Recommendations for cyclin­dependent kinase 4/6 inhibitor treatments in the context of co­morbidity and drug interactions (Review).

Breast cancer is most frequently diagnosed among women aged 65-74 years and the prevalence of comorbidities in elderly patients with breast cancer is 32.2%. In addition, polypharmacy is quite common in these patients. Understanding the interaction between breast cancer treatment modalities and comorbidities is important, particularly in elderly patients, as comorbidities affect the choice of appropriate treatment and are independent risk factors for survival. A total of three oral cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), palbociclib, ribociclib and abemaciclib, notably prolonged progression-free survival when combined with endocrine therapy (ET), compared with ET alone in patients with advanced breast cancer (ABC). The present review article therefore addressed the safety, tolerability and toxicity of CDK4/6i treatment in ABC management, compiled real-world data on how multiple clinical and pharmacological features may affect the choice of these drugs and provided practical recommendations for clinical approaches. Before starting treatment with CDK4/6i drugs, all ongoing medical conditions should be inventorized and re-graded, and examination should be performed for any additional disease that the patient may not be aware of. It is also important to obtain a detailed history of concomitant drugs, including prescription and over-the-counter drugs, vitamins, supplements and herbal products. In addition, patients should be advised to consult their oncologist before starting any new medication.

Beyond traditional therapies: clinical significance of complex molecular profiling in patients with advanced solid tumours-results from a Turkish multi-centre study.

OBJECTIVE: The objective of this multi-centre, real-world study was to examine the potential influence of comprehensive molecular profiling on the development of treatment decisions or adjustments for patients with advanced solid malignancies. We then evaluated the impact of these informed choices on patient treatment outcomes. METHODS: The study encompassed 234 adult patients (mean age: 52.7 ± 14.3 years, 54.7% women) who were diagnosed with solid tumours at 21 different medical centres in Turkey. Remarkably, 67.9% of the patients exhibited metastasis at the time of diagnosis. We utilized an OncoDNA (Gosselies, Belgium) platform (OncoDEEP) integrating next-generation sequencing with additional tests to harvest complex molecular profiling data. The results were analyzed in relation with two specific outcomes: (i) the impact on therapeutic decisions, including formulation or modifications, and (ii) associated treatment response. RESULTS: Out of the 228 patients with final molecular profiling results, 118 (50.4%) had their treatment modified, whilst the remaining 110 (47.0%) did not. The response rates were comparable, with 3.9 versus 3.4% for complete response, 13.6 versus 29.3% for partial response, 66.9 versus 51.7% for progressive disease and 15.5 versus 15.5% for stable disease for treatments informed and not informed by complex molecular profiling, respectively (P = 0.16). CONCLUSION: Our real-world findings highlight the significant impact of complex molecular profiling on the treatment decisions made by oncologists for a substantial portion of patients with advanced solid tumours. Regrettably, no significant advantage was detected in terms of treatment response or disease control rates.

Prognostic Significance of Tumor Tissue NeuGcGM3 Ganglioside Expression in Patients Receiving Racotumomab Immunotherapy.

Expression of N-glycolyl GM3 (NeuGcGM3) ganglioside was detected in the tumor specimens of patients who were on Racotumomab anti-idiotype vaccine maintenance treatment, and prognostic significance as a biomarker was investigated. No statistically significant association was observed in the multivariate analysis between overall survival and tissue NeuGcGM3 IHC levels. Although numerically there was a difference favoring less intense IHC for better prognosis, this did not reach statistical power. However, there was a strong correlation between Racotumomab doses and overall survival (OS). Mean OS of the patient with more than 10 Racotumomab application was significantly longer than the patient who had less than 10 injections (70.7 months vs. 31.1 months, p < 0.001). We propose that, regardless of staining intensity, the presence of NeuGcGM3 in patient tissues might be an indicator of benefit in Racotumomab treatment.

Associations between clinicopathological prognostic factors and pAkt, pMAPK and topoisomerase II expression in breast cancer.

This study aimed to examine the associations between mitogen activated protein kinase (MAPK), Akt, and topoisomerase II expression and other well established clinical and pathological prognostic factors in patients with breast cancer. A total of 42 women with breast cancer who underwent anthracycline based chemotherapy were included in this retrospective study. Immunohistochemical methods were utilized to examine the expression of phosphorylated MAPK (pMAPK), phosphorylated Akt (pAkt), HER-2/neu and topoisomerase IIα (topo IIα) in tissue blocks. Subsequently, the associations between pMAPK, pAkt, and topoisomerase IIα (topo IIα) expression characteristics and disease stage (T and N), tumor grade, estrogen/progesteron receptor status, and HER-2/neu expression were explored. Median age of the patients was 63 years (range, 37-82). There was a significant association between N stage and topoisomerase IIα expression (P = 0.021), with increasing rates of positivity in higher grades: N0, 22.7%; N1, 11.1%; N2, 42.9%; N3, 100%. In addition, topo IIα expression was higher in estrogen receptor-positive versus estrogen receptor-negative tumors (50% vs. 0%, P = 0.0004) and MAPK expression was more frequent among progesteron receptor-positive versus negative tumors (64.0 versus 20.0%, P = 0.027). Our results show that the tissue expression of topo IIα and MAPK, which play a role in the intracellular signal pathways, is associated with certain established prognostic factors in breast cancer. Further studies examining survival rates and involving larger sample populations are warranted to better define the importance of the observed associations.

Clinical outcome of Turkish metastatic breast cancer patients with currently available treatment modalities--single center experience.

BACKGROUND: Breast cancer is the most common malignancy and the second leading cause of cancer-related death among women in the developed countries. Despite advances in screening, improved local therapies and adjuvant systemic treatments, median survival of metastatic breast cancer patients (MBC) is in the range of 2-3 years at most. We aimed to investigate whether the prognostic factors and therapeutic responses of our Turkish patients are similar to those in the literature. MATERIALS AND METHODS: We reviewed the medical records of MBC patients who had been treated in our institution between 1999-2009 and analyzed their clinicopathological features and survival outcomes retrospectively. RESULTS: A hundred and sixty patients were included. Median age was 47 (23-82), median follow up was 24 (2-186) months. At the time of diagnosis 59% of patients were under the age of 50 and 46% were postmenopausal. The majority (37%) had multiple sites of metastases. Forty percent received endocrine therapy and 40% chemotherapy as first line metastatic treatment. Thirty (20%) patients were treated with molecular targeting agents like trastuzumab, lapatinib and sunitinib, frequently combined with a chemotherapy agent. Five-year overall survival (OS) was 32% and median OS was 38 months for the whole group. Five year progression free survival (PFS) was 10% and median PFS was 10 months. Menopausal status, hormone receptor expression and disease free status had a significant impact on overall survival in the multivariate analysis (p 0.018, p 0.018 and p:0.003, respectively). CONCLUSIONS: All our patients were treated with the modern oncologic therapies recommended by the international guidelines. From our data, MBC patients live up to 3-4 years, indicating that further improvement beyond that requires development of new treatment modalities. The survival outcomes of our patients were consistent with the data reported in the literature.

Pregnancy a short time after multimodal therapy for bilateral breast cancer: a case report and review of literature.

Pregnancy occurring after multimodal therapy in a woman with breast cancer with a 1-year follow-up period is a relatively rare condition and has been defined as pregnancy-associated breast cancer. A patient can become pregnant after chemotherapy for breast cancer while she is on tamoxifen. However, the effects of tamoxifen on fetus and on the course of the pregnancy are still unknown. Here, we present a 39-year-old woman treated with chemotherapy and radiotherapy for bilateral breast cancer, and who became pregnant while taking tamoxifen.

Weight gain after adjuvant chemotherapy in patients with early breast cancer in Istanbul Turkey.

Weight gain is a well-known and unwanted complication of adjuvant chemotherapy in breast cancer. We observed that the female Turkish cancer patients frequently gain weight with adjuvant treatment of breast cancer and planned to examine the magnitude of this problem in early breast cancer patients treated at our hospital. A total of 176 early breast cancer patients who received their adjuvant systemic therapy in Marmara University Hospital between 2003 and 2007 are included in the study. We recorded their weight before and after chemotherapy and also a year after chemotherapy to find out whether the change with weight is transitory. We have also recorded demographic information, including the educational level, menopausal status, the type of chemotherapy or hormonal treatment administered stage of disease, marital status, occupation and the underlying diseases to analyze the relationship between change in weight and these parameters. Median age of patients was 53 and 72% of patients were postmenopausal. Educational level was equally distributed for primary education (27%), high school (40%), and university (33%). The majority of the patients (76%) was married, had two children (69%) and was housewife (60%). Family history of any cancer was high (32%). Most of the patients had stage II cancer (56%), received anthracyclines+/- taxane based chemotherapy (98%) and had no underlying disease (68%). The majority also did not smoke (73%) or drink alcohol (93%). A total of 67% and 72% patients gained weight upon completion and one year after completion of chemotherapy. Mean weight before the chemotherapy, upon completion of chemotherapy and one year after completion of chemotherapy were 68.9 kg, 70.6 kg (P = 0.000) and 71.9 kg (P = 0.000) respectively. Mean body mass index was 27.1 at baseline, 27.8 upon completion of chemotherapy (P = 0.000) and 28.3 one year after completion of chemotherapy (P = 0.000). Age, menopausal status, multiparity and presence of comorbid diseases had statistically significant impact on weight gain following adjuvant therapy in breast cancer patients (P = 0.000, P = 0.008, P = 0.015 and P = 0.017 respectively). This study shows that Turkish women with early breast cancer gain weight after adjuvant systemic therapy, in line with European and American counterparts. This increase in weight is maintained at least one year after adjuvant therapy. Given the adverse consequences of weight gain in terms of both breast cancer prognosis and general health, it is necessary to inform patients about this change and to develop strategies for weight maintenance during and after systemic therapy.

The relationship between glycemic control and platelet activity in type 2 diabetes mellitus.

AIMS: Platelet activity and aggregation potential, which are essential components of thrombogenesis and atherosclerosis, can be conveniently estimated by measuring mean platelet volume (MPV) as part of whole blood count. It has been shown that MPV was significantly higher in diabetes mellitus (DM); however, the effect of glycemic control on MPV has not been studied. The aim of this study was to investigate the relationship among MPV, glycemic control, and micro- and macrovascular complications in type 2 DM. METHODS: Seventy patients with type 2 DM and 40 age- and sex-matched healthy individuals were enrolled. Diabetic patients were grouped into those with glycated hemoglobin (HbA1c) levels 7% (Group B, n=35 patients). Initially, both groups were compared with regard to MPV, HbA1c, serum lipid levels, coronary artery disease, retinopathy, neuropathy, and nephropathy. Thereafter, Group B was called to monthly visits to obtain improved control glycemic control, which was defined as achievement of HbA1c