Search

Bisphosphonates are the most commonly used agents in the treatment of osteoporosis, and bisphosphonate therapy reduces the risk of skeletally related complications in patients with bone metastases due to malignancy. However, the effect of oral alendronate treatment on clinical and pathological properties of breast cancer has not been reported. Thus, we aimed to investigate retrospectively the demographic and clinico-pathological characteristics of new diagnosis of breast cancer patients with oral alendronate users for longer than 1 year, compared with non-users. Newly diagnosed breast cancer patients from 1998 to 2010 in our clinic were retrospectively analyzed. Patient’s demographics, including survival data and tumor characteristics, were obtained from medical charts. Breast cancer patients who were taking oral alendronate more than 12 months at the time of breast cancer diagnosis were enrolled as an alendronate users (n = 44), where the patients matched with the same age who were not taking oral alendronate were included as a control group (n = 444). A total of 488 patients were included in this study. Forty-four patients received an oral alendronate treatment more than 1 year, and 444 patients were considered as non-users. Median age of both alendronate users and non-users was 57 (33–89). Lower incidence of histological grade III, T3–T4 tumor, and node positivity was seen in alendronate users but not statistically significant. A similar trend for lower incidence of triple negative and higher incidence ER (P = 0.13), progesterone receptor (P = 0.12), and HER2 positivity (P = 0.21) was also seen in alendronate users but not statistically significant. Estimated median disease-free survival was 150 months in alendronate users where as 70 months in non-users (P = 0.015). Five-year survival rate in alendronate users was 97.4 %, whereas in non-users was 89.8 % (P = 0.13). The use of oral alendronate for longer than 1 year at the time of breast cancer diagnosis was associated with better clinico-pathological properties and significantly improved disease-free survival in breast cancer patients.

Recent studies have shown some degrees of discordance in ER, PR and HER-2 immunohistochemical expression between primary and recurrent/metastatic lesions (RML). Analysis was made on 78 patients with MBC whose ER, PR and/or HER-2 status were known both on the tissue samples of primary and RML. Among the RML sites, 29.5% were locoregional, 70.5% were distant metastatic sites. Among 75 patients with known ER expression on both primary and RML, 36% (n = 27) showed discordance on ER expression. Among 72 patients with known PR expression on both primary and RML, 54.2% (n = 39) showed discordance on PR expression. Among 61 patients with known HER-2 expression on both primary and RML, 14.7% (n = 9) showed discordance on HER-2 expression. No differences were observed when we compared patients who have discordant ER and HER-2 status with patients who have concordant results between the primary tumor and paired RML with respect to site of biopsy (locoregional vs distant metastasis) and prior therapies (chemotherapy and endocrine therapy). As these discordant results make changes in treatment decision, a biopsy of the metastatic lesion could be recommended in patients with MBC when feasible. Larger series are needed to identify the potential effect of prior therapies and site of metastasis on discordant results.

Esophageal carcinoma is an extremely deadly disease, and prognosis is poor. We retrospectively evaluated stage III esophageal carcinoma patients in our center. Median age of the patients was 52. Men to women ratio were 3/1. Epidermoid carcinoma was the major histology. Incidence of esophageal carcinoma was higher in the distal and middle third of the esophagus. In 19 patients tumor size was more than 5 cm. In total of 17 of the patients were operated. About 58 patients were irradiated. About 45 of the patients were irradiated with curative intent, 31 of them were primarily irradiated and 14 of them were irradiated postoperatively. Only 13 of the patients received concurrent chemoradiotherapy. Overall 1, 2, 3, and 4 year survival rates were 38.9%, 11.1%, 5.6%, and %1.9, respectively and median survival was 12 months. Median survival for tumors located in cervical esophageal, middle esophagus, and distal esophagus were 23, 8, and 14 months, respectively. One, 2, 3, 4 year survival rates of operated patients were 58.8%, 29.4%, 17.6%, 5.9%, respectively and median survival was 23 months. For inoperable patients 1 and 2 year survival rates were 29.7% and 2.7% and median survival was 8 months. Differences between operable and inoperable patients were statistically significant (P: 0.0003). One, 2, 3, 4 years survival results of patients treated with surgery and postoperative radiotherapy was 62.5%, 25%, 12.5%, 12.5% and median survival was 21 months, 1, 2, 3, 4 years survival results of patients treated with surgery and concurrent chemoradiotherapy was 55.6%, 33.3%, 22.2%, and 0% and median survival was 27 months. There was no statistically significant difference between groups (P: 0.5390). During the therapy, disphagia was the major side effect observed in seven patients. Fatigue, pain, and mild weight loss were the other side effects. Three patients could not tolerate the treatment and left the therapy. We demonstrated that stage III esophageal carcinoma is an extremely deadly disease, and in spite of major advances in cancer treatment, prognosis is still poor.

We performed retrospective review of 29 adult patients with cerebellar medulloblastoma/primitive neuroectodermal tumor (PNET) who received craniospinal radiotherapy in Ankara Oncology Hospital between years 2000 and 2005. All patients were operated followed by craniospinal irradiation; 11 of 29 patients also received chemotherapy. All patients had no distant or spinal metastases at the time of diagnosis. Median follow up time was 26 months. Progression-free survival was 86% at 2 years, 55% at 5 years. Mean progression-free survival was 25 months in patients with PNET; 61.4 months in patients with medulloblastoma (P = 0.0016). Mean survival was 61.33% months in patients25 age, 38 months in patients25 age. (P = 0.04). Overall mean survival was 59.80 months in patients who received chemotherapy and 41.4 months in patients who did not have chemotherapy (P = 0.15). Cranial relapses were observed in 3 of 29 patients, and 3 of 29 patients had distant metastases. The mean time to cranial recurrence was 19 months; to distant metastases was 18 months. In conclusion, adult patients with PNET have worse survival rates than patients with medulloblastoma, like in childhood patients. Patients younger than 25 years of age also had statistically significant better survival.

Primary thymic epithelial neoplasms (PTENs) are uncommon tumors of anterior mediastinum with a broad range of biological characteristics. We retrospectively reviewed 58 consecutive patients with a diagnosis of PTENs that were confirmed pathologically during 28 yr. There were 58 patients, 31 males (53.4%) and 27 females (46.6%), with a mean age of 43.6 +/-13.8 yr (range, 17-73 yr). Twenty-one (36.2%) patients presented at the Masaoka stage I, 13 (22.4%) patient at stage II, 18 (31.0%) patient at stage III, and 6 (10.4%) patients at stage IV. Forty-five (77.7%) patients had myasthenia gravis, 1 (1.7%) immune deficiency, 1 (1.7%) pancytopenia, and 1 (1.7%) nephrotic syndrome. No paraneoplastic syndrome was associated in 10 (17.2%) patients. Complete resection was accomplished in 41 (70.7%) patients, while incomplete resection was performed in 8 (13.8%) patients. In nine (15.5%) patients only biopsy was carried out. Radiotherapy was administered to 19 (32.8%) patients. Eleven (19.0%) out of 58 who presented at advanced stages (at least III) received chemotherapy. Median follow-up period was 59 mo (range, 1-278 mo). During the follow-up period, 17 deaths occurred. Five patients (29.4%) died of tumor-related causes, and the remaining 12 patients died of other causes (cardiovascular diseases [n = 1, 5.9%], sepsis [n = 4, 23.5%], and MG-related respiratory insufficiency [n = 7, 41.2%]). The overall survival rates at 5 yr and 10 yr were 63.9% and 54.2%, respectively. Tumor-related survival rates at 5 yr and 10 yr were 89.0% and 83.2%, respectively. In our series, disease stage, presence or absence of myasthenia gravis, and tumor size did not affect survival (p0.05), either. Complete resection of the tumor seems to be the best predictive factor for long-term survival.

WOS: 000250069000004, PubMed: 17917085, In this prospective study, we investigated the effects of hypofractionated radiotherapy for patients with high-grade gliomas. About 31 patients with glioblastoma multiforme or anaplastic astrocytoma were studied between October 2003 and December 2004. Hypofractionated radiotherapy (3 Gy/fraction/day) was delivered to a total dose of 45 Gy in 15 fractions in 10 patients (32%) who had total excision before radiotherapy and to a total dose of 54 Gy in 18 fractions in 21 patients (68%) who had subtotal excision or biopsy alone. Sex, age, type of surgery, tumor grade, Karnofsky performance status, time between surgery and initiation of radiotherapy, and total radiotherapy dose were analyzed as potential prognostic factors for survival using the univariate log-rank method. The median follow-up was 15 months (4-16 months). A total of 15 patients (48%) died of their illness; 16 patients (52%) were still alive at the last follow-up. The median survival time was 8 months. Actuarial 1-year overall survival was 40%. Type of surgery, timing of radiotherapy after surgery, and initial Karnofsky performance status were significant prognostic factors for survival. No grade 3-4 acute or late neurotoxicity was observed. The tolerance of patients to hypofractionated RT was not different from that for con- ventional radiotherapy. This treatment schedule can be used for patients with high-grade gliomas. Future investigations are needed to determine the optimal fractionation for high-grade gliomas.

Combined use of pentoxifylline and vitamin E is reported to reduce radiation-induced toxicity in normal tissues at molecular level. We plan to evaluate the role of combined use of pentoxifylline (PTX) and alpha-tocopherol (vitamin E; Vit E) for minimizing radiation-induced lung toxicity. A total of 91 lung cancer patients were randomized. Among them, 44 received PTX (400 mg three times a day orally and Vit E 300 mg twice a day orally during the entire period of radiotherapy. PTX and Vit E were further administered at doses of 400 mg once a day and 300 mg once a day, respectively for 3 months after radiotherapy. A total of 47 patients were assigned as a control group. Radiation related acute and late toxicities are evaluated by radiation RTOG/EORTC toxicity scale. Median age was 59 (range, 41-75). Median follow-up was 13 months (range, 3-28 months). Radiation-induced lung toxicity was more frequent in control group for all phases than in pentoxifylline and alpha-tocopherol group (acute phase, P = 0.042, subacute phase P = 0.0001, late phase P = 0.256). PTX and Vit E combination might be considered especially in patients with lung cancer who receive concurrent chemo-radiotherapy, or have a poor respiratory function tests.

To the editor, Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors, are widely used in both primary and secondary prevention of cardiovascular diseases [1]. Statins, by interrupting the pathway of mevalonate, inhibit several critical pathways for cancer growth and progression. In vitro studies showed that statins have antiproliferative, antiapoptotic, antiangiogenetic and immunomodulatory effect which prevent cancer growth [2]. A meta-analysis of randomized controlled trials failed to show reduced risk of breast cancer with statin use, but a meta-analysis of case controlled studies has showed reduced risk of breast cancer and any other cancer risk [3]. As a result of the published studies and meta-analyses, there were contradictory results with statin use on breast cancer risk. But the effect on clinical and pathological properties of breast cancer with statin use was not known exactly. In this study, we aimed to investigate retrospectively the effect of statin usage on clinicopathological characteristics and recurrence risk of patients with

The differential diagnosis of eosinophilia may sometimes be difficult. Eosinophilia may occur in a diverse array of conditions from parasitic infestations to malignacies. Idiopathic hypereosinophilic syndrome has also been described. A 65-year-old male patient presenting with eosinophilia of obscure etiology is described in the present report. Three years after the diagnosis of eosinophilia, metastatic anaplastic carcinoma of unknown primary was detected. Differential diagnosis is disscussed briefly. It is stressed that patients with hypereosinophilia of unknown etiology must be screened for malignancy regularly during follow up.

There was a contradictory data with metformin use on breast cancer risk, but there is growing evidence that the use of metformin in diabetic patients was associated with lower risks of breast cancer mortality and incidence. The effect of metformin on clinical and pathological properties of breast cancer was not known exactly, and we aimed to investigate the demographic and clinico-pathological characteristics of patients with metformin users at the time of breast cancer diagnosis. Patients with breast cancer diagnosed from 2000 to 2012 in our clinic were retrospectively analyzed. Patient's demographics, including survival data and tumor characteristics were obtained from medical charts. Breast cancer patients who were taking metformin at the time of breast cancer diagnosis were enrolled as metformin users (n = 148), where the patients matched with the same age who were not taking metformin were included as a control group (n = 636). A total of 784 patients were included in this study. Median age of both metformin users and nonusers was 57 (23-87). There were no significant differences in baseline tumor size (P = 0.60), tumor stage (P = 0.76), and node positivity (P = 0.13) between the two groups. Metformin user patients compared to nonusers had significantly lower incidence of histological grade III tumor (P = 0.03). A similar significant trend for lower incidence of triple negative (P = 0.01) and higher incidence ER positivity (P = 0.008) and PR positivity (P = 0.01) was also seen in metformin users. In survival analysis, the estimated median disease-free survival was 118 months in metformin users, whereas 69 months in nonusers (P = 0.09). Median overall survival (OS) could not be obtained due to low events. In patients with metformin users, OS rate was 98.4, 97.1, and 93.8 %, and in nonusers was 99.6, 94.4, and 90.5 %, the first, third, and fifth years, respectively. The use of metformin at the time of breast cancer diagnosis was associated with better clinico-pathological properties and nonsignificantly improved disease-free survival in breast cancer patients.

To the Editor, A 43-year-old woman had been operated for infiltrative ductal carcinoma of the left breast with modified radical mastectomy in 2006. She was staged as T2N1M0 disease with positive ER/PR and her2/neu. She was given 3 cycles of adjuvant chemotherapy with CEF (cyclophosphamide, epirubicin, 5-fluorouracil), followed by weekly paclitaxel for 12 weeks. She received radiotherapy to the chest wall and surrounding lymphatic regions for 5 weeks. Then, she received adjuvant tamoxifen for two years. Her breast cancer has been in clinical remission after an uneventful follow-up of three years. However, she has experienced gingival bleeding and thrombocytopenia in September 2009. Peripheral smear and bone marrow aspiration and biopsy revealed acute promyelocytic leukemia (APL) with chromosal abnormality of t (15; 17) on cytogenetic examination. Her medical history was noncontributory except for breast fibroadenoma for 20 years and hypothyroidism. The patient was diagnosed as APL secondary to adjuvant therapy for breast cancer, and treatment with alltrans retinoic acid and idarubicin was initiated. We present a rare case of therapy-related APL (classified as AML-M3 in the French-American-British (FAB) classification) that may have been caused by adjuvant chemotherapy and/or regional radiation for breast cancer. Chemotherapy and radiotherapy are important in breast cancer therapy for improving survival of women with high-risk breast cancer [1]. The most common adjuvant chemotherapy agents used for breast cancer are alkylating agents (cyclophosphamide) and anthracyclines (epirubicin, doxorubicin). Although these agents have beneficial effects for the breast cancer, secondary malignancy including acute myeloblastic leukemia (AML) or myelodysplastic syndrome (MDS) may develop with alkylating agents (within 2–3 years) and anthracyclines (within 3–8 years) after the initial cancer treatment [2–4]. The combinations of these leukemogenic antineoplastic agents including epirubicin and cyclophosphamide may increase the risk of treatmentrelated AML and/or MDS. Additionally, the use of regional irradiation for patients with node-positive breast cancer may contribute to this increased risk [5]. Different chromosal abnormalities, especially those involving loss of all or part of chromosome 5 and/or 7, are noted with therapy-related AML/MDS [6]. On the other hand, it has been shown that patients with breast cancer have a higher susceptibility to develop a second malignancy even among patients undergoing only surgical approaches [3, 7]. Although the overall risk for a second malignancy in female patients with breast cancer appeared to be small (20–30% excess risk), it has been established that young age at diagnosis predicts for an increased risk for second malignancy [8]. Age-specific incidences showed peak among women in 40s, and 2.02% of the patients developed secondary malignancy [8]. The series of secondary APL are mostly clustered in patients with breast cancer in the literature. Interestingly, there is a correlation between the BRCA2 mutation and the risk of hematologic malignancy, and that the break point on chromosome 17 in the t (15;17) translocation is at or near the location of BRCA2 [9]. It is also noteworthy that there is an increased incidence of hypothyroidism (as in our case) in acute leukemia patients at diagnosis [10]. Thyroid hormone and retinoic acid receptor genes belong to the same family of nuclear receptor gene superfamily, and thyroid hormones are important regulators of hematopoiesis using receptors similar to differentiating factors such as retinoids [10]. O. Kara E. Ozdemir C. Arslan E. Dogan K. Altundag (&) Department of Medical Oncology, Hacettepe University Institute of Oncology, Sihhiye, Ankara 06100, Turkey e-mail: altundag66@yahoo.com

To The Editor, Patients with breast cancer survive longer after advances in treatment options [1]. During their follow-up, they may develop secondary malignancies or became patients with breast cancer secondary to previously diagnosed malignancies. The aim of our study was to evaluate the other malignancies among patients with breast cancer. Between years 2004 and 2009, 987 consecutive patients with breast cancer presenting at Hacettepe University Institute of Oncology were evaluated retrospectively. Median follow-up of all patients was 3.6 years (range 0.3–28). Of all the study population, 19 (1.9%) had other malignancies. Among all patients with breast cancer, 14 and 5 patients developed secondary malignancies before and after the diagnosis of breast cancer, respectively. The most frequently observed ones were ovarian cancer. The frequency of other malignancies was shown in Table 1. Median age of breast cancer diagnosis was 49, while median age of previous malignancies was 45 years old. Patients with breast cancer can survive longer after the advances in treatments. This can cause enough time to develop secondary malignancies. Secondary malignancies may develop sporadically, or due to environmental factors, genetic susceptibility and treatment complications [2]. Ewertz et al. reported the risk of second primary cancer in approximately 55,000 patients with breast cancer. They found that risk of a developing second malignancy was 13% [3]. In our study, frequency of other malignancies was 1.9%. This is most probably due to the short follow-up period. In our series, nearly 50% malignancies diagnosed were gynecological tumors. Therefore, close follow-up of patients who had gynecological tumors is very important due to risk of developing secondary cancer, especially breast cancer.

To The Editor, Taxaneand anthracycline-containing chemotherapy regimens are commonly used for the treatment of breast cancer both in the adjuvant and in the neoadjuvant settings. Recently, there has been a concern about the sequencing of these two drugs. In a recent randomized phase III study by the Hellenic Oncology Research Group, three weekly docetaxel followed by epirubicin/cyclophosphamide (E/C) combination was compared with epirubicin/cyclophosphamide/5-fluorouracil (FEC) regimen as adjuvant chemotherapy in women with axillary node-positive early breast cancer (1). Five-year disease-free survival was found to be better in the sequential docetaxel followed by E/C group (72.6 vs. 67.2%, P = 0.041). Furthermore, the first report of the Neo-tAnGo study, a neoadjuvant randomized phase III trial of E/C and paclitaxel ± gemcitabin in high risk early breast cancer has also concluded that the sequence of taxane first regimen had a significant advantage in pathological complete response rate than sequence of anthracycline first regimen (20 vs. 15%, P = 0.03) (2). Some proposals were put forward for the mechanism of this sequencing. A study by Taghian et al. (3) evaluated the interstitial fluid pressure (IFP) and oxygenation before and after neoadjuvant chemotherapy with weekly paclitaxel and doxorubicin in breast cancer patients with a tumor size of C3 cm. Paclitaxel was found to significantly increase IFP and oxygenation, whereas doxorubicin not. Thus, paclitaxel may exhibit positive effects by altering the IFP barrier, which may restrict the tumor cells to enter the circulation. It may also increase the anthracycline drug concentration at tumor tissue level if taxane is given before the anthracyline administration. In conclusion, we propose that taxane followed by anthracycline administration may be a more optimal regimen than anthracycline first followed by taxane schedule for both neoadjuvant and adjuvant treatment of breast cancer patients. Further studies are needed to confirm this proposal.

To the Editor, We read with great interest the article by Bonomi et al. [1] in which they evaluated the renal toxicity and osteonecrosis of jaw (ONJ) in 398 cancer patients treated with bisphosphonates (BP). They found that 16 patients (4%) developed renal toxicity after a median of 24 months of BP treatment and 10 patients (2.5%) were diagnosed as having ONJ after a median of 39 months on BP. Concerning the renal safety of intravenous BP, we also want to give information about our study [2] in which we retrospectively evaluated 43 breast cancer patients with bone metastases who received zoledronic acid (ZA) more than 24 months. We also found no statistically significant differences in the preand post-treatment levels of serum creatinine, blood urea nitrogen. Our results also support the current study that patients treated with BP showed low incidence of renal toxicity. Concerning the ONJ, our previous study [3] performed in large series of cancer patients receiving IV BP showed that 16 of 1,338 patients with breast cancer (1.2%) and 13 of 548 patients with multiple myeloma (2.4%) developed ONJ. Supporting the current study that the median dose and duration of treatment with pamidronate or zoledronic acid in our study were significantly higher in patients with ONJ. In conclusion, BP clearly provides an important enhancement in the quality of life by reducing skeletal-related events and reducing pain. Osteonecrosis of the jaw and renal toxicities related to BP should be kept in mind especially in cancer patients receiving BP in long-term period.