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Inflammatory breast carcinoma (IBC) is the most aggressive, lethal, and rare form of breast cancer. IBC is characterized by the rapid development of erythema, edema, and peau d’orange over a third or more of the skin of the breast due to the occlusion of dermal mammary lymphatics by tumor emboli. IBC is associated with rapid progression, with a high risk of axillary lymph node involvement and distant metastases at initial diagnosis. The most striking progress in the management of IBC has been the sequential incorporation of preoperative systemic chemotherapy [an induction regimen containing an anthracycline and a taxane (plus trastuzumab in HER2-positive patients)], followed by surgery and radiation therapy. This multidisciplinary approach has essentially transformed IBC from a uniformly fatal disease with 5-year overall survival rates of less than 5 % to one in which 5-year overall survival rates range from 46 % to 61 % and 15-year survival rates vary between 20 % and 30 %. The response to primary chemotherapy is a strong indicator of survival. The 15-year survival rate is 44 % in patients who achieve a pathological complete response after primary chemotherapy. In this chapter, preoperative systemic therapy for the disease is discussed after a brief outline of inflammatory breast carcinoma.

WOS: 000473357300009, PubMed ID: 31312795, Objective: Breast cancer is a heterogenous disease, and genetic profiling helps to individualize adjuvant treatment. The Oncotype DX is a validated test to predict benefit of adjuvant systemic treatment. The aims of this study are to determine the costs of chemotherapy in government hospitals in Turkey and evaluate the cost-effectiveness of the Oncotype DX from the national insurance perspective. Materials and Methods: A Markov model was developed to make long term projections of distant recurrence, survival, quality adjusted life expectancy, and direct costs for patients with ER+, HER2-, node-negative or up to 3 node-positive early stage breast cancer. Turkish decision impact study patient data were captured for model reference. In that study, ten academic centers across Turkey participated in a prospective trial. Of 165 patients with pT1-3, pN0-N1mic, ER-positive, and HER-2 negative tumors, 57% had low recurrence score (RS), 35% had intermediate RS, and 8% had high RS, respectively. The overall rate of change in chemotherapy treatment decisions following Oncotype DX was 33%. Results: The cost of adjuvant chemotherapy in public hospitals was estimated at $3.649, and Oncotype Dx test was $5.141. Based on the cost-effectiveness analysis, Oncotype DX testing was estimated to improve life expectancy (+0.86 years) and quality-adjusted life expectancy (+0.68 QALYs) versus standard care. The incremental cost-effectiveness ratio (ICERs) of Oncotype DX was estimated to be $7207.9 per QALY gained and $5720.6 per LY gained versus current clinical practice. Conclusion: As Oncotype DX was found both cost-effective and life-saving from a national perspective, the test should be introduced to standard care in patients with ER+, HER-2 negative early-stage breast cancer in Turkey.

Inflammatory breast carcinoma (IBC) is the most aggressive, lethal, and rare form of breast cancer and is characterized by the rapid development of erythema, edema, and peau d’orange over a third or more of the skin of the breast due to the occlusion of dermal mammary lymphatics by tumor emboli. IBC is associated with rapid progression, with a high risk of axillary lymph node involvement and distant metastases at initial diagnosis. The treatment plan is preoperative systemic chemotherapy [an induction regimen containing an anthracycline and a taxane (plus trastuzumab in HER2-positive patients)], followed by surgery and radiation therapy. The 5-year overall survival rate was less than 5% with only surgery, but with this multidisciplinary approach, the overall survival rates now range from 46% to 61%, and the 15-year survival rates vary between 20% and 30%. The response to primary chemotherapy is a strong indicator of survival. The 15-year survival rate is 44% in patients who achieve a pathologic complete response after primary chemotherapy. In this chapter, preoperative systemic therapy for the disease is discussed after a brief outline of inflammatory breast carcinoma.

WOS: 000397930400218 … Genekor The study was supported by a grant provided by Genekor.

Staging systems are essential for understanding disease, in predicting the outcome, and therapeutic decision making in any tumor as well as chronic lymphocytic leukemia (CLL). In this study, we compared the clinical correlation of the Rai and Binet classification systems in 133 CLL patients. The distribution of 133 patients according to the Rai system was as follows, stage 0:17, I:13, II:45, III:30, IV:28, and in the Binet system stage A:35, B:40, C:58 patients. Median survival of patients according to the Rai staging system was >67.0, >91.0, 63.8, 20.9 and 9.8 months, and >91.0, 63.4, 16.0 months according to Binet, respectively. Although no difference was found between Rai stages 0, I, II (p > 0.05) in terms of median survival, the difference between these stages and stages III and IV was statistically significant (p < 0.05). In the Binet staging system statistically significant survival difference was found between all stages (p < 0.05). We concluded that although both systems are comparable in terms of staging and predicting the outcome of patients with CLL, the Rai staging system appears to have an advantage over the Binet system by defining a subset of patients with excellent prognosis (stage 0) which is included within stage A of the latter.

Aims and Background Capecitabine, as all fluoropyrimidines, interferes with vitamin metabolism and may thus have an impact on hematopoiesis. It is metabolized to its active form 5-fluoruracil by the enzyme thymidine phosphorylase, which exists in higher concentrations in tumor tissue and liver than in normal tissues. In the study, we investigated the changes in mean corpuscular volume (MCV) of red blood cells and the possible correlation of these changes with the clinical outcome of capecitabine treatment in women with metastatic breast cancer. Methods and Study Design Data from 75 metastatic breast cancer patients were analyzed retrospectively. Capecitabine was used at a dose of 2500 mg/m2 daily for 14 days of every 3-week period. Mean corpuscular volume of red blood cells and other parameters of complete blood count were recorded at the beginning of the treatment, in the ninth week, and periodically thereafter. Results Mean age was 51.5 ± 10.8 and 61.3% of the patients were premenopausal. Capecitabine was administered as the median 3rd line (min-max: 1–9) treatment and a median of 6 cycles (min-max: 1–24) for metastatic breast cancer. Median ΔMCV level (post-treatment values at ninth week - baseline) was 8. ΔMCV was ≥8 in 37 patients and Conclusions Capecitabine increases the mean corpuscular volume levels of red blood cells by a yet unidentified mechanism. Early increment of mean corpuscular volume levels is higher than 8, i.e. by the 9th week, might predict clinical benefit from the treatment.

The aim of this study was to evaluate the response characteristics of vincristine, adriamycin and dexamethasone (VAD) as a first-line chemotherapy and to determine the efficacy of maintenance alpha-interferon (alpha-IFN) in multiple myeloma (MM). Between January 1985 and December 1994, a prospective trial was performed in stage II and III MM patients. The study population received only VAD with no maintenance therapy before 1990 (n=31), and those recruited after 1990 (n=33) were planned to be maintained with alpha-IFN (5 mU, 3 times per wk) during the plateau to a maximum of 2 yr. Median follow-up duration (44 vs. 39 months), time to response (3.4 vs. 3.5 months) and rate of objective response (61.3%, 19/31 and 63.6%, 21/33) were similar in VAD-only and VAD+IFN groups, respectively. The survival analyses revealed higher median progression-free (39.6 vs. 12 months) and overall survival (65+ vs. 24 months) durations in VAD+IFN group compared to VAD-only group. VAD regimen was well tolerated and IFN-related side effects were reversible. These findings denote that IFN maintenance prolongs the duration of response obtained by VAD.

WOS: 000382992100003, PubMed ID: 28331745, Objective: Breast cancer is the most common malignancy among Turkish women and the rate of early stage disease is increasing. The Oncotype DX 21-gene assay is predictive of distant recurrence in ER-positive, HER2-negative early breast cancer. We aimed to evaluate the correlations between Recurrence Score (RS) and routine risk factors. Materials and Methods: Ten academic centers across Turkey participated in this prospective trial. Consecutive patients with breast cancer who had pT1-3, pN0-N1mic, ER-positive, and HER2-negative tumors were identified at tumor conferences. Both pre- and post-RS treatment decisions and physician perceptions were recorded on questionnaire forms. Correlations between RS and classic risk factors were evaluated using univariate and multivariate analyses. Results: Ten centers enrolled a total of 165 patients. The median tumor size was 2 cm. Of the 165 patients, 57% had low RS, 35% had intermediate RS, and 8% had high RS, respectively. Multivariate analysis indicated that progesterone receptor (PR) and Ki67 scores were significantly related to RS. Conclusion: Oncotype DX Recurrence Score does not seem to have a significant correlation with the majority of classic risk factors, but it may have a correlation with PR score and Ki67 score., Genomic Health (Inc.; California, USA), Genomic Health (Inc.; California, USA) has provided an educational grant for the genomic testing in this trial.

WOS: 000453611000008, PubMed ID: 27081583, Introduction: Breast cancer is the most common malignancy among Turkish women and the rate of early stage disease is increasing. The Oncotype DX (R) 21-gene assay is predictive of distant recurrence in ER-positive, HER2-negative early breast cancer. We aimed to evaluate the impact of the Recurrence Score (R) (RS) on treatment decisions and physician perceptions in Turkey. We also studied correlations between RS and routine risk factors. Patients and Methods: Ten academic centers across Turkey participated in this prospective trial. Consecutive breast cancer patients with pT1-3, pN0-N1mic, ER-positive, and HER2-negative tumors were identified at multidisciplinary tumor conferences. The initial treatment decision was recorded before tumor blocks were sent to the central laboratory. Each case was brought back to tumor conference after receiving the RS result. Both pre- and post-RS treatment decisions and physician perceptions were recorded on questionnaire forms. Correlations between RS and classical risk factors were evaluated using univariate and multivariate analyses. Results: Ten centers enrolled a total of 165 patients. The median tumor size was 2 cm. Of 165 patients, 57% had low RS, 35% had intermediate RS, and 8% had high RS, respectively. The overall rate of change in treatment decision was 33%. Initially, chemotherapy followed by hormonal therapy (CT+HT) was recommended to 92 (56%) of all patients, which decreased to 61 (37%) patients post-RS assay (p

To evaluate the efficacy of postoperative radiotherapy and to investigate prognostic factors for early-stage cervical cancer patients. From December 1993 to December 2001, 141 patients with stage I-II cervical cancer without para-aortic lymph node (LN) metastases and treated by surgery and postoperative radiotherapy (RT) were included in this study. Indications for postoperative external RT were based on pathologic findings, including LN metastasis, positive surgical margins, parametrial involvement, pT2 tumor, and presence of any two minor risk factors like lymphvascular space involvement, deep stromal invasion, and tumor diameter between 2-4 cm. Sixty-six (47%) patients received RT alone, whereas 59 (42%) were treated with RT and concomitant chemotherapy (CT), and 16 received neoadjuvant CT. Patients with positive vaginal margins also received 27.5 Gy high-dose rate vaginal cuff brachytherapy in five fractions. Median follow-up time was 55 months. The actuarial 5-year overall (OS), disease-free (DFS), locoregional recurrence-free (LRFS), and distant metastases-free (DMFS) survival rates are 70%, 68%, 77%, and 88%, respectively. Univariate and multivariate analyses revealed that level and number of metastatic LNs and concomitant CT were unique significant prognostic factors for OS, DFS, and LRFS. Endometrial involvement, on the other hand, was proven to be significant for DFS and DMFS. Patients with less than three LN metastases or having only obturator LN involvement showed similar prognosis with their counterparts having no LN metastases. On the other hand, patients with either common iliac LN or more than three LN metastases had significantly worse outcome. Our results indicate that level and number of metastatic LNs are the most important prognostic factors determining the survival rates, and patients with upper lymphatic involvement or more than three metastatic LNs seem to need more effective treatment approaches.

Objective: To report 2 cases of severe hypertriglyceridemia associated with the use of oral capecitabine. Case Summaries: The first patient was a 73-year-old woman with metastatic breast carcinoma who received capecitabine 2500 mg/m2/day in 2 divided doses for 2 weeks followed by a one week rest period. The baseline triglyceride level was 324 mg/dL; after 2 cycles of capecitabine, levels increased to 916 mg/dL. Although lipid-lowering treatment was initiated, triglyceride levels peaked at 1782 mg/dL by the end of the seventh cycle. Eight weeks after capecitabine treatment was stopped, triglyceride levels decreased to 118 mg/dL. The second patient was a 59-year-old man with metastatic colorectal carcinoma who was placed on capecitabine treatment at a dosage of 2500 mg/m2/day in 2 divided doses for 2 weeks followed by a one week rest period. The baseline triglyceride level was 244 mg/dL; levels peaked at 1455 mg/dL at the end of the fifth cycle. Capecitabine treatment was discontinued due to disease progression, and triglyceride levels decreased to 154 mg/dL after 11 weeks. Discussion: The most frequently reported adverse effects of capecitabine are gastrointestinal and hematologic effects and palmar-plantar erythrodysesthesia. Drug-induced hyperlipidemia may appear more readily in individuals with hereditary lipoprotein lipase deficiency because decreased lipoprotein lipase activity might make these individuals more susceptible to a rise in triglyceride levels. The Naranjo probability scale indicated a probable relationship between capecitabine and severe hypertriglyceridemia. Conclusions: Capecitabine should be prescribed with care, especially in patients with preexisting hypertriglyceridemia. The question of whether capecitabine actually causes hypertriglyceridemia needs careful consideration, and the possible mechanism by which it may cause this adverse effect requires further investigation.

Our primary objective was to determine the response rate; secondary objectives were to assess the toxicity rate, and disease-free and overall survival rates in patients with locally advanced breast cancer (LABC) receiving a cyclophosphamide (500 mg/m2), mitoxantrone (12 mg/m2) and 5-fluorouracil (500 mg/m2) (CMF) chemotherapy regimen.The data from 74 patients with LABC with neoadjuvant CMF chemotherapy were analyzed retrospectively. Preoperatively, all patients received 3 cycles of CMF on day 1, repeated every 21 days. In 3 (4.1%) patients, breast-conserving surgery was given and in 71 (95.9%) modified radical mastectomy. All patients received radiotherapy and 3 additional cycles of CMF chemotherapy after surgery.Median age of the patients was 47 years (range: 17-74). 43 patients were premenopausal, whereas 31 were postmenopausal. 54 patients were in stage IIIA, and 20 were in stage IIIB. The overall clinical response rate was 88%; 11 (14.9%) had a complete response, 54 (73%) had a partial response, and 2 (2.8%) had progression. 14 (18.9%) had a pathological complete response. The median follow-up was 62 months. The median disease-free survival was 64.9 months, and the median overall survival was 97.5 months. The 5-year disease-free and overall survival rates were 52% and 79.9%, respectively. Most frequent side-effects were nausea/vomiting, mucositis, alopecia and leukopenia.The CMF regimen has a high overall response rate and an acceptable side effect profile in the treatment of locally advanced breast cancer. Further studies are needed to evaluate its effectiveness in breast-conserving strategies.

Aims and background We evaluated the efficacy and tolerability of weekly irinotecan as a second-line treatment in patients with colorectal cancer failing 5-fluorouracil-based chemotherapy and searched for predictive and prognostic factors. Methods A total of 36 patients were included. Median age was 53 years (range, 33-72). One treatment cycle consisted of irinotecan, 100 mg/m2 weekly, for 4 weeks followed by a 2-week rest. Gender, age, primary site, number of metastatic sites, histologic subtype, differentiation, pretreatment CEA, CA 19-9 and lactate dehydrogenase levels and marker response to treatment were investigated as predictive factors for response to treatment and as prognostic factors in the overall survival and time to progression of the patients. Results A total of 120 cycles (median, 3 cycles) was delivered. An overall 14% objective response rate (1 complete and 4 partial responses) was achieved. The median response duration was 4 months (range, 2-7). Another 36% of the patients had stable disease for a median duration of 4 months (range, 2-8). Median time-to-disease progression was 4 months and overall median survival was 12 months (95% confidence interval, 9-15). Pretreatment serum CA 19-9 level and marker response to two courses of treatment were found to be clinically significant in time to progression and overall survival. Younger age (≤45 years) was a poor prognostic factor associated with a shorter time to progression. The major toxicity was grade 3-4 diarrhea, which occurred in 28% of the patients, and treatment was discontinued in 3 (8%) patients due to toxicity. Other hematological and non-hematological toxicities were mild and manageable. Conclusions We concluded that weekly irinotecan at the dose of 100 mg/m2 is an effective and tolerable treatment option, with a 50% disease control rate, for patients with colorectal cancer failing previous 5-fluorouracil-based chemotherapy.

Primary breast carcinoma is the commonest neoplasm in women. Although rare, metastases of solid tumors from elsewhere to the breast may occur. Apart from cross-lymphatic metastasis from contralateral primary breast carcinoma, hematopoietic neoplasms occasionally involve the breast. As far as we know, less than 500 patients with secondary extramammary solid neoplasms involving the breasts have been reported in the English literature, of which malignant melanoma and lung tumors constitute the leading cause. Herein, five additional adult cases are reported and literature is reviewed. Two of the patients had primary rhabdomyosarcomas, two ovarian carcinomas, and one colon carcinoma. In one case with ovarian carcinoma, breast mass was the only manifestations of the disease relapse. All, except one with disseminated disease, had pathological diagnosis. Two of the patients died soon after the detection of breast metastasis. As a result, breast mass can be the first manifestation of relapse or part of a disseminated disease, and usually predicts poor survival.

Cancer is the uncontrolled division and accumulation of cells in any part of the body. Surgery, radiotherapy, and systemic therapies are the main treatment strategies against cancers. However, systemic chemotherapy has various side effects, including nausea, vomiting, myelosuppression, cardiotoxicity (with anthracyclines), neurotoxicity (with mitotic spindle poisons), and nephrotoxicity (with platinum analogs). Although surgery can be curative in some cases, the main purposes of cancer treatments, especially in metastatic cancer patients, are the palliation of symptoms and increasing survival with better quality of life. Increasing the efficacy and decreasing the toxicity of chemotherapeutic agents are currently the main challenges in cancer treatment, for which substantial effort has been given for years. Melatonin is a hormone produced in the pineal gland from the essential amino acid tryptophan. It is one of the strongest antioxidants identified, with additional chemopreventive, oncostatic, and tumor inhibitory effects in a variety of in vitro and in vivo experimental cancer models. In addition to melatonin synthesis, tryptophan is involved in numerous metabolic activities in the human body, including the biosynthesis of serotonin, kynurenine, and nicotinamide, thereby regulating circadian rhythm, learning, memory, sleep, behavior, mood, appetite, aging, growth, reproduction, immune system, and cancer development. Therefore, tryptophan-related metabolic pathways and catabolites have gained considerable attention, especially in improving cancer treatment and predicting disease activity as well as patient survival. This chapter mainly focuses on the relationship between tryptophan metabolism and chemotherapy; the prognostic value of tryptophan catabolites as cancer biomarkers, tryptophan metabolism, and cancer-related fatigue; the association between melatonin and cancer therapy as well as chemotherapy side effects; and the significance of chronochemotherapy after an initial brief introduction about chemotherapeutic agents.

PubMedID: 24338610 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. © 2013, The Japanese Breast Cancer Society.

Aims and background Sixty-three patients with local-regionally advanced breast cancer were treated with neoadjuvant chemotherapy consisting of docetaxel (Taxotere), epirubicin, and 5-fluorouracil (TEF). Methods and study design Preoperatively, patients received four cycles of Taxotere (80 mg/m2), epirubicin (60 mg/m2), and 5-fluorouracil (500 mg/m2), repeated every 21 days. Following completion of four cycles of chemotherapy, appropriate surgery was performed. After the surgery, patients received one cycle of the TEF chemotherapy regimen; following chemotherapy, radiotherapy was applied, and at the end two more cycles of TEF chemotherapy regimen were given. Results Sixty-three patients with locally advanced breast cancer were treated. Three patients were excluded from the study before the evaluation of response. Median age of the patients was 50 years (range, 25–77). Twenty-seven and 33 patients were premenopausal and postmenopausal, respectively. Thirty-nine patients were in stage IIIA and 21 in stage IIIB. Complete and partial responses were observed in 15 (25%) and 42 (70%) of the patients following four cycles of preoperative TEF chemotherapy regimen, respectively. Overall response was 95%, and primary lesion progressed only in 3 (5%) patients. The mean disease-free survival was 15.9 ± 6.8 (range, 3.5–28) months and the mean overall survival was 18.6 ± 7.2 (range, 5–30) months. The most frequent side effects were nausea-vomiting, mucositis, alopecia and leukopenia. Conclusions TEF therapy is a treatment with a high overall response rate and toxicities similar to other taxotere combinations. A longer follow-up of patients is necessary for the determination of disease-free survival and overall survival.

A patient with dysphagia and a history of breast cancer 11 yr ago was admitted to the hospital. A tumor presumably originating from the esophagus was detected. It could not be surgically removed and biopsy revealed adenocarcinoma. The patient received radiotherapy and chemotherapy consisting of etoposide, adriamycin, and cisplatin. An unexpectedly good response was achieved and the possibility of metastatic breast cancer was reinvestigated. Biopsy specimens showed positive estrogen and progesterone receptor staining. Tamoxifen treatment was started. The patient is well after 5 yr following relapse. Solitary esophageal metastasis of breast cancer is a rare event, especially after a remission period lasting more than a decade. Dysphagia in breast cancer patients should raise the suspicion of metastatic disease as well as esophageal cancer and benign strictures.

Objectives In this study, we tried to evaluate the efficacy of locoregional treatment (LRT) in patients with metastatic breast carcinoma (MBC). Materials and methods The medical records of 227 patients with MBC at initial presentation between April 1999 and January 2013 were retrospectively evaluated. The median age at diagnosis was 50 years (range, 27–83 years). Thirty-nine patients (17%) had no LRT. Among patients who had LRT, 2 (1%) had locoregional radiotherapy (RT) alone, 54 (29%) had surgery alone [mastectomy, n = 50; breast conserving surgery (BCS), n = 4] and 132 (70%) had surgery (mastectomy, n = 119; BCS, n = 13) followed by locoregional RT. Results The median follow-up time was 35 months (range, 4–149 months). Five-year OS and PFS rates were 44% and 20%, respectively. In both univariate and multivariate analysis LRT per se did not affect OS and PFS rates. However, the 5-year OS and PFS rates were significantly higher in patients treated with locoregional RT than the ones who were not. The corresponding rates were 56% vs. 24% for OS and 27% vs. 7% for PFS ( p Conclusion Our study showed that patients with MBC who received postoperative locoregional RT may have a survival advantage compared with patients who were only treated by surgery. A phase III trial testing the role of adjuvant locoregional RT may help to distinguish patients who will benefit from adjuvant RT.

The aim of this study is to evaluate clinicopathologic characteristics and the multi-disciplinary treatment results of metaplastic breast cancer (MBC) patients treated in a single institute. Seventeen female patients with MBC treated in our department between June 2000 and January 2012 were identified and retrospectively evaluated. The median age at diagnosis was 46 years (range, 26-66 years). The median tumor size at diagnosis was 3.5 cm (range 1.5-12 cm). Six (35%) patients underwent breast conservation surgery and 11 (65%) mastectomy. Axillary lymph node metastasis was found in 6 (35%) patients. Twelve (71%) had triple negative tumors. Postoperative RT and systemic adjuvant treatment was given to all patients accordingly to stage and biological characteristics. Median follow-up time was 27 months (range, 12-151 months). At the time of this analysis, 14 (82%) patients were alive with no evidence of disease, and 1 (6%) was alive with disease. The 3-year OS was 91% and 5-year 80%, and DFS rates were 76% and 76%, respectively. Despite the young age of our patients with mostly high grade tumors, larger tumor size and higher rates of lymph node metastasis, the survival outcomes in our study are favorable in comparison with previously reported series.

Background. Metastasis to the breast from extramammary malignancies is rare. Case. A 35-year-old woman presented with bilaterally inflammatory breast involvement, 2 years after the diagnosis of stage IIIC epithelial ovarian cancer. Neoplastic tissue was immunohistochemically positive using antibodies against OC125 and negative for gross cystic disease fluid protein-15 (BRST-2) and estrogen receptor in biopsy material in the breast. Combination chemotherapy consisting of paclitaxel, cisplatin, and anthracycline was started. She died 18 months after the breast metastasis. Conclusion. Ovarian carcinoma usually presents with signs and symptoms related to the tumor burden within the abdominal cavity. The finding of isolated, distant metastases such as breast involvement without intraabdominal disease is extremely rare. Determining the origin of the primary tumor is important in directing the actual therapy.

Our objective was to assess the efficacy of a standard dose ifosfamide and doxorubicin containing regimen in the treatment of advanced soft tissue sarcomas. Forty consecutive patients with a median age of 35.5 years were treated. Ifosfamide was administered at a dose of 2.5 g/m(2)/day as 72-hour continuous infusion with mesna at the same dosage and schedule. Doxorubicin was given at the dose of 60 mg/m(2)/day as 2-hour infusion on day 1. Six patients had a complete response (15%), and 9 (22.5%) had a partial response, fourteen patients (35%) stable disease, and 11 (27.5%) did not respond to chemotherapy. The median duration of response was 13 and 5 months for the complete and partial responders, respectively. The median survival was 37 months. Febrile neutropenia was encountered in 9 cases (22.5%). The present ifosfamide and doxorubicin combination is a moderately effective and well-tolerable regimen in the treatment of advanced soft tissue sarcomas.

This study was undertaken to define the natural history and treatment results of patients with primary breast non-Hodgkin's lymphoma (NHL). Twelve female patients who had been followed at Hacettepe University Hospital between 1973 and 1997 were retrospectively evaluated. All patients presented with breast masses (6 in the right breast and 6 in the left) that had recently enlarged. The most common histologic subtype was diffuse, small cleaved-cell lymphoma. Chemotherapy regimens were employed in 9 patients. Radiotherapy was delivered to the breast and its lymphatics in 8 patients. Lumpectomy, simple or modified radical mastectomy was performed in 5 cases. An objective response was attained with surgery, chemotherapy, or radiotherapy alone in 2, 1, and 1 cases, respectively. Combined modality treatment including either two or three modalities was successful in 7 cases. The median progression-free and overall survival times were 49 and 56 months, respectively. Although primary NHL of the breast is a rare disease compared to carcinoma, it should be considered in the differential diagnosis of breast masses.

Two consecutive phase II clinical studies were designed to evaluate the efficacy and safety of bolus and continuous infusion (CI) mitoxantrone (MTZ) in 39 patients with newly diagnosed acute lymphocytic leukemia (ALL). MTZ was used as part of the classical ALL induction regimen. Twenty patients were treated with bolus MTZ (10 mg/m2 for 3 days) combined with vincristine and prednisone. The same regimen was given to a second set of 19 patients, except that MTZ was administered as a 24-hr CI. Both groups received bimonthly intensifications with vincristine and prednisone for 3 years, along with oral maintenance therapy. Patients in the CI-MTZ study arm received additional MTZ on the first day of intensification cycles. Seventeen patients (85%) in the bolus arm and 15 patients (79%) in the CI arm achieved complete remission (CR). Median disease-free survivals (DFS) in the bolus and CI groups were 11 and 15 months after median follow-ups of 16 (3.5-96) and 13 (2.3-32) months, respectively. At 2.5 years, DFS rates were 29.4% and 34.4% in the bolus and CI groups (p > 0.05). There were no significant differences between two groups in rates of early death, degree of organ toxicity, or duration of neutropenia and thrombocytopenia. Significant cardiac toxicity was not observed in either group. Bolus or CI administration of MTZ was equally effective and was well tolerated. Neither the mode of administration nor increasing the dose intensity of MTZ by incorporating intensification cycles reduced relapse rates. Development of new antileukemia agents and novel treatment approaches are still needed to improve the high relapse rates in adult ALL once a complete response is achieved.

Aims and background Ifosfamide is an active alkylating agent in the treatment of breast cancer, as a first-line therapy and in advanced disease. Since the combination of etoposide with an alkylating agent produces a synergistic and tolerable activity in various malignancies, in the present study, ifosfamide and etoposide were administered to patients with advanced breast cancer to evaluate the response characteristics and the toxicity profile. Study design The combination of ifosfamide, mesna and etoposide was prospectively administered to 41 previously treated patients with stage IV breast carcinoma. The treatment schedule consisted of ifosfamide, 1500 mg/m2, infused over 24 hrs with 1500 mg/m2 mesna on days 1 to 5 and 120 mg/m2 etoposide, infused over 1 hr on days 1 to 3, to be repeated every 4th week. Results After a median follow-up of 10 months, an objective response rate of 23% (overall 2.5% complete remission and 20.5% partial remission) and a median response duration of 5.3 months were obtained in 39 assessable patients. The non-responder group consisted of 28.3% stable disease and 48.7% progressive disease. The prior status of chemotherapy was the only significant prognostic factor with an impact on the response rate. The overall toxicity was generally mild, with grade 3 myelotoxicity encountered in 25.7% of patients. Conclusions The tolerable side effect profile of the ifosfamide and etoposide combination might be advantageous as regards the quality of life. To improve the rate and/or the duration of response and to clarify the precise role of the ifosfamide-etoposide combination in previously treated advanced breast cancer, further trials are warranted.

A total of 370 patients with metastatic breast, carcinoma who had been followed at Hacettepe Oncology Department between 1980 and 1991 were retrospectively analyzed for the factors influencing the distribution of metastases and survival. Median age was 47 years. Radical or modified radical mastectomies were performed in 199 (53.8%). Infiltrative ductal carcinoma was the most common pathologic subtype (69.4%). In 191 patients who were evaluated for estrogen receptor (ER) status, 101 (52.9%) were positive and 90 (47.1%) were negative. The distribution of first metastases did not differ between the soft tissue, bone, and visceral sites. The second, third, and fourth metastases were more common in visceral sites (p < 0.05). ER and menopausal status did not affect distribution. Mortality rate was significantly lower in the group having the first metastasis to the bone (p < 0.05). Of interest, first metastases were predominantly found in visceral sites in patients having radical or modified radical mastectomies (p < 0.05). Response to therapy, presence of initial metastases, axillary status, and age were the important factors influencing the overall survival in univariate analysis, whereas response to therapy, ER status, age, and presence of initial metastases were the important factors according to the multivariate analysis.

This study was aimed to evaluate the efficacy of G-CSF (Granulocyte colony stimulating factor) administration to 37 patients with neutropenia following intensive combination chemotherapy. The patients were divided into two subgroups including solid tumors given ifosfamide and etoposide combination chemotherapy (IMET subgroup) and acute myeloid leukemia (AML) patients treated with mitoxantrone and cytarabine. Control group consisted of 31 acute myeloid leukemia patients. G-CSF was started on the first day of absolute neutropenia until the absolute neutrophil count was above 1000/mm(3) for two consecutive days. G-CSF was found to be effective for early recovery of neutrophil count. Expected response was achieved within 14 days in 91.5% of the courses with a median of fifth day of G-CSF treatment. In conclusion, this study showed the efficacy of G-CSF in early recovery of neutrophil count without any reduction in the incidence of febrile episodes and documented rates of bacterial and fungal infections in patients with acute myeloid leukemia.

The ifosfamide, mesna and epirubicin (IMEpi) combination is administered to 16 patients having advanced metastatic breast carcinoma as second-line chemotherapy. We observed complete response in 6%, partial response in 44% (total overall response rate of 50%), stable disease in 12% and progressive disease in the remaining 38% of the patients. The median remission duration in responders was calculated to be 9.6 months. IMEpi regimen had a tolerable toxicity profile including alopecia, nausea and vomiting, microscopic hematuria, leukopenia and neurotoxicity in which serious complications necessitating discontinuation of the chemotherapy were not encountered. It might be concluded that IMEpi chemotherapy combination is an effective alternative among schedules in the management of patients with stage IV breast carcinoma without serious side effects.

The incidence of multiple primary cancers is reported to be 0.3-4.3%.A 70-year-old man was admitted to the hospital because of fatigue, weight loss, epigastric pain with melena. A biopsy taken from a tumoral lesion in the gastric corpus revealed squamous cell carcinoma. A nodular lesion was also detected on the nasal columella and biopsy from this lesion also showed squamous cell carcinoma. Computed tomography performed as a part of metastatic work-up revealed a lesion in the left pulmonary lower lobe. Bronchoscopic biopsy from this lesion also demonstrated squamous cell carcinoma.We report a case with synchronous squamous cell carcinoma of the lung, skin and stomach and discuss the multiple synchronous occurrence of carcinoma with the same histopathology in different sites with a review of the literature.

The diagnosis of cervical squamous cell carcinoma with concurrent T-cell rich B cell lymphoma in dissected lymph nodes has not been reported to our knowledge. In our case, the biopsy of an exophytic lesion at the uterine cervix showed squamous cell carcinoma in a 50-year-old woman presenting with postcoital bleeding. Type III hysterectomy, bilateral salpingo-oophorectemy, bilateral pelvic, para-aortic lymph node dissections were performed. Pathologic examination revealed a T-cell rich B cell lymphoma in some lymph nodes beside squamous cell carcinoma in several of others. ELISA for human immuno-deficiency virus (HIV) was negative. The cervical carcinoma was staged as FIGO clinical stage IB1 and the lymphoma as Ann Arbor IIA. Six cycles of CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolon) chemotherapy for the lymphoma and concomitant pelvic chemoradiotherapy with cisplatin for cervical cancer were given. In this rare coincidence, the best available therapy for each of the diseases should be considered individually. We also suggest that HIV screennig test be carried out, because both diseases may be related to human immuno-deficiency virus, although our patient is HIV-negative.

The aim of this prospective clinical study is to evaluate the relationship between changes in functional cardiac parameters following anthracycline therapy and carbonyl reductase 3 (CBR3p.V244M) and glutathione S transferase Pi (GSTP1p.I105V) polymorphisms. Seventy patients with normal cardiac function and no history of cardiac disease scheduled to undergo anthracycline chemotherapy were included in the study. The patients' cardiac function was evaluated by gated blood pool scintigraphy and echocardiography before and after chemotherapy, as well as 1 year following therapy. Gene polymorphisms were genotyped in 70 patients using TaqMan probes, validated by DNA sequencing. A deteriorating trend was observed in both systolic and diastolic parameters from GG to AA in CBR3p.V244M polymorphism. Patients with G-allele carriers of GSTP1p.I105V polymorphism were common (60%), with significantly decreased PFR compared to patiens with AA genotype. Variants of CBR3 and GSTP1 enzymes may be associated with changes in short-term functional cardiac parameters.

Paclitaxel is highly active against a variety of solid tumors including breast lung, ovarian and head and neck cancer. Although peripheral neurotoxicity is well-known side effect, central nervous system (CNS) toxicity-related standard dose of paclitaxel is extremely uncommon, because paclitaxel dose not cross the blood–brain barrier and is not detectable in the cerebrospinal fluid. We present a patient with advanced stage breast carcinoma who developed acute and spontaneous resolving encephalopathy after weekly dose of paclitaxel. The patient did not have brain metastasis, or prior whole-brain irradiation, or any type of neurosurgery. Radiological imaging studies showed no abnormalities. CNS toxicity of paclitaxel should be kept in mind in patients without a previous history of brain metastasis or brain irradiation and even with low weekly doses.

Purpose: Assessment of expression levels of Wwox, Wwox-interacting proteins Ap2α, Ap2γ, and ErbB4, the Ap2γ transcriptional target protein Her2, and the possible Ap2α transcriptional target PrkaRIα, in breast cancers, to determine their roles in tamoxifen resistance. The hypothesis was that sequestration of Wwox interactors in the cytoplasm might control tamoxifen response. Experimental Design: Tissue sections from 51 tamoxifen-sensitive and 38 tamoxifen-resistant, estrogen receptor α–positive breast cancers were stained for the above proteins, as well as progesterone receptor (PR). The relation of tamoxifen resistance and other clinical features, with level of expression of these proteins, and pairwise correlations among various immunohistochemical markers were determined. Results: Menopausal status, tumor, node, and stage, loss of PR, lost or reduced expression of Wwox, and high level of expression of PrkaRIα, Ap2γ, and Her2 were significantly correlated with tamoxifen resistance. In multivariate analysis, Wwox, PrkaRIα, Ap2γ, and ErbB4 were found to be independent markers of tamoxifen resistance. Reduced Wwox expression was better than PR in prediction of resistance, especially in high-risk patients, and nuclear Ap2γ expression was better than Her2, especially in low-risk patients. Conclusion: The results illustrate the complex relationships among the marker proteins assessed in this in vivo study and suggest new markers for prediction of response to tamoxifen treatment as well as possible new targets for treatment of breast cancer. Wwox and Ap2γ emerge as new biomarkers that may be superior to PR and Her2 in predicting tamoxifen response.

The purpose of this study was to compare the effect of paclitaxel plus platinum-based chemotherapy in the treatment of extraovarian peritoneal serous papillary carcinoma (EPSPC) and ovarian serous papillary cancer (OSPC). Only the patients treated with initial surgery plus postoperative adjuvant chemotherapy and having FIGO stage IIIC disease with omental and/or peritoneal involvement were analyzed. Thirty-two patients with EPSPC and 43 with OSPC were included in this study. The median age, mean CA-125, and volume of ascitis were higher in patients with EPSPC. There was no significant difference between the two groups with respect to other prognosticators. The median overall survival (OS) durations were 30 months (95% CI 24.8-35.3) in patients with EPSPC and 28 months (95% CI 21.1-34.9) in those with OSPC (P= 0.35). The 3-year OS rates in the patients and controls were 28% and 31%, respectively (P= 0.84). In patients with EPSPC, only optimal cytoreduction was significantly related to progression-free survival and OS durations as a prognostic factor. In the EPSPC group, 65.5% of the patients (19/29) had lymphatic involvement, compared to 88.4% (38/43) in the OSPC group (P= 0.02). As an adjuvant therapy, the paclitaxel plus platinum-based combination regimen had similar effects on survival in the EPSPC and OSPC groups.

In this study, tumour tissue samples of 85 primary breast cancer patients were evaluated for phosphatase and tensin homolog deleted on chromosome ten (PTEN), cyclin D1 and P27/Kip1 expression patterns. The results were correlated with clinicopathological parameters. Loss of PTEN protein expression was present in 32.5% of the cases. Cyclin D1 was overexpressed in 54.2% and P27/Kip1 in 89.3% of the cases. Statistically significant associations were found between PTEN and cyclin D1 expression patterns, and cyclin D1 expression and tumour size.

The FHIT and WWOX genes encompass the FRA3B and FRA16D fragile sites at chromosomes 3p14.2 and 16q23.3, respectively. Reduced Fhit and Wwox expression has been reported in approximately two-thirds of invasive breast tumors. Expression of these fragile gene products, as well as ErbB2 and p53, were evaluated immunohistochemically in 44 pure and 31 adjacent-to-invasive ductal carcinoma in-situ (DCIS) cases. Reduced Fhit and Wwox expression were observed in (i) 70% and 68% of pure DCIS; (ii) 52% and 55% of DCIS adjacent-to-invasive tumor cases; and (iii) 20% and 50% of adjacent normal tissue in pure DCIS cases. Reduced Wwox expression in adjacent normal tissue was observed in 30% of cases in the DCIS adjacent-to-invasive group. Reduced Fhit and Wwox expression was observed in 61% of adjoining invasive tumors. In all normal, pure DCIS, and DCIS adjacent-to-invasive lesions, Fhit and Wwox expression was positively associated (P = 0.034, P = 0.042, P = 0.004, respectively) and in the invasive component there was a positive trend toward association (P = 0.075). Fhit and Wwox were more frequently reduced in high-grade lesions in the DCIS adjacent-to-invasive (P = 0.025, P = 0.004, respectively). In the pure DCIS group, there was a statistically significant negative association between Fhit and ErbB2 expression in DCIS (P = 0.035). In summary, reduced Fhit and Wwox expression in in-situ breast cancer was associated, which may contribute to the high-grade DCIS-invasive tumor pathway.

The incorporation of a taxane into an anthracycline-containing regimen in the adjuvant treatment of breast cancer is a promising approach. In this study, we aimed to evaluate the safety and efficacy of four cycles of FEC (fluorouracil 500 mg/m(2), epirubicin 70 mg/m(2), cyclophosphamide 500 mg/m(2), every 3 weeks) followed by four cycles of paclitaxel (175 mg/m(2) every 3 weeks) in the adjuvant treatment of node-positive and other high-risk breast cancer patients. A total of 88 female patients were enrolled. Mean age (&PLUSMN; SD) of the patients was 47 &PLUSMN; 10 (min: 24; max: 71). The patients were followed for a median of 48 months ( min: 20; max: 64). The most common side effects were nausea-vomiting ( grade I-II: 91%; grade III: 2%), as well as hematological toxicity ( grade I-II: 70%; grade III: 3%). Although all patients experienced some degree of toxicity, it was severe enough to be classified as grade III or IV in only 10 (11%) of the cases. Of note, six (8%) patients had grade I and only one (1%) had grade II cardiotoxicity. No grade III or IV cardiotoxicity was observed. The full eight cycles of study treatment could be administered to 75 patients (85%). Side effects necessitated the reduction of the doses of FEC and paclitaxel in one ( 1%) and three patients ( 3%), respectively. Median overall ( OS) and disease-free survival (DFS) have not yet been reached. Five-year OS and DFS have been estimated to be 78% and 61%, respectively. We conclude that FEC followed by paclitaxel is a well-tolerated and feasible regimen in the adjuvant treatment of early breast cancer. Its efficacity is comparable with other commonly used regimens and merits evaluation in a phase III study.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) is characterised by a rare multisystem disorder of unknown pathogenesis. Although its pathophysiology is not well understood, overexpression of proinflammatory cytokines has been implicated. Gastrointestinal system disorders have not been reported among the components of the syndrome. A case is reported of POEMS syndrome with gastrointestinal involvement shown by gastrointestinal endoscopy.

Background: Alprazolam, a newer benzodiazepine, may be useful in the control of nausea and vomiting in breast cancer patients. Methods: Nineteen operable breast cancer patients were included in this randomized prospective crossover open-label trial. Patients received either granisetron (G) alone, or in combination with alprazolam (A). Group A patients received G+A first and then crossed over to G-alone after the 2nd or 3rd cycle. Group B patients received the reverse order. Eighty-four cycles were evaluated. Results: In group A, complete remission (CR) plus major response (MR) was higher (93.9%) with G+A than with G-alone (83.3%; p = 0.0001) in the first 24-hour period. In group B, CR plus MR was higher in G+A cycles (100%) than in G-alone cycles (85.7%; p = 0.035) in the 24-hour period and in the 25- to 129-hour period (92 vs. 90.5%, respectively; p = 0.022). Conclusion: Alprazolam increases the efficacy of granisetron in patients with breast cancer treated with an anthracycline-containing regimen.

Objective: In this study, we evaluated the efficacy and tolerability of biweekly irinotecan (CPT11) plus 5-fluorouracil (5-FU) and folinic acid (FA) regimen (IFL) in patients with advanced stage colorectal cancer. Methods: A total of 28 patients were examined. The median age was 51 years (range, 30–74 years). One treatment cycle consisted of CPT-11 180 mg/m 2 on days 1 and 15; 5-FU 425 mg/m 2 on days 1, 2, 15 and 16; and FA 20 mg/m 2 on days 1, 2, 15 and 16, every 4 weeks. A total of 119 cycles (median, 4.0 cycles) were administered. Of the 28 patients, 18 received the chemotherapy as first line treatment, seven received it as second line and three received it as third line. Results: An overall objective response rate of 21.5% was achieved in the patient group. However, the overall response rate for the 18 patients receiving first line treatment was 27.7%. The median response duration was 10.5 months (range, 3–19 months). An additional 28.6% of the patients had stable disease for a median duration of 6.5 months (range, 3–8 months). Median time to disease progression was 4.5 months (range, 1–22+ months) and median overall survival time was 11+ months (95% confidence interval, 9–15 months). Toxicities were mild and manageable. Conclusions: We conclude that biweekly IFL is a practical and tolerable treatment option with a disease control rate of 50.1% in patients with advanced stage colorectal cancer.