Oncology Treatments during the COVID-19 Pandemic in Israel: the ONCOR Study.

BACKGROUND: The increased susceptibility of cancer patients to coronavirus disease-2019 (COVID-19) infections and complications calls for special precautions while treating cancer patients during COVID-19 pandemics. Thus, oncology departments have had to implement a wide array of prevention measures. OBJECTIVES: To address issues associated with cancer care during the COVID-19 pandemic and to assess the implementation of measures aimed at containment of COVID-19 diffusion while allowing continuation of quality cancer care. METHODS: A national survey among oncology departments in Israel was conducted between 12 April 2020 and 14 April 2020. Eighteen heads of hospital-based oncology departments completed a self-report questionnaire regarding their institute's preparedness for treatment of cancer patients during the COVID-19 pandemic. RESULTS: In this national survey, prevention measures against COVID-19 spread were taken prior to patients' arrival and at arrival or while staying in the departments. Most participants (78-89%) reported using a quick triage of patients and caregivers prior to their entrance to the oncology units, limiting the entrance of caregivers, and reducing unnecessary visits to the clinic. Switching to oral therapies rather than intravenous ones when possible was considered by 82% and shortage in personal protective equipment was reported by five (28%) heads of oncology departments. Some differences between large and small/medium sized medical centers were observed regarding issues related to COVID-19 containment measures and changes in treatment. CONCLUSIONS: Oncology departments in Israel were able to prepare and adapt their services to guidelines and requirements related to the COVID-19 pandemic with little harm to their treatment capacity.

The yield of targeted genotyping for the recurring mutations in BRCA1/2 in Israel.

BACKGROUND: Hereditary breast cancer is predominantly associated with germline mutations in the BRCA1 or BRCA2 genes. A few recurring mutations in these genes were reported in ethnically diverse Jewish populations. Since 2013, most oncogenetic laboratories in Israel adopted a two-step approach for BRCA1/2 genotyping, where the first step is genotyping for 14 seemingly recurring mutations-first-pass genotyping. The aim of this study was to assess the yield of this targeted BRCA sequencing. METHODS: Clinical and genotyping data of all individuals who underwent oncogenetic counseling and first-pass BRCA genotyping at the Oncogenetic Service Sheba and Assaf Harofeh Medical Centers from 1 February 2013 to 30 June 2017 were reviewed. All study participants were unrelated to each other. RESULTS: Overall, 5152 oncogenetic tests were reviewed in the present study, of which 4452 had no a priori known familial mutation. The majority of participants (68.6%) were genotyped because of personal history of cancer; 20.6% were tested because of family history of cancer, and details for the remaining 10.7% were missing. Overall, 256/4452 (5.8%) carriers were detected, 141 BRCA1 and 115 BRCA2 mutation carriers. In 54% of cancer-free carriers, no clinically suspicious family history of cancer was ascertained. CONCLUSIONS: The currently used scheme of first-pass genotyping in Israel seems to have a high yield of mutation detection even in the absence of a significant family history of cancer. The challenge is to optimize the currently used targeted panel of common mutations and adjust it to the accumulating new data in the Israeli population.

Inherited predisposition to breast and ovarian cancer in non-Jewish populations in Israel.

PURPOSE: The contribution of genetic factors to cancer in non-Jewish populations in Israel is understudied. Yet the early, mostly premenopausal age at breast cancer diagnosis is suggestive of an inherited predisposition. METHODS: High-risk cancer cases of non-Jewish origin who were counseled at the Oncogenetics unit, Sheba Medical Center and the oncology institute at the Ziv medical center from January 1, 2000 to December 31 2016 were eligible. DNA extracted from leukocytes was subjected to massive parallel, next-generation sequencing using the Color Genomics platform. Data were analyzed for pathogenic and likely pathogenic mutations using existing pipelines. RESULTS: Overall, 68 cases, each representing a unique high-risk breast/ovarian family, were genotyped: 32 Druze, 26 Muslim Arabs, and 10 Christian Arabs. Fifty-nine had breast cancer (mean age at diagnosis 42.7 ± 7.6 years), and 9 had ovarian cancer (51.6 ± 9.7 years). Overall three pathogenic mutations one each in BRCA1, PALB2, and BRIP1 genes were detected mostly in Druze families. In addition, 29 variants of unknown significance were also detected, and in 36 cases no sequence variants were noted in any of the genotyped genes. CONCLUSION: The contribution of the known cancer susceptibility genes to the burden of inherited breast/ovarian cancer predisposition in non-Jews in Israel is modest. Other genes or molecular mechanisms account for the familial breast/ovarian cancer clustering in this population.

[EFFECT OF YOUNG AGE ON CLINICAL, PATHOLOGICAL FEATURES AND SURVIVAL OF PATIENTS WITH COLORECTAL CANCER].

BACKGROUND: Colorectal cancer is one of the most common malignancies in the Western World and in Israel. Most patients with colon cancer are older than 50 years of age. There is no consensus in the literature regarding the behavior of this disease in young patients. AIM: The aim of the present study is to compare clinical and ic pathological features of colon cancer between young and sold patients. METHODS: All clinical and pathological characteristics of 200 patients with colon cancer treated at our center during the period 2001-2006 were retrospectively reviewed. RESULTS: Twenty five patients (12.5%) were <50 years age (young patients) at diagnosis (mean age 41 years) and 175 were >50 years (mean age 68 years). Males were 56% of the young group and 60.1% of the old one. Arab patients were 52% of the young group, although their total number was 35 of the 200 patients. No significant difference was found in the stage of tumor at diagnosis between the two groups. Histopathological grade 3 tumors were found in 33.3% of young versus 7.7% in old patients. Surgery and chemotherapy were performed in 96% and 88% versus 95.4% and 69.7% in the two groups respectively. In a median follow-up period of 96 months, 35% of young patients died of their disease compared to 33.1% of the old patients. CONCLUSIONS: Other than histological grade, no difference was found in colon cancer features and survival of young compared to old patients. Further studies with higher numbers of patients are suggested to clarify our findings.

Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer.

IMPORTANCE: Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. OBJECTIVE: To identify mutation-specific cancer risks for carriers of BRCA1/2. DESIGN, SETTING, AND PARTICIPANTS: Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. EXPOSURES: Mutations of BRCA1 or BRCA2. MAIN OUTCOMES AND MEASURES: Breast and ovarian cancer risks. RESULTS: Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95% CI, 1.22-1.74; P = 2 × 10(-6)), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95% CI, 1.01-1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% CI, 1.22-1.55; P = 6 × 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% CI, 0.56-0.70; P = 9 × 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95% CI, 1.10-2.40; P = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% CI, 1.69-3.16; P = .00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% CI, 0.44-0.60; P = 6 × 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% CI, 0.41-0.80; P = .001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers. CONCLUSIONS AND RELEVANCE: Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.

Bleomycin-induced pneumonitis in three patients treated with chemotherapy for primary advanced seminoma.

PURPOSE: Bleomycin, etoposide and cisplatinum (BEP) comprise the most common regimen in the treatment of advanced testicular tumors, including seminoma. Common side effects are of hematologic, renal, and cardiovascular origin. One of the most prominent side effects is pulmonary toxicity attributed to bleomycin. We describe three patients who developed bleomycin-induced pneumonitis (BIP) with full recovery. METHODS: Pre-and post-treatment clinical, biochemical (including specific tumor markers) and radiological response assessment of 26 patients with primary advanced seminoma (AS) who were referred to our hospital for platinum-based chemotherapy between 1989-2010 are described. RESULTS: All patients were assessable for evaluation and all achieved long-term complete remission. Side effects were mild and manageable. Three patients developed bleomycin pulmonary toxicity after reaching cumulative doses of 180-240 units. All three patients presented with classical symptoms of non-productive cough, exertional dyspnea, and low-grade fever. Radiologically, the patients presented in the first months following completion of chemotherapy with initial bilateral interstitial and alveolar infiltrates, which worsened and progressed into consolidation and then regressed until total disappearance. All patients were treated with high-dose steroids and broad-spectrum antibiotics. CONCLUSION: AS is a very chemotherapy-responsive and sensitive disease, and approximately 90% of the patients enjoy complete regression of tumor masses and durable and sustained long-term survival with no evidence of disease. BIP may be a dangerous acute and chronic side effect, even in doses lower than 360 units. Considering the favorable clinical outcome of our patients, prompt diagnosis should be made and rapid medical intervention should be implemented.

Is salivary pH a marker of depression among older spousal caregivers for cancer patients?

The pH in saliva, which decreases due to the activation of the sympathetic nervous system, may serve as a biomarker of psychological distress in caregivers but has rarely been studied in this context. The aims are to examine the levels of salivary pH as a possible biomarker of depression among caregivers and whether depression mediates the association between caregiving status (cancer caregivers vs. non-cancer caregivers) and pH levels. Cross-sectional data were collected from 68 consecutive-sampled spouses of cancer patients, and 42 age-matched individuals. Lower levels of pH saliva were found among caregivers of cancer patients than in the comparison group. Being a caregiver, poor subjective health, higher depression, and lower mastery predicted lower pH levels. In addition, depression mediated the associations of mastery with pH levels. The study provides preliminary evidence that salivary pH may serve as an easily tested indicator of the stress of caregiving and its related depression.

Radiotherapy for Stage IIA seminoma: The Northern Israel Oncology Center Experience, 1971-2010.

AIM: To evaluate treatment details, outcome, relapse rate and side-effects in Stage IIA seminoma irradiated and followed for a period of 39 years. BACKGROUND: Seminoma is a very radiosensitive disease and radiation therapy alone is able to achieve long-term disease-free survival, even in advanced Stage disease. Due to the lack of long-term prospective studies, it is of value to follow patients and try to determine the appropriate volume to be irradiated and the dose which can achieve total cure with minimal acute and chronic side-effects. PATIENTS AND METHODS: A retrospective review of 24 Stage IIA seminoma patients irradiated between 1971 and 2010 was performed. All patients underwent orchiectomy and meticulous clinical, biochemical and radiological staging. RESULTS: Median age at diagnosis was 36 years and median follow-up was 84 months. A majority of patients received the "hockey-stick" irradiation schedule (para-aortic lymph nodes and hemi-pelvis) to a total dose of 2250-2500 cGy and a boost to radiologically involved nodes of 500-1000 cGy. Treatment was well-tolerated. Twenty-one (88%) patients are alive with no evidence of disease. Two patients died due to unknown causes, while one patient died due to head of the pancreas carcinoma, most probably radiation-induced. CONCLUSIONS: In Stage II seminoma, radiotherapy can provide excellent results with low rates of toxicity. Reduction of total dose and size of fields without affecting the good results should be considered. Due to prolonged survival, awareness of second primary tumor is indicated.

Arterial elasticity in obese subjects with coronary slow flow phenomenon.

BACKGROUND: Coronary slow flow phenomenon (CSFP) is a functional and structural disease that is diagnosed by coronary angiogram. OBJECTIVES: To evaluate the possible association between CSFP and small artery elasticity in an effort to understand the pathogenesis of CSFP. METHODS: The study population comprised 12 patients with normal coronary arteries and CSFP and 12 with normal coronary arteries without CSFP. We measured conjugated diene formation at 234 nm during low density lipoprotein (LDL) oxidation, as well as platelet aggregation. We estimated, noninvasively, arterial elasticity parameters. Mann-Whitney nonparametric test was used to compare differences between the groups. Data are presented as mean +/- standard deviation. RESULTS: Waist circumference was 99.2 +/- 8.8 cm and 114.9 +/- 10.5 cm in the normal flow and CSFP groups, respectively (P = 0.003). Four patients in the CSFP group and one in the normal flow group had type 2 diabetes. Area under the curve in the oral glucose tolerance test was 22% higher in the CSFP than in the normal group (P = 0.04). There was no difference in systolic and diastolic blood pressure, plasma concentrations of total cholesterol, triglycerides, high density lipoprotein, LDL and platelet aggregation parameters between the groups. Lag time required until initiation of LDL oxidation in the presence of CuSO4 was 17% longer (P = 0.02) and homocysteine fasting plasma concentration was 81% lower (P = 0.05) in the normal flow group. Large artery elasticity was the same in both groups. Small artery elasticity was 5 +/- 1.5 ml/mmHg x 100 in normal flow subjects and 6.1 +/- 1.9 ml/mmHg x 100 in the CSFP patients (P = 0.02). CONCLUSIONS: Patients with CSFP had more metabolic derangements. Arterial stiffness was not increased in CSFP.

Comprehensive Genetic Analysis of Druze Provides Insights into Carrier Screening.

BACKGROUND: Druze individuals, like many genetically homogeneous and isolated populations, harbor recurring pathogenic variants (PV) in autosomal recessive (AR) disorders. METHODS: Variant calling of whole-genome sequencing (WGS) of 40 Druze from the Human Genome Diversity Project (HGDP) was performed (HGDP-cohort). Additionally, we performed whole exome sequencing (WES) of 118 Druze individuals: 38 trios and 2 couples, representing geographically distinct clans (WES-cohort). Rates of validated PV were compared with rates in worldwide and Middle Eastern populations, from the gnomAD and dbSNP datasets. RESULTS: Overall, 34 PVs were identified: 30 PVs in genes underlying AR disorders, 3 additional PVs were associated with autosomal dominant (AD) disorders, and 1 PV with X-linked-dominant inherited disorder in the WES cohort. CONCLUSIONS: The newly identified PVs associated with AR conditions should be considered for incorporation into prenatal-screening options offered to Druze individuals after an extension and validation of the results in a larger study.

Differences in pathological and clinical features of breast cancer in Arab as compared to Jewish women in Northern Israel.

Breast cancer (BC) does not affect ethnic groups equally. BC mortality is higher in Israeli Palestinian Arab women than among Israeli Jewish women. This study aims to compare clinical, biological and pathological characteristics of breast cancer in the two populations. Records of 1,140 women with BC treated at Northern Israel between 2002 and 2007 were reviewed: 872 Jews and 268 Arabs. Age at diagnosis, tumor stage, pathological differentiation, estrogen receptor (ER) and HER-2 expression were evaluated. The main age at diagnosis was 49.9 years for Arabs and 59.4 years for Jews (p < 0.0001). Mean tumor size was < 2 cm in 25% of Arabs and 53% of Jews (p < 0.0001). Lymph node metastases presented in 64.6% of Arabs and 37.2% of Jews (p < 0.0001). Stage I disease was 19% in Arab and 49.2% in Jewish women while Stages III and IV disease was 42% and 11.3% respectively (p < 0.001). ER was positive in 69% of Arabs and in 78.5% of Jews (p < 0.001). Poorly differentiated tumors were found in 28.8% of Arabs vs. 12.8% in Jews (p < 0.0001). Overexpression of HER-2 was present in 35.4% of Arab and 22% of Jewish women (p < 0.001). We found that race is an important predictive factor for breast cancer. Arab women are diagnosed at younger age, with more advanced stage and biologically more aggressive disease than in Jewish women. Socioeconomic factors alone are not sufficient to explain significant effects of race on tumor characteristics. Findings suggest a different genetic susceptibility in the two populations which needs further research.

Recurrent germline mutations in BRCA1 and BRCA2 genes in high risk families in Israel.

The spectrum of germline mutations among Jewish non Ashkenazi high risk breast/ovarian cancer families includes a few predominant mutations in BRCA1 (185delAG and Tyr978X) and BRCA2 (8765delAG). A few additional recurring mutations [A1708E, 981delAT, C61G (BRCA1) R2336P, and IVS2 + 1G > A (BRCA2)] have been reported in Jewish non Ashkenazi families. The 4153delA*BRCA1 C61G*BRCA1 and the 4075delGT*BRCA2 has been reported to recur in Russian/Polish non Jews and Ashkenazim, respectively. The rate of these recurring mutations has not been reported in Israeli high risk families. Genotyping for these recurring mutations by restriction enzyme digest and sequencing method was applied to high risk, predominantly cancer affected, unrelated Israeli individuals of Ashkenazi (n = 827), non Ashkenazi (n = 2,777), non Jewish Caucasians (n = 193), and 395 of mixed ethnicity. Jewish participants included 827 Ashkenazi, 804 Balkans, 847 North Africans, 234 Yemenites, and 892 Asians (Iraq and Iran). Age at diagnosis of breast cancer (median ± SD) (n = 2,484) was 47.2 ± 9.6 for all women participants. Males (n = 236) were also included, of whom 24 had breast cancer and 35 had pancreatic cancer. Overall, 8/282 (2.8%) of the Balkan cases carried the BRCA1*A1708E mutation, 4/180 (2.2%) the R2336P mutation, and 0/270 the IVS2 + 1G > A BRCA2 mutations, respectively. Of North Africans, 7/264 (2.65%) carried the BRCA1*981delAT mutation. The BRCA1*C61G mutation was detected in 3/269 Ashkenazi, non Ashkenazi, and non Jewish Russians; the BRCA1*Tyr978X mutation was detected in 23/3220 individuals of non Ashkenazi origin, exclusively of Asian ethnicity (23/892, 2.6% of the Asians tested). The BRCA1*4153delA mutation was noted in 2/285 non Jewish Caucasians, and none of the Ashkenazim (n = 500) carried the BRCA2*4075delGT mutation. Jewish high risk families of North African, Asian, and Balkan descent should be screened for the 981delAT, Tyr978X, A1708E BRCA1, and the R2336P BRCA2 mutations, respectively.

First-line treatment with capecitabine combined with irinotecan in patients with advanced colorectal carcinoma: a phase II study.

GOALS: To evaluate the efficacy and toxicity of capecitabine with irinotecan as first-line treatment in metastatic colorectal cancer. BACKGROUND: The addition of irinotecan to infusional 5 fluorouracil and leucovorin significantly improves the response rate and survival compared with 5 fluorouracil/leucovorin alone in metastatic colorectal cancer. Capecitabine with irinoteacan was reported to yield comparable results in phase II studies. STUDY: Patients older than 75 years, Eastern Cooperative Oncology Group ≤0 to 3, with measurable disease, no previous treatment for advanced disease, previous adjuvant chemotherapy >6 months, and adequate hepatic, renal, and hematological function were included. The treatment protocol included capecitabine 1000 mg/m twice daily given for 14 days (days 1 to 14) and irinotecan (100 mg/m) given on days 1 and 8. Treatment was repeated on day 21. RESULTS: Thirty patients were included. All were assessable for response and toxicity. Average age was 64 years, male/female ratio 20/10. Fifteen had liver metastases; 9 had abdominal metastases; 5 had liver and lymph nodes metastases; and 1 had lung metastases. The median number of cycles was 8. Grades III and IV diarrheas were observed in 20%, mild vomiting in 20%, grades III and IV leukopenia in 23%, and hand and foot syndrome grade III in 1 patient (3%). A complete response was achieved in 3 (10%) patients, a partial response in 16 (53%), disease stabilization in 6 (20%), and tumor progression in 5 (17%). Progression-free survival was 8.4 months. Overall survival was 19.3 months. CONCLUSIONS: This regimen was provided on an outpatient basis with significant antitumor activity and without the need for indwelling catheters and seems to be feasible for patients of all ages, with acceptable toxicity.

Germline mutations in BRCA1 and BRCA2 genes in ethnically diverse high risk families in Israel.

Three mutations in BRCA1 (185delAG, 5382InsC) and BRCA2 (6174delT) predominate among high risk breast ovarian cancer Ashkenazi Jewish families, with few "private" mutations described. Additionally, the spectrum of BRCA1 and BRCA2 germline mutations among high risk Jewish non Ashkenazi and non Jewish Israelis is undetermined. Genotyping by exon-specific sequencing or heteroduplex analysis using enhanced mismatch mutation analysis was applied to 250 high risk, predominantly cancer affected, unrelated Israeli women of Ashkenazi (n = 72), non Ashkenazi (n = 90), Moslem (n = 45), Christian Arabs (n = 21), Druze (n = 17), and non Jewish Caucasians (n = 5). All Jewish women were prescreened and did not harbor any of the predominant BRCA1 or BRCA2 Jewish mutations. Age at diagnosis of breast cancer (median ± SD) (n = 219) was 40.1 ± 11.7, 45.6 ± 10.7, 38.7 ± 9.2, 45.5 ± 11.4 ± and 40.7 ± 8.1 years for Ashkenazi, non Ashkenazi, Moslem, Christian, and Druze participants, respectively. For ovarian cancer (n = 19) the mean ages were 45.75 ± 8.2, 57.9 ± 10.1, 54 ± 8, 70 ± 0, and 72 ± 0 for these origins, respectively. Overall, 22 (8.8%) participants carried 19 clearly pathogenic mutations-10 BRCA1 and 9 BRCA2 (3 novel): 3 in Ashkenazim, 6 in 8 non-Ashkenazim, 6 in 7 Moslems, 2 in Druze, and 2 in non Jewish Caucasians. Only three mutations (c.1991del4, C61G, A1708E) were detected in 2 seemingly unrelated families of Moslem and non- Ashkenazi origins. There were no inactivating mutations among 55 Ashkenazi high risk breast cancer only families. In conclusion, there are no predominant recurring germline mutations in BRCA1 or BRCA2 genes among ethnically diverse Jewish and non Jewish high risk families in Israel.

Curcuma as a functional food in the control of cancer and inflammation.

PURPOSE OF REVIEW: Several nutritional compounds are the focus of public attention because of their potential beneficial health effects. Turmeric is a spice that comes from the root Curcuma longa. Extensive research over the past half century and especially in recent years has revealed important functions of curcumin and a timely review of clinical state-of-the-art using curcumin. RECENT FINDINGS: In-vitro and in-vivo research has shown various activities, such as anti-inflammatory, antiviral, antifungal, cytokines release, antioxidant, immunomodulatory, enhancing of the apoptotic process, and antiangiogenic properties. Curcumin also have been shown to be a mediator of chemo-resistance and radio-resistance. SUMMARY: Various in-vitro and in-vivo and scarce number of clinical studies on curcumin were identified. The various effects and properties of curcumin are summarized in this review, including preclinical and especially clinical studies. This review concentrates on recent knowledge and research with curcumin clinical applications, and clinical studies, focusing on studies published between 2008 and 2011 demonstrating the gap between preclinical and clinical research.

Comparison of Arab breast cancer survivors and healthy controls for spousal relationship, body image, and emotional distress.

BACKGROUND: Cultural perceptions and norms affect individuals' psychological reactions to cancer and quality of life, but very few studies have assessed reactions to breast cancer in specific cultural groups. Such assessments are especially rare for Arab women with breast cancer. AIMS: To assess the effect of spousal support, sharing household tasks, and body image in relation to emotional distress in Arab breast cancer survivors compared with matched healthy controls. METHOD: Fifty-six Israeli Arab breast cancer survivors (stages I-III), and 66 age- and education-matched women answered Brief Symptoms Inventory-18, Perceived Body Image, Perceived Spousal Support and Division of Household Labor scale questionnaires. RESULTS: Breast cancer patients experienced higher psychological distress, especially anxiety and somatization. They reported receiving more support from their spouses and higher sharing of household tasks than did matched healthy controls, but were not different regarding body image. Twenty-eight percent of the variance of psychological distress was explained, with group, perceived support, and group × body image interaction. Thus, higher psychological distress was more likely to occur in participants receiving lower support and in breast cancer survivors with lower body image. CONCLUSIONS: The study described the effects of breast cancer on Arab women compared to healthy women. It highlights the need for culture-sensitive care for Arab breast cancer patients, as well as other patients from minority groups residing in other Western countries.

Effect of letrozole on plasma lipids, triglycerides, and estradiol in postmenopausal women with metastatic breast cancer.

PURPOSE: The aromatase inhibitor letrozole effectively treats breast cancer by decreasing estrogen levels in postmenopausal women. The aim of this prospective study was to evaluate the effect of letrozole on plasma lipids, triglyceride lipase (TGL), and estradiol levels in women with metastatic breast cancer (MBC). MATERIALS AND METHODS: Fifty-two postmenopausal women with MBC received letrozole, 2.5 mg/day. Blood samples for assessment of plasma levels of total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, TGL, and estradiol were taken at baseline and after 3, 6, and 12 months of treatment. RESULTS: A nonsignificant increase was found in TC and HDL cholesterol levels after 3 months, which returned to baseline levels after 6 months (p = .794 and p = .444, respectively). LDL cholesterol increased nonsignificantly after 6 months and returned to baseline thereafter (p = .886). The mean estradiol level was suppressed from 44 pmol/l before treatment to <18 pmol/l after 6 months (p = .014). No difference was found in the estradiol suppression rate whether baseline levels were >40 or <40 pmol/l. CONCLUSION: Letrozole has a safe effect on the lipid and TGL profiles of postmenopausal women with MBC. Estradiol levels were maximally suppressed within 6 months of treatment. The increased levels of TC during treatment were reversible and returned to normal levels after 3 months.

A novel MSH2 germline mutation in a Druze HNPCC family.

Germline mutations in DNA mismatch repair (DNA-MMR) genes, mainly MLH1, MSH2, and MSH6, underlie Hereditary non-polyposis colorectal cancer (HNPCC) and are mostly family-specific, with few reported founder mutations in MSH2 (Ashkenazim) MLH1 (Finnish). No mutations in colon cancer susceptibility genes have ever been reported in Druze individuals, a Moslem related faith encompassing approximately 1,000,000 individuals worldwide. A novel MSH2 mutation is described in a Druze HNPCC family: a multigenerational family with 10 members in 4 generations affected with colorectal cancer (mean age of diagnosis 46.5 years), two with gastric cancer and one--endometrial cancer. Mutational analysis of the MSH2 gene using denaturing gradient gel electrophoresis (DGGE) and direct sequencing revealed the c.702delA mutation in codon 234 of exon 4 of the MSH2 gene leading to a premature early stop in codon 245, p.Thr234fsX245. Analysis of mutation-carrying or presumed carriers individuals' offspring, revealed 11/42 asymptomatic mutation carriers, age range 17-50 years. The mutation was not present in two additional Druze HNPCC families and 20 Druze sporadic colon cancer patients. This is the first mutation ever reported in a colon cancer susceptibility gene in a Druze family and it appears not to be a founder mutation in Druze individuals with HNPCC.

Outcome after combined modality treatment for uterine papillary serous carcinoma: a study by the Rare Cancer Network (RCN).

OBJECTIVES: Uterine papillary serous carcinoma (UPSC) is a rare subtype of endometrial carcinoma, characterized by a poor outcome. We sought to better analyze the effect of surgery and adjuvant therapies on this disease. METHODS: A retrospective analysis was performed on the records of 138 women diagnosed with UPSC between 1986 and 2003 in the framework of the Rare Cancer Network. RESULTS: Median age at diagnosis was 67 years. Pure UPSC was found in 107 patients and mixed histology in 30. Fifty-four patients had stage I, 20 stage II, 41 stage III and 23 stage IV disease. Median follow-up for the surviving patients was 44 months. Surgery was performed in 129 patients, after which 122 were rendered free of gross disease and comprised the adjuvant group. Of these, 23 received platinum-based chemotherapy. Radiotherapy was applied in 52 patients and 28 underwent combined chemo-radiotherapy. At last follow-up, 57 patients were alive free of disease, 10 were alive with disease, 62 died of disease, 8 died of other causes and 1 died due to toxicity. Five-year disease-free survival (DFS), disease-specific survival (DSS) and overall survival for the 122 patients treated with curative intent were 42%, 56% and 54%, respectively. In multivariate analysis, age, stage, histology and adjuvant chemotherapy were significant for DFS; age, stage and histology were significant for DSS. Radiotherapy reduced the pelvic recurrence rate from 29% to 14% (p=0.047). CONCLUSIONS: UPSC harbours a moderate prognosis, with age, stage and histology as significant prognosticators. Conservative surgery followed by adjuvant chemotherapy and pelvic radiotherapy can be suggested as an appropriate treatment approach for patients treated with curative intent.

Ezetimibe's effect on platelet aggregation and LDL tendency to peroxidation in hypercholesterolaemia as monotherapy or in addition to simvastatin.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Statins demonstrate a pleiotropic effect which contributes beyond the hypocholesterolaemic effect to prevent atherosclerosis. WHAT THIS STUDY ADDS: Ezetimibe has an antioxidative effect when given as monotherapy or as an add-on to the statin, simvastatin. AIMS To investigate the effect of lowering low-density lipoprotein-cholesterol (LDL-C) on platelet aggregation and LDL tendency to peroxidation by ezetimibe alone or with simvastatin in hypercholesterolaemia. METHODS: Sixteen patients with LDL-C >3.4 mmol l(-1) received ezetimibe for 3 months (Part I). Twenty-two patients on fixed simvastatin dose with LDL-C >2.6 mmol l(-1) were enrolled (Part II). Part II patients continued simvastatin treatment 20 mg day(-1) for 6 weeks, then received 20 mg day(-1) simvastatin combined with ezetimibe 10 mg day(-1) for another 6 weeks. The tendency of LDL to peroxidation measured by lag time in minutes required for initiation of LDL oxidation and by LDL oxidation at maximal point (plateau) was measured before and after ezetimibe treatment. RESULTS: Part I: Ezetimibe 10 mg daily for 3 months decreased plasma LDL-C level 16% (P = 0.002), prolonged lag time to LDL oxidation from 144 +/- 18 min to 195 +/- 16 min (P < 0.001), decreasing maximal aggregation from 83 +/- 15% to 60 +/- 36% (P = 0.04). Part II: Serum level LDL-C decreased 23% (P = 0.02) and lag time in minutes to LDL oxidation was prolonged from 55.9 +/- 16.5 to 82.7 +/- 11.6 (P < 0.0001) using combined simvastatin-ezetimibe therapy. There were no differences in platelet aggregation. CONCLUSIONS: Ezetimibe was associated with decreased platelet aggregation and LDL tendency to peroxidation. Treatment with ezetimibe in addition to simvastatin has an additive antioxidative effect on LDL.