Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

Body image disturbance and surgical decision making in egyptian post menopausal breast cancer patients

<p>Abstract</p> <p>Background</p> <p>In most developing countries, as in Egypt; postmenopausal breast cancer cases are offered a radical form of surgery relying on their unawareness of the subsequent body image disturbance. This study aimed at evaluating the effect of breast cancer surgical choice; Breast Conservative Therapy (BCT) versus Modified Radical Mastectomy (MRM); on body image perception among Egyptian postmenopausal cases.</p> <p>Methods</p> <p>One hundred postmenopausal women with breast cancer were divided into 2 groups, one group underwent BCT and the other underwent MRM. Pre- and post-operative assessments of body image distress were done using four scales; Breast Impact of Treatment Scale (BITS), Impact of Event Scale (IES), Situational Discomfort Scale (SDS), and Body Satisfaction Scale (BSS).</p> <p>Results</p> <p>Preoperative assessment showed no statistical significant difference regarding cognitive, affective, behavioral and evaluative components of body image between both studied groups. While in postoperative assessment, women in MRM group showed higher levels of body image distress among cognitive, affective and behavioral aspects.</p> <p>Conclusion</p> <p>Body image is an important factor for postmenopausal women with breast cancer in developing countries where that concept is widely ignored. We should not deprive those cases from their right of less mutilating option of treatment as BCT.</p

The effect of treatment interruptions in the postoperative irradiation of breast cancer

Objective: There is much evidence for the detrimental effect of treatment interruptions on tumor control, particularly in head and neck cancer. In order to determine the outcome of the treatment interruptions in postoperative irradiation of breast cancer, 853 female patients treated between 1990 and 1999 inclusive were retrospectively analyzed. Methods: Locally advanced breast cancer patients who received neoadjuvant chemotherapy were not included in the study. Five hundred and forty-six patients (64%) treated with mastectomy and 307 patients (36%) with breast-conserving surgery were analyzed. A total dose of 50 Gy (46-54 Gy) was given to the chest wall/breast and regional lymph nodes in 1.8- to 2-Gy daily fractions, 5 times per week. A 14-Gy (10- to 20-Gy) photon or electron boost was given to the tumor bed of the patients with breast-conserving surgery. Unplanned treatment interruptions occurred in 741 (87%) of the patients and the median duration of the gaps was 13 days (1-91 days). A total of 348 patients (41%) had no treatment break or interruptions of 1 week or less, whereas 505 patients (59%) had treatment interruptions of more than 1 week. The locoregional control (LC) and overall survival (OS) rates were estimated with the Kaplan-Meier method. A Cox proportional hazard regression model was used to evaluate the influence of host- and treatment-related factors on LC and OS (age, menopausal status, histological subtype, grade, hormonal receptor status, pT stage, pN stage, type of surgery, adjuvant treatment, number of gaps and duration of gaps). Results: For all patients LC rates for 5 and 10 years were 95 and 87%, respectively, and OS rates were 78% for 5 years and 62% for 10 years. LC rates for the group of patients with no treatment break or interruptions of 1 week or less, for 5 and 10 years were 94 and 90%, whereas the LC rates for 5 and 10 years were 89 and 86%, for the group of patients with interruptions of more than 1 week (p=0.019). Treatment interruptions of more than 1 week and premenopausal status appeared to be independent adverse prognostic factors in multivariate analyses affecting the LC (p=0.043 and p=0.005, respectively). The OS rates for the patients without treatment interruptions or interruptions of 1 week or less were also significantly better than for the patients with treatment interruptions of more than 1 week (p=0.026) in multivariate analyses. Conclusion: Interruptions more than 1 week during postoperative irradiation of breast cancer adversely affect the treatment outcome. Copyright (C) 2005 S. Karger AG, Basel

Continuous hyperfractionated accelerated radiotherapy in the treatment of high-grade astrocytomas

Between May 1993 and January 1995, 36 patients with high-grade astrocytomas were treated with 1.05 Gy continuous hyperfractionated accelerated radiotherapy three times daily to a total target dose of 59.85 Gy in 19 days with 6-h intervals. The median age of the patients was 51 years and the median follow-up was 58 weeks. The median survival rate was 58 weeks and the cumulative survival rare was 22% at 2 years, No severe toxicity occurred in patients treated with this fractionation scheme. These results suggest that continuous hyperfractionated accelerated radiotherapy is an altered fractionation schedule for: high-grade astrocytomas with tolerable acute toxicity and survival rates comparable to conventional fractionation and to other altered fractionation schedules. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved

Lymphoepithelioma-like carcinoma of the breast: is it a distinct entity? Clinicopathological evaluation of two cases and review of the literature

Lymphoepithelioma-like carcinomas (LELCs) are tumors with morphologic features identical to those of undifferentiated nasopharyngeal carcinoma. They are characterized by a pronounced lymphocytic infiltrate, often obscuring the neoplastic epithelial component. LELCs have been described in several organs, but are extremely rare in the breast. In this report, two cases of LELC of the breast are presented with their histological and immunohistochemical features. In situ hybridization for Epstein-Barr viral genome was negative in both cases. We discuss the differential diagnosis of LELC of the breast and review the reports of this entity that have appeared in the literature. (C) 2004 Elsevier Ltd. All rights reserved

Radiotherapy for breast cancer in countries with limited resources: Program implementation and evidence-based recommendations

Radiotherapy is an essential part of the multimodality treatment of breast cancer. Applying safe and effective treatment requires appropriate facilities, staff, and equipment, as well as support systems, initiation of treatment without undue delay, geographic accessibility, and completion of radiotherapy without undue prolongation of the overall treatment time. Radiotherapy can be delivered with a cobalt-60 unit or a linear accelerator (linac). In early stage breast cancer, radiotherapy is an integral part of breast-conserving treatment. Standard treatment includes irradiation of the entire breast for several weeks, followed by a boost to the tumor bed in women age 50 years or younger or those with close surgical margins. Mastectomy is an appropriate treatment for many patients. Postmastectomy irradiation with proper techniques substantially decreases local recurrences and improves survival in patients with positive axillary lymph nodes. It is also considered for patients with negative nodes if they have multiple adverse features such as a primary tumor larger than 2 cm, unsatisfactory surgical margins, and lymphovascular invasion. Many patients present with locally advanced or inoperable breast cancer. Their initial treatment is by systemic therapy; after responding to systemic therapy, most will require a modified radical mastectomy followed by radiotherapy. For those patients in whom mastectomy is still not possible after initial systemic therapy, breast and regional irradiation is given, followed whenever possible by mastectomy. For patients with distant metastases, irradiation may provide relief of symptoms such as pain, bleeding, ulceration, and lymphedema. A single fraction of irradiation can effectively relieve pain from bone metastases. Radiotherapy is also effective in the palliation of symptoms secondary to metastases in the brain, lungs, and other sites. Radiotherapy is important in the treatment of women with breast cancer of all stages. In developing countries, it is required for almost all women with the disease and should therefore be available