High rates of undiagnosed and untreated osteoporosis in postmenopausal women receiving medical services in the area of Upper Silesia.

INTRODUCTION: High social cost and high risk of disability make postmenopausal osteoporosis one of major public health problem in the 21st century. The aim of this study was to assess frequency of undiagnosed and untreated osteoporosis in postmenopausal women in the Upper Silesia Region of Poland. Additionally, we compare estimation of the 10-year probability of major osteoporotic fractures (MOF) and hip fractures (HF) based on fracture risk assessment tool (FRAX) with and without bone mineral density (BMD). MATERIAL AND METHODS: The survey included 450 postmenopausal women (age 65 ±11 years). A detailed questionnaire included demographic and anthropometric data, comorbidity, history of previous low-energy fractures, family medical history, and treatment for osteoporosis. The FRAX calculator was used to estimate the risk of MOF and HF. RESULTS: Osteoporosis was previously diagnosed in 23.7% women. Of those 70.2% were receiving vitamin D, 27% calcium preparations, 33% bisphosphonates, and 22% were untreated. Only 42.2% women with previous fractures had been diagnosed with osteoporosis and 42.8% received any treatment. 12.5% women with FRAX-BMD ≥ 10% had no risk factors of osteoporosis and < 10% risk of MOF and HF in FRAX without BMD. CONCLUSIONS: Osteoporosis often remains undiagnosed and untreated in postmenopausal women. There is a great need to popularize FRAX without BMD calculator among physicians, especially GPs, as the risk calculation justify the implementation of antiosteoporotic therapy. Women with burden of risk factors of fractures and borderline FRAX without BMD values, should be referred to a densitometry examination, as having greater risk of fracture than shown by FRAX without BMD.

Inhibitory PARP w terapii raka jajnika.

Treatment of the malignant ovarian tumors remains challenging. Some of the reasons are as follows: lack of effective screening technique, usually asymptomatic early stages of the disease, which effects in detecting the disease in advanced stage, and eventually poor prognosis. Treatment of the relapse remains palliative. Inventing new drugs - like PARP inhibitors - gives hope for improvement of the treatment outcomes. This review paper presents actual knowledge on PARP inhibitors in the ovarian cancer therapy.

Systemic treatment of non-small cell lung cancer brain metastases.

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.

Prognostic value of PIK3CA mutation status, PTEN and androgen receptor expression for metastasis-free survival in HER2-positive breast cancer patients treated with trastuzumab in adjuvant setting.

Resistance to trastuzumab in patients with HER2-overexpressing breast cancer is associated with higher risk of progression or cancer death, and might be related to activation of PI3K/AKT/mTOR and Ras/Raf/MAPK signaling cascades and a decreased level of their inhibitor (PTEN). HER2-overexpressing breast cancer patients (n=75) treated with radical local therapy and trastuzumab in adjuvant setting were included into the study. Deoxyribonucleic acid isolated from paraffin sections was used to assess mutational status of the PIK3CA gene (p.H1047R and p.E545K mutations) by the quantitative polymerase chain reaction technique. Expression of selected proteins (ER, PgR, AR, Ki-67, EGFR) was assessed using immunohistochemistry. In the studied group we found significantly higher Ki-67LI in EGFR-positive carcinomas (p=0.048). Moreover, EGFR immunonegativity was observed more frequently in low-grade (G1/G2) carcinomas as well as in estrogen/progesterone and androgen receptor immunopositive tumors (p=0.042, p=0.016, p=0.044, respectively). Favorable metastasis-free survival was observed in patients with pN0 and pN1 (vs. pN2+3) stage (p=0.040) and with tumors characterized by low Ki-67LI (≤50% vs. >50%) (p=0.014). Patients with tumor androgen receptor immunonegativity (weak or lack of expression) or strong PTEN expression survived 3 years without metastases (p=0.007). The results of our study suggest that androgen receptor and PTEN status might be considered as indicators of trastuzumab sensitivity.

An Unusual Radiologic Image of Extensive Tumor Mass Infiltrating Hepatic Hilum without Signs of Cholestasis-A Case Report and a Literature Review of Non-Cancerous Lesions Mimicking Intrahepatic Cholangiocarcinoma.

BACKGROUND: Mass-forming intrahepatic cholangiocarcinoma (mICC) is the most frequent type of ICC. In contrast-enhanced computed tomography, mICC is visualized as a hypodense lesion with distal dilatation of intrahepatic bile ducts. The presented case illustrates the unusual manifestation of mICC in a 71-year-old male patient, where despite the extensive tumor mass and the hilar infiltration, the dilatation of intrahepatic bile ducts and cholestasis were not noted. METHODS: A literature review on PubMed was performed. Primarily, 547 records were identified, and the titles and abstracts were systematically searched. Regarding the inclusion and exclusion criteria, 31 papers describing the non-cancerous liver lesions mimicking ICC were included in the further analysis. RESULTS: In 41.9% of the analyzed non-cancerous lesions, the obstruction of the bile ducts was not noted, similar to our patient. A significant cholestasis has been found in 30.03% of analyzed patients. The invasion of the liver hilum was noted in one-third of the patients. CONCLUSIONS: Atypical radiological features in lesions suspected of ICC, such as the absence of intrahepatic bile-duct dilation, are common in benign lesions. In the case of radiologically atypical lesions suspected of ICC, the diagnostic imaging needs to be correlated with clinical data, and the diagnosis should be confirmed with a pathological examination.

Evaluation of vinorelbine-based chemotherapy as the second or further-line treatment in patients with metastatic breast cancer.

AIM OF THE STUDY: The study examined the response rate, response duration and toxicity of vinorelbine and fluorouracil or vinorelbine alone in pretreated metastatic breast cancer. MATERIAL AND METHODS: Between June 2001 and September 2009, a group of 103 patients with locally advanced or metastatic breast cancer, who had progressed after anthracycline/taxane chemotherapy, was treated with a vinorelbine-based regimen. The treatment consisted of vinorelbine 25 mg/m(2) and 5-fluorouracil (5-FU) 500 mg/m(2) administered intravenously on days 1 and 8 of each cycle (53 patients) or vinorelbine alone at a dose of 30 mg/m(2) on day 1 and 8 of the cycle, every 3 weeks (50 patients). Patients received chemotherapy as a second or further line of therapy. Treatment was continued until disease progression or unacceptable toxicity. The median age of patients treated with vinorelbine with 5FU was 54 years (range 38-76), and 55.5 years (range 38-73) in the group receiving vinorelbine monotherapy. A total of 417 cycles of chemotherapy were administered - 177 cycles of vinorelbine with 5-FU and 137 cycles of vinorelbine monotherapy. Patients were treated for a median of 4 cycles (range: 1 to 11 cycles). The evaluation of treatment effect was possible in 93 patients (10 patients received only one treatment cycle). RESULTS: The overall response rate (ORR) was 17% (7), including 2 (4%) complete responses (CR) and 5 (10.5%) partial responses (PR). Stable disease (SD) was observed in 50% of patients receiving vinorelbine with 5-FU (24 patients). In a group receiving vinorelbine alone the ORR was 20% (9), including 9 PR (20%) and 16 SD (35.5%). The median time to progression (TTP) for the entire group was 18 weeks (95% CI), 22 weeks among patients treated with vinorelbine with 5-FU and 16 weeks for a second group. The most common hematologic adverse events were neutropenia (20% of cycles) and thrombocytopenia (4%), with grade 3/4 incidence of 8% and 1.5% [according to National Cancer Institute Common Toxicity Criteria (NCI CTC)]. Nausea and vomiting were the most frequent non-hematologic forms of toxicity, occurring in 13% of cycles. The doses of cytotoxics were reduced in 26 (25%) cases. There were no treatment-related deaths. CONCLUSIONS: Vinorelbine alone or in combination with 5-FU is an effective and safe treatment for pretreated advanced/ metastatic breast cancer patients. The combination of vinorelbine with 5-FU appears to be a more efficacious regimen than vinorelbine alone.

Results of systemic treatment of cutaneous melanoma in inoperable stage III and IV.

AIM OF THE STUDY: The incidence of melanoma is increasing rapidly worldwide. Metastatic melanoma is still an incurable disease, although an era of new drugs is approaching. Current methods to predict outcomes in patients with advanced, metastatic melanoma are limited. A retrospective analysis of a contemporary large group of advanced melanomas was performed to determine clinical prognostic factors that accurately predict survival in patients with metastatic melanoma before the era of new targeted/immunological therapy. MATERIAL AND METHODS: The retrospective analysis of 427 patients with metastatic melanoma treated between 1995 and 2005 at two reference oncological centres. RESULTS: The median overall survival time (OS) was 7.1 months (95% CI: 6.7-7.9) and the 1-year, 2-year and 5-year survival rates were 32.3%; 12.5%; 3.9%, respectively. The median progression-free survival time (PFS) after the first line of treatment was 3.5 months (95% CI: 3.1-3.8). There were 19.1% objective responses (CR - 6.1%, PR - 13.0%) and SD - 45.5% after the first line of therapy. The most common adverse events were anaemia, neutropenia, thrombocytopenia, nausea and vomiting. IN MULTIVARIATE ANALYSES: PS (performance status) 0-1, normal serum levels of lactate dehydrogenase (LDH) and aspartate transaminase (AspAT), older age in women, palliative surgical treatment and palliative radiotherapy, type of the first line of therapy (DTIC), and metastatic melanoma of unknown primary site were independent positive predictors for survival. CONCLUSIONS: The survival rate of patients with metastatic melanoma has not changed significantly over the last years. We identified a set of independent positive predictors for OS treated with systemic therapy. DTIC still may be useful in treatment of patients in a good general condition and with normal serum levels of LDH. Because the results of treatment of metastatic melanoma are still not satisfactory, the majority of patients should be treated within prospective, randomized clinical trials.

Factors Affecting Sexual Function and Body Image of Early-Stage Breast Cancer Survivors in Poland: A Short-Term Observation.

INTRODUCTION: Knowing the important factors influencing sexual function and body image might facilitate the recovery process of breast cancer survivors. Surgery type, relationship quality, and partner support might be modified to create a space for psychosexual intervention. PATIENTS AND METHODS: This retrospective questionnaire-based study was performed on 128 women aged 18 to 65 years who were free of disease at time of study entry and who underwent surgical treatment for breast cancer. Diagnostic and Statistical Manual of Mental Disorders criteria were used to assessed female sexual dysfunction (FSD). Changes in Sexual Functioning Questionnaire (CSFQ) were used to measure sexual function, whereas the Body Image After Breast Cancer Questionnaire (BIBCQ) was used to assess body image. The support of the partner was evaluated by the Provisions of Social Relation Scale (PSRS). RESULTS: The median age of the studied respondents was 52.5 ± 10.1 years. FSD was diagnosed in 27.3% women. Lower physical satisfaction in relationship (odds ratio [OR] = 2.3), undergoing mastectomy (OR = 4.1) higher level of anxiety (OR = 4.2), and shorter duration of relationship (OR = 1.1) as well as not receiving adjuvant chemotherapy (F = 3.54), higher level of emotional satisfaction in relationship (F = 20.32), longer time after completion of oncologic treatment (F = 8.76), undergoing breast-conserving therapy (compared to mastectomy) (F = 13.21), and lower level of anxiety (F = 31,25) were important factors for the prevalence of FSD and positive body image, respectively. CONCLUSION: Type of surgery, time after completion of treatment, level of anxiety, adjuvant chemotherapy, partner support, and satisfying quality of relationship are important factors for sexual function, sexual quality of life, and body image in female breast cancer survivors.

Proteins Involved in HER2 Signalling Pathway, Their Relations and Influence on Metastasis-Free Survival in HER2-Positive Breast Cancer Patients Treated with Trastuzumab in Adjuvant Setting.

AIM: Resistance to trastuzumab (which is a standard therapy for breast cancer patients with HER2 overexpression) is associated with higher risk of progression or cancer death, and might be related to activation of signalling cascades (PI3K/AKT/mTOR, Ras/Raf/MAPK) and decreased level of their inhibitors. MATERIAL AND METHODS: Formalin-fixed paraffin-embedded tumour specimens from 118 HER2-overexpressing breast cancer patients treated with radical local therapy and trastuzumab in adjuvant setting were used for the assessment of: (1) PIK3CA gene mutations (p.H1047R and p.E545K) by qPCR, and (2) expression of Ki-67, EGFR, MUC4, HER3 and PTEN by immunohistochemistry. RESULTS: Lower Ki-67LI was observed in EGFR-immunonegative and in PTEN-immunopositive tumours. MUC4-immunonegative tumours more frequently were PTEN- and HER3-immunonegative. Favourable metastasis-free survival was observed in patients with tumours characterized by Ki-67LI≤50% (p=0.027), HER3 immunonegativity or PTEN immunopositivity (vs. tumours with HER3 expression and lack of PTEN expression, p=0.043), additionally, the trend was observed for patients with pN0+pN1 pathological tumour stage (vs. pN2+pN3) (p=0.086). Cox model revealed that independent negative prognostic factors were: (i) Ki-67LI>50% (p=0.014, RR=4.6, 95% CI 1.4-15.4), (ii) HER3 immunopositivity together with PTEN immunonegativity (p=0.034, RR=3.7, 95% CI 1.1-12.5). CONCLUSION: The results of our study suggest that combined analysis of HER3 and PTEN expression might bring information on trastuzumab sensitivity in the group of HER2-positive breast cancer patients treated with trastuzumab in adjuvant setting.

Prognostic role of lymphatic vessel density and lymphovascular invasion in chemotherapy-naive and chemotherapy-treated patients with invasive breast cancer.

It is assumed that the spread of breast cancer cells via the lymphatic system might be influenced by inflammatory reactions and/or the application of chemotherapy or molecularly targeted therapy. Therefore, we analysed survival according to lymphatic vessel density (LVD), lymphovascular invasion (LVI) (both assessed using podoplanin as immunohistochemical marker of lymphatic endothelium) and well-established clinico-pathological features in a group of 358 patients with invasive ductal breast cancer: 139 chemotherapy-naïve (pT1-2/pN0/M0) and 219 treated with chemotherapy (pT1-4/pN1-3/M0). Univariate analysis revealed that high LVD was related to unfavourable disease-free survival (DFS) in pN0/chemotherapy/trastuzumab-naïve patients (P = 0.028). Conversely, in pN+/chemotherapy-treated individuals high LVD was related to favourable DFS (P = 0.019). LVI was a significant indicator of survival (P = 0.005) only in pN0/chemotherapy/trastuzumab-naïve patients. The following parameters were significant independent adverse prognostic factors for DFS: (i) in pN0/chemotherapy/trastuzumab-naïve patients: high LVD (LVD > 7 vessels/mm2; RR = 2.7, P = 0.039), LVI (RR = 3.3, P = 0.046) and high tumor grade (G3 vs. G1 + G2; RR = 2.6, P = 0.030); (ii) in pN+/chemotherapy/trastuzumab-treated patients: low LVD (RR = 1.8, P = 0.042), the number of involved lymph nodes (pN3 vs. pN1-2; RR = 2.3, P = 0.012) and the breast cancer subtype (expression of steroid receptors together with HER2 immunonegativity and high proliferation index vs. other breast cancer immunophenotypes; RR = 3.0, P < 0.001). High LVD may identify high progression risk in pN0/chemotherapy/trastuzumab-naïve patients, and low progression risk in pN+/chemotherapy-treated patients. This phenomenon might be explained by potential involvement of lymphangiogenesis in two processes related to cancer eradication: a chemotherapy-stimulated activity of the immune system against cancer cells, or increased tumour drainage influencing the efficacy of cytotoxic drugs.

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.

Prognostic Role of Nodal Status and Clinically Asymptomatic Valvular Insufficiency in Patients with HER2-positive Breast Cancer Treated with Chemotherapy, Radiotherapy and Trastuzumab in an Adjuvant Setting.

AIM: The aim of the present study was to assess metastasis-free survival of 134 patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with chemotherapy, radiotherapy and trastuzumab in an adjuvant setting, according to sub-clinical cardiac side-effects (parameters not tested previously) evaluated before, during and after trastuzumab therapy, as well as selected clinicopathological parameters. RESULTS: In our series, left ventricular ejection fraction decreased significantly from 68.1% before trastuzumab treatment to 66.7% after therapy (p<0.001). Further analysis revealed that this decrease was significant only in patients who received radiotherapy and developed valve insufficiency during or after (but not before) trastuzumab therapy (p<0.001). Cox multivariate analysis revealed that both pN2a tumor stage and valve regurgitation during/after trastuzumab therapy (vs. lack of valve insufficiency or insufficiency before trastuzumab therapy) were significant independent factors for a negative prognosis. CONCLUSION: Valve insufficiency diagnosed during or after trastuzumab application might be cancer-unrelated indicator of decreased sensitivity to trasuzumab.