Role of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio and platelets in prognosis of patients with prostate cancer.

The aim of the present analysis was to evaluate the platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelets (PLT) and neutrophil level for their prognostic values in patients with prostate cancer who had been treated with radiotherapy. A retrospective analysis of 152 patients who were treated in the Radiotherapy Department at Maria Sklodowska-Curie National Research Institute of Oncology (Gliwice, Poland) between January 2012 and December 2014 was performed. The prognostic value (overall survival; OS) of the pre-treatment PLR, NLR, LMR, PLT, neutrophil level and other laboratory factors such as: leukocyte, lymphocyte, monocyte, hemoglobin, RBC, prostate-specific antigen level (PSA), Gleason score, age, smoking and comorbid condition were assessed using univariate analysis. The cut-off point was determined for NLR as 'elevated' at >4.66, LMR >3.26 and the PLR was considered 'elevated' at >89.6. Median follow-up was 4.9 years. The 5 and 7-year OS rates were 81.5 and 72.2%, respectively. In univariate analysis higher NLR (P=0.007), higher level of PLT (P=0.004), higher level of neutrophils (P=0.013), elevated level of leukocyte (P=0.043) and lymphocyte (P=0.043) were factors significantly associated with decreased OS. No difference was found for PLR (P=0.308) and LMR (P=0.109). The other factor associated with decreased OS were: higher Gleason score (>7; P=0.005), higher PSA level (>20 ng/dl; P=0.0001), smoking (P=0.003) and older age (>70 years; P=0.018). In multivariate analysis, NLR, LMR, leukocyte and RBC were independently associated with prognosis in patients with prostate cancer. Elevated pre-treatment NLR [hazard ratio (HR)=10.83; P=0.001), LMR (HR=3.14; P=0.007) and higher leukocyte level (HR=3.14; P=0.007) were independently associated with increased mortality risk. Overall, pre-treatment NLR, PLR, leukocyte and RBC levels were revealed to be independent prognostic factors.

Overall survival analysis of > 65-year-old patients with breast cancer based on their molecular, clinicopathological and laboratory factors.

Introduction: The objective of the present study was to characterize > 65-year-old patients with breast cancer according to clinicopathological, molecular and laboratory factors. Methods: A total of 723 breast cancer patients, who had been diagnosed and treated during 2005-2019, were retrospectively reviewed. Patients > 65 years of age (92 patients) were compared with < 50-year-old women (306 patients). We analyzed 398 women from 723 patients. Results: Overall survival analysis was conducted for both groups, separately and combined. Patients with BC aged > 65 years were characterized by G1-2, higher lymphocyte values, lower platelet (PLT) counts and lower NLR or PLR values than patients < 50 years of age. Conclusions: Age > 65 years is a negative prognostic factor independent of other factors.

Assessing the impact of antiemetic guideline compliance on prevention of chemotherapy-induced nausea and vomiting: Results of the nausea/emesis registry in oncology (NERO).

BACKGROUND: Evidence-based antiemetic guidelines offer predominantly consistent recommendations for chemotherapy-induced nausea and vomiting (CINV) prophylaxis. However, studies suggest that adherence to these recommendations is suboptimal. We explored inconsistencies between clinical practice and guideline-recommended treatment with a registry evaluating the effect of guideline-consistent CINV prophylaxis (GCCP) on patient outcomes. PATIENTS AND METHODS: This was a prospective, non-interventional, multicentre study. The primary objective was to assess the overall (Days 1-5) complete response (CR: no emesis/no rescue use) rates in patients who received GCCP or guideline-inconsistent CINV prophylaxis (GICP) using diaries for 5 days following chemotherapy. Cycle 1 results are presented in patients who received either (1) anthracycline/cyclophosphamide (AC) highly emetogenic chemotherapy (HEC), non-AC HEC or carboplatin, with GCCP for all these groups consisting of prophylaxis with an NK1 receptor antagonist (RA), 5-HT3RA and dexamethasone prior to chemotherapy or (2) moderately emetogenic chemotherapy (MEC), with GCCP consisting of a 5-HT3RA and dexamethasone prior to chemotherapy as per MASCC/ESMO 2016 guidelines, in place at the time of the study. RESULTS: 1,089 patients were part of the cycle 1 efficacy evaluation. Overall GCCP was 23%. CR rates were significantly higher (P < 0.05) in patients receiving GCCP (62.2%) versus GICP (52.6%) in the overall population, as well as in the subsets of patients receiving AC/non-AC HEC (60.2% versus 47.8%), MEC (73.8% versus 57.8%) and in those non-naïve to the chemotherapy received (65.9% versus 53.8%). No impact on daily living due to CINV (FLIE assessment) was observed in 43.4% patients receiving GCCP versus 28.5% GICP (P < 0.001). CONCLUSION: Consistent with prior studies, GCCP was very low; a significant benefit of almost 10% improved prevention of CINV was observed with GCCP. As per MASCC/ESMO guidelines, such an absolute difference should be practice changing. Comprehensive multifaceted strategies are needed to achieve better adherence to antiemetic guidelines.

Outcome of COVID-19 infection in cancer patients during active systemic anticancer treatment. Single-institution experience. A retrospective analysis.

INTRODUCTION: Patients with cancer undergoing active systemic anticancer treatment (chemotherapy, immunotherapy, targeted, or combination therapy) are at greater risk of COVID-19 infection than persons without cancer. In this paper, the authors analyse the spread of the coronavirus among cancer patients undergoing systemic therapy, and the impact of COVID-19 infection on the continuation of cancer treatment and its outcome at one community hospital in a mid-sized city in the south of Poland. MATERIAL AND METHODS: Nasopharyngeal swab was the only collection method used to obtain specimens for testing via real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Only those with positive RT-PCR results were considered as confirmed SARS-CoV-2 cases. We analysed the medical records of patients quarantined in a hospital clinical oncology ward due to confirmed COVID-19 infection in one member of the group. Qualitative measures are presented as the percentage of their occurrence, and these were evaluated with Fisher's test. Differences were considered significant at p < 0.05. RESULTS: Cancer patients had more frequent confirmed COVID-19 infection than other patients (3.7% vs. 1.2%). Among cancer patients COVID-19 infection was significantly more frequent in women than in men, p = 0.005. The fatality rate was 27.3% in cancer patients undergoing active anticancer therapy, compared to 3% in the general Polish population. Neither heparin nor G-CSF use had any influence on COVID-19 infection. CONCLUSIONS: In this analysis, the only significant negative factor for COVID-19 infection was female sex, RR (95% CI) = 4.5 (1.3-15.8), (p = 0.005), and this was attributable to individual behaviour.

BRCA1/BRCA2 variants of uncertain significance in clinical practice: A case report.

The influence of BRCA1/2 variants of uncertain significance (VUSs) on the cancer risk and their association with the response to treatment is uncertain. The aim of the present study was to evaluate the role of BRCA VUS in patients with breast cancer. A total of two cases of breast cancer patients with the BRCA VUS were described. The complete coding sequence of BRCA1/2 genes was analyzed from the genomic DNA material by next generation sequencing on the Ion Torrent platform. The presence of c.3454G>A (p.Asp1152Asn) VUS in the BRCA1 gene was reported in a 64-year-old woman with invasive breast carcinoma. The characteristics of the breast tumors were the following: moderately differentiated-intermediate grade (NG-2 G-2), HER2 (+), estrogen receptor (ER) (+++), progesterone receptor (PR) (+++), luminal A subtype and pT2 N1a Mx. The second detected VUS was the c.2374T>C (p.Tyr792His) variant in the BRCA2 gene. This variant was reported in a 33-year-old woman who was diagnosed with right breast cancer (cT2N1M0). The invasive breast carcinoma was characterized as follows: NG-2 G-2, ER (+++), PR (+++), Ki-67 10%, HER2 (+++) and luminal B subtype. The data demonstrated that patients with VUSs should be managed based on their family history of cancer and clinicopathological characteristics. The clinical significance of the VUS in BRCA1/2 may change over time and reclassification of the variant to 'pathogenic' or 'benign' should be undertaken. Patients with VUS should be followed up regularly.

Clinicopathological characteristics of breast cancer patients with NOD2 mutation according to age.

INTRODUCTION: The purpose of the present study was to characterise patients with breast cancer (BC) and NOD2-mutation (age ≥ 50 years) according to their clinicopathological factors or family history. Patients aged ≥ 50 years were compared with the control group and with NOD2-mutation carriers aged < 50 years. MATERIAL AND METHODS: Prognostic factors were analysed in patients with BC with confirmed NOD2 c.3016_3017insC (n = 150) mutations. The control group was selected from patients with BC without mutations (n = 376). RESULTS: There were significant differences between NOD2-mutation carriers and the control group aged ≥ 50 years, according to HER2 overexpression (p = 0.0001), ER (-) (p = 0.007), PR (-) (p = 0.003), T1-T2 (p = 0.011), and G3 (p = 0.036). Similarly, significant differences were observed between NOD2-mutation carriers and the control group aged < 50 years, according to HER2 overexpression (p = 0.0001), ER (-) (p = 0.049), and N (+) (p = 0.038). In patients aged ≥ 50 years, family history of cancer, including BC, was observed more often in NOD2-mutation carriers compared with the control group of patients (OR = 1.66; p = 0.072, for BC in family history: OR = 2.65; p = 0.002). NOD2-mutation carriers aged ≥ 50 years had significantly less frequent G3 (p = 0.004) and HER2 overexpression (p = 0.043) compared with patients with NOD2 mutation aged < 50 years. CONCLUSIONS: The presence of the NOD2 mutation is not only characteristic of younger patients but also in patients > 50 years of age. In NOD2-mutation carriers aged ≥ 50 years, the presence of larger tumour size, G3, or HER2 overexpression were lower compared with younger patients with NOD2 mutation.

Prognostic Value of the Neutrophil-Lymphocyte, Platelet-Lymphocyte, and Monocyte-Lymphocyte Ratios in Male Breast Cancer Patients.

BACKGROUND: The aim of the present study was to assess the blood neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) as prognostic factors in male breast cancer (BC) patients. METHODS: A retrospective analysis of 38 male BC patients who were treated at the Institute of Oncology (Gliwice, Poland) between January 2005 and December 2018 was performed. The prognostic value (in terms of overall survival [OS]) of the pretreatment PLR, NLR, and MLR was assessed by univariate analysis. RESULTS: We observed a tendency towards worse OS among male BC patients with lymph node metastases (N+) (5-year OS: 43.5 vs. 73.9%; p = 0.087), a greater tumor size (T4 vs. T1 + T2) (42.0 vs. 70.5%; p = 0.061), and a negative steroid receptor status (PR-) (28.6 vs. 65.6%; p = 0.109). Patients with a family history of cancer had significantly better 5-year OS than patients without a family history of cancer (86.3 vs. 35.0%; p = 0.001). Younger male BC patients (age ≤56 years) had better 5-year OS than patients >56 years of age (82.5 vs. 42.3%; p = 0.028). The 5-year OS was lower among patients with a lower lymphocyte value (≤1.82 × 103) (29.0 vs. 75.6%; p = 0.010). There was a tendency towards worse OS among patients with a higher platelet count (>281 × 103) (4.5-year OS: 16.7 vs. 65.8%; p = 0.056). The 5-year OS was insignificantly lower in the group with NLRs >2.74 than in the group with NLRs ≤2.74 (37.5 vs. 62.8%; p = 0.078). A worse OS rate was associated with an elevated PLR (>169.1) (22.2 vs. 70.1%; p = 0.008). Similarly, there was worse OS in the group with higher MLR (>0.30) (41.8 vs. 78.3%; p = 0.025). CONCLUSIONS: The present results reveal that elevated MLRs (>0.30) and PLRs (>169.1) are associated with poor OS among male BC patients. Similarly, but insignificantly, an elevated NLR (>2.74) affected OS.

Prognostic value of the neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratio in breast cancer patients.

The aim of the present study was to assess the blood the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR) as prognostic factors in breast cancer (BC) patients. A retrospective analysis of 436 BC patients who were treated at COI (Gliwice, Poland) between January 2005 and June 2018 was performed. The prognostic value [overall survival (OS)] of the pre-treatment PLR, NLR and MLR was assessed by univariate and multivariate analysis. The 5-year OS was lower in the NLR >2.65 compared with that in the NLR≤2.65 group (82.5 vs. 89.6%; P=0.053), and significantly lower in the subgroup of triple-negative breast cancer (TNBC; 70.3 vs. 89.3%; P=0.034) and in patients whose tumors had an estrogen receptor-negative [ER(-)] status (66.6 vs. 83.6%; P=0.018). The 5-year OS was lower in patients with PLR >190.9 compared with that in the PLR≤190.9 group (78.7 vs. 89.4%; P=0.020). A poor OS rate associated with an elevated PLR was also observed in the subgroups with TNBC (68.2 vs. 88.5%; P=0.032) and with ER(-) status tumors (57.7 vs. 83.6%, P=0.002). An elevated MLR (>0.28) was not associated with OS time (P=0.830). Multivariate analysis revealed that the NLR and PLR were insignificant negative prognostic factors, except for the subgroup of patients with ER(-) tumors, where an elevated NLR [hazard ratio (HR)=2.40; 95% confidence interval (CI): 1.20-4.80; P=0.013] and a higher PLR (HR=2.51; 95%CI: 1.23-5.14; P=0.012) were independent prognostic factors for poor OS together with lymph node metastasis ((HR=5.47; 95%CI: 2.46-12.15; P=0.0001 and HR=4.82; 95% CI: 2.15-10.78; P=0.0001), respectively. The present results revealed that an elevated NLR (>2.65) and PLR (>190.9) are associated with poor OS in BC patients. In the ER(-) subgroup of patients, an elevated NLR and PLR were significant independent prognostic factors. However, the MLR did not affect OS.

Molecular characteristics of breast cancer according to clinicopathological factors.

The purpose of the present study was to evaluate the correlation between molecular factors such as BRCA1 DNA repair associated (BRCA1), checkpoint kinase 2 (CHEK2) and nucleotide binding oligomerization domain containing 2 (NOD2) gene mutations and clinicopathological factors in patients with breast cancer (BC). Prognostic factors were analyzed in BC patients with confirmed BRCA1 (n=73), CHEK2 (n=51) and NOD2 (n=31) mutations. The control group was selected from BC patients without mutations (n=392). The BRCA-associated cancer cases were significantly more often triple negative compared with sporadic cancer (62% vs. 14%; P=0.0001). Luminal B HER2-positive and HER2-positive non-luminal subtypes were observed more often in the control group (33 and 17%). The luminal A subtype was detected in 53% of CHEK2 mutation carriers and 45% of NOD2 mutation carriers. A lower histological grade was observed significantly more often in patients with CHEK2 mutations in comparison with the control group (88 vs. 69%; P=0.003). Lymph nodes without metastases were reported more frequently in NOD2 mutation carriers (74 vs. 54%; P=0.038), in BRCA1 mutations (73 vs. 54%; P=0.004) and, although not significantly, in CHEK2 mutation carriers (69 vs. 54%; P=0.071) compared with the control group. In conclusion, BRCA1 mutation was associated with TNBC and the luminal B HER2 (-) subtype. HER2-positive subtypes were characteristic of the control group. CHEK2 and NOD2 mutation carriers had a more favorable profile of prognostic factors.

The Role of Neutrophil-Lymphocyte Ratio, Platelet-Lymphocyte Ratio, and Platelets in the Prognosis of Metastatic Renal Cell Carcinoma.

OBJECTIVE(S): The aim of this analysis was to evaluate the platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), platelets (PLT), and neutrophil level for their prognostic value in patients with metastatic renal cell carcinoma (mRCC). MATERIALS: We retrospectively reviewed medical records of 141 patients with mRCC (2006-2016). Univariate and multivariate analyses were performed with the Cox proportional hazards regression model. The cutoff value of NLR was "elevated" as >3.68 and the PLR cutoff value was "elevated" as >144.4. RESULTS: The median PFS and OS were shorter in elevated NLR and PLR. A higher value of PLT was associated with worse median OS and higher neutrophil level with worse OS and PFS. In multivariate analysis, higher NLR (p = 0.007) and PLR (p = 0.006) were independent prognostic factors for shorter OS together with BMI ≤30 (p = 0.004), higher Fuhrman grade (p = 0.0002), lower level of hemoglobin (p= 0.010), and ZUBROD 2 (p = 0.0002). Higher PLR (p = 0.0002) was an independent negative prognostic factor for PFS together with higher Fuhrman grade (p = 0.001), higher neutrophil level (p = 0.001), and lower lymphocyte level (p = 0.013). CONCLUSION: Elevated pretreatment NLR, PLR, PLT, and neutrophil count are associated with shorter OS and PFS in patients with mRCC. NLR and PLR are independent prognostic factors for OS. However, PLR and neutrophil count are independent prognostic factors for PFS.

BRCA1 mutation in breast cancer patients: Analysis of prognostic factors and survival.

The presence of BRCA1 mutations is associated with an increased risk of breast and ovarian cancer. The present study compared clinicopathological characteristics and overall survival (OS) of hereditary and sporadic breast cancer. Using data collected from a previous study conducted between 2007-2016 at the Maria Sklodowska Curie Cancer Center and Institute of Oncology (Gliwice, Poland), the prognostic factors and survival in 60 breast cancer mutation carriers were analyzed. A control group was selected from the breast cancer patients without BRCA mutations (n=386). BRCA mutation carriers had significantly worse survival when compared with non-carriers (P=0.017). The 10-year OS rate was 78.0% for all analyzed groups: 65.9% for BRCA mutation carriers and 81.1% for non-carriers. In the univariate analyses, BRCA mutation carriers had a significantly higher risk of mortality in comparison to non-carriers [hazard ratio (HR)=1.87; 95% confidence interval (CI) 1.08-3.25]. Increased tumor size (HR=3.64), lymph node metastases (HR=2.45) and higher histological grade (HR=2.84) were significant factors for worse OS. Positive estrogen receptor status was associated with a better OS (HR=0.49, P=0.022). Age ≤40 years (HR=0.48, P=0.081) was an insignificantly favorable factor. The 10-year survival rate was significantly decreased in patients with BRCA1 mutation. Therefore, negative factors for OS in mutation carriers included lymph nodes metastases, negative steroid receptor status and increased tumor size.

BRCA2 genemutation, c.2808_2811delACAA (p.Ala938Profs), in malebreastcancer - clinicopathologicalanalysisbased on a case report.

Male breast cancer (MBC) is a rare disease that occurs in ~0.2% of all neoplasms among men. The risk of developing MBC is higher in men with a BRCA2 genetic mutation (7%). The aim of this study was to evaluate the association between c.2808_2811del ACAA (p.Ala938Profs) BRCA2 mutation in MBC and clinicopathological factors. A 75-year-old patient was admitted to the Genetic Outpatient Clinic with a diagnosis of right breast cancer and with a family history of cancer (two daughters who were diagnosed with breast cancer at ages 46 and 38 years). Postoperative histopathological examination revealed tumor type pT2 N1a Mx, NST NG-3 G-3, Ki-67 (75%), HER2 (+), ER (+++), PR (+++), invasive carcinoma and luminal B subtype. The complete coding sequences of the BRCA1 and BRCA2 genes were analyzed for genomic DNA material using next generation sequencing on the Ion Torrent platform. The c.2808_2811delACAA (p.Ala938Profs) mutation was observed in the BRCA2 gene. The presence of the c.2808_2811delACAA (p.Ala938Profs) mutation in the BRCA2 gene was confirmed using the Sanger method. The same BRCA2 gene mutation was reported in one of the patient's daughters. The detected mutation causes the frameshift mutation, resulting in the creation of an additional translation termination codon and the synthesis of an abnormal protein. This mutation was associated with a later age of disease, a higher histological degree, a higher mitotic index, a positive steroid receptor status and the luminal B subtype HER2- breast cancer.

TP53 mutations and SNPs as prognostic and predictive factors in patients with breast cancer.

Tumor protein 53 (TP53) is a tumor suppressor gene that encodes tumor protein p53. Tumor protein p53 regulates the expression of target genes in response to cellular stress. Additionally, p53 participates in the regulation of cell cycle checkpoints, DNA repair and apoptosis. Mutations in the TP53 gene are associated with numerous types of human cancer, including breast cancer, sarcomas, brain tumors and adrenal cortical carcinomas. In breast cancer, TP53 mutations are a negative prognostic factor. Tumors with TP53 mutations are more likely to be aggressive (triple-negative or human epidermal growth factor receptor 2-positive breast cancer), and resistant to chemotherapy and radiotherapy. In addition to a well-known TP53 mutation, a number of single nucleotide polymorphisms have been systematically identified and evaluated in human populations. In the present article, the role of TP53 mutations and polymorphisms in clinical practice and breast cancer treatment has been described. Additionally, the existing data on TP53 polymorphisms in breast cancer as prognostic and predictive factors have been summarized. A literature search of these topics was performed through PubMed and abstracts of the main cancer congresses in recent years.

Checkpoint Kinase 2 (CHEK2) Mutation in Renal Cell Carcinoma: A Single-Center Experience.

Renal cell carcinoma (RCC) occurs in sporadic and heritable forms. Genetic mutations have been identified as risk factors in 1-2% of RCC. The aim of this study was to evaluate I157T and CHEK2*1100delC mutations of checkpoint kinase 2 (CHEK2) gene in RCC. Medical records of 40 clear cell RCC patients who had genetic tests and consultation at the Genetic Outpatient Clinic, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland, were reviewed retrospectively. Mutation profile was assessed by ASA-PCR and RFLP-PCR techniques. Only three female patients had CHEK2 mutation (I157T). No CHEK2*1100delC was observed in any of the patients. These tumors were N0, and two were Grade 3. One showed capsular infiltration. No blood vessel infiltration or metastases was observed. Overall, RCC from patients with CHEK2 mutation did not display any special characteristics when compared with those without the mutation. While no association between CHEK2 mutation and RCC could be established, all three patients with CHEK2 mutation developed second neoplasms many years after first diagnosis. Further studies, especially regarding CHEK2 mutation as a predictive factor for second neoplasm in RCC patients, are warranted.

The association of tumor lymphocyte infiltration with clinicopathological factors and survival in breast cancer.

Recent studies have confirmed the role of tumor-infiltrating lymphocytes (TILs) in carcinogenesis and cancer progression. The aim of this study was to evaluate the correlation between the level of tumor lymphocyte infiltration and well-known clinicopathological factors in breast cancer patients. We also evaluated the influence of TILs on overall survival. Paraffin sections were retrospectively evaluated in 76 cases in early stage breast cancer patients who underwent surgery followed by systemic treatment. Tumor-infiltrating lymphocytes were classified as absent (grade 0), mild (grade 1), moderate (grade 2), or severe (grade 3). Tumor-infiltrating lymphocytes were found in 87% of patients (severe grade in 8% of them). Higher grade (grades 2-3) TILs were present more frequently in younger patients (under 65 years) than older women (47% vs. 24%; p = 0.099). Higher grades of tumor-infiltrating lymphocytes (grades 2-3) appear to be associated with clinicopathological factors such as negative steroid receptor status (p = 0.001), HER2 overexpression (p = 0.016) and higher histological grade (G3) (p = 0.095). Tumor-infiltrating lymphocytes were not a significant prognostic factor for overall survival in our group. Only HER2 overexpression significantly increases the risk of death (HR = 4.3, p = 0.020). In the subgroup of patients who had tumors with HER2 overexpression there was non-significantly worse OS independently of TIL grade (p = 0.086).

Current therapeutic strategies of anti-HER2 treatment in advanced breast cancer patients.

The HER2/neu (ERBB2) oncogene is amplified and/or overexpressed in approximately 20% of breast cancers, and is a strong prognostic factor for relapse and poor overall survival, particularly in node-positive patients. It is also an important predictor for response to trastuzumab, which has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. Treatment with the anti-HER2 humanized monoclonal antibody - trastuzumab significantly improves progression-free and overall survival among patients with HER2-positive breast cancer. However, in most patients with HER2-positive metastatic breast cancer, the disease progresses occurred, what cause the need for new targeted therapies for advanced disease. In clinical trials, there are tested new drugs to improve the results of treatment for this group of patients. This paper presents new drugs introduced into clinical practice for treatment of advanced breast cancer, whose molecular target are receptors of the HER2 family. In addition, new therapeutic strategies and drugs that are currently in clinical researches are discussed.

Skin toxicity in BRAF(V600) mutated metastatic cutaneous melanoma patients treated with vemurafenib.

INTRODUCTION: The use of orally available BRAF kinase inhibitor - vemurafenib is associated with numerous adverse skin reactions. AIM: To assess the safety and early side effects of vemurafenib treatment in the unselected group of patients treated at the outpatient clinic, in particular the assessment of the incidence of skin cancer. MATERIAL AND METHODS: We carried out a systematic study of patients (pts) treated with vemurafenib. Skin toxicity during vemurafenib therapy was analyzed. Toxicity was determined on the basis of the toxicity scale CTCAE, version 4.0. RESULTS: The most common cutaneous side effects were hyperkeratotic perifollicular rash (69%) and photosensitivity (15%). Skin rash developed more frequently in the first month of treatment. Squamous cell carcinoma occurred in 38% of patients. Patients with skin cancer development during vemurafenib therapy had non-significantly longer overall survival (OS) than patients without skin cancer, p = 0.4. Skin cancer developed more often in women than in men (60% vs. 25%), p = 0.249. It was detected only in patients with normal weight compared to overweight patients (55% vs. 0), p = 0.09. The median OS was 26 months and median OS from the time of distant metastases diagnosis was 9.8 months. In patients with a low body mass index, shorter OS was observed, p = 0.09. CONCLUSIONS: The incidence of squamous cell carcinoma was high (38%). This study has many limitations mostly due to a small group of patients. That is why the results should be taken into consideration with caution. The proper symptomatic treatment in cooperation with dermatologists allows to continue the vemurafenib therapy.

A Comparison between CHEK2*1100delC/I157T Mutation Carrier and Noncarrier Breast Cancer Patients: A Clinicopathological Analysis.

OBJECTIVE: The suppressor gene CHEK2 encodes a cell cycle checkpoint kinase, involved in cell cycle regulation, apoptosis and response to DNA damage. The aim of this study was to analyze the differences between CHEK2 mutation carriers (CHEK2*1100delC/I157T) and noncarriers with respect to clinicopathological factors. METHODS: We reviewed the medical records of 100 early breast cancer patients (46 mutation carriers and 54 noncarriers) who were treated with chemotherapy, hormonotherapy or trastuzumab. RESULTS: CHEK2 mutation carriers were older (>65 years) than noncarriers (17 vs. 7%; p = 0.215). Twenty-five (54%) of them had a history of cancer in the family. Gastric cancer in the family history was detected in 11% of mutation carriers and in 2% of noncarriers (p = 0.092). There was a trend for more frequent lymph node metastases in patients without the mutation in comparison to mutation carriers (46 vs. 28%; p = 0.098). Luminal B type breast cancer was detected more often in carriers (39 vs. 20%; p = 0.048). Breast-conserving treatment was also conducted more often in mutation carriers (57 vs. 31%; p = 0.015). Histologic grades G1/G2 were detected more frequently in mutation carriers (82 vs. 70%; p = 0.212). CONCLUSION: Mutation carriers were characterized by older age, a history of gastric cancer in the family, locally advanced disease, lower histologic grade and luminal B type breast cancer.

Risk factors for disease progression in HER2-positive breast cancer patients based on the location of metastases.

INTRODUCTION: Trastuzumab therapy significantly improves progression-free and overall survival in HER2-positive [HER2(+)] breast cancer (BC) patients. However, in most patients with HER2(+) metastatic BC, the disease progress occurred. The aim of this study was to evaluate the clinicopathological risk factors for progression in HER2-positive breast cancer patients during trastuzumab therapy. MATERIAL AND METHODS: The analysis included medical records of HER2(+) metastatic BC patients treated with trastuzumab between 2006 and 2013. RESULTS: The most common site of progression during trastuzumab therapy were lungs 25 (39%), central nervous system (CNS) 8 (13%), skin 9 (14%), locoregional lymph nodes 19 (30%), liver 18 (28%) and bone 17 (27%). Patients with lung metastases significantly more often had a history of cancer in the family than women with other metastasis sites (24% vs. 2.6%), p = 0.048. Metastases to lungs occurred also more often during therapy containing trastuzumab with chemotherapy than trastuzumab alone 17/8 (58% vs. 41%), p = 0.043. Central nervous system metastases were observed insignificantly more frequently in postmenopausal women than premenopausal patients 8/0 (22% vs. 0%), p = 0.093. There was reported a tendency to liver metastases in ER-negative tumors 13/20 (72% vs. 44%, p = 0.053). Bone metastases were associated with the positive steroid receptor status (p = 0.019) and second neoplasm in history (p = 0.06). CONCLUSIONS: Risk factors for disease progression were the menopausal status (CNS metastases), steroid receptor status (liver, lymph nodes and bone metastases), history of cancer in the family (lung metastases) and history of cigarette smoking (liver metastases).