Signatures of post-zygotic structural genetic aberrations in the cells of histologically normal breast tissue that can predispose to sporadic breast cancer.

Sporadic breast cancer (SBC) is a common disease without robust means of early risk prediction in the population. We studied 282 females with SBC, focusing on copy number aberrations in cancer-free breast tissue (uninvolved margin, UM) outside the primary tumor (PT). In total, 1162 UMs (1-14 per breast) were studied. Comparative analysis between UM(s), PT(s), and blood/skin from the same patient as a control is the core of the study design. We identified 108 patients with at least one aberrant UM, representing 38.3% of cases. Gains in gene copy number were the principal type of mutations in microscopically normal breast cells, suggesting that oncogenic activation of genes via increased gene copy number is a predominant mechanism for initiation of SBC pathogenesis. The gain of ERBB2, with overexpression of HER2 protein, was the most common aberration in normal cells. Five additional growth factor receptor genes (EGFR, FGFR1, IGF1R, LIFR, and NGFR) also showed recurrent gains, and these were occasionally present in combination with the gain of ERBB2. All the aberrations found in the normal breast cells were previously described in cancer literature, suggesting their causative, driving role in pathogenesis of SBC. We demonstrate that analysis of normal cells from cancer patients leads to identification of signatures that may increase risk of SBC and our results could influence the choice of surgical intervention to remove all predisposing cells. Early detection of copy number gains suggesting a predisposition toward cancer development, long before detectable tumors are formed, is a key to the anticipated shift into a preventive paradigm of personalized medicine for breast cancer.

Human Epididymis Protein 4 (HE4) in Patients with Small-Cell Lung Cancer.

BACKGROUND: The aim of the present study was to compare the diagnostic utility of HE4 with NSE, ProGRP, CYFRA 21-1, CEA, and CA 125 and evaluate their prognostic value in patients with small-cell lung cancer (SCLC). METHODS: HE4, ProGRP, NSE, CYFRA 21-1, CEA, and CA 125 assays were performed in 63 patients with smallcell lung cancer (limited disease (LD) - 41, extensive disease (ED) - 22) and in 66 individuals of the reference group. RESULTS: Area under the ROC curves for HE4, ProGRP, NSE, CA 125, CYFRA 21-1, and CEA were 0.884, 0.923, 0.826, 0.796, 0.739, and 0.704, respectively. The tumor marker serum concentrations were associated with tumor stage (HE4, ProGRP, NSE, CYFRA 21-1, CEA), and disease progression occurred within one year (HE4, ProGRP, NSE, CYFRA 21-1). The tumor advancement, performance status, gender and tumor markers, except CEA and CA 125, were significantly associated with survival. Independent, unfavourable prognostic factors included extensive disease (HR 4.14, p < 0.0001) and NSE concentration above 35 g/l (HR 2.62, p = 0.0009). CONCLUSIONS: Diagnostic utility of HE4 was similar to that of NSE and ProGRP. Complementary to NSE, determination of HE4 seems to be helpful in evaluation of SCLC patients' prognosis.

Pure and Mixed Mucinous Carcinoma of the Breast: A Comparison of Clinical Outcomes and Treatment Results.

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.

Malignant phyllodes tumor of the breast: treatment and prognosis.

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 <1 cm and subsequently radiotherapy was performed. Among 70 patients, 58 (82.9%) had no evidence of disease (NED) after 5 years. The extent of surgery was not significantly related to the 5-year NED survival rates (82.4% in patients who underwent mastectomy and 83.3% in patients who underwent BCS only or BCS with adjuvant irradiation). The 5-year NED survival rates in BCS (tumor-free margin ≥1 cm) and BCS with irradiation (tumor-free margin <1 cm) groups were identical (83.3%). Our data support the potential use of BCS in patients with MPTB. Mastectomy is indicated only if tumor-free margins cannot be obtained by BCS. Adjuvant radiotherapy may be considered if tumor-free margins are <1 cm.

Changes in the clinical characteristics, treatment options, and therapy outcomes in patients with phyllodes tumor of the breast during 55 years of experience.

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 <50 years of age, with tumor <5 cm in diameter, undergoing breast-conserving therapy, as well as no evidence of disease at 5-year survival had increased and this change was statistically significant. In addition, malignant PT cases had decreased in frequency. CONCLUSIONS: The results of this study show that patients with PT are increasingly younger, the breast tumors at diagnosis are smaller, malignant PT is becoming less frequent, and BCT is now the treatment of choice. Most importantly, the general treatment outcomes are significantly better.

Radiation therapy complications in patients with primary invasive vaginal carcinoma.

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.

Invasive lobular carcinoma of the breast: cytometric and immunohistochemical characteristics of 96 cases.

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 Sklodowska-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.

Hematogenous metastases in patients with Stage I or II endometrial carcinoma.

AIMS: The aim of this study was to present the characteristics, methods of treatment, and the survival of patients with hematogenous metastases from endometrial carcinoma, free from local and other distant recurrences. PATIENTS AND METHODS: In 1,610 endometrial carcinoma patients managed with surgery and postoperative radiotherapy, we defined hematogenous metastases as a tumor spread to the lung or other sites via hematogenous routes. RESULTS: A total of 110 patients with stage I and II endometrial carcinoma, presenting with 134 metastases sites (69 in the lungs, 32 in the liver, 23 in the bones, and 10 in the brain), were observed. Progestin and combination chemotherapy were the most commonly used therapies. Primary treatment consisted of surgery in patients with solitary metastases to the lung (30 patients), liver (2 patients), and brain (2 patients). Radiotherapy was performed in 32 patients with metastases to the brain and bones. Presenting with a 36-month survival rate were 11.6% (8/69) of patients with metastases to the lungs, 6.3% (2/32) of patients with metastases to the liver, 8.7% (2/23) of patients with metastases to the bones, and 20.0% (2/10) of patients with metastases to the brain. CONCLUSIONS: Hormonal therapy and chemotherapy play a major role in the palliative management of patients with hematogenous metastases from endometrial carcinoma to the liver, lungs, and bones. Radical treatment in patients with metastases to the lung or liver consists of resection of the metastasis combined with chemo- and/or hormonotherapy for metastases to the bones treatment consists of radiotherapy + chemotherapy, for metastasis to the brain treatment consists of resection combined with radiotherapy.

Utility of ProGRP determinations in cancer patients.

BACKGROUND: The aim of this study was to assess the utility of ProGRP determinations in patients with selected cancer localization, during and after therapy. MATERIALS AND METHODS: The study involved a reference group and a population of lung, breast, ovarian, and prostate cancer patients. ProGRP was evaluated using two-step chemiluminescent microparticle immunoassay (CMIA) manufactured by Abbott Diagnostics, and Architect i2000 analyzer. RESULTS: During follow-up of SCLC patients, an increased value for ProGRP was found in 51% and for NSE only in 25.5% of the patients, whereas in NSCLC patients, percentages with elevated ProGRP and CYFRA 21-1 were 8.6% and 55.7%, respectively. SCLC patients also had the highest AUC values for ProGRP. In other cancers, the frequency of elevated ProGRP results were as follows: 13.1%--in breast cancer patients, 19.6%--in ovarian cancer patients, and 15.1%--in prostate cancer patients. CONCLUSIONS: The presented study revealed that ProGRP is a tumor marker of choice in SCLC, because of its high diagnostic specificity in relation to the reference group and to the group with other malignancies.

Primary soft tissue giant cell tumour of the neck. Cytological and histological characteristics of the tumour and differential diagnosis.

Giant cell tumour of soft part is a very rare neoplasm. The majority of these tumours are located superficially (in subcutaneous tissue) and occur in the proximal parts of the extremities. The deep-situated giant cell tumours of the neck are extremely rare. That is why we report a case of primary giant cell tumour of soft part localized in the trapezius muscle of a 19-year-old woman. We present both cytological and histological picture of the neoplasm. The cytological image of the smear is so representative that the proper diagnosis can be settled basing on the fine-needle aspiration cytology.

[Prognostic value of laboratory factors of performance status in lung cancer patients]. / Wartosc prognostyczna laboratoryjnych wykladników stanu ogólnego u chorych na raka pluca.

Clinical observations indicate that the utility of classical prognostic factors in the assessment of probability of disease free or overall survival of lung cancer patients is not completely satisfactory. This is the cause for search of indices which results would contribute to optimization of this estimation. Of potential value in this aspect may also be the results of laboratory determinations which characterize patient's performance status. Dependencies between the times of overall survival in respect to chosen hematological and biochemical factors from the pretreatment period were analyzed in a group of 233 patients with lung cancer (adenocarcinoma - 44, squamous cell lung cancer - 156, small cell lung cancer - 33 patients) in different stages of disease. Apart from stage of disease and histological type of tumor, independent prognostic factors turned out to be the actual ideal body mass ratio and the number of leucocytes. In patients with less advanced stages of disease, such independent factors, apart from histological type are alpha-1 globulin and gamma globulin.

A prospective study to validate the Polish language version of the European Organisation for Research and Treatment of Cancer (EORTC) Colorectal Liver Metastases (QLQ-LMC21) module.

PURPOSE: This validation study was designed to assess the psychometric validity and quality of the Polish translation of the EORTC QLQ-LMC21 questionnaire in Polish colorectal patients suffering with liver metastases. METHODS: Patients with either histopathological or imaging confirmation of colorectal cancer with liver metastases, with a minimum of three months survival, were eligible for this study. These patients completed the Polish version of the EORTC core QLQ-C30, the QLQ-LMC21 module, and a demographic data questionnaire. The questionnaires were completed twice, once before undergoing either hepatectomy (n = 63) or palliative treatment (n = 97) and three months after the primary treatment. Standardized analyses of validity and reliability were performed. RESULTS: One hundred and sixty patients were enrolled in this study with the mean age of the hepatectomy group 64.3 ± 14.1 and 66.1 ± 12.7 for the palliative treatment group. The QLQ-LMC21 exhibited positive internal consistency with Cronbach's alpha coefficients ranging from 0.72 to 0.90. The multi-trait scaling analysis demonstrated adequate convergent and discriminant validity. Test-retest reliability was undertaken with 40 patients (25%) with the ICCs for each item ranging from 0.64 to 0.88. The hepatectomy group had a significantly greater Karnofsky Performance Score than the palliative treatment group (p.<0.001). Overall there were weak correlations between the two questionnaires which confirm that the QLQ-LMC21 addresses health issues not assessed in the QLQ-C30. CONCLUSION: The Polish version of the QLQ-LMC21 proved to be a valid and reliable questionnaire to use in conjunction with the QLQ-C30 core questionnaire.

Analysis of adverse events of sunitinib in patients treated for advanced renal cell carcinoma.

INTRODUCTION: Treatment of the metastatic stage of renal cell carcinoma is specific because classical chemotherapy is not applicable here. The treatment is mainly based on molecularly targeted drugs, including inhibitors of tyrosine kinases. In many cases the therapy takes many months, and patients often report to general practitioners due to adverse events. In this article, the effectiveness and side effects of one of these drugs are presented. The aim of the study was to analyse of the toxicity and safety of treatment with sunitinib malate in patients with clear cell renal cell carcinoma in the metastatic stage. MATERIAL AND METHODS: Adverse events were analyzed using retrospective analysis of data collected in a group of 39 patients treated in the Department of Systemic and Generalized Malignancies in the Cancer Center in Krakow, Poland. RESULTS: Toxicity of treatment affected 50% of patients. The most common side effects observed were hypertension, thrombocytopenia, stomatitis, diarrhea and weakness. Grade 3 serious adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) version 4 affected up to 10% of patients. The most common serious adverse events were hypertension and fatigue. CONCLUSIONS: Sunitinib malate is characterized by a particular type of toxicity. Knowledge of the types and range of adverse events of this drug is an important part of oncological and internal medicine care.

Palliative thoracic radiotherapy for patients with advanced non-small cell lung cancer and poor performance status.

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.

[The effectiveness of postoperative external beam radiotherapy for incompletely resected non-small cell lung cancer]. / Ocena skutecznosci pooperacyjnej teleradioterapii chorych na niedrobnokomórkowego raka pluca po niedoszczetnym zabiegu operacyjnym.

In a retrospective analysis of 150 incompletely resected NSCLC patients treated with adjuvant external beam radiotherapy 32 (21.3%) survived 3 years with no symptoms of disease. Ipsilateral mediastinal/hilar lymph node involvement and macroscopic incomplete surgery were the prognostic factors that unfavourably influenced survival in Cox's proportional hazards model. Postoperative external beam radiotherapy was the efficient adjuvant treatment method in microscopically incompletely resected NSCLC, predominantly with no nodes involvement, but had no benefit in those with macroscopic incomplete surgery.

[The efficacy of adjuvant thoracic radiation therapy in NSCLC patients with ipsilateral mediastinal/hilar lymph nodes involvement (clinical trial)]. / Ocena skutecznosci pooperacyjnej teleradioterapii chorych na NDRP zoperowanych miejscowo doszczetnie z obecnoscia przerzutów w usunietych wezlach chlonnych sródpiersia albo wneki (kontrolowane doswiadczenie kliniczne).

Between 1992 and 1999 at the Oncology Centre in Cracow 138 NSCLC patients after complete resection of the tumour with mediastinal/hilar node involvement were included in the prospective clinical trial. The analysis of the results did not show any improvement of survival in the postoperatively irradiated group. Three-year survival rates with no symptoms of disease in postoperative radiotherapy patients compared to surgery alone group were 30% and 29% respectively. In this study adjuvant radiotherapy significantly improved local recurrence rate from 28% in surgery only group to 9% in postoperatively treated patients.

Palliative thoracic radiotherapy in non-small cell lung cancer. An analysis of 1250 patients. Palliation of symptoms, tolerance and toxicity.

PURPOSE: To present our experience with short-time, split-course palliative thoracic radiotherapy (PTR) in patients with advanced non-small cell lung cancer (NSCLC) with special regard to palliation of symptoms, tolerance and toxicity of PTR treatment. PATIENTS AND METHODS: Between 1980 and 2005, a group of 1250 patients with locally advanced or metastatic NSCLC was treated with PTR in our Center. All patients presented with moderate or severe symptoms related to local cancer growth. RESULTS: The response rate defined as palliation of NSCLC symptoms after PTR was 54.1% for cough, 68% for haemoptysis, 51.1% for thoracic pain, 38.3% for dyspnoea, 12% for hoarseness, and 8% for dysphagia. Tolerance of PTR, expressed in terms of patient compliance to the treatment, was good in 92% of patients (i.e., 2 series of radiotherapy were given at the planned dose and time). Early treatment toxicity was observed in 4.6% of patients and included pneumonitis in 2.3%, intense nausea and vomiting in 0.6%, lung hemorrhage in 0.6%, and severe oesophagitis in 0.5% of patients. Lhermitte's syndrome and broncho-oesophageal fistula were observed in 0.4% and 0.2%, respectively. Six out of 70 patients who survived longer than 2 years developed chronic pulmonary fibrosis with respiratory insufficiency and one patient presented symptoms of radiation-induced myelopathy. CONCLUSIONS: The analysis of our results and data from the literature show that short-time, split-course PTR is a safe and effective method of palliative treatment in patients with advanced NSCLC.

The intraoperative assessment of the effectiveness of computed tomography in the detection of the residual mass of the retroperitoneal space in patients with nonseminoma testicular tumors after chemotherapy.

BACKGROUND: The incidence of testicular tumors in Poland accounts for 2.4 new cases per 100.000 men a year. When investigating the incidence with regard to age, we may notice three age ranges with the highest incidence rate: babyhood, 25-40 years of age, and age of about 60 years. A routine examination in patients with testicular cancer after the first course of chemotherapy is computed tomography of the retroperitoneal space which aims to exclude the presence of residual masses and to assess the effectiveness of the treatment. AIM OF THE STUDY: The assessment of the effectiveness of computed tomography in the intraoperative investigation of patients with nonseminoma testicular tumors after chemotherapy. MATERIAL/METHOD: This detailed retrospective analysis included 182 men with nonseminoma testicular tumor treated at the Center of Oncology in Cracow, between the yeas 1990-1999. Men with tumors in stage from IA to IIC made up 79.68% of the patients. Twenty patients after chemotherapy, with residual masses in the retroperitoneal cavity revealed in computed tomography, underwent retroperitoneal lymphadenectomy. The investigation was carried out with GE CT spiral scanner before and after intravenous contrast administration. CONCLUSIONS: Computed tomography is a method of a satisfactory sensitivity in the assessment of residual masses in the retroperitoneal cavity in postchemotherapy patients, as concerns the location of the tumor, its size, number of foci, and the fact whether it can be operated on or not. Together with tumor markers, it allows for a precise qualification to retroperitoneal lymphadenectomy of residual masses in postchemotherapy patients.

IL-6 and VEGF in small cell lung cancer patients.

Recent data suggest a link between chronic inflammation, angiogenesis, and the development of cancer. The aim of this study was the evaluation of serum IL-6 and VEGF in comparison with the tumor markers NSE and ProGRP, with respect to the prognosis of small cell lung cancer patients. The study of IL-6, VEGF, NSE, ProGRP and platelet count was performed in a group of 72 patients with previously untreated small cell lung cancer at different stages of disease: 40 with limited and 32 with extensive disease. Significantly higher IL-6 and VEGF concentrations and platelet count, as well as NSE and ProGRP levels, were found in patients with small cell lung cancer in comparison with the reference group. Patients with extensive cancer had significantly higher levels of IL-6, VEGF, NSE and ProGRP than those with limited cancer. Elevated VEGF levels, with no significant differences in frequency of elevated NSE and ProGRP concentrations, were often observed in patients with IL-6 levels higher than 5.1 ng/l. Univariate analysis confirmed a significant relationship not only between overall survival and stage of disease or gender, but also with VEGF, IL-6, NSE and ProGRP levels. Moreover, multivariate analysis revealed that only the extent of the disease and IL-6 may be independent prognostic factors in the group of small cell lung cancer patients under investigation. However, simultaneous determinations of ProGRP and IL-6, as well as ProGRP and VEGF, in addition to the extent of the disease, may serve as additional, independent prognostic factors in small cell lung cancer.