Comparative efficacy study of 5-year letrozole or anastrozole in postmenopausal hormone receptor-positive early breast cancer.

PURPOSE: To compare the efficacy of adjuvant anastrozole and letrozole in hormone receptor-positive postmenopausal patients with early breast cancer. METHODS: A total of 569 hormone receptor-positive postmenopausal early breast cancer patients were included and analyzed in this study. Of them 238 were taking adjuvant anastrozole and 331 adjuvant letrozole. Demographic and medical data including age, menopausal status, weight, height, treatment history and comorbid diseases were collected from their medical charts. RESULTS: In both anastrozole and letrozole users, the baseline clinicopathologic characteristics and the treatment history with radiotherapy and chemotherapy were similar. The median patient follow-up was 26.4 months. In the anastrozole arm disease free survival (DFS) was 94.9, 81.3 and 66.0%, whereas in the letrozole arm DFS was 90.6, 78.7 and 68.5% in the first, third and fifth years, respectively (p=0.25). Median overall survival (OS) could not be reached due to the low number of events in both arms. Three-year survival rate in the anastrozole arm was 98.8%, whereas in the letrozole arm it was 96.7% (p = 0.20). CONCLUSION: This study showed that both letrozole and anastrozole have similar effects on DFS and OS in the adjuvant hormonal treatment of postmenopausal hormone receptor-positive breast cancer. We believe that this retrospective study is the first to directly compare the efficacy of letrozole and anastrozole.

Evaluation of changes in biologic markers ER, PR, HER 2 and Ki-67 index in breast cancer with administration of neoadjuvant dose dense doxorubicin, cyclophosphamide followed by paclitaxel chemotherapy.

PURPOSE: The aim of this study was to assess the changes in biologic markers of breast cancer ER, PR, HER 2 and Ki-67 in locally advanced breast cancer patients after neoadjuvant chemotherapy. METHODS: Data from 63 locally advanced breast cancer patients (stage II or III), whose histological diagnosis was made by core biopsies were retrospectively evaluated. The patients were given 4 cyles of 600 mg/m(2) cyclophosphamide, 60 mg/m(2) doxorubicin every 15 days followed by 4 cycles of paclitaxel 175 mg/m(2) every 15 days, and they underwent surgery within two weeks after the last chemotherapy cycle. Expressions in the preoperative and postoperative status of ER, PR, HER 2 and Ki-67 were compared. RESULTS: The patient mean age was 49.2 ±10.7 years and most (57.1%) were premenopausal. Clinical stages of patients ranged between T2N1 and T3N2. The pathological complete response (pCR) rate was 14.9 % (N=9). Two (5.7%) patients who were ER positive prior to treatment showed ER negativity after treatment. In 7 (21.17percnt;) patients PR became negative after neoadjuvant chemotherapy and in 3 (9.0%) patients PR became positive. Changes in ER and PR receptors were not statistically significant (ER p=0.500 and PR p=0.549, respectively), whereas in 2 (5. 8%) patients hormonal status changed significantly when compared to initial biopsies (p=0.003). In addition, median value for PR intensity decreased from 20 to 10% (p=0.003) and Ki-67 values decreased from 10 to 1% (p<0.001) following neoadjuvant therapy. Six (17%) patients exhibited some changes in HER 2 staining. HER 2 expression became 2+ in 3 patients who were HER 2 negative prior to treatment, and HER 2 expression became negative in two patients with HER 2 1+ and 2+ prior to treatment following neoadjuvant chemotherapy. CONCLUSION: The biological markers ER, PR, HER 2 and Ki- 67 index demonstrated differences after neoadjuvant treatment in breast cancer patients. These changes may affect the treatment decision.

Evaluation of changes of biologic markers ER, PR, HER 2 and Ki-67 in breast cancer with administration of neoadjuvant dose-dense doxorubicin, cyclophosphamide followed by paclitaxel.

PURPOSE: To assess the changes of biologic markers estrogen receptors (ER), progesterone receptors (PR), HER 2 and Ki-67 in locally advanced breast cancer patients after neoadjuvant chemotherapy. METHODS: Data from 63 locally advanced breast cancer patients (stage II or III), whose histological diagnosis was made by core biopsies were retrospectively evaluated. The patients were given 4 cycles of 600 mg/m(2) cyclophosphamide, 60 mg/m(2) doxorubicin every 15 days, followed by 4 cycles of paclitaxel 175 mg/m(2), followed by mastectomy within 2 weeks after the last chemotherapy cycle. The changes in ER, PR, HER 2 and Ki-67 status of the operated tumor tissue were compared with the material obtained by initial core biopsies. RESULTS: The patient mean age was 49.2±10.7 years. Most (57.1%) were premenopausal. Clinical disease stages ranged between T2N1 and T3N2. Pathological complete response (pCR) rate was 14.9 7 percent; (n=9). Two (5.7%) patients who were ER positive prior to treatment showed ER negativity after treatment. In 7 (21.1%) patients PR became negative and in 3 (9.0%) became positive after neoadjuvant chemotherapy. Changes in ER and PR receptors were not statistically significant (p=0.500 and PR p=0.549, respectively), whereas in 2 (5.8%) patients hormonal status changed significantly when compared to initial biopsies (p=0.003). In addition, the median value of PR intensity decreased from 20 to 10% (p=0.003) and Ki-67 decreased from 10 to 1% (p<0.001) following neoadjuvant therapy. Five (14.1%) patients exhibited some changes in HER 2 expression: HER 2 expression became 2+ in 3 patients previously being HER 2 negative, and in 2 patients HER 2 became negative whilst it was 1+ and 2+ prior to neoadjuvant chemotherapy. CONCLUSION: It was observed that the biologic markers ER, PR, HER 2 and Ki-67, from the same tumor material demonstrated differences after neoadjuvant treatment in breast cancer patients. These changes may affect the treatment decision.

Impact of the obesity on lymph node status in operable breast cancer patients.

PURPOSE: Although many studies have shown association of obesity and tumor size, the association with the lymph node status is not clear. We examined the relationship of the lymph node status and obesity and other possible factors in early breast cancer patients. METHODS: In this retrospective cohort study, 1295 breast cancer patients who had axillary dissection were included. Patients were grouped according to their body mass index (BMI) values at the time of diagnosis. We analyzed the relationship between BMI and patient and tumor characteristics, especially lymph node status. RESULTS: The median patient age was 48 years (range 20- 84). Of the patients 69.6% had modified radical mastectomy and the remaining 30.4% had breast-conserving surgery and axillary dissection. Median BMI of the patients was 27.2 kg/m(2) and 33.1% (N-429) of them had normal BMI, 36% (N-471) were overweight and 30.5% (N=395) were obese at the time of the diagnosis. Of the patients, 44.2% had N0 disease, and 55.8% had lymph node metastasis. N1 disease had 28.3% (N=367), 13.8% (N=179) had N2 and 13.7% (N=177) had N3 disease. When patients were classified as normal (≤24.9 kg/m(2)) and obese (>24.9 kg/m(2)) group, the total number of lymph nodes removed was higher in the obese group and this difference was statistically significant (18.12±10.48 and 20.36±11.37, respectively, p= 0.001). There was strong correlation between the number of the dissected lymph nodes and BMI (r=0.11; p<0.001). However, there was no statistically significant correlation between the number of metastatic lymph nodes and BMI. The mean number of the dissected and involved lymph nodes was higher in the HER2 positive group compared to the negative ones (21 vs 19, p=0.008; 6 vs 3, p<0.001; respectively) CONCLUSION: The number of the dissected lymph nodes was slightly higher in obese patients but there was no correlation between metastatic lymph node number and BMI. The number of the dissected and involved lymph nodes was higher in the HER2 positive group.

The prognostic impact of obesity on molecular subtypes of breast cancer in premenopausal women.

PURPOSE: The increasing incidence of obesity throughout the world will result in expansion of the number of women at risk for developing breast cancer. Obesity is associated with adverse outcomes in postmenopausal women with breast cancer. In premenopausal women, the association is less clear. We investigated the impact of obesity on tumor features, hormonal status, recurrence and mortality in premenopausal breast cancer patients, classified according to molecular subtypes. METHODS: 818 premenopausal women with nonmetastatic breast cancer were analysed. Patients were classified into 3 groups according to body mass index (BMI): i) normal body weight (BMI: 18.5-24.9 kg/m(2)); ii) overweight (BMI: 25-29.9 kg/ m(2)); and iii) obese (BMI:>30 kg/ m(2)). Clinocopathologic characteristics and survival rates were analyzed for triple negative, HER-2 overexpressing and luminal subtypes. RESULTS: Obese patients compared with normal-weight women were older at diagnosis (p<0.001) and more often had high grade tumor (57.1 vs 42.3%; p=0.04) with lymphovascular invasion (79.5 vs 63.9%; p=0.03). The median follow-up period after diagnosis was 29 months. According to the molecular subtypes, overall survival (OS) and disease free survival (DFS) were significantly shorter in obese patients with triple negative breast cancer (TNBC) (p=0.001 and p=0.006, respectively). Obesity (HR 1.4; 95% CI 1.0-2.1; p=0.04) and lymphovascular invasion (HR 2.1; 95% CI 1.3- 3.3; p=0.02) were found to be independent prognostic factors for TNBC mortality. CONCLUSION: Obesity is associated with estrogen (ER) and progesterone receptor (PR) negative tumors and poor OS in premenopausal women with breast cancer.

Variations in tumor marker levels in metastatic breast cancer patients according to tumor subtypes.

PURPOSE: To investigate whether serum CA 15-3 and CEA levels show differences among subgroups of breast cancer patients at the time of diagnosis of early-stage disease and at disease relapse. METHODS: Patients with metastatic breast cancer diagnosed from 2000 to 2010 were retrospectively analyzed. Data were obtained from medical charts. CA 15-3 and CEA levels of patients with metastatic disease at the time of diagnosis or who relapsed during follow-up were evaluated. Four different breast cancer subtypes were defined: estrogen receptor (ER) and/or progesterone receptor (PR) positive and HER-2 negative (luminal A), ER and/or PR positive and HER-2 positive (luminal B), ER and PR negative and HER-2 positive (HER-2 overexpressing) and triple negative (ER, PR and HER-2 negative). Fifty-eight (13.7%) of the patients were metastatic at the time of diagnosis. RESULTS: 423 metastatic breast cancer patients were included. Of the patients, 232 (54.8%) had luminal A disease, 70 (16.5%) luminal B, 53 (12.5%) HER-2 overexpressing, and 68 (16.1%) triple negative disease. Preoperative CA 15-3 levels were raised in 48.1% of the luminal A group, in 42.8% of the luminal B group, in 26.0% of the HER-2 overexpressing group, and in 33.3% of the triple negative group. CA 15-3 levels after relapse were raised in 44.5% of the luminal A group, in 33.3% of the luminal B, in 28.9% of the HER-2 overexpressing, and in 38.8% of the triple negative group. Preoperative CEA levels were elevated in 44.3% of the luminal A group, in 28.5% of the luminal B, in 43.4% of the HER-2 overexpressing, and in 14.3% of the triple negative group. CEA levels after relapse were raised in 60.8%, 54.7%, 51.1%, and 36.0% of the patients in the 4 subgroups, respectively. CONCLUSION: This study showed that there are differences between the breast cancer subgroups in terms of tumor marker levels in metastatic breast cancer patients. Tumor marker elevation was lower in the triple negative group as compared to the luminal groups. Monitoring CEA levels in luminal A group may be beneficial in determining early relapses. However, this retrospective study requires further prospective confirmative cohort studies.

Breast cancer in octogenarian women: clinical characteristics and outcome.

PURPOSE: Breast cancer incidence increases in the elderly but data on treatment and outcomes of elderly patients is limited. We assessed the clinicopathological features and outcomes of our patients with breast cancer aged ≥80 years in comparison with their younger postmenopausal counterparts. METHODS: The records of 83 patients diagnosed with breast cancer after the age of 80 (group 1) between 2003 and 2011 in 4 different centers were retrospectively evaluated and the clinicopathological features and outcomes were assessed in comparison with a control group (group 2) of 249 patients aged between 60-70 years. RESULTS: Median ages at diagnosis were 82 years (range 80-95) and 64 years (range 60-70) for group 1 and group 2, respectively. The incidence of invasive cancers other than ductal or lobular type was higher in group 1 than in group 2 (20 vs 8%; p=0.0177rpar;. More patients in group 1 had Charlson Comorbidty scores ≥1 than those in group 2 (49 vs 36%; p=0.011). Patients in group 1 had more conservative operations and less axillary node dissections (ALND) and they received chemotherapy, trastuzumab or radiotherapy less frequently compared to their younger counterparts in group 2. Median follow up period was 36 months (range 1-178) in group 1 and 24 months (range 12-217) in group 2. Five-year disease free survival (DFS) was 53.7 and 75.9) (p=0.005), 5-year overall survival (OS) was 61.9% and 80.47percnt; in group 1 and group 2 (p=0.001), respectively. Advanced stage (stage IV vs stage I, II, III, p=0.051) and cerbB2 positivity (p<0.001) were found to be associated with shorter DFS in patients ≥80 years of age. CONCLUSION: Although the majority of patients were undertreated in our study according to the current guidelines, mortality rates were quite low. Different biology of the disease in the elderly might explain this difference.

Efficacy of adjuvant aromatase inhibitor in hormone receptor-positive postmenopausal breast cancer patients according to the body mass index.

BACKGROUND: Increased adiposity may trigger signalling pathways that induce aromatase expression. As aromatase inhibitors exert their effects by blocking the aromatase enzyme, higher body mass index (BMI) can reduce the effect of aromatase inhibitors. Thus, we aimed to investigate retrospectively the effect of BMI on the efficacy of aromatase inhibitors in hormone receptor-positive postmenopausal patients with breast cancer. METHODS: Newly diagnosed hormone receptor-positive breast cancer patients who were postmenopausal and non-metastatic were enrolled to the study. Patients with BMI ranging between 18.5 and 24.9 kgm(-2) were considered as normal weight patients (Arm A, n=102), and patients with a BMI ranging ≥ 25 kgm(-2) were grouped as overweight and obese patients (Arm B, n=399). RESULTS: In both normal weight and overweight patients, the baseline clinico-pathologic properties and the treatment history with radiotherapy and chemotherapy were similar, and with no statistically significant difference. In normal weight patients disease-free survival (DFS) rate was 93.7% and 77.6%, whereas in overweight and obese patients DFS rate was 96.8% and 85.5% in the first and third years, respectively, (P=0.08). Three year survival rate in Arm A patients was 98.3%, whereas in Arm B was 98.0% (P=0.57). When anastrozole was compared with letrozole in the subgroup analysis no difference with regard to DFS and overall survival was detected. CONCLUSION: These results, contradictory to the prior results, show that BMI has no worse effect on outcomes of aromatase inhibitors in postmenopausal hormone receptor-positive breast cancer patients. In the subgroup analysis, letrozole and anastrozole had similar survival outcomes.

Promising therapeutic options in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) has a greater risk of recurrence despite more aggressive therapy even in lowrisk category. TNBC is high grade, hormone receptor and HER-2 negative, it exhibits a high level of Ki-67 staining and expresses the epithelial growth factor receptor (EGFR). Because of its expression profile, treatment options are limited to cytotoxic chemotherapy. Molecular defects that give rise to BRCA1-associated breast cancer also occur in TNBC. Thus, the combination of poly-(ADP-ribose)-polymerase (PARP) inhibitors with drugs that cause DNA breakages, such as alkylating agents and topoisomerase I inhibitors, could theoretically potentiate the efficacy of each drug in patients with TNBC. Clinical trials with various targeted approaches alone or in combination with different chemotherapeutic agents are currently underway. In this review, current and future treatment approaches in TNBC with novel targeted agents are discussed.

Taxanes in the adjuvant treatment of node-negative breast cancer patients.

PURPOSE: Although the use of regimens with adjuvant taxanes is a standard approach in node-positive breast cancer, the use of taxanes in node-negative breast cancer is still controversial. In this search, we aimed to evaluate the data about the use of taxanes in high-risk node-negative patients. METHODS: Studies were retrieved by searching the Pubmed database. Randomized phase III studies on the use of regimens with adjuvant taxanes in early-stage breast cancer were screened and, among them, the studies that included node-negative patients were included in the evaluation. RESULTS: Data on the adjuvant use of taxanes in nodenegative patients were classified into 3 categories: a) studies that evaluated both node-positive and node-negative patients; b) meta-analyses on the use of adjuvant taxanes; and c) studies that included node-negative patients alone. The results of the studies that evaluated both node-positive and node-negative patients and the meta-analyses were evaluated according to the node-negative subgroup analyses. While two of these studies did not show difference in disease-free survival (DFS) for the node-negative subgroup, one study showed a difference in DFS. The only data for the adjuvant use of taxanes in only node-negative breast cancers belong to GEICAM 9805 study and, according to its results, docetaxel provided a difference in DFS in high-risk node-negative patients. CONCLUSION: Data about the adjuvant use of taxanes in node-negative patients are limited compared to the studies in which both node-positive and node-negative subgroups are evaluated. In the light of these studies, it is impossible to make a comment about the use of taxanes in node-negative patients. However, GEICAM 9805 study has shown positive results on DFS in high-risk node-negative breast cancer patients with adjuvant taxanes.

Metabolic syndrome and breast cancer: an overview.

Worldwide, breast cancer is the most frequently diagnosed life-threatening cancer in women and the most important cause of cancer-related deaths among women. This disease is on the rise in Turkey. Metabolic syndrome is a cluster of metabolic disturbances including insulin resistance, dyslipidemia, hypertension, abdominal obesity and high blood sugar. Several studies have examined the association of the individual components of the metabolic syndrome with breast cancer. More recent studies have shown it to be an independent risk factor for breast cancer. It has also been associated with poorer prognosis, increased incidence, a more aggressive tumor phenotype. Basic research studies are now in progress to illuminate the molecular pathways and mechanisms that are behind this correlation. Given the fact that all of the components of metabolic syndrome are modifiable risk factors, preventive measures must be established to improve the outcome of breast cancer patients. In this review we set the background by taking into account previous studies which have identified the components of metabolic syndrome individually as breast cancer risk factors. Then we present the latest findings which elaborate possible explanations regarding how metabolic syndrome as a single entity may affect breast cancer risk.

ERCC1 expression in triple negative breast cancer.

PURPOSE: Excision repair cross-complementation group 1 (ERCC1), which is a component of nucleotide excision repair (NER) pathway, removes platinum-induced DNA adducts. Overexpression of ERCC1 has been associated with resistance to platinum-based chemotherapy in ovarian and lung cancers. Detecting ERCC1 overexpression is important in considering treatment options for triple negative breast cancer (TNBC), and in conducting and interpreting trials that search to find specific chemotherapy regimens for TNBC. In this study we aimed to study ERCC1 overexpression in patients with TNBC. METHODS: A monoclonal antibody against ERCC1 was used for immunohistochemical (IHC) analysis of tumor samples. Tumor samples from 45 patients were evaluated by two experienced pathologists who were blinded to clinical data. A semi-quantitative H score (intensity staining scale ranging from no staining/0 to very intense staining/3+) was calculated by multiplying staining intensity with extent score. Tumors with H score ≥ 1 were classified as ERCC1-positive. RESULTS: ERCC1 expression was positive in 73.3% of the tumor samples with an H score ≥ 1 and 26.7% of the tumor samples stained negative with an H score lt; 1. Of the tumor samples 15.5% stained diffusely and intensively. CONCLUSION: Our study demonstrated that about two thirds of the TNBC showed positive expression of ERCC1, which may be predictive of a poor response to platinum-based chemotherapy.

Tumor heparanase expression in predicting response to induction chemotherapy in patients with locally advanced laryngeal cancer.

PURPOSE: Induction chemotherapy is a feasible alternative to surgery for the treatment of locally advanced laryngeal cancer. Determining predictive factors associated with a better response to chemotherapy would help choose the patients most likely to benefit from larynx preservation. METHODS: Eighty-four patients diagnosed with locally advanced laryngeal cancer (stage III-IV) between April 1999 and May 2006 were retrospectively reviewed. Eightytwo of them received 2 cycles and 2 received only 1 cycle of cisplatin and 5-fluorouracil (5-FU) chemotherapy. Patients were then grouped, based on response to treatment, as either having complete response (CR), partial response (PR), stable (SD) or progressive disease (PD). Factors predicting response to treatment were evaluated. Paraffin blocks were immunohistochemically examined for heparanase activity to see for any link between heparanase expression and response to treatment. RESULTS: There were 73 males and 11 females with a mean age of 59 years. After induction chemotherapy (cisplatin and 5-FU), 33 patients achieved PR and 20 CR. SD and PD occurred in 9 and 21 patients, respectively. Patients with stage III disease had better overall (CR and PR) response rates when compared with those with stage IV disease. Moreover, development of bone marrow suppression and heparanase positivity were both associated with better overall response rates. CONCLUSION: This study supports the hypothesis that heparanase positivity is associated with better responses to induction chemotherapy, regardless of TNM stage. Furthermore, a higher overall response rate was observed in patients who developed myelosuppression secondary to chemotherapy.

Association between family history and clinicopathologic characteristics in 1987 breast cancer patients: single institution experience from Turkey.

PURPOSE: To evaluate the clinicopathologic characteristics and survival of patients with family history of breast/ ovarian cancer (FHBOC). METHODS: In this study with 1987 breast cancer patients, we analyzed their tumor characteristics and outcomes, as well as the total number, degree and age of affected relatives, and their type of cancer. Results were assessed using Pearson chi-square test, Kaplan-Meier method and Cox regression analysis. RESULTS: 24.1% (n=479) of the patients had FHBOC. Patients with FHBOC were younger (47.7 vs. 49.1 years; p=0.03) and tended to have node-negative breast cancer (45.4 vs. 39.8%; p=0.006). The median overall survival (OS) was shorter in patients with FHBOC with a borderline p-value (p=0.063), compared to patients with no family history. The median OS was shorter in patients who had ≥ 2 relatives with breast cancer (p=0.014), in those having first degree relatives with breast cancer, presenting with metastatic disease (p= 0.020). FHBOC patients with triple negative breast cancer had the highest risk of death (p<0.0001) and recurrence (p<0.0001). Patients who had at least one relative with breast cancer aged ≤ 50 years were also at increased risk of recurrence (p7equals;0.006). CONCLUSION: Our results suggest that patients with FH7horbar;BOC are younger, tend to have small tumor size, node-negative disease and their survival is shorter compared to patients without family history. This is the first study evaluating the clinicopathologic differences of patients with and without FHBOC in Turkish population.

ABO and Rh blood groups frequency in women with HER2 positive breast cancer.

PURPOSE: The role of genetic factors in the development of cancer is widely accepted. Data on the role of ABO blood group and Rh factor in breast cancer is inconclusive. The aim of this study was to investigate the presence of a possible association between HER2 (+) breast cancer in Turkish women and ABO blood groups and Rh factor. METHODS: In 294 female patients with HER2 (+) breast cancer, ABO blood groups and Rh factor were examined. The relationship of blood groups with age, menopausal status, and family history of cancer, estrogen receptor (ER), progesterone receptor (PR) and HER2 status of these patients was evaluated. Blood groups distribution of 22,821 healthy blood donors was also assessed and compared with the patients' blood groups distribution. RESULTS: The median patient age was 47 years (range 20-80) and 56% of the patients were premenopausal. ER and PR were positive in 50 and 60% of the patients, respectively. Overall, the ABO blood group distribution of the 294 HER2 (+) breast cancer patients was similar to that of the healthy blood donors (p=0.36). Likewise there was no correlation between blood type and ER, PR and menopausal status. Rh (-) patients had more frequent family cancer history and this difference was significant for patients with blood group B Rh (-) and O Rh (-) (p = 0.04). CONCLUSION: In the present study we didn't find any relationship between HER2 status and ABO blood group and Rh factor. However, further studies with larger number of patients are needed to establish the role (if any) of blood groups in patients with breast cancer.

Clinical and pathological characteristics of occult breast cancer and review of the literature.

PURPOSE: Occult breast cancer is defined as axillary metastasis without clinically and/or radiologically evident primary tumor. In female patients presenting with isolated axillary nodes with adenocarcinoma, the most likely primary cancer is an invasive breast carcinoma. Herein we present our experience over this issue, together with a brief review of the literature about this clinically challenging condition. METHODS: We retrospectively analyzed 1215 consecutive breast cancer patients treated at our clinic between 2004- 2010. Four of these patients presented with axillary nodal metastasis without clinical and radiological evidence of a primary breast tumor. RESULTS: The incidence of occult breast cancer in our clinic was 0.32%. Median follow-up was 8 months. All patients were alive and remained free of disease at the end of the follow-up period. CONCLUSION: The prognostic factors for occult breast carcinoma are similar to that of its overt counterpart. The number of axillary lymph node involved and the hormone receptor status are considered significant prognostic predictors. Further studies with randomization and longer followup are needed for the establishment of a safe management plan.

Malignancies after rituximab treatment: just coincidence or more?

PURPOSE: Rituximab has been successfully used in the treatment of B-cell non-Hodgkin's lymphoma (NHL) and some autoimmune diseases nearly for a decade. Several other malignancies and CD20-negative lymphomas have been reported in the literature after rituximab treatment. We aimed to investigate whether there is an association between rituximab treatment and the development of second malignancies. METHODS: A detailed search in English language literature on reports about rituximab treatment and secondary malignancies was made through Medline. The papers were reviewed and the cases were summarized according to secondary tumor types, intervals between rituximab treatment and second malignancy occurrence, indications for rituximab treatment and cytotoxic chemotherapy administration. RESULTS: There were 26 previously reported cases of CD20-negative lymphoma and solid tumors after rituximab treatment. The median age of these cases was 62 years (range 34-80). The median time period from the initiation of rituximab treatment to diagnosis of second malignancies was 5 months (range 1-40). The most frequently reported solid tumors were skin tumors (squamous cell carcinoma and Merkel cell carcinoma) (n=7; 27%), CD20-negative lymphomas (n=5; 20%), Kaposi sarcoma (n=4; 15%), and others (n=10; 38%). CONCLUSION: Association between rituximab and subsequent development of second malignancies might be a coincidence. However, we suggest close monitoring for second malignancies, particularly skin tumors, in patients treated with rituximab. This issue should be evaluated in further studies.

Secondary hematological malignancies after treatment of non-metastatic breast cancer.

PURPOSE: To determine the frequency of secondary hematological malignancies in non-metastatic breast cancer (BC) patients who received adjuvant chemotherapy and radiotherapy. METHODS: Data of BC patients followed at Hacettepe University Institute of Oncology, Department of Medical Oncology between 2004 and 2010 were retrospectively analysed. RESULTS: There were 1,475 BC patients followed between 2004 and 2010 at our department; 1,319 (89.4%) of them had not metastatic disease. One thousand, one hundred eighty three (89.7%) early-stage BC patients received at least one treatment modality (radiotherapy and/or chemotherapy). The number of patients receiving only chemotherapy or only radiotherapy were 228 (17.3%) and 117 (8.9%), respectively. Eleven (1%) out of 1,066 BC patients receiving adjuvant/neoadjuvant chemotherapy were also treated with granulocyte colony stimulating factor (G-CSF). The frequency of secondary hematological malignancies among adjuvant or neoadjuvant chemotherapy BC patients was 0.56% (6/1,066); it was 0.59% (7/1,183) among radiotherapy and/or chemotherapy treated non-metastatic BC patients. Five patients developed acute myeloid leukemia (AML); 3 of them were AML-FAB M3 and 2 could not be subclassified. The 6th patient had multiple myeloma and the 7th had diffuse large B cell lymphoma (DLBCL). However, the latter did not receive cytotoxic chemotherapy for BC. CONCLUSION: Treatment-associated secondary hematological malignancies, especially myeloid leukemias, are a growing problem due to high prevalence of BC and the dismal outcome of secondary leukemias. Further studies are needed to determine the risk for other hematological malignancies, possible responsible agents, and mechanisms.

Temozolomide-related infections: review of the literature.

Temozolomide (TMZ) is an alkylating, antineoplastic agent which is being used to treat cases of refractory anaplastic astrocytoma, newly-diagnosed glioblastoma multiforme and metastatic melanoma. TMZ causes lymphopenia and T-cell dysfunction in most of the patients. Related to this toxicity several opportunistic infections have been reported in the literature, but were not well characterized. To further investigate this topic, relevant English language studies were identified through Medline. There were 36 previously reported cases of infection related to TMZ. The median age of the cases was 55 years (range 33-73). The most frequently experienced infections were mucocutaneous candidiasis (n=11; 28.2%), herpes zoster (n=5; 12.8%), herpes simplex virus (n=4; 10.2%), cytomegalovirus (CMV) (n=5; 12.8%), pneumocystis carinii pneumonia (PCP) (n=3; 7.6%), hepatitis B virus (HBV) (n=2; 5.1%) and others (n=9; 23%). Mortality rates were 28.5% (n=4/14) in patients with reported outcome. In this survey, about one third of the TMZ-related severe infections resulted in death. Patients treated with TMZ are at increased risk for opportunistic viral and bacterial infection. Therefore, close monitoring of patients receiving TMZ for opportunistic infections should be carried out.