Prognostic role of inflammatory biomarkers in metastatic breast cancer.

PURPOSE: The effects of inflammation on the prognosis, life expectancy and several parameters such as response to treatment of breast cancer have been previously studied. The purpose of this study was to investigate the effect of inflammatory markers on prognosis in patients with metastatic breast cancer. METHODS: This study was conducted on 81 patients with metastatic breast cancer who have been followed up at the Department of Medical Oncology, Hacettepe University Institute of Oncology, between December, 2009 and March, 2014. For all studied parameters Kaplan-Meier survival estimates and p values computed by log-rank test were calculated. A p value < 0.05 was considered statistically significant. RESULTS: Median follow-up time was 26 months. There were 38 deaths due to disease progression during the follow up. The levels of serum albumin, and erythrocyte sedimentation rate (ESR) were not associated with a significant effect on overall survival (OS). Among patients with a higher serum C-reactive protein (CRP), the estimated mean survival was 84±36 months, compared to 278±113 months among patients with a normal serum CRP (p=0.032). When patients with higher and normal lactate dehydrogenase (LDH) levels were compared, their 2-year OS survival rates were 68.2 and 87.7%, respectively (p=0.034). Among patients with higher serum ferritin levels, the estimated mean survival was 29±10 months, compared to 212±113 months for normal serum ferritin (p=0.01). Among patients with higher serum beta-2 microglobulin (ß2-M), the estimated mean OS survival was 28±8 months, compared to 84±57 months for those with normal levels (p<0.01). CONCLUSION: Serum CRP, ferritin and ß2-M can be useful prognostic factors for OS in patients with metastatic breast cancer.

Risk factors and histopathological features of breast cancer among women with different menopausal status and age at diagnosis.

PURPOSE: Although there are studies that investigate different risk factors and clinicopathological features of breast cancer in women at different age groups and menopausal status, there is a need for studies with larger study populations due to controversial findings. We conducted this study to identify demographic parameters in breast cancer patients and histopathological features of the tumors for different age groups and compare them to demonstrate significant differences, if any. METHODS: 3325 women diagnosed with breast cancer in Hacettepe University Oncology Hospital Outpatient Clinic between January 1994 and March 2014 were included in this study. RESULTS: Postmenopausal women who were older than 65 were found to have higher number of children, higher rates of oral contraceptive use, greater age at menarche, and have higher rates of first full-time pregnancy before the age of 30. On the other hand, higher rates of grade 3 tumors, advanced lymph node stage, lymphovascular invasion, and triple negative breast cancers were more frequently seen in premenopausal women below the age of 35. Since earlier age at the time of diagnosis is associated with bad prognosis, early diagnosis of breast cancer gains importance in younger women. CONCLUSION: Implementing targeted screening programs of breast cancer for younger women may become a need in the future. Meanwhile, well-education on risks of breast cancer and regular self-examination for early diagnosis need to be emphasized for the prevention of breast cancer and related diseases in young ages.

Patients' understanding of treatment goals and disease course and their relationship with optimism, hope, and quality of life: a preliminary study among advanced breast cancer outpatients before receiving palliative treatment.

PURPOSE: The aims of this study were to explore advanced breast cancer patients' knowledge of treatment intent and expectation of illness course and to evaluate their relationship with optimism, hope, and quality of life (QoL). METHODS: Patients with advanced breast cancer (n = 55) who were treated in the ambulatory clinic of the University of Hacettepe were included in the study. They completed Life Orientation Scale, The Hope Scale, and the European Organization for Research and Treatment of Cancer Quality of Life questionnaires. The data regarding the knowledge of illness progression and the perceptions of therapy intent were assessed using self-administered open-ended questionnaires that were answered by the patients. RESULTS: The data revealed that 58.2 % of the patients had an inaccurate perception of treatment intent, believing the aim of treatment was cure, whereas only 38.2 % of the patients had a realistic expectation that their disease may remain stable or may progress over a year. In addition, the awareness of disease progression and perception of goals of treatment was significantly related to hope and optimism scores but not to QoL. CONCLUSIONS: A large proportion of patients diagnosed with advanced breast cancer believed that their treatment was "curative", and they would improve within a year. Findings of our study suggest that patients with inaccurate perception of treatment intent and unrealistic expectation of prognosis have higher hope and optimism scores than those who do not, but there were no significant differences in terms of global health status.

Trastuzumab 1-year vs 9-week in early-stage HER2-positive, lymph node negative breast cancer patients.

PURPOSE: Optimal duration of adjuvant trastuzumab therapy in early-stage HER2-positive, lymph node-negative breast cancer is unknown. To establish this, we compared 1-year and 9-week trastuzumab regimens in HER2-positive, lymph node-negative early-stage breast cancer patients. METHODS: We retrospectively analyzed 4374 breast cancer patients. There were 181 early-stage, lymph node-negative breast cancer patients who were treated with adjuvant trastuzumab for either 9-week or 1-year schedule. A total of 101 patients received trastuzumab for 9 weeks and the remaining 80 patients received this adjuvant therapy for 1 year. Disease free survival (DFS) and overall survival (OS) rates of both groups were calculated. RESULTS: There was no difference between groups according to OS. Five-year OS rates were 95.5% in the 9-week group and 93.3% in the 1-year group (p=0.78). DFS was affected by age, having tamoxifen therapy and disease stage. Nine-week trastuzumab group was superior to 1-year group and 5-year DFS rates were 91% in 9-week group and 81.2% in 1-year group (p=0.02). However, the 1-year group had more stage II patients than the 9-week group. We did not find any difference between groups regarding developing congestive heart failure. CONCLUSION: It appeared that 9-week trastuzumab treatment was not inferior to 1-year trastuzumab treatment in early-stage, lymph node-negative breast cancer patients.

Efficacy and safety of eribulin monotherapy in patients with heavily pretreated metastatic breast cancer.

PURPOSE: Eribulin is a non-taxane microtubule inhibitor, which can be used after anthracycline and taxane treatment in patients with metastatic breast cancer (MBC). The purpose of this study was to investigate the efficacy and safety of eribulin monotherapy in heavily pretreated MBC patients. METHODS: In this single-center trial, a total of 66 MBC patients who received eribulin monotherapy in Hacettepe University Cancer Institute between 2013 and 2015 were retrospectively analyzed. Kaplan-Meier survival analysis was carried out for progression free survival (PFS) and for overall survival (OS). Two-sided p values <0.05 were considered as statistically significant. RESULTS: Sixty-six patients who received at least one cycle of eribulin were registered. Most patients were heavily pretreated with a median of 4 (range 2-7) previous chemotherapy lines prior to eribulin. Median patient age was 50 years (range 28-67). Most patients were treated with eribulin at 4th or 5th line (33.3 and 27.3%, respectively). Brain metastases were present in 19 (28.8%) patients at the time of initial eribulin administration. Median PFS was 5 (95% CI 4.1-5.8) and median OS was 8 (95% CI 6-9.9) months. Fifteen patients (22.7%) responded to treatment with partial remission (PR) and 36 (54%) had stable disease (SD). No hypersensitivity reactions and no toxic deaths were observed. Three (5%) patients experienced grade 4 neurotoxicity. Fourteen (21.5%) patients developed grade 3-4 neutropenia. CONCLUSION: Eribulin monotherapy is an effective and safe regimen for MBC patients. Its low toxicity profile compared to other intravenous cytotoxic agents and the ease in its intravenous administration make this agent a preferable option for both physicians and patients.

Left laterality is an independent prognostic factor for metastasis in N3 stage breast cancer.

PURPOSE: Development of metastasis in patients with breast cancer (BC) is the most important negative prognostic factor and this process mainly begins with lymphatic involvement. Therefore, axillary, subclavicular, internal mammary or supraclavicular nodal involvement is a crucial step before metastasis. Anatomical differences between the right and left lymphatic drainages of the breasts may significantly affect the rate, site and time to development of distant metastasis. The purpose of this study was to investigate if laterality is an independent prognostic factor for metastasis in N3 breast cancer patients. METHODS: From a total of 4215 BC patients diagnosed between 1994 and 2015 in our center, 305 non-metastatic women with pathological N3 (pN3) nodal status at presentation were enrolled in this study. Patients were divided into two groups: left and right BC. Analysis of overall survival (OS) and time to first metastasis (TTM) was performed according to Kaplan-Meier method with log-rank test. RESULTS: The median number of lymph node involvement and lymph node ratio (number of positive lymph nodes / total number of excised lymph nodes) between the two groups was equal (14 and 0,66 respectively). Recurrence was observed in 123 patients [53 (35%) right vs 70 (44%) left group]. Patients with left BC had significantly higher rate of axial bone metastases compared with the right BC group (55.7 vs 35.8%, p<0.02, respectively). TTM was significantly shorter in the left BC group [49.1 months (95% CI 36.5-61.8) vs 103.6 months (95% CI 47.0-160); p7equals;0.03, respectively]. Median OS did not differ between the groups, however, there was a trend towards lower OS in patients with left BC (p=0.68). CONCLUSION: Left laterality in patients with pN3 non-metastatic BC is an independent prognostic factor associated with shorter TTM, increased risk of distant metastases and axial bone involvement compared with right laterality.

Correlation of educational status and clinicopathological characteristics of breast cancer: a single center experience.

PURPOSE: Educational status may be an important parameter in assessing breast cancer risk and prognosis. The purpose of this study was to investigate the correlation between the level of education and clinicopathological characteristics of breast cancer, including tumor grade, HER-2 and estrogen receptor (ER) status, tumor size, axillary lymph node involvement and metastasis. METHODS: The study included 1800 women who were diagnosed with invasive breast cancer during 2005-2013 at Hacettepe University Cancer Institute. Patients were divided into three groups according to their educational status at the time of diagnosis as follows: low (illiterate and elementary school, 5 years or less of education), medium (secondary school and upper secondary school, 6-12 years of education) and high (university level, more than 12 years of education). The associations between educational status and clinicopathologic features of breast cancer at the time of diagnosis were evaluated. RESULTS: In all patient, a significant relationship was found between educational status and T stages (p<0.0001). Patients with higher educational levels were reported to have smaller tumor size regardless to their age and were less likely to have axillary lymph node involvement (p=0.001) or metastasis (p=0.001). A significant correlation was found between educational status and ER positivity in patients over 50 years of age (p=0.03). When the patients of all ages were evaluated, no statistically significant correlation was shown (p=0.27) between educational status and ER positivity. A significant relationship was found between educational status and HER-2 status (p=0.003), regardless of the patients' age. HER-2 positivity increased in patients with low educational status, however this significance was lost in patients over the age of 50 (p=0.1). CONCLUSION: The relationship between educational status and biological factors in breast cancer are not conclusive as yet, but this particular study revealed that educational status played a major influence in each of the five breast cancer prognostic factors: ER status, HER-2 status, tumor size, lymph node status and metastasis.

The effect of renin-angiotensin-system inhibition on survival and recurrence of N3+ breast cancer patients.

PURPOSE: The purpose of this study was to evaluate the association between the rennin-angiotensin system (RAS) inhibition and the risk of breast cancer (BC) recurrence and progression in N3 positive patients. METHODS: The medical records of patients treated for N3 positive BC in Hacettepe Cancer Institute between 2005 and 2012 were evaluated. Angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARB) users were defined as patients who took these medications for at least 6 months in no evidence of disease (NED) stage after the initial diagnosis. The primary and secondary outcome was disease-free survival (DFS) and overall survival (OS). Kaplan-Meier and Cox proportional hazard models were used. RESULTS: A total of 218 pathologic N3 BC patients were included. Follow up ranged from 12 to 212 months (median 49.58). Thirty one patients used ACE inhibitors/ARBs. Univariate analysis showed BC recurrence was lower and OS was higher among patients who used ACE inhibitors/ ARBs, however without reaching statistical significance (p=0.38 and p=0.24, respectively). RAS inhibition was associated with reduced risk of pathologic N3 BC recurrence. CONCLUSION: To the best of our knowledge this is the second study showing that the use of ACE inhibitors/ARBs may be effective in N3 BC. Because of the limited therapeutic options in BC, new drugs or new therapeutic modalities should be considered. In the future, studies with long-term follow-up may be helpful for their implication in clinical practice.

The effect of obesity on recurrence pattern in early breast cancer patients.

PURPOSE: Obesity is a well known risk factor for breast cancer recurrence and poor prognosis. We studied the effect of body mass index (BMI) on recurrence pattern in early breast cancer patients. METHODS: This retrospective cross-sectional study analyzed the data of 2731 early stage breast cancer patients. Patients who had metastatic disease at the time of diagnosis and with unknown BMI values were excluded from study (N=276). Patients were classified into three BMI categories: normal body weight, overweight, and obese. The recurrent/metastatic sites of patients were grouped in 8 categories: local, contralateral, lymph node, bone, lung, liver, brain and others. The association between first relapse site of early breast cancer patients and BMI categories were evaluated. RESULTS: The median patient age was 48 years (range 18-92). The median follow up time was 40 months (range 1-284). During follow-up, 469 (17.1%) patients developed recurrence and/or metastasis. Of 2455 total patients, 853 (34.6%) were classified as having normal weight, 898 (36.2%) were overweighted and 704 (29.2%) were obese. In the whole patient group no relation between metastatic sites and BMI groups was noticed. The first primary metastatic sites were also not associated with BMI groups in pre and postmenopausal subpopulations. In obese patients, disease free survival (DFS) was shorter compared to normal weighted patients, but the difference was not significant. There was no significant difference between site-specific DFS in relation to BMI categorization. Obese and overweighted patients had significantly shorter overall survival (OS) compared to the normal-weight group (p=0.003). CONCLUSION: Although obesity had no effect on recurrence pattern of early breast cancer patients, obese early breast cancer patients had shorter OS compared to their normal-weight counterparts.

Chemotherapy might not be beneficial in lymph node- negative, hormone-positive, and HER2-negative breast cancer patients: a long-term retrospective analysis.

INTRODUCTION: In lymph node-negative, hormone-positive, and Her2-negative breast cancer patients, the benefits of adding adjuvant chemotherapy to hormonal therapy continue to be debated, especially for low to intermediate grade and small tumors. METHODS: Excluding patients with T4 disease, we retrospectively reviewed the records of patients with long-term follow-up at our center between 2003 and 2014. Among node-negative, hormone-positive and HER2-negative breast cancer patients, we compared two groups of patients: those given both chemotherapy (doxorubicin+cyclophosphamide) and hormonotherapy, and those prescribed hormonotherapy alone. The primary endpoints were progression-free (PFS) and overall survival (OS). RESULTS: Overall, no difference was observed between these two treatment groups in either DFS or OS. However, for both outcomes, there was a trend towards improved DFS and OS favoring the hormone-only group. CONCLUSIONS: In selected subgroups of breast cancer patients, administering adjuvant hormonal therapy alone seems to be at least as good if not better than combining hormonotherapy and chemotherapy.

The lymph node ratio as an independent prognostic factor for non-metastatic node-positive breast cancer recurrence and mortality.

PURPOSE: To examine the prognostic value of lymph node ratio (LNR) in pathological nodal (pN) stage breast cancer patients. Also, to analyse additional clinical and pathologic prognostic factors and the impact of LNR among molecular subtypes. METHODS: Among a total of 3088 patients, 1004 women with non-metastatic lymph node-positive breast cancer were analysed. The patients were classified into low (≤0.20), intermediate (0.20 to 0.65) and high-risk (>0.65) LNR groups. Univariate and multivariate Cox proportional hazards regression model for disease-free survival (DFS), and overall survival (OS) were performed to evaluate the prognostic value of LNR. RESULTS: The median LNR was 0.17 (range 0.02-1.00). Of the patients, 55.7% were in low, 32.1% in intermediate, and 12.3% in high risk group. When compared with low risk group, high risk group had more often large tumor size and high grade tumor with lymphovascular invasion. The median follow-up period was 46.8 months. The 5-year breast cancer-specific OS and DFS rates for patients with low, intermediate, and high were 88%-67%, 65%-48% and 53%-24%, respectively (both plog-rank<0.0001). On multivariate analysis, pN stage and LNR were both independent predictors of survival, however, an overlapping between N1 (250 months, 95% confidence interval [CI] 88.15-413.21) and N2 (176 months, 95% CI 129.51-222.93) curves in pN staging was determined. We also observed clear prognostic separation for triple negative breast cancer with LNR survival over pN staging. CONCLUSION: The LNR predicts survival more accurately than pN staging in node-positive breast cancer patients. The use of LNR may standardize the staging and guide decisions for adjuvant treatments.

A retrospective analysis of adjuvant CAF, AC-T and TAC regimens in triple negative early stage breast cancer.

PURPOSE: To compare the effectiveness of adjuvant chemotherapy regimens in triple negative breast cancer (TNBC) for which no protocol has been determined to be treatment of choice. METHODS: In this single-center retrospective trial, we analyzed the adjuvant regimens of 164 TNBC patients among 3253 breast cancer patient records. Adjuvant TAC (docetaxel, doxorubicin, cyclophosphamide), CAF (cyclophosphamide, doxorubicin, 5fluorouracil), and AC-T (doxorubicin, cyclophosphamide followed by docetaxel) regimens were compared in terms of disease free survival (DFS) and overall survival (OS). RESULTS: In terms of both DFS and OS TAC was significantly superior to AC-T in node positive TNBC. When node negative and positive patients were analyzed together, TAC was still significantly superior to AC-T in terms of DFS and OS. There was a trend favoring CAF over AC-T, however, it was only significant in terms of OS when all node negative and positive TNBC patients were incorporated together. CONCLUSION: In the adjuvant setting, especially in node positive patients, TAC should be the treatment of choice in TNBC patients. CAF is probably better than AC-T in TNBC.

Molecular subtypes in patients with inflammatory breast cancer; a single center experience.

PURPOSE: The purpose of this study was to investigate the frequency and prognosis of inflammatory breast cancer (IBC) according to molecular subtypes. METHODS: Demographic data were examined for 78 patients diagnosed with IBC among breast cancer patients monitored in our clinic. Patients were staged according to the 2010 AJCC guidelines. Physical examination and radiographic findings classified on the basis of Response Evaluation Criteria in Solid Tumors (RECIST) guidelines were employed in the evaluation of clinical response to systemic therapy. Subtype analysis was performed in patients with IBC and subtypes were compared. Patients were divided on the basis of metastatic or non metastatic status and survival analysis was performed on the basis of molecular subtypes. RESULTS: Distribution analysis of molecular subtypes revealed a lower incidence of luminal A and a higher incidence of both HER 2 (+) and triple negative breast cancer in IBC. Molecular subtypes had no effect on survival in the non metastatic (p=0.61) and metastatic patient group (p=0.08). CONCLUSION: This study showed that IBC frequency is higher in HER2 overexpressing and triple negative subtypes. No survival differences were noticed in relation to molecular subtypes in IBC patients.

The relationship between urotensin II and its receptor and the clinicopathological parameters of breast cancer.

BACKGROUND: Urotensin II is a vasoactive polypeptide. It is known that some vasoactive polypeptides are produced and secreted by tumor cells, and act as a paracrine growth stimulant. The aim of this study was to examine the relationship between urotensin II and its receptor's messenger RNA expression in breast cancer. MATERIAL/METHODS: Fifty-nine women with breast cancer were included in this study. The median age was 48 years. The relationships between urotensin II and urotensin II receptor mRNA expressions, which were derived from fresh breast cancer tissues and adjacent normal breast tissues, and clinical and pathological parameters, were assessed. RESULTS: We found expressions of urotensin II mRNA and its receptor in 55 of 59 breast cancer tissues and in 55 of 59 normal breast tissues. We found a positive significant correlation between urotensin II and its receptor (p=0.001, r=0.632), and found a negative, but insignificant, correlation between urotensin II and age (p=0.038, r=-0.281). Urotensin II levels were higher in the premenopausal group compared to the postmenopausal group (p<0.05). The mean urotensin II receptor expression was higher in the premenopausal group (p<0.05) compared to the postmenopausal group, and its expression was also higher in the group without extra-nodal invasion compared to that of the group with extra-nodal invasion (p=0.001). Urotensin II levels were higher in the group without lymphatic invasion compared to the group with lymphatic invasion (p=0.048). CONCLUSIONS: This study is the first in the English medical literature to determine the urotensin II and its receptor mRNA expressions in breast cancer tissues. Consequently, urotensin II seems be associated with menopausal status, and extra-nodal and lymphatic invasion.

The antibodies cyclic citrullinated peptides (anti-CCP) positivity could be a promising marker in brucellosis patients presented with peripheric arthritis.

INTRODUCTION: The anti-cyclic citrullinated peptide (anti-CCP) enzyme-linked immunosorbent assay has a high sensitivity and specificity for rheumatoid arthritis (RA). It has been used in especially early diagnosis of RA, and used to discriminate from other forms of arthritis. Anti-CCP positivity is unknown in brucellosis presented with peripheric arthritis (BPA), like other rheumatic diseases. The objective of this study was to investigate the positivity of anti-CCP in patients with BPA in contrast to the patients with RA and healthy controls. Additionally, we have aimed to monitor changes of anti-CCP levels following the brucellosis treatment. METHODS: The study group consisted of 137 subjects. 62 brucellosis patients presented with peripheric arthritis. Additionally, 33 RA patients and 42 healthy subjects selected as control groups. The anti-CCP, rheumatoid factor and anti-nuclear antibody levels of the subjects were measured. RESULTS: Concerning the 62 BPA, 20 % (13 patients) of them had elevated anti-CCP levels. On the other side, of the 33 RA patients, 78.78 % (26 patients) of them had increased anti-CCP levels. Only one healthy subject's anti-CCP level was positive. There was statistically significant difference among the groups. After brucellosis treatment, monitorisation of the 13 patients with BPA who have the positive anti-CCP levels, were challengingly interesting because none of the patients had positive anti-CCP levels. CONCLUSIONS: Anti-CCP may be positive marker in the diagnosis of BPA but clinicians need to be careful during the follow up period because it may turn into normal ranges. Additionally, patients presented with peripheric arthritis and anti-CCP positivity need to be evaluated also for the differential diagnosis of BPA.

A novel targeted therapy in breast cancer: cyclin dependent kinase inhibitors.

Breast cancer is the most common cancer in women worldwide. Understanding the biology of this tumor is a prerequisite for selecting an appropriate treatment. Cell cycle alterations are seen in many cancers such as breast cancer. Newly popular targeted agent in breast cancer are cyclin dependent kinase inhibitors (CDKIs) which are agents inhibiting the function of cyclin dependent kinases (CDKs). They are categorized as selective and non-selective inhibitors of CDK. CDKIs have been tried as monotherapy and combination therapy. Palbocyclib is now a promising CDKI used in breast cancer. Nowadays palbocyclib is designed for a phase III trial for estrogen receptor (ER) positive breast cancer after showing favorable results in progression free survival in a phase II trial.

Impact of inflammatory markers on the prognosis of patients with operable breast cancer.

PURPOSE: To investigate the effect of inflammatory markers on the prognosis of patients with operable breast cancer. METHODS: This study was conducted on breast cancer patients followed up between December 2009 and December 2012 at the Division of Medical Oncology, Department of Internal Medicine, Hacettepe University Medical School. A total of 704 patients with stages I to III disease whose inflammatory markers were assessed at the time of diagnosis were included the study. Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, ferritin, ß2 microglobulin (ß2-M), and lactate dehydrogenase (LDH) levels were evaluated as inflammatory markers. RESULTS: The median age at diagnosis was 50 years (range 25-92). Of the patients 42.8% were premenopausal and 48.2 % postmenopausal. Invasive ductal carcinoma was the most common histology (76.5 %). Serum ferritin, LDH, ß2-M, ESR, and CRP were higher than the normal values in 1.0, 4.3, 9.5, 32.4 and 36.4 % of the patients, respectively. Serum albumin levels were lower than the normal values in 1.7 % of the patients. The median patient follow-up period was 22 months (range 3-227). During follow-up, metastatic disease developed in 31 patients (4.4%) and 11 patients (1.56%) died due to disease progression. Two-year overall survival (OS) and disease free survival (DFS) rates were not statistically different among patients with normal and abnormal values with respect to albumin, ferritin, LDH, ß2-M, CRP, and ESR. CONCLUSION: Our study is the first study to investigate the effect of inflammatory markers on the prognosis of operable breast cancer patients. We showed that inflammatory markers such as ESR, CRP, ferritin, ß2-M, albumin and LDH have no effect on prognosis.