. In the non-selected group of patients with BMF-NSCLC, the overall response rates after gefitinib or erlotinib treatment range from 10% to 38%, and the duration of response ranges from 9 to 13.5 months. In the case of present activating EGFR mutation, the response rate after EGRF-TKIs is greater than 50%, and in selected groups (adenocarcinoma, patients of Asian descent, never-smokers, asymptomatic BMF-NSCLC) even 70%. Gefitinib or erlotinib treatment improves survival of BMF-NSCLC patients with EGFR mutation in comparison to cases without the presence of this mutation. There is no data on the activity of the anti-EML4-ALK agent crizotinib. Bevacizumab, recombinant humanised monoclonal antibody anti-VEGF, in the treatment of advanced non-squamous NSCLC patients is a subject of intense research. Data from a clinical trial enrolling patients with pretreated or occult BMF-NSCLC proved that the addition of bevacizumab to various chemotherapy agents or erlotinib is a safe and efficient treatment, associated with a low incidence of CSN haemorrhages. However, the efficacy and safety of bevacizumab used for therapeutic intent, regarding active brain metastases is unknown.

Wystąpienie przerzutów do mózgu u chorych na raka piersi (BMBC — brain metastases from breast cancer) związane jest z wyraźnie niekorzystnym rokowaniem. Mediana przeżycia u takich chorych waha się od 2 do 16 miesięcy, w zależności od wielu czynników prognostycznych oraz związanych z nimi możliwości leczenia. W piśmiennictwie prezentowane są czynniki prognostyczne ujawniające się w badaniach jedno- lub wieloośrodkowych, głównie, choć nie jedynie, w analizach wieloczynnikowych, oraz czynniki uwzględnione w indeksach prognostycznych, opracowanych dla chorych z przerzutami do mózgu z różnych nowotworów lub — w szczególności — dla chorych z BMBC. Zebrane i zweryfi kowane dane piśmiennictwa pozwalają uznać, że na chwilę obecną podstawowymi, powszechnie uznanymi czynnikami prognostycznymi u chorych z BMBC są: stan sprawności chorych oraz stan procesu nowotworowego poza mózgiem w momencie ujawnienia się przerzutów do mózgu (BM — brain metastases). Stan sprawności chorych oceniany jest prawie wyłącznie skalą Karnofsky'ego, natomiast stan procesu nowotworowego jest różnie defi niowany: czynny vs nieobecny, kontrolowany vs niekontrolowany, obecność przerzutów odległych poza mózgiem vs brak tych przerzutów itp. Niestety, stwarza to możliwość różnych interpretacji. Potencjalnymi czynnikami prognostycznymi prezentowanymi przez wielu autorów, ale nieuznawanymi powszechnie, są: wiek chorych, podtyp molekularny raka piersi oraz liczba BM. Wyniki przeprowadzonych analiz oceniających wartości poszczególnych indeksów prognostycznych wskazują, że pomimo niewątpliwych ich zalet, w praktyce klinicznej winny być stosowane z rozwagą u chorych z BMBC. The development of brain metastases from breast cancer (BMBC) relates to poor prognosis. The median survival rate averages from 2 to 16 months and depends on various prognostic factors and therapeutic possibilities. There are some prognostic factors which were found in trials as a results of multivariate analyses and factors from prognostic scores in patients with brain metastases. According to the literature the important prognostic factors are performance status and status of the disease outside the brain. Performance status usually is evaluated according to the Karnofsky scale. Whereas the disease status is estimated variously as: presence versus no disease, controlled or uncontrolled disease, presence or not of distant metastases outside the brain. Many authors revealed that age, molecular type of breast cancer and number of brain metastases are potential prognostic factors. Published results of analyses showed that the role of some prognostic factors is limited in patients with BMBC.

Surgery remains the mainstay of the treatment in patients with malignant phyllodes tumor of the breast (MPTB); however, the extent of surgery (breast conserving surgery [BCS] versus mastectomy) and the role of adjuvant radiotherapy have been controversial. We report a single institution's experience with MPTB. We discuss controversial therapeutic aspects of this rare tumor. Seventy patients with MPTB treated primarily with surgery were evaluated. The mean age was 50 years (21-76), and the mean size of the tumor was 6 cm. Thirty-four (48.6%) patients were treated with total mastectomy, and 36 (51.4%) were treated with BCS (lumpectomy or wide local excision). Microscopic surgical margins were free of tumor in all cases. In 64 (91.4%) patients, margins were ≥1 cm. Remaining 6 (8.6%) patients treated with BCS margins were

BACKGROUND Data from the literature suggests that the clinical picture of phyllodes tumor (PT) of the breast, as well as treatment options and perhaps therapy outcomes, have significantly changed. The aim of this work was to review these changes by analysis of consecutive patients with PT over a 55-year period at a single institution. MATERIAL AND METHODS From 1952 to 2007, 280 women with PT were treated surgically at the Maria Sklodowska-Curie Memorial Institute of Oncology, Cancer Center in Cracow. Age, size of breast tumor, microscopic type, extent of surgery, and therapy outcomes were compared between 2 groups: 190 patients treated from 1952 to 1991 vs 90 patients treated from 1992 to 2007. RESULTS The results show that the 1992-2007 group compared to the 1952-1991 included more patients

Objectives: The aim of the study was to estimate acute and late complications of radiation therapy in primary invasive vaginal carcinoma (PIVC) patients. Material and methods: The analysis was performed for the group of 152 PIVC patients given radical radiotherapy in the Krakow Branch of Centre of Oncology during the 1967–2005 period. Twenty five (16.5%) patients in I stage with primary tumour of the thickness not larger than 0.5 cm were treated with intracavitary brachytherapy alone; for 120 (78.9%) patients (stages I – IVA) intracavitary brachytherapy was combined with external radiation therapy; and 7 (4.6%) patients in stage IVA were given only external radiotherapy. In total, 145 (95.4%) patients were treated with intracavitary LDR brachyterapy by means of Ra-226 or afterloaded Cs-137 sources, and 127 (83.5%) received external radiation therapy using Co-60 and linac 10MV or 6MV photon beams. Results: Early radiotherapy tolerance was good in the investigated group; 146 (96.1%) patients completed full planned radiation therapy treatment. Late complications of radiation therapy were observed in 21 (13.8%) patients: 3 (2%) patients reported mild complications, 12 (7.9%) moderate complications, and 6 (3.9%) severe complications. Severe complications of radiation therapy in the investigated group included: recto-vaginal fistula (5 patients) and vesico-vaginal fistula (1 patient). None of the patients in the group died of radiation therapy complications. Conclusions: Early tolerance of radiotherapy in PIVC patients is generally good. Late radiation therapy complications, particularly the severe, are rare and can be efficiently managed with conservative therapy or surgical treatment.

Aim of the study was the assessment of prognostic factors in the group of primary invasive vaginal carcinoma (PIVC) patients subjected to radical radiation therapyThe analysis was performed for the group of 152 PIVC patients treated with intracavitary brachytherapy alone (16.5%), the combination of brachytherapy and external radiotherapy (78.9%), or external radiotherapy alone (4.6%). The relationship was investigated between treatment outcome and the following demographic, clinical and histopathological features: age, duration of pathological symptoms, number of births given, prior hysterectomy haemoglobin level, Karnofsky performance status score, primary tumour location in vagina, length of vagina involved, FIGO stage, gross appearance, histological type, and tumour grade.Five-year disease-free survival was observed in 46.1% of the patients (70/152). Patients below 60 years of age, with Karnofsky score of 80-90, diagnosed with PIVC in stage 10 or 110, and with tumour of grade G1 or G2 had significantly higher 5-year disease-free survival. Multifactoral analysis showed that age below 60 and FIGO stage 10 and 110 are independent favourable prognostic factors.The independent prognostic factors in PIVC patients treated with radical radiotherapy are patient age and FIGO stage.

Objectives: We aimed at evaluation of the influence of the extent of axillary lymph node dissection, measured by the total number of lymph nodes harvested, on the drainage volume. We also looked at the lymph node positivity (N+) and the number of metastatic axillary lymph nodes as a potential prognostic factors in this regard. Material and methods: We have analysed the data of 63 patients (F/M: 62/1) with breast cancer, who underwent radical modified mastectomy in 2008-2009 in the single department of surgical oncology. Results: We observed no significant correlation between the 1) total number of axillary lymph nodes harvested during lymphadenectomy, 2) presence of metastatic lymph nodes (node positive disease), 3) number of metastatic axillary lymph nodes and: drainage volume on the day of surgery, drainage volume on three consecutive postoperative days and drainage volume from the day of surgery to drain removal. Conclusion: The extent of axillary lymph node dissection, measured by the total number of lymph nodes excised, did not influence drainage volume after radical modified mastectomy. Neither total number of metastatic lymph nodes excised nor the node positivity (N+) were associated with increased drainage volume after mastectomy with axillary dissection.

The aim of the study was to present microscopic, cytometric and immunohistochemical characteristics of a group of 96 invasive lobular carcinomas (ILC) of the breast. Ninety six patients treated surgically at the Department of Surgical Oncology, Centre of Oncology - Maria Skłodowska-Curie Memorial Institute, Cracow Branch, between 1983 and 1996, were included into the study. In 56 (58.3%) cases, a classical pattern of ILC was diagnosed, whereas atypical variants (solid, pleomorphic, pleomorphic with signet ring cells, signet ring cell, and tubulolobular) were recognized in 40 (41.7%) cases. ILC was characterized by lack of E-cadherin expression, high rate of steroid receptor expression, low rate of P53 and c-erb-B2 expressing tumours, low MIB-1 labelling index, and low S phase fraction, as well as high rate of diploid lesions.

Ovarian cancer (OC) remains a challenge for gynecologic oncologists due to poor prognosis and increasing morbidity. About 10% of cases is hereditary and BRCA1 gene mutation-dependant. Some authors claim that clinical features, the course of the disease and prognosis of BRCA1-dependent OC vary between sporadic cases.To analyze clinical features and disease courses of BRCA1-dependent OC in the material from Center of Oncology Cracow Branch.Between 2004 and 2008, 66 mutations of BRCA1 gene were found in patients with OC. All patients were treated with primary surgery followed by platinum-based chemotherapy Outcomes were assessed by means of clinical examination and imaging tests. Patients with complete response were followed up in the outpatient office. Secondary chemotherapy was administered if persistent or progressive disease was diagnosed.In the analyzed group of 66 (100%) patients, the following mutations of BRCA1 gene were found: in 31 (47%) - C61G (exon 5), in 21 (31,8%) - 5382insC (exon 20), in 6 (9.1%) - 185delAG and in 8 (12.1%) - other (exon 11). Mean patient age was 48. FIGO stage I and stage II were diagnosed in 7 (10,6%), stage III in 58 (89,9%) and stage IV in 1 patient (1,5%). Twenty five (37.9%) patients underwent complete macroscopic primary cytoreduction. Platinum-based chemotherapy was administered to all 66 patients after surgery Complete response (CR), partial response (PR) and progressive disease (PD) was achieved in 31 (46.9%), 30 (45,5%) and 5 (7.6%) patients, respectively Secondary surgery was performed in 29 (43.9%) of patients after completion of adjuvant therapy Second-line chemotherapy was administered in 40 (60.6%) patients due to residual or progressive disease. Mean time of follow-up was 65 months. Forty one (62. 1%) patients died due to OC progression.Clinical features and disease courses in BRCA1-dependent OC patients in the analyzed group were similar to other results reported in the literature.

Material and methods Between December 2006 and August 2011 seventy five women with BRCA1 mutation and diagnosed with breast cancer stage I to III were enrolled. Patients were treated with Cisplatin at dose 75 mg/m2 every three weeks for four cycles. After chemotherapy mastectomy was performed and followed with conventional chemotherapy. Seven patients had prior chemotherapy for a previous cancer diagnosis. Four patients received prior chemotherapy for their current cancer diagnosis and then received therapy according to our protocol. In the group of 67 patients treated with Cisplatin in first line of treatment 32 met the standard criteria for neoadjuvant chemotherapy, and in 35 cases the criteria were not met. Pathologic complete response was determined by review of surgical specimens. Complete pathologic response was defined as no residual invasive disease in both the breast and axilla. Information was collected on clinical stage, grade, hormone receptor status and HER2 status prior to treatment.

Purpose To estimate the risk of breast cancer in a woman who has a CHEK2 mutation depending on her family history of breast cancer. Patients and Methods Seven thousand four hundred ninety-four BRCA1 mutation–negative patients with breast cancer and 4,346 control women were genotyped for four founder mutations in CHEK2 (del5395, IVS2+1G>A, 1100delC, and I157T). Results A truncating mutation (IVS2+1G>A, 1100delC, or del5395) was present in 227 patients (3.0%) and in 37 female controls (0.8%; odds ratio [OR], 3.6; 95% CI, 2.6 to 5.1). The OR was higher for women with a first- or second-degree relative with breast cancer (OR, 5.0; 95% CI, 3.3 to 7.6) than for women with no family history (OR, 3.3; 95% CI, 2.3 to 4.7). If both a first- and second-degree relative were affected with breast cancer, the OR was 7.3 (95% CI, 3.2 to 16.8). Assuming a baseline risk of 6%, we estimate the lifetime risks for carriers of CHEK2 truncating mutations to be 20% for a woman with no affected relative, 28% for a woman with one second-degree relative affected, 34% for a woman with one first-degree relative affected, and 44% for a woman with both a first- and second-degree relative affected. Conclusion CHEK2 mutation screening detects a clinically meaningful risk of breast cancer and should be considered in all women with a family history of breast cancer. Women with a truncating mutation in CHEK2 and a positive family history of breast cancer have a lifetime risk of breast cancer of greater than 25% and are candidates for magnetic resonance imaging screening and for tamoxifen chemoprevention.

Hereditary ovarian cancer is often believed to be as a distinct disease. It is diagnosed earlier than its sporadic type; serous subtypes and more advanced stages are usually observed. Mutations of genes like BRCA1, BRCA2, MMR (MLH1, MSH2, PMS1, PMS2) are strictly associated with the heredity of ovarian and also breast cancer. Systematic controls and specific procedures to lower the risk of those tumors are required for mutation carriers. Most authors emphasize better prognosis for patients with inherited type of ovarian cancer when comparing to sporadic one. It probably results from dysfunction of BRCA1 gene, inducing better response to platinum-based cytostatic drugs. This phenomenon, called "BRCAness profile", is also observed in non-hereditary ovarian cancers and it arises from somatic mutation or hypermetylation of BRCA1 promoter. Thus, the process of DNA repair is defective. Currently new groups of drugs using the BRCA1 dysfunctions are being introduced into clinical practice.

Germinal mutations of BRCA1/BRCA2 genes are one of the important reasons of breast and ovarian cancer development. The prevalence of BRCA1 mutations in Polish population is relatively frequent, particularly among families at high-risk of breast and/or ovarian cancer. Moreover, the presence of "founder effect" is characteristic for those families. The aim of this paper was analysis of the incidence of BRCA1 mutation among such families in province of Malopolska, Poland.In the Genetic Outpatient Clinic of Center of Oncology, Cracow Department 630 families with positive and characteristic for hereditary breast and/or ovarian cancer familial history were registered since 2004. The main criterion were recommendations for genetic testing of families at high-risk, expressed in National Program for Cancer Control in Poland. The BRCA1 test was done in 710 representatives of families at high-risk of breast and/or ovarian cancer.The BRCA1 mutations were found in 101 (16%) families. The domination of 3 types of mutation--5382insC, C61G and 4153delA--typical for Polish population, was described. They have been found in 94.6% of all mutation carriers.The prevalence of BRCA1 mutations in families at high-risk of breast and/or ovarian cancer is relatively frequent. Among the carriers, the founder mutations were found in the most of cases.

Identification of mutations in the BRCA2 gene and estimation of their clinical consequences for women and men treated in the Maria Sklodowska-Curie Memorial Cancer Center Warsaw, Poland in the years 1998-2008. The probands (97 women and 8 men) had a family history of breast and ovarian cancer (median age 46). The presence of molecular changes was examined in DNA isolated from peripheral blood lymphocytes. Germline mutations in 27 exons of the BRCA2 gene were screened by 'touchdown' PCR amplification, DHPLC and sequencing. Missense mutations were classified by multiple-sequences alignments of orthologous BRCA2 protein sequences with T-Coffee software. 39 molecular changes (8 novel) were identified in the BRCA2 gene in 105 investigated patients. In 12 patients the following pathogenic mutations were identified: 5467insT, 6174delT, 6192delAT, 6675delTA, 8141del5, 9152delT, 9326insA, 9631delC, IVS23-2A > G and E394X. The presence of 10 missense type mutations was detected including the following: D1420O, T1915 M, N3124I. The determination of pathogenic status of molecular variants detected in BRCA2 gene, described in the BIC mutation database as 'UV' depends on many parameters. Important is the assessment of the evolutionary conservation of their protein sequences and studying of the frequency of molecular variants detected in breast cancer patients and in population. A high diversity was found of the pathogenic mutations detected in BRCA2 gene in the Polish population.

Objective The goal of the study was to compare conventional mammography (MG) and contrast-enhanced spectral mammography (CESM) in preoperative women. Materials and Methods The study was approved by the local Ethics Committee and all participants provided informed consent. The study included 152 consecutive patients with 173 breast lesions diagnosed on MG or CESM. All MG examinations and consults were conducted in one oncology centre. Non-ionic contrast agent, at a total dose of 1.5 mL/kg body weight, was injected intravenous. Subsequently, CESM exams were performed with a mammography device, allowing dual-energy acquisitions. The entire procedure was done within the oncology centre. Images from low and high energy exposures were processed together and the combination provided an "iodine" image which outlined contrast up-take in the breast. Results MG detected 157 lesions in 150 patients, including 92 infiltrating cancers, 12 non-infiltrating cancers, and 53 benign lesions. CESM detected 149 lesions in 128 patients, including 101 infiltrating cancers, 13 non-infiltrating cancers, and 35 benign lesions. CESM sensitivity was 100% (vs. 91% for MG), specificity was 41% (vs. 15% for MG), area under the receiver operating characteristic curve was 0.86 (vs. 0.67 for MG), and accuracy was 80% (vs. 65% for MG) for the diagnosis of breast cancer. Both MG and CESM overestimated lesion sizes compared to histopathology (p < 0.001). Conclusion CESM may provide higher sensitivity for breast cancer detection and greater diagnostic accuracy than conventional mammography.

The term polyp refers to any overgrowth of tissue from the surface of mucous membranes. Intestinal polyps grow out of the lining of the small and large bowels. The polyps that arise as a result of proliferative dysplasia are termed as adenomatous polyps or adenomas. They are true neoplastic lesions and are precursors of carcinoma. The hamartomatous polyps are formed as a result of abnormal mucosal maturation. They are non-neoplastic and do not have malignant potential. There are several hereditary diseases that produce large numbers of intestinal polyps. These disorders include: familial adenomatous polyposis of the colon (MIM 175100), familial adenomatous polyposis type 2(MIM 608456), Lynch's syndrome (MIM 120435), Peutz-Jeghers syndrome (MIM 175200), Juvenile polyposis syndrome (MIM 174900) PTEN Hamartoma Tumor Syndrome (PHTS) PHTS Includes: Bannayan-Riley-Ruvalcaba Syndrome (MIM 153480), Cowden Syndrome (MIM 153480), PTEN-Related Proteus Syndrome, Proteus-Like Syndrome. Here we present spectrum of mutation detected in over six hundred Polish families with intestinal polyposis. The studies have encompassed over 30 families with Juvenile polyposis syndrome and PHTS, over 40 families with Peutz-Jeghers syndrome and almost 600 families with familial adenomatous polyposis of the colon. The study was in part financed by the Ministry of Education and Science, Poland, grant number N402 481537, N401 331936.

Genetic testing for the two major breast cancer susceptibility genes, BRCA1 and BRCA2 is widely available in North America and Europe. A few other highly-penetrant breast cancer genes have been found, including p53, BRIP1 and PALB2, but families with mutations in these are exceedingly rare. Arguably, the most relevant of the post-BRCA genes, from a clinical point of view, is CHEK2, which was first linked to breast cancer susceptibility in 2002. In Poland, there are four founder mutations of CHEK2. Three of these (IVS2+1G>A, del5395 and 1100delC) are protein-truncating mutations and one (I157T) is a missense variant. We estimated the lifetime risk of breast cancer for carriers of CHEK2 truncating mutations to be 20% for a woman with no affected relative, 28% for a woman with one second-degree-relative affected, 34% for a woman with one first-degree relative affected, and 44% for a woman with both first- and one-second degree relative affected in the Polish population. In addition we estimated that the lifetime risk for breast cancer for women who carried two different CHEK2 mutations (a truncating mutation and the missense mutation) to be 42%. Our results confirm that CHEK2 mutation screening detects a clinically meaningful risk of breast cancer, and women with a truncating mutation in CHEK2 and a positive family history of breast cancer, and women who carry two different CHEK2 mutations (the missense mutation I157T and a truncating mutation) face a lifetime risk of breast cancer above 25% and are candidates for MRI screening and for tamoxifen chemoprevention.

StreszczenieNowotwory indukowane napromienianiem są rzadkim powikłaniem odległym radioterapii. Histologicznie są to w ogromnej większości mięsaki tkanek miękkich lub kości. Przypadki zlokalizowane w miednicy mniejszej są zwykle późno rozpoznawane i rokują źle. Opisujemy przypadek popromiennego mięsaka trzonu macicy u chorej leczonej 7 lat wcześniej napromienianiem z powodu raka szyjki macicy, która pomimo przeprowadzonego chirurgicznego leczenia radykalnego zmarła wkrótce z powodu gwałtownej progresji. Przedstawiamy krótki przegląd aktualnego piśmiennictwa o częstości występowania, najczęstszych typach histologicznych, a także możliwych mechanizmach powstania wtómych nowotworów popromiennych. Kontrola chorych po skutecznym leczeniu napromienianiem powinna być prowadzona przez wiele lat. Wiedza o możliwości rozwoju wtórnych nowotworów upowszechniona wśród lekarzy pierwszego kontaktu może pozwolić na wcześniejsze rozpoznanie i skuteczniejsze leczenie tych nowotworów.SummaryPostirradiation tumors are rare kind of late complication of radiation therapy. The most of them are histologicaly confirmed sarcomas of bones or soft tissues. The pelvic location of malignance are usualy recognised late and has poor prognosis. We report a case of the postirradiation sarcoma developing in uterus 7 years after radiation therapy for cervical cancer. The rapid progresion was cause of death of observed patient, nevertheless radical surgery treatment. A short references review, concerning frequency, the most common histological types and possible mechanisms of secondary postirradiation malignancies has been presented. According to reccurence, dissemination and secondary malignancies risks the follow-up after radiation therapy should last for many years. Acknowledgement of the nature of postirradiation malignancies among primary care doctors may result in earlier diagnosis and better treatmant efficacy.

Introduction The purpose of this investigation was to evaluate the efficacy of cisplatin chemotherapy in BRCA1 mutation carriers with metastatic breast cancer. Methods In a phase II, open-label study, 20 patients with metastatic breast cancer who carried a mutation in BRCA1 were treated with cisplatin 75 mg/m2 intravenously every 3 weeks as part of a 21-day cycle for 6 cycles. Restaging studies to assess response were performed after cycles 2 and 6, and every three months thereafter. Results Between July 2007 and January 2009, 20 patients were enrolled. Baseline characteristics were as follows: 65% had prior adjuvant chemotherapy, 55% had prior chemotherapy for metastatic breast cancer; mean age was 48 years (ranges 32 to 70); 30% estrogen receptor (ER) or progesterone receptor (PR)+, 70% ER/PR/Human Epidermal Growth Factor Receptor 2 (HER2)- and 0% HER2+. Overall response rate was 80%; nine patients experienced a complete clinical response (45%) and seven experienced a partial response (35%). Overall survival was 80% at one year, 60% at two years and 25% at three years. Four of the 20 patients are alive four years after initiating treatment. The median time to progression was 12 months. The median survival from the start of cisplatinum treatment was 30 months. Cisplatin-related adverse events, including nausea (50%), anemia (5%) and neutropenia (35%) were mostly mild to moderate in severity. Conclusions This phase II study demonstrates that cisplatin chemotherapy has high activity in women with a BRCA1 mutation and metastatic breast cancer and is generally well tolerated. Trial registration This trial is registered retrospectively on the clinical trials website ClinicalTrials.gov. The identifier is NCT01611727.

ted with cisplatin 75 mg/m 2 every three weeks for four cycles, followed by mastectomy and conventional chemotherapy. Eight patients had prior chemotherapy for a previous cancer diagnosis. Three patients received prior chemotherapy for their current cancer diagnosis but received protocol therapy and thus were followed for toxicity and evaluated for response. Information was collected on clinical stage, grade, hormone receptor status and Her2neu (HER2) status prior to treatment. Pathologic complete response was determined by review of surgical specimens. Results 47 patients were enrolled in the study, including 39 patients for whom this was the first primary breast cancer and who had no previous chemotherapy and 8 patients who had previously received chemotherapy. A pathologic complete response (pCR) was observed in 34 patients (68%) including 82% of women who had no previous chemotherapy and 18% of women who had previously received chemotherapy. Conclusions Platinum-based chemotherapy is effective in a high proportion of patients with BRCA1-associated breast cancer, but may be less effective in women who have been previously been treated with another form of chemotherapy.

Background Neoadjuvant chemotherapy is administered to control disease, make surgical resection possible and increase the possibility of breast tissue conservation. A further advantage of neoadjuvant therapy is that it helps to assess chemo-sensitivity to a particular agent. Induction of a pathological complete response (pCR) is one of the primary goals of neoadjuvant therapy in order to achieve a better disease-free and overall survival. Experimental data suggest that BRCA1 related breast cancer may have increased sensitivity to platinum-based chemotherapy, but clinical data are limited. The aim of this study was to evaluate the frequency of complete pathologic response after neo-adjuvant treatment with cisplatin chemotherapy in women with breast cancer and a BRCA1 mutation.