Ten years of using adjuvant trastuzumab in breast cancer in Serbia - Single institution experience.

PURPOSE: The purpose of this study was to determinate disease-free interval (DFI) and overall survival (OS) in HER2-positive breast cancer patients who received adjuvant trastuzumab at the University Clinic of Nis, Serbia, and to investigate the influence of clinicopathological and biological characteristics of the tumor on prognosis. The second aim was to determinate the most frequent cause for the treatment discontinuation, recurrence rate, as well as the site of most common localization of the first recurrence of disease. METHODS: This research was conducted as a retrospective study at the University Oncology Clinic, Clinical Centre in Nis. The study included 238 patients who were operated and treated for HER2-positive breast cancer between January 1st, 2007 to September 30th, 2012 and followed up until December 31st, 2016. Trastuzumab was administered concurrently with taxanes, if administered, or after the completed anthracycline-based chemotherapy. RESULTS: After a median follow up of 69 months the 5-year DFI was 65.9% and 5-year OS was 81.8% and, as expected, significantly longer in the group of patients with smaller tumors, a smaller number of positive axillary lymph nodes, as well as a lower stage of disease (p<0.0001). Patients older than 65 years had a longer DFI compared to the 45-65 and under 45 age groups of patients (p=0.01). No statistical significance was found in the length of DFI in relation to the histological tumor subtype, tumor grade, or the status of hormone receptors. Unlike DFI, a longer OS was recorded in the group of patients with lower tumor grade (p=0.03) and there was no statistically significant difference in survival regarding the age of patients (p=0.07). Recurrence occurred in approximately one third of the patients (38.23%), mostly in the form of local recurrence. Adjuvant therapy with trastuzumab was not completely carried out in 18.49% of the patients, the most common reason being the progression of disease. CONCLUSIONS: A long median follow up period of 69 months indicated that anti-HER2 monoclonal antibody trastuzumab, after anthracycline-based chemotherapy or concurrently with taxanes, is efficient and safe in treating early breast cancer.

Serbian consensus of neoadjuvant therapy for breast cancer: NeoPULSE.

Even though surgery is the primary treatment of operable breast cancer, it has been known for decades that the administration of postoperative adjuvant or preoperative neoadjuvant therapy is extremely important. Indications for neodjuvant therapy administration have been expanded over the years, and nowadays this kind of treatment represents an inevitable option in early breast cancer treatment. The NeoPULSE project, which gathered a group of experts in the field of breast cancer from five Serbian university centres, was formed with the aim to define optimal breast cancer diagnosis, indications for neoadjuvant therapy, therapeutic combinations in relation to molecular/biological parameters of breast cancer, as well as the treatment after neoadjuvant therapy. During two separate expert meetings involving surgeons, medical oncologists, radiation oncologists, a pathologist, and a "Blueprint" workshop, the project participants answered questions over the indications for neoadjuvant therapy. The first part covered local practice and referred to the existence and work of a multidisciplinary team, as well as commonly applied therapeutic regimens in the neoadjuvant setting. Experts analysed personal views regarding indications for the administration and benefits of neoadjuvant therapy, their perception on the correlation between achieving a pathological complete response (pCR) and the outcome of treatment, as well as the attitude towards controversies about this type of treatment, primarily regarding a possible change in the receptor status after therapy and therapeutic options after a suboptimal response. The analysis of the answers pointed to problems and deviations from recommendations in everyday clinical practice, based on which appropriate solutions were proposed. The establishment of such a panel and consensus is an attempt to modernize multidisciplinary teams in Serbia, achieve reaching uniform decisions of all subjects dealing with breast cancer, and therefore, at least in one segment, improve breast cancer treatment in Serbia.

Stressful life events and breast cancer risk: a hospital-based case-control study.

PURPOSE: Elucidation of the factors contributing to the incidence of breast cancer is of crucial importance for the development of preventive or therapeutic strategies targeting the disease. Research on stress and breast cancer has been documented by various studies published over the years. In view of breast cancer importance as the most commonly occurring malignancy in females in Serbia, this study was undertaken to examine the association between stressful life events and breast cancer risk. METHODS: The present hospital-based case-control study comprised 120 new breast cancer cases and 120 hospital controls matched with respect to age (± 2 years). This study used the Paykel Life Events Scale to obtain information about stressful life events in the years before diagnosis. The SPSS statistical package was used and odds ratios (OR) and 95% confidence intervals (95% CI) were calculated from multivariate conditional logistic regression model. RESULTS: Multiple conditional logistic regression analysis revealed six independent predictors of breast cancer risk: experience of severe and moderate threats (first 25 life events from the scale) (OR=3.15, 95% CI=2.01-4.93), son's military service (OR=6.09, 95% CI=4.17-12.37), death of close family member (OR=7.98, 95% CI=2.18-9.14), moderate financial difficulties (OR=3.26, 95%CI=1.24-8.56), maternal death in childhood (OR=3.46, 95% CI=1.21-9.92) and serious financial difficulties (OR=3.55, 95% CI=1.20-10.52). CONCLUSION: Stress exposure has been proposed to contribute to the etiology of breast cancer. There is a need for understanding the differing physiological effects of types or times of stress exposure.

Young age and pathological features predict breast cancer outcome - report from a dual Institution experience in Serbia.

PURPOSE: The aim of this study was to investigate the influence of clinicopathological and biological characteristics on prognosis, disease free survival (DFS) and overall survival (OS), of very young patients (≤35 years of age) with breast cancer. METHODS: We retrospectively collected information of 150 women diagnosed with breast cancer, aged ≤35 years, who were operated and treated at two University Hospitals in Serbia between January 2009 and February 2011. RESULTS: After a median follow up of 44 months patients ≤30 had shorter DFS and OS compared to patients aged 31-35 years (p=0.004 and p=0.037, respectively). The differences in DFS and OS were significant with decreased survival associated with higher tumor grade (p=0.005 and p=0.0001, respectively). Tumor size and number of positive nodes were predictors of outcome with decreased survival associated with higher tumor size (p=0.0019 for DFS and p<0.0001 for OS) and increasing number of nodes (p<0.0001 for both). HER 2 receptor did not seem to have a prognostic influence while patients with hormonal receptors (HRs) positive tumors had a better DFS (p=0.034) and OS (p=0.046) than those with HRs negative tumors. In univariate survival analysis, a significant difference in DFS (p=0.0003) and OS (p=0.0003) was found between patients with vs without lymphovascular invasion (LVI). CONCLUSION: Diagnosis of breast cancer at very young age (<30) was associated with increased risk of death and shorter DFS than women aged 31-35. Negative impact on survival was seen in patients with presence of LVI, negative HRs and higher grade and stage at the time of presentation.

Mantle cell lymphoma-current literature overview.

Mantle cell lymphoma (MCL) is a distinct subtype of lymphoma identified as a particular entity in the early 1990s. The prognosis of MCL is generally poor, and is considered one of the worst among all B-cell lymphomas. In general, conventional chemotherapy is only palliative and the median duration of remissions is only 1-2 years. With the exception of allogeneic hematopoietic stem cell transplantation (allo-SCT), current treatment approaches are not curative and the corresponding survival curve is characterized by a relatively steep and continuous decline, with a median survival of about 4 years and <15% long-term survivors. Only a small proportion of patients may be exempted from this disappointing picture, because they have an indolent course of the disease and could be handled with watch and wait strategy. Optimal first-line therapy in MCL is not established yet. Very intensive regimens, including autologous (auto-SCT) and allo-SCT, seem to be required to improve the outcome. Allogeneic stem cell transplantation is the only therapy that can achieve a plateau in the survival curve, but, however, it is not applicable in most of the cases due to the patients' older age when the disease mostly occurs. Molecular knowledge of MCL has progressed and therefore a large number of molecular targeted therapies have been introduced in relapsed and refractory disease.

Clinical benefit of cetuximab and prognostic value of cetuximab-related skin toxicity in metastatic colorectal cancer: a single institution analysis.

PURPOSE: To evaluate the clinical benefits of cetuximab (CTX) and the prognostic value of CTX-related skin toxicity in metastatic colorectal cancer (mCRC) patients. METHODS: Sixty patients were tested for KRAS mutation at the Department of Oncology, Clinical Centre Nis. We assessed 34 wild-type KRAS mCRC patients treated with CTX. All of them were refractory to prior fluoropyrimidine, oxaliplatin and irinotecan-based regimens. The maximum grade skin toxicity according to treatment cycle was analyzed. Skin toxicity was grouped into clinically non-relevant skin toxicity (grade 0-1: Group 1) and clinically relevant skin toxicity (grade 2-4: Group 2). RESULTS: Ten out of 33 patients (30.30%) achieved partial response (PR). Eight additional patients (24.24%) showed stable disease (SD), whereas 15 (45.45%) had disease progression (PD). No patient achieved complete response (CR). Overall response rate (ORR) was 30.30%, whereas the disease control rate (DCR) was 54.54%.The median progression free survival (PFS) was 14 weeks. Some degree of skin toxicity was observed in 79.41% (27/34) of the patients. Clinically non-relevant skin toxicity was observed in 50% (17/34), and clinically relevant in 50 % (17/34) of the patients. Grade 4 skin toxicity was documented in 1 patient. The mean PFS in Group 1 was 12.65±5.59 weeks and in Group 2 22.82±12.16 (p<0.05). The results showed that grade 2-4 skin toxicity was associated with significantly better response to treatment than skin toxicity grade 0-1, with regard to ORR (80.00 vs 20.00%; p<0.05) and DCR ( 66.66 vs 33.33%; p<0.05). CONCLUSION: Cetuximab has clinical benefit when given alone or in combination with irinotecan in patients with irinotecan-refractory CRC. Skin toxicity was one of the predictors of response and it was in line with what was expected.

[Assessment of axillary lymph nodes involvement in patients with breast cancer depending on the tumor size and its histological and nuclear grades].

BACKGROUND/AIM: There are a lot of studies aiding to the opinion that the involvement degree of axilla lymph nodes grows depending on increase of breast tumor size, and its histological and nuclear grades. The aim of this study was to assess the risk of axillary lymph nodes involvement, as well as the relation between the tumor size, histological and nuclear grades in a group of female patients who underwent breast cancer surgery, including levels 1-3 axillary dissection. METHODS: Investigationcovered 900 patients operated on during 2005-2008 who underwent modified radical mastectomy including axillar dissection. We assessed a number of involved lymph nodes, depending on tumor macroscopic size (T), histological grade (HG) and nuclear grade (NG). RESULTS: A total number of examined lymph nodes was 9977. The incidence of involved lymph nodes was from 18.6% with T1 tumor size up to 60.2% with T4 tumor size. Concerning histological grade, the number of involved lymph nodes ranged from 14.2% (HGI) to 45.1% (HGIII); while in terms of nuclear grade, the number of involved lymph nodes ranged from 17.4% (NGI) to 54.5% (NGIV). By using chi2-test for trend and odds ratio (OR), the results showed that the axillary lymph nodes involvement degree was increased with the increase of the tumor size and its histological and nuclear grades. The risk of axillary lymphatic nodes involvement was 1.43 times higher in the group of T2 tumors size compared to the smaller tumors T1 size, and even up to 6.62 times higher in case of T4 tumor size. It was also increasied from 1.79 times for HGII to even 4.98 times for HGIII, and from 1.44 times for NGII to 5.71 times for NGIV. CONCLUSION: In breast cancer patients, there is a strong correlation between tumor size, its histological and nuclear grades and the risk of axillary lymph nodes involvement.

[Significance of serum tumor markers monitoring metastases in carcinomas of unknown primary site].

BACKGROUND/AIM: Unknown primary tumors represent a heterogeneous group of malignancies that are indicative of ominous prognosis. Cancer of unknown primary site (CUP) is defined as the lack of any detectable primary site after full evaluation, and accounts for approximately 3-5% of all newly diagnosed patients with malignancies. The aim of this report was to present the prognostic and predictive value of 8 serum tumor markers in this group of patients. METHODS: The study involved 63 patients. On histological examination, all the patients were presented with metastatic tumors whose primary site (origin) could not be detected with noninvasive diagnostic techniques. Following the routine light microscopy, all histological findings were classified into one of the following three groups: plano-cellular carcinoma--8 patients; adenocarcinoma--33 patients; unclassifiable (undifferentiated) carcinoma--22 patients. In all the cases we evaluated 8 serum tumor markers: alpha-fetoproteins (AFP), chronic gonadotrophin beta submit, human (beta-HCG), neuron specific enolase (NSE), marker of malignant ovarian tumors (CA 125), prostate-specific antigene (PSA), marker of malignant brest tumor (CA 15-3), marker of malignant pancreas tumor and gastrointestinal tumor (Ca 19-9), carcinoembryonic antigen (CEA) at the time of diagnosis. The patients on chemotherapy had the markers determined after the third and sixth chemocycle, i.e. at the time of illness progression observation, if present. The patients responding to chemotherapy with complete response (CR), partial response (PR) or stable disease (SD) had the markers determined after three-month periods until the time of relapse or progression. Chemotherapy was applied in 32 patients (20 females and 12 males), aged 29-70 years, who met the inclusion criteria. The following chemotherapy regimen was used: doxorubicin 50 mg/m2 (day 1), cisplatin 60 mg/m2 (day 1), and etoposide 120 mg/m2 (days 1-3). The period between two chemotherapy cycles was three weeks, and maximum five weeks in the case of prolonged hematological toxicity. RESULTS: Most commonly elevated were NSE values (82.54%), while AFP values were least commonly elevated (11.11%). Average survival time was 17.89 months (95% CI 12.96; 22.83). The probability of 24 months' survival was 0.228. The group of 32 patients treated with chemotherapy had 12 (37.5%) fatal outcomes in the observed period (72 months). Average survival time was 26.6 months (95% CI 19.5; 33.7). Average tumor marker values before and after the chemotherapy were significantly lower for NSE and CA 125. Survival was significantly better in cases of NSE and CA 125 decrease of more than 20%. CONCLUSION: Increased values of serum tumor markers are very often in CUP. The tumors show nonspecific overexpression of tumor markers. The NSE and CA 125 levels show good correlation with response to the given chemotherapy. However, a routine evaluation of commonly used serum tumor markers has not been proven of any prognostic and predictive assistance.