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Purpose: This study evaluated the efficacy and safety of everolimus (EVE) plus exemestane (EXE) in hormone-receptor positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancer (MBC) patients in real-life settings., Methods: Overall, 204 HR+, HER2- MBC patients treated with EVE + EXE after progressing following prior endocrine treatment were included. Overall survival (OS) and progression-free survival (PFS) and safety data were analyzed., Results: The objective response rate, median PFS, and median OS were 33.4%, 8.9 months, and 23.4 months, respectively. Multivariate analysis revealed that negative progesterone receptor status was a significant determinant of poor treatment response ( p  = 0.035) and PFS ( p  = 0.024). The presence of bone-only metastasis was associated with better treatment response ( p  = 0.002), PFS ( p  < 0.001), and OS ( p  = 0.001)., Conclusion: We confirmed the favorable efficacy and safety profile of EVE + EXE for HR+, HER - MBC patients.

Objective: To examine the effects of yoga on shoulder and arm pain, quality of life (QOL), depression, and physical performance in patients with breast cancer., Methods: This prospective, randomized study included 42 patients. The patients in Group 1 underwent a 10-week Hatha yoga exercise program. The patients in Group 2 were included in a 10-week follow-up program. Our primary endpoint was arm and shoulder pain intensity., Results: The group receiving yoga showed a significant improvement in their pain severity from baseline to post-treatment, and these benefits were maintained at 2.5 months post-treatment. When compared to the control group, there were no statistically significant differences between the 2 groups with respect to the parameters assessed at the end of week 10., Conclusion: Yoga was an effective and safe exercise for alleviating shoulder and arm pain, which is a complication with a high prevalence in patients with breast cancer., (Copyright © 2018. Published by Elsevier Ltd.)

Objective Heart rate variability (HRV) is a good indicator of the autonomic nervous system (ANS) activity. A few studies have been conducted recently and have shown a relationship between reduced HRV and conditions that lead to neuropathic pain (NP). In this study, we aimed to investigate whether NP is associated with changes in cardiac sympathovagal activity in patients with breast cancer (BC). Methods We used the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) questionnaire to evaluate NP in 70 patients with BC. The patients were subjected to a 24-h Holter ECG monitorization to determine heart rate variability (HRV). Standard deviation (SD) of the normal-to-normal RR intervals (SDNN), SD of the mean of the RR intervals (SDAAN), mean of the SD of the NN interval (SDNN Index), low-frequency component/high-frequency component ratio (LF/HF), and the mean heart rate of the patients were recorded. Results According to the LANSS questionnaire, 18 (25.7%) of the patients were classified as NP (+). The SDNN (P = 0.001), SDAAN (P = 0.003), and SDDN index (P = 0.007) were significantly lower in patients with NP than in patients without NP, whereas LF/HF ratio (P = 0.000) and mean heart rate were found to be significantly higher in patients with NP (P = 0.006). Conclusion According to our findings, NP (+) patients with BC had increased cardiac sympathetic activity, which was suggested to be associated with increased cardiovascular morbidity and mortality.

Purpose: Cytotoxic treatment may cause weight gain and important alterations in the metabolic status of breast cancer (BC) patients. The aim of this study was to investigate the changes in metabolic and anthropometric parameters of patients with BC who received adjuvant chemotherapy., Methods: All consecutive women treated with adjuvant TAC (docetaxel 75 mg/m(2), doxorubicine 50 mg/m(2), cyclophosphamide 500 mg/m(2)) chemotherapy for node-positive breast carcinoma at our Institution between 2008 and 2010 were included., Results: Among 104 patients, 84 of them were stage II and 20 of them were stage III. When we compared the measurements between 1(st) and 6(th) adjuvant chemotherapy, we observed statistically significant increases in weight and serum triglyceride levels, and decreases in high density lipoprotein, apolipoprotein A-1, transferrin, albumin and prealbumin levels. An elevation of follicle stimulating hormone, luteinizing hormone together with the decrease of estradiol was detected. Waist-to-hip ratio has also increased significantly. In subgroup analyses, we observed dramatic changes in body mass index in pre-menopausal women whereas no significant change was seen in the post-menopausal group., Conclusions: Adjuvant chemotherapy may contribute to an increased risk for metabolic syndrome in patients with BC and these changes are more profound in pre-menopausal patients., (© The Author(s) 2014.)

Background: Optimal duration of adjuvant trastuzumab in early breast cancer is an unresolved issue. In this observational study, we compared the outcome of 9 weeks and 1 year adjuvant trastuzumab in early breast cancer patients in Turkey., Methods: Records of 680 patients with HER2-positive early breast cancer who received adjuvant trastuzumab plus chemotherapy were obtained and patients were followed up to compare the disease-free survival (DFS) outcome of 9 weeks versus 1 year trastuzumab., Results: Nine weeks and 1 year trastuzumab was given to 202 (29.7 %) and 478 (70.3 %) patients, respectively. There was a significantly lower rate of patients with negative lymph nodes in the 9-week trastuzumab group. At median 3 years of follow-up from the date of starting trastuzumab, the DFS rates were 88.6 and 85.6 %, respectively (p = 0.670). When adjusted for all the prognostic factors that were significant on univariate analysis, again there was no significant difference in DFS between the groups (HR 0.675; 95 % CI 0.370-1.231; p = 0.200). Cardiac toxicity defined as a ≥15 % decrease in LVEF was significantly higher in the 1-year trastuzumab group (1.88 % versus none for 1-year and 9-week trastuzumab groups, respectively; p = 0.050)., Conclusion: The results of this observational study suggest that DFS outcome of 9 weeks of adjuvant trastuzumab may be comparable to 1 year adjuvant trastuzumab: this needs confirmation by randomized trials.

Purpose: Docetaxel (DTX) is widely used for the treatment of metastatic prostate and breast cancers. Despite the clinical success of DTX, drug-related cumulative toxicity restricts its clinical use in cancer therapy. Thus, there is an urgent need for new therapeutic options. Octreotide (OCT) is a synthetic somatostatin analog that induces apoptosis in different cancer cell lines in vitro. In this study, we investigated the possible synergistic apoptotic effects of DTX in combination with OCT in prostate and breast cancer cell lines., Methods: The XTT cell viability assay was used to determine cytotoxicity. Apoptosis was evaluated by Cell Death Detection ELISA(Plus) Kit. The expression levels of apoptotic proteins were assessed by human apoptosis antibody array. Levels of SSTR2 and SSTR5 proteins were determined by western blot analysis., Results: DTX and OCT combination induced apoptosis in both breast and prostate cancer cells in a concentration- and time-dependent manner. Moreover, combination treatment resulted in inhibition of anti-apoptotic proteins such as Bcl-2 and Bcl-xL and induction of pro-apoptotic proteins Bax, Cytochrome c and IAPs in all of the tested cancer cell lines. SSTR2 and SSTR5 protein levels were induced as compared to any agent alone., Conclusions: These results indicate that this combination treatment is a significant inducer of apoptosis in a synergistic manner in breast and prostate cancer cells. This strong synergism helps to lower the dose of DTX in both types of cancers, thus letting DTX to be used for longer periods by delaying resistance development and lesser side effects.

Skin metastases of breast cancer are usually late events in the course of tumor progression and signify a poor prognosis. They may remain as a therapeutic challenge especially after failure of standard treatments. Topical interventions, together with or without radiotherapy, may only palliate the symptoms temporarily. However, there may be alternative treatment modalities for unresectable breast cancer skin metastases resistant to chemotherapy and radiotherapy. There are various genetic alterations in tumors and therapeutic potential of expression patterns for factors like epidermal growth factor receptor may have important clinical implications in case of disease refractory to the conventional treatments. Here, we clarified the therapeutic options and genetic alterations in skin metastatic breast cancer patients refractory to standard chemotherapeutics.

The aim of this study was to explore the effects of exercise on angiogenesis and apoptosis-related molecules, quality of life, fatigue and depression in patients who completed breast cancer treatment. Sixty breast cancer patients were randomised into three groups, as supervised exercise group, home exercise group and education group. Angiogenesis and apoptosis-related cytokine levels and quality of life (EORTC QOL-C30: European Organisation for Research and Treatment of Cancer Quality of Life C30), fatigue (Brief Fatigue Inventory) and depression (BDI: Beck Depression Inventory) scores were compared before and after a 12-week exercise programme. After the exercise programme, statistically significant decreases were found in interleukin-8 and neutrophil activating protein-78 levels in the home exercise group (P < 0.05). The education group showed a statistically significant increase in monocyte chemoattractant protein-1 level (P < 0.05). Functional score and global health score of EORTC QOL-C30 in the supervised exercise group and functional score of EORTC QOL-C30 in the home exercise group increased significantly after exercise programme (P < 0.05). BDI score was significantly lower in the supervised exercise group after the exercise programme (P < 0.05). Changes in angiogenesis and apoptosis-related molecules in the study groups suggest a possible effect of exercise on these parameters. Exercise programmes are safe and effective on quality of life and depression in breast cancer patients whose treatments are complete., (© 2013 John Wiley & Sons Ltd.)

Trabectedin (Yondelis, ET-743), a semi synthetic tetrahydroisoquinoline alkaloid that was originally derived from the marine tunicate Ecteinascidia turbinata. The objective of this study was to investigate whether trabectedin mediated apoptosis shows any diversity in human breast cancer cell lines with different genotypes. Trabectedin induced cytotoxicity and apoptosis in both breast cancer cells in a time and concentration-dependent manner. The expression levels of the death receptor pathway molecules, TRAIL-R1/DR4, TRAIL-R2/DR5, FAS/TNFRSF6, TNF RI/TNFRSF1A, and FADD were significantly increased by 2.6-, 3.1-, 1.7-, 11.2- and 4.0-fold by trabectedin treatment in MCF-7 cells. However, in MDA-MB-453 cells, the mitochondrial pathway related pro-apoptotic proteins Bax, Bad, Cytochrome c, Smac/DIABLO, and Cleaved Caspase-3 expressions were induced by 4.2-, 3.6-, 4.8-, 4.5-, and 4.4-fold, and the expression levels of anti-apoptotic proteins Bcl-2 and Bcl-XL were reduced by 4.8- and 5.2-fold in MDA-MB-453 cells. Moreover, trabectedin treatment increased the generation of ROS in both breast cancer cells. We have shown that trabectedin causes selective activation of extrinsic and intrinsic apoptotic pathways in two genotypically different breast cancer cells. This preliminary data might guide clinicians to choose appropriate combination agents with trabectedin based on different molecular subtypes of breast cancer., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily and has been shown to induce extrinsic pathway of apoptosis in many types of cancer cells. AT-101, an (-)-enantiomer of gossypol, is a potent anticancer agent that is shown to be an inhibitor of Bcl-2/Bcl-XL. In this study, we searched whether pretreatment with either of these drugs would result in the enhancement of apoptosis through induction of death receptors and activation of mitochondrial pathways within breast cancer cells., Methods: Human breast cancer (MCF-7 and MDA-MB-231) and normal breast cells (MCF-10A) were treated with drugs alone/in combination/sequentially. XTT cell viability assay was used to evaluate cytotoxicity. For showing apoptosis, both DNA Fragmentation and caspase 3/7 activity measurements were done. ELISA and Western blot analysis were done to assess DR4 and DR5 protein levels. The expression levels of apoptotic proteins were assessed by human apoptosis antibody array., Results: The sequential treatment of AT-101 followed by TRAIL resulted in significant synergistic cytotoxicity and apoptosis. Moreover, pretreatment of breast cancer cells with AT-101 and then with TRAIL caused enhancement of the expression levels of DR4 and DR5 in both cancer cell lines, suggesting that these cells were under strong apoptotic stimuli., Conclusions: These findings all together, strongly suggest that pretreatment with AT-101 enhances TRAIL-induced death-inducing signaling complex resulting in the engagement of the mitochondrial pathway to apoptosis in breast cancer cells. These promising, preliminary results make AT-101 and TRAIL a novel combination treatment candidate for breast cancer.

Thymus (T.) serpyllum (wild thyme) is an aromatic medicinal plant due to its several biological properties, including anticancer activity. Breast cancer is one of the most common malignancies and increasing evidence supports that it is not only a genetic but also an epigenetic disease. Epigenetics investigates changes in gene expression caused by mechanisms that do not involve alterations in DNA sequence. DNA methylation and histone acetylation are the most widely studied epigenetic changes in cancer cells. This study evaluated the effects of T. serpyllum on apoptosis and epigenetic events in breast cancer cells. XTT cell viability assay was used to determine cytotoxicity. DNA fragmentation and caspase 3/7 activity assays were used in the assesment of apoptosis. DNA methyltransferase (DNMT) and histone deacetylase (HDAC) activities were evaluated by ELISA and verified by qRT-PCR. T. serpyllum extract induced significant cytotoxicity in breast cancer cells (MCF-7 and MDA-MB-231) but not in normal cells. It also induced apoptosis and inhibited the DNMT and HDAC activities in MDA-MB-231 cells. In the present study, the first preliminary data on the effects of the methanolic extract of T. serpyllum in normal and breast cancer cells were obtained and suggest that T. serpyllum may be a promising candidate in the development of novel therapeutic drugs for breast cancer treatment.

Background: There are very few randomized controlled studies on exercise in cancer patients. Consequently, there are no guidelines available with regard to the exercises that can be recommended and difficulties are encountered in the clinical practice as to which exercise is more suitable to the patients., Aim: The purpose of this study was to investigate the impact of pilates exercises on physical performance, flexibility, fatigue, depression and quality of life in women who had been treated for breast cancer., Design: Randomized controlled trial., Setting: Out patient group, Department of Physical Medicine and Rehabilitation and Medical Oncology Department, University Hospital., Population: Fifty-two patients with breast cancer were divided into either pilates exercise (group 1) and control group (group 2)., Methods: Patients in Group 1 performed pilates and home exercises and patients in group 2 performed only home exercises. Pilates exercise sessions were performed three times a week for a period of eight weeks in the rehabilitation unit., Main Outcome Measures: Subjects were assessed before and after rehabilitation program, with respect to, 6-min walk test (6MWT), modified sit and reach test, Brief Fatigue Inventory (BFI), Beck Depression Index (BDI) and the European Organisation for Research and Treatment of Cancer Quality of Life C30 (EORTC QLQ-C30) and EORTC QLQ BR23., Results: After the exercise program, improvements were observed in Group 1 in 6-minute walk test, BDI, EORTC QLQ-C30 functional, and EORTC QLQ-C30 BR23 functional scores (P<0.05). In contrast, no significant improvement was observed in Group 2 after the exercise program in any of parameters in comparison to the pre-exercise period (P>0.05). When the two exercise groups were compared, there were significant differences in 6MWT in pilates-exercise group (P<0.05)., Conclusion: Pilates exercises are effective and safe in female breast cancer patients. There is a need for further studies so that its effect can be confirmed., Clinical Rehabilitation Impact: This study addressed the effects of pilates exercise, as a new approach, on functional capacity, fatigue, depression and quality of life in breast cancer patients in whom there are doubts regarding the efficacy and usefulness of the exercise.

Over 80% of patients with advanced breast and prostate cancer ultimately develop bone metastases. Ibandronic acid has proven efficacy for treatment of bone metastasis secondary to breast cancer. This study was designed to investigate the cytotoxic and apoptotic effects of ibandronic acid on hormone- and drug-refractory prostate carcinoma DU-145 and human breast cancer MCF-7 cell lines. Cytotoxicity was evaluated using an XTT cell proliferation kit, and apoptosis was assessed by enzyme-linked immunosorbent assay (histone-DNA fragmentation) and measurement of caspase 3/7 activity. With increasing concentrations of ibandronic acid there was a dose- and time-dependent decrease in cell numbers. MCF-7 cells were more resistant than DU-145 cells (half maximal inhibitory concentrations of 122 and 90 microM, respectively). Ibandronic acid induced apoptosis in both cell lines. The study showed an apoptosis-mediated cytotoxic effect for ibandronic acid (in addition to the already known osteoclast inhibiting effect) in breast cancer patients with bone metastases; which was also observed in prostate cancer cells. Further clinical studies involving breast and prostate cancer patients with bone metastases are warranted to confirm these findings.

Purpose: To evaluate the necessity and direct cost effectiveness of screening and staging procedures in breast cancer patients having ≥4 positive axillary lymph nodes and to identify further possible biopathological risk factors associated with increased risk of metastasis., Methods: We reviewed the demographic and clinicopathological data from the medical records of 1897 newly diagnosed breast cancer patients. Patients having ≥4 positive axillary lymph nodes after primary surgery for breast cancer and who had staging examinations for metastasis were eligible. The impact of staging procedures (thoracoabdominal CT, bone scan etc.) for detecting metastasis, decision of adjuvant treatment and direct costs were analyzed in 329 patients with operable breast cancer., Results: Thirty-five (10.6%) patients were found with metastasis at diagnosis. Seven (20.0%) among them had multiple metastases. Eighteen (51.4%) had lung, 17 (48.6%) bone, and 7 (20.0%) liver metastasis. Twenty-one (60.0%) patients needed further radiological investigation for metastasis confirmation. Treatment decision was changed in 27 (77.1%) patients. No statistically significant risk factor was identified among the metastatic patients by means of conventional demographic and biopathological parameters. The cost of screening was lower when compared to the cost of treatment without any screening procedure., Conclusion: Since the conventional clinicopathological data seems not sufficient to define the risk of developing metastasis in breast cancer patients with ≥4 axillary lymph node involvement, all of them should undergo full staging examinations until new parameters based on genomic level are defined. Staging procedures need modification for high risk breast cancer patients.

Breast cancer is the most common malignancy diagnosed among women. According to the new molecular subclassification, basal like and Her-2 positive breast cancers have the worst outcome and these are the ones in which chemotherapy is a must as a part of adjuvant treatment. New treatment options that could be used as an adjuvant maintenance treatment are still being investigated. Insulin hormone is one of the reasons of breast cancer recurrence and death in breast cancer survivors. Targeting insulin as a therapeutic modality in breast cancer could be an option in the adjuvant treatment of breast cancer. It seems that insulin may signal to activate a cascade of proliferative and anti-apoptotic events in the cancer cell. Metformin, an oral anti-diabetic known for 50 years, may also have direct effects on cancer cells. Metformin causes Her-2 suppression via the inhibition of mTOR in breast cancer cells. Thus, we believe that the time has arrived both to target insulin reduction and to alter Her-2 oncogene based molecular pathogenetic steps in breast cancer by using metformin as an adjuvant therapy in breast cancer patients.

Purpose: Gossypol is a natural polyphenolic compound extracted from cotton plant (Gossypium species) which has shown potent inhibitory effect on cell growth of many types of cancers. In this study, we aimed to evaluate the interaction of gossypol with some conventional drugs known to be effective in the treatment of breast cancer, like taxanes, doxorubicin, gemcitabine, cisplatin and vinorelbine, in MCF-7 breast cancer cells., Materials and Methods: The XTT viability assay was used to evaluate the cytotoxicity of various cytotoxic agents alone and in combination with gossypol in MCF-7 breast cancer cells. The combination effect analysis of Chou and Talalay was used to identify the most synergistic drug combinations. The possible synergistic effects of the combination of drugs on apoptosis were also evaluated by using two different apoptosis assays., Results: We identified strong synergistic cytotoxic and apoptotic activity of gossypol with taxanes among all other studied cytotoxic drugs., Conclusion: This study provides proof that gossypol combined with taxanes may have potential as a novel future treatment for breast cancer.

Objective: The study was aimed at investigating the clinical and biological features and survival outcomes of patients who were treated for metastatic inflammatory and noninflammatory breast carcinoma., Subjects and Methods: One hundred and sixty-seven metastatic breast cancer patients were enrolled into this study and divided into two groups: inflammatory (n = 46) and noninflammatory (n = 121). The clinical and hormone receptor status, c-erbB-2, Ki-67, and p53 expression, based on the immunohistochemical staining patterns, were compared between the two groups., Results: The inflammatory breast carcinoma group had a younger patient population, higher rate of adjuvant anthracycline therapy, number of lymph node metastases, rates of extranodal extension and c-erbB-2 overexpression than noninflammatory breast cancer patients (p < 0.05). With regard to survival, there were slightly better outcomes in the noninflammatory breast carcinoma group (30 months) compared to the inflammatory breast carcinoma group (23 months), but the difference was not statistically significant (p = 0.08). While survival results of p53-negative inflammatory and noninflammatory breast carcinoma patients were similar, p53-positive survival was significantly worse (p < 0.05) in inflammatory breast cancer carcinoma patients., Conclusion: Because of c-erbB-2 overexpression in inflammatory breast carcinoma patients, treatment options including trastuzumab could have given better survival outcomes. Survival of inflammatory breast carcinoma patients with a low p53 immunohistochemistry staining appeared similar to that for noninflammatory breast carcinoma. For this reason, new treatment options are needed especially in inflammatory breast carcinoma patients with high p53 positivity., ((c) 2008 S. Karger AG, Basel.)

Objective: To compare initial metastatic breast carcinoma (MBC) with recurrent MBC and assess their biologic phenotypes and clinical behaviors., Methods: A comparison of clinical and biological characteristics and median overall survival times were assessed in the 251 patients with MBC at the Division of Medical Oncology, Ege University School of Medicine, and the Division of Radiation Oncology, Tepecik Government Hospital, Izmir, Turkey between 1995 and 2004. Hormone receptors, c-erbB-2, Ki-67, and p53 expressions were performed by immunohistochemistry., Results: Out of 251 MBC patients, 206 patients had recurrent MBC, and 45 had initial MBC. Regarding survival, there was no difference between the recurrent MBC group and the initial MBC group. The initial MBC group had a higher proportion of T4 tumors (46% versus 27%), a lower proportion of T1-2 tumors (31% versus 55%; p=0.01), and a higher percentage of patients with high Ki-67 expression (64% versus 49%; p=0.05). Multivariate analysis showed that T stage was an independent prognostic factor (p=0.02)., Conclusion: Patients with initial MBC tended to present with larger tumors. This relationship can be explained by delayed diagnosis. The potential for reducing death rates from breast cancer is contingent on educational improvement and increased screening rates.

This study was conducted to investigate the serum levels of her-2/neu and survivin in patients with early-stage breast cancer and their relationship with known histological parameters. Forty-one patients with early-stage breast cancer were investigated. Serum samples were collected from patients on their first admission before adjuvant chemotherapy, and from healthy controls. Serum her-2/neu and survivin levels were determined using an enzyme-linked immunosorbent assay. There was no difference in the levels of serum her-2/neu and survivin between the breast cancer patients and the control group. Serum her-2/neu concentration showed moderate correlations with disease stage and the Ki-67 level, and the serum survivin level showed a moderate correlation with progesterone receptor concentration. Serum levels of her-2/neu and survivin were not significantly related to age and histological parameters in patients with early-stage breast cancer. However, much research continues on the prognostic value of serum her-2/neu and survivin levels, and important new knowledge may ultimately emerge.

Previous findings showed that paclitaxel induces interleukin-8 (IL-8) transcription and secretion in ovarian cancer cells in vitro. We hypothesized that paclitaxel treatment, which is a standard care for ovarian cancer patients, may increase the secretion of IL-8, resulting in the elevated serum IL-8 levels. In this study, we investigated the relationship between paclitaxel exposure and IL-8 levels of an ovarian and a breast carcinoma cell line in vitro and serums of patients with ovarian carcinoma. Both MDAH 2774 ovarian and MCF-7 breast carcinoma cell lines were sensitive to paclitaxel-mediated cytotoxicity. However, supernatant levels of IL-8 assessed by enzyme-linked immunosorbent assay before and after treatment with different concentrations of paclitaxel were significantly lower in MCF-7 than in MDAH 2774. Serum IL-8 levels were measured in serum samples from patients with ovarian carcinoma before and after paclitaxel-containing treatment regimens. Forty-eight patients were included in the study. The basal level of IL-8 after paclitaxel-containing treatment was found to be significantly higher in the serums of patients who had high tumor burden than in patients who had optimal debulking surgery and low tumor burden. These data strongly suggest that IL-8 may be an important predictive marker for tumor volume as well as sensitivity to paclitaxel.

The authors compare results obtained from weekly paclitaxel treatment in advanced breast cancer patients with biological and clinical prognostic factors. Expression of c-erbB-2, Ki-67, p53 and hormone receptors (HR) was examined by immunohistochemistry in samples of breast tissue from 30 patients. Univariate analysis showed that Ki-67 positivity and low performance status (PS) were associated with poor outcome (P <0.05). We observed that expression of p53 and c-erbB-2 did not have any negative effect on response to chemotherapy and survival. HR-negative patients had better response and slightly statistically significant overall survival (OS) rates compared to HR-positive patients (P >0.05). In a multivariate analysis low PS was the only significant predictor of shorter survival (P <0.05). In conclusion, while the expression of p53 and c-erbB-2 did not have any effect on treatment results, negative Ki-67 expression and negative HR status were associated with better OS in this patient population. PS was the only significant predictor for OS.

Anthracyclines and docetaxel are frequently used agents in the chemotherapy of breast cancer. In this study we examined the role of inducible nitric oxide synthase (iNOS) expression during the cytotoxicity of these drugs in the MCF-7 breast cancer cell line. Cell viability and cytotoxicity were evaluated by the trypan blue dye exclusion method. Apoptosis and necrosis were determined by the acridine orange/ethidium bromide dye method. The percentage of apoptotic cells was significantly higher with doxorubicin. However, total cytotoxic cell numbers were higher in the docetaxel group compared with doxorubicin, with respect to the control. Most of the cells were seen to be necrotic with the dye method. Cell extracts during the apoptotic process were applied to immunoblot by anti-iNOS monoclonal antibodies. While there was an increase in iNOS expression during docetaxel induced-cytotoxicity, a significant decrease in iNOS expression was detected during doxorubicin-induced cytotoxicity. The Griess method was used for detection of nitrate levels. It was compatible with immunoblot results. These data open a window for further studies to understand the mechanism underlining the cytotoxicity of docetaxel and doxorubicin.

Retinoids exert different effects on malignant cells with various phenomena. They can induce differentiation and apoptosis in various cancer cells. However, the underlying mechanism of these effects is not clear. There are data related to the role of protein phosphatases during retinoid-induced leukemic cell differentiation. The aim of this study was to evaluate effects of the All trans retinoic acid (ATRA) on protein/serine phosphatases during ATRA induced apoptosis in the breast cancer cells. The MTT assay was used to determine drug-mediated cytotoxicity. A cell death detection ELISA kit was used for detection of the DNA fragments. The activity of serine/threonine protein phosphatases was assayed by the serine/threonine phosphatase system. The expression of serine/threonine protein phosphatases was evaluated by Western blot. During ATRA treatment, a significant decrease in the activity of serine/threonine phosphatases 2A, B and C occurred. The decreased activity of PP2A correlated with the up-regulation of PP2A catalytic and PP2A/B gamma, PP2A/B alpha regulatory subunits. The decrease in activity of the PP2B correlated with down-regulation of PP2B catalytic and up-regulation of PP2B regulatory subunit expression. In addition, there was an up-regulation in PP4C and down regulation in PP2C alpha/beta subunits protein expression. We demonstrated clear alteration in the activity and expression of serine/threonine protein phosphatases in breast cancer cells during ATRA treatment, and we suggest that the ATRA-induced apoptosis of the MCF-7 cells is significantly related to the phosphorylation dynamics.