Expression of Estrogen Receptor Alpha and Beta in Breast Cancers of Pre- and Post-menopausal Women

Expression of estrogen receptors (ER) is clinically relevant in designing therapeutic strategies. The relative importance of the two types of estrogen receptors (ER-alpha and ER-beta) in human breast cancers in pre- and post-menopausal women has not been properly defined. To determine the possible association between the expression of estrogen receptor and serum estradiol levels in pre- and post-menopausal women with breast cancer. 44 patients with invasive ductal carcinoma of the breast were studied and a breast tissue biopsy was taken. ER-alpha and ER-beta were detected by immunocytochemistry. Serum levels of estradiol and estrone were measured by radioimmunoassay and FSH was measured using IRMA. We studied 21 pre- and 23 post-menopausal women with breast carcinoma. Examining the number of cases with tumors positive for ER, we found no differences in the frequency of ER-alpha between pre- and post-menopausal women, but ER-beta decreased marginally after menopause (p < 0.051). In cases with tumors positive for ER, the proportion of cells positive for ER-alpha was similar post-menopausally (53.95%) and pre-menopausally (57.21%), but for ER-beta the number of positive cells decreased significantly after menopause (p < 0.051). In pre-menopausal women there was a correlation between serum estradiol levels and ER-beta; in post-menopausal women there was a correlation between serum FSH levels and ER-alpha. These results indicate that estradiol levels in women with mammary carcinoma are related to ER-beta expression in the breast tumor tissue.     

Thirteen-week oral toxicity study of difluoromethylornithine in combination with tamoxifen citrate in female dogs

Purpose: Cancer chemoprevention is the use of pharmacologic or natural agents to inhibit the development of cancer. Difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase, the rate-limiting enzyme in the biosynthesis of polyamines. DFMO has demonstrated chemopreventive efficacy in animal models of tumorigenesis. Tamoxifen (TAM), a nonsteroidal antiestrogen, is approved for use in the treatment of estrogen receptor-positive breast carcinoma and has demonstrated efficacy in chemoprevention of breast cancer in women at high risk for the disease. The administration of TAM with DFMO is being considered for development by the National Cancer Institute as a potential drug regimen for the chemoprevention of breast carcinoma. Methods: The toxicity of DFMO in combination with TAM was evaluated in female Beagle dogs following 13 weeks of daily oral administration by capsule. Dose levels in milligrams per kilogram body weight per day were: 0 (vehicle control), 100 DFMO, 0.1 TAM, 1.0 TAM, 0.1 TAM + 100 DFMO and 1.0 TAM + 100 DFMO. Results: No mortalities occurred. Diarrhea was produced by TAM and vaginal discharge, due to reproductive tract lesions, was produced by both DFMO and TAM, either alone or in combination. DFMO decreased reticulocyte counts and TAM increased counts of mature neutrophils. DFMO alone resulted in lesions to the intestines and ovaries, and cornified epithelium of vagina and cervix. TAM produced cornified epithelium of vagina and cervix, and numerous lesions in the ovaries, fallopian tube, uterus, cervix and vagina which were likely due to an estrogen agonist effect. Coadministration of DFMO increased the incidence and/or severity of these reproductive tract lesions. Each compound alone produced ovarian atrophy, and antral follicles and corpora lutea were completely absent in the 1.0 TAM + 100 DFMO group. Conclusions: Coadministration of DFMO and TAM resulted in additive toxicity involving the female reproductive system. Received: 1 July 1998 / Accepted: 25 September 1998     

Adherence to a randomized controlled trial of aerobic exercise in breast cancer survivors: the Yale exercise and survivorship study

Purpose  To examine predictors of exercise adherence in breast cancer survivors. Methods  Seventy-five breast cancer survivors were randomly assigned to exercise (n = 37) or usual care (n = 38). Demographic, prognostic, physiologic, and psychosocial information was collected at baseline and 6 months. The exercise goal was 30 min of exercise 5 days/week for 6 months. Results  Women randomized to exercise participated in moderate-intensity recreational exercise for 123 ± 52 min/week (81% of the prescribed 150 min/week) over 6 months. Baseline variables associated with better adherence were lower body mass index (BMI), smaller waist circumference, higher amounts of physical activity 6 months prior to enrollment, being in the preparation vs. contemplation Stage of Change and higher FACT-B breast cancer subscale score. After adjusting for these variables, lower BMI and higher Stage of Change continued to be associated with better adherence (p < 0.05). Conclusions  Future studies of exercise and breast cancer prognosis should target obese women for participation, as well as women just beginning to contemplate participation and its benefits after a cancer diagnosis.     

Difluoromethylornithine in combination with tamoxifen in female rats: 13-week oral toxicity study

Purpose: Cancer chemoprevention is the use of pharmacologic or natural agents to inhibit the development of cancer. Difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase, the rate-limiting enzyme in the biosynthesis of polyamines. DFMO has demonstrated chemopreventive efficacy in animal models of tumorigenesis. Tamoxifen (TAM) is currently used for treatment of estrogen receptor-positive breast carcinoma and has demonstrated efficacy in chemoprevention of breast cancer in women at high risk for the disease. The administration of tamoxifen with DFMO is being considered for development by the National Cancer Institute as a potential drug regimen for the chemoprevention of breast carcinoma. Methods: The toxicity of DFMO in combination with TAM was evaluated in female rats following 13 weeks of daily administration by gavage. Dose groups were vehicle control, DFMO (1000 mg/kg per day), low TAM (0.25 mg/kg per day), high TAM (2.5 mg/kg per day), low combination (1000 + 0.25) and high combination (1000 + 2.5). Results: No mortalities occurred in the study. Clinical signs of toxicity were limited to dermal lesions consisting of scab formation and abrasions produced by DFMO. Administration of either DFMO or TAM resulted in decreased body weight gains, with coadministration having an additive effect. Serum albumin, total protein, cholesterol and triglyceride levels were decreased in all drug-treated dose groups, although histologic evidence of liver lesions were not seen. TAM resulted in increased numbers of red blood cells, whereas DFMO produced a slightly anemic response. DFMO produced lesions in the small intestine consisting of necrosis of crypt epithelium and crypt microabscess, which were enhanced by TAM coadministration. Administration of TAM resulted in histologic changes in the ovaries, fallopian tube, vagina, cervix and uterus, indicating that inhibition of ovulation and reproductive cycle arrest in the proestrus stage had occurred. Coadministration with DFMO did not affect the changes to the reproductive system induced by TAM. Conclusions: Coadministration of DFMO with tamoxifen did not result in toxicity unique to the combination drug regimen, but rather toxicity resulted from administration of each drug. Under the conditions of the study, the overall toxicity produced by dual administration of DFMO with tamoxifen was additive with respect to the toxicity associated with each agent alone. Received: 27 October 1998 / Accepted: 9 April 1999     

Comorbidities, therapy, and newly diagnosed conditions for women with early stage breast cancer

Purpose  To describe comorbidities in breast cancer patients at diagnosis and examine factors associated with self-reported comorbidities 30 months post-diagnosis. Methods  Nine hundred forty one of 1,171 women had a medical record abstract and a follow-up survey in the Health, Eating, Activity and Lifestyle Study. Results  We compared our breast cancer cohort to a contemporaneous nationally-representative sample of age, race/ethnicity and education matched women without cancer (n = 865). Breast cancer patients did not have substantially more comorbidities than women without breast cancer. Women with a hospital record of congestive heart failure significantly less often received chemotherapy or radiation following breast conserving surgery. In multivariate analysis, women who received chemotherapy alone (OR = 3.2; 95% CI: 1.5–6.8), chemotherapy plus radiation (OR = 1.9; 95% CI: 1.02–3.7) or radiation plus tamoxifen (OR = 1.9; 95% CI: 1.1–3.2) were significantly more likely to report at least one new comorbid condition following breast cancer diagnosis than women who received no chemotherapy, tamoxifen or radiation. Overall, women who received adjuvant therapy were more likely to have new comorbidities. Conclusions  Comorbidities were not substantially different in breast cancer patients than the non-cancer matched controls. Future research should focus on efforts to minimize comorbidities related to chemotherapy and other combination therapy. Funding source  N01-PC-35139, N01-PC-35142, N01-PC-35138     

Monthly versus 3-monthly goserelin acetate treatment in pre-menopausal patients with estrogen receptor-positive early breast cancer

This study compared the efficacy and safety of a 3-monthly 10.8-mg depot goserelin (Zoladex^TM) injection with the current 3.6 mg monthly dose in pre-menopausal Japanese women with estrogen receptor-positive (ER+) early breast cancer. This was a multicenter, open-label, randomized study. Primary endpoint was a non-inferiority analysis (10.8/3.6 mg) of the area under the concentration–time curve (AUC) of estradiol (E₂) over the first 24 weeks. Secondary endpoints included E₂ and follicle-stimulating hormone (FSH) concentrations, menstruation, and safety and tolerability. In total, 170 patients were randomized to receive goserelin 10.8 mg every 3 months (n = 86) or 3.6 mg every month (n = 84). Mean AUCs for E₂ were similar between treatment groups (18.32 and 18.95 pg/ml·week for goserelin 10.8 and 3.6 mg, respectively). AUC ratio was 0.974 (95% confidence interval, 0.80, 1.19), indicating non-inferiority for goserelin 10.8 mg. Serum E₂ and FSH remained suppressed throughout the study and no patient experienced menses after week 16. No clinically important differences in safety and tolerability were observed between the two groups. In terms of E₂ suppression, 3-monthly goserelin 10.8 mg was non-inferior to monthly goserelin 3.6 mg in pre-menopausal women with ER+ breast cancer.     

Preliminary Assessment of Cognitive Function in Breast Cancer Patients Treated with Tamoxifen

Background. Tamoxifen is an anti-estrogen used in the treatment of breast cancer and to reduce the incidence of breast cancer in high risk women. Although the brain is an estrogen target organ and several studies have found a beneficial effect of estrogen on cognitive function, the effect of tamoxifen on cognition has not been reported. Therefore, we initiated a follow-up study of women who had participated in a study of breast cancer to assess the effect of tamoxifen treatment on cognitive function. Methods. We recruited previously interviewed patients who were cases in a population-based case-control study of 2,653 women with primary breast cancer diagnosed between 1987 and 1996 at ages 55–72 years in Los Angeles County, California, USA. In November 1997, each case was mailed a follow-up questionnaire. Cognitive function was assessed by (1) clock drawing, (2) copying a box drawing, and (3) narrative writing to describe a pictured scene. Women reporting treatment with tamoxifen were categorized as standard-term users (4–5 years), short-term users (<4 years) or long-term users (6+years) and compared to never users. Tamoxifen users were also classified as past or current users. Differences in the mean cognitive test scores were tested after adjusting for age, age at diagnosis, stage of disease, radiation therapy, chemotherapy, race, education, marital status, previous use of oral contraceptives, type of menopause, age at last menstrual period, previous use of hormone replacement therapy, and depressive symptoms using analysis of covariance. All p-values for differences in the proportion of women who had errors on the tests are 2-sided and adjusted for age, stage of disease at diagnosis, and chemotherapy. Findings. Information from 1,163 women aged 57–75 years of age was analyzed; 710 had taken tamoxifen. There was little difference between women who had used tamoxifen for the standard five years and never users on the three cognitive tests. However, more women who had used tamoxifen for the standard term reported seeing their physician for memory problems than non-users (3.8% vs 1.5%, p=0.04). This was especially true for current users of standard-term (8.0%, p=0.003). Current users also had a significantly lower mean complexity score (p=0.03) on the narrative writing task. No differences were seen between past users and non-users. Interpretation. Our study suggests that current use of tamoxifen may adversely effect cognition. Further study of tamoxifen and cognition is needed so that healthy women considering tamoxifen for the primary prevention of breast cancer have comprehensive information about the side effects of the treatment.     

A Teaching Model for Aromatase Inhibitors After Tamoxifen

Breast cancer is the most common cancer diagnosed in women. The present study evaluated the family physicians' (FPs) understanding of adjuvant hormonal therapies for an early breast cancer. FPs were invited to attend teaching workshops on this topic, which utilized a pretest, didactic and interactive teaching, and posttest format. FPs (n = 23) showed an improvement (p < 0.001) in pretest to posttest score. It is clear that, with a targeted teaching, FPs can quickly become more knowledgeable on the topic of hormonal therapies in breast cancer, with the potential of applying this information in their own practice.     

Predictors of Breast and Cervical Cancer Screening among Chamorro Women in Southern California

This study examined the role of sociodemographic characteristics, health insurance, cancer knowledge, perceived health risk, and having a recent physicians’ visit on breast and cervical cancer screening utilization among a randomly selected group of Chamorro women (n = 250) residing in San Diego, California. Data were collected by a telephone survey and analyzed using multiple logistic regression models. After adjusting for covariates, having a recent full exam was the strongest predictor of having had a Pap exam in the past 2 years for women 21 years and older and a clinical breast exam in the past 2 years for women 40 years and over.     

Increased N-myc downstream-regulated gene 1 expression is associated with breast atypia-to-carcinoma progression

N-myc downstream-regulated gene-1 (NDRG1) has been identified as a protein involved in the differentiation of epithelial cells. As a newly metastasis suppressor gene, whether it contributes to carcinogenesis of breast cancer is still unknown. This study aimed to clarify the possible role of NDRG1 for breast cancer carcinogenesis, and further to investigate its clinicopathological significance in invasive breast cancer. We examined the expression of NDRG1 in normal epithelium of breast (n = 35), usual ductal hyperplasia (n = 22), atypical ductal hyperplasia (n = 33), atypical lobular hyperplasia (n = 8), ductal carcinoma in situ (n = 16), lobular carcinoma in situ (n = 6), invasive ductal carcinoma (n = 50), and invasive lobular carcinoma (n = 45) by immunohistochemistry and analyzed the correlation between NDRG expression and clinicopathological features of invasive breast cancer. Western blot analysis was carried out to investigate the expression of NDRG1 in 20 invasive ductal breast cancer and the paired non-tumor portion of the same case. NDRG1 expression in invasive breast cancer (70/95, 73.7%) was higher than that in noninvasive breast lesions (29/85, 34.1%; p < 0.05) which was higher than that in normal breast epithelium (5/35, 14.3%; p < 0.05). Statistical analysis revealed a significant correlation between NDRG1 expression with tumor stage in invasive breast cancer, and its expression in invasive ductal carcinoma is significantly higher than invasive lobular carcinoma (p < 0.05). It was not associated with age, menopausal status, tumor size, and lymph node metastasis. NDRG1 protein levels were significantly higher in invasive ductal breast cancer compared to the paired non-tumor portion of the same case by Western blot analysis (p < 0.05). Increased NDRG-1 expression is associated with breast atypia-to-carcinoma progression. NDRG1 expression might participate in the carcinogenesis and progression of invasive breast cancer. These findings provide further evidence that NDRG1 may serve as an important biomarker for invasive breast cancer.     

Risk of subsequent dementia diagnoses does not vary by types of adjuvant chemotherapy in older women with breast cancer

Objective Little is known about long-term cognitive side effects of adjuvant chemotherapy for breast cancer. We thus examined incidence of dementia diagnoses in older women diagnosed with breast cancer, stratified by types of chemotherapy regimen. Methods We identified patients with incident dementia diagnoses through Medicare claims linked to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) tumor registry data. The study population (n = 6,932) consisted of women at least 68 years of age, who were diagnosed with early-stage breast cancer from 1994 through 2002 in one of the SEER areas and received chemotherapy as part of their cancer treatment. Excluded were women with a diagnosis of dementia within the 3 years prior to their cancer diagnosis. Results Our sample comprised mostly white women. The mean age was 74. Fifty-seven percent were estrogen receptor positive. Over 70% had no comorbidity. The use of taxol and anthracycline-based treatments increased from mid-1990s to early 2000. Increasing age at cancer diagnosis, Black ethnicity, living in a census tract with lower level of education, and increasing number of comorbidities were associated with new claims of dementia diagnoses after chemotherapy. There was no significant association between types of chemotherapy agents and risk of subsequent dementia diagnoses. Conclusion No association was found between types of adjuvant chemotherapy agents for breast cancer and risk of new dementia diagnoses. Our findings suggest that concerns about post-chemotherapy dementia should not be a major factor in determining type of adjuvant chemotherapy regimen to prescribe for older women with breast cancer.     

Dimensions of physical activity and their relationship to physical and emotional symptoms in breast cancer survivors

Background  Many breast cancer survivors experience long term sequelae, including fatigue, decreased physical functioning, pain, and psychological distress. Physical activity can ameliorate these problems, but there is little research on how activity should be performed to be most beneficial. This study explores how dimensions of physical activity (total energy expenditure, frequency, and duration) are associated with symptoms among breast cancer survivors. Methods  We conducted a secondary analysis of data on physical activity behavior and symptoms in a cross-sectional study (n = 148) of breast cancer survivors who were off treatment and had been diagnosed within the past 5 years. Results  Multivariate analyses showed that total energy expenditure was associated with better general health (p = 0.006) and fewer depressive symptoms (p = 0.014), while frequency of activity was linearly related to physical functioning (p = 0.047), pain (0.057), general health (p < 0.001), and depressive symptoms (p < 0.001). Duration was related to physical functioning, pain, and general health, but the worst outcomes were reported by the participants with the shortest and longest duration of activity (quadratic trend p values = 0.002, 0.003, 0.008, respectively). Discussion/Conclusions  Greater total energy expenditure, higher physical activity frequency, and moderate duration were associated with better outcomes for most symptoms, although there was no relationship between any of the dimensions of physical activity and fatigue. Implications for cancer survivors  The association of better outcomes with higher energy expenditure, higher frequency of activity, and moderate duration indicates that increasing activity through multiple short bouts may be the most beneficial for breast cancer survivors. However, randomized studies are needed to confirm this finding.     

Variants in estrogen metabolism and biosynthesis genes and urinary estrogen metabolites in women with a family history of breast cancer

We examined associations between polymorphisms in genes related to estrogen metabolism (CYP1B1 codon 432G → C rs#1056836, CYP1B1 codon 453A → G rs#1800440, COMT codon 158G → A rs#4680) and biosynthesis (CYP17 T → C promoter rs#743572, CYP19 exon 4 TTTA repeat) and urinary estrogen metabolites (2-hydroxyestrogens (2-OHE), 16α-hydroxyestrone (16α-OHE1), and their ratio) in a pilot study of 64 pre- and post-menopausal women with a family history of breast cancer. Women were participants in the Metropolitan New York Registry of Breast Cancer Families, one of six international sites of the National Cancer Institute’s Breast Cancer Family Registry. We used linear regression to examine the effects of genetic variants on log-transformed urinary estrogen metabolites. After adjusting for menopausal status, BMI, and age, carriers of the CYP1B1 codon 453G variant allele had 31.0% lower levels of 2-OHE (P-value = 0.05) and 40.2% lower levels of 16α-OHE1 (P = 0.01). Results were similar after restricting the analyses to pre-menopausal women (n = 41). Consistent with other studies, among pre-menopausal women, carriers of the COMT codon 158A variant allele had increased 2-OHE levels (P = 0.03) and an increased 2-OHE/16α-OHE1 ratio (P = 0.04); carriers of the CYP17 C promoter variant allele had increased 2-OHE levels (P = 0.08). To our knowledge this is the first report showing associations between the CYP1B1 codon 453G variant allele and urinary 2-OHE and 16α-OHE1 metabolites. Further larger studies should be conducted to confirm these results. Future identification of individuals with genetic polymorphisms that affect estrogen metabolism and biosynthesis may help characterize women at higher breast cancer risk and could guide breast cancer prevention strategies for those individuals.     

Profiles of tamoxifen-related side effects by race and smoking status in women with breast cancer

Background: Tamoxifen (TAM) is a selective estrogen receptor modulator (SERM) that is widely used as adjuvant therapy in breast cancer patients; however, it is also associated with undesirable side effects. The goal of this study was to investigate TAM-related side effects, and determine profiles of side effects by race and by smoking status. Methods: A secondary data analysis was conducted using cross-sectional study data from 138 African American and Caucasian women with breast cancer taking TAM 20 mg daily for at least 30 days prior to enrollment. Participants completed questionnaires that obtained information about demographic characteristics, reproductive history, health and lifestyle characteristics, TAM use and its related side effects. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals. Results: Compared to never smokers, a significantly greater percentage of current smokers reported ever experiencing TAM-related nausea (28.0% versus 5.0%, P = 0.007), depression (40.0% versus 7.1%, P = 0.001) and migraines (19.2% versus 1.7%, P = 0.02). These differences remained statistically significant after controlling for race, age, obesity, tumor stage, and duration of TAM treatment. No significant differences by race were noted in women reporting TAM side effects. Conclusion: The findings from this study suggest that current smokers with breast cancer should be informed of the increased probability of reporting TAM-related side effects such as nausea, depression and migraines, and counseled about smoking cessation which may reduce the incidence of these side effects.     

Evaluation of estrogen and progesterone receptors in non-neoplastic breast tissue of women of reproductive age exposed to tamoxifen and raloxifene: a randomized, double-blind study

The objective of the present study was to compare the effects of tamoxifen and raloxifene in non-neoplastic breast epithelium. A randomized, double-blind study was carried out in 57 ovulatory, premenopausal women of 18–40 years of age, who had been diagnosed with fibroadenoma of the breast. The patients were divided into three groups: Group A: placebo, n = 20; Group B: tamoxifen 20 mg/day, n = 21; and Group C: raloxifene 60 mg/day, n = 16. The study medication was given for 22 days starting on the first day of the menstrual cycle. On the 23rd day, the fibroadenoma was removed and a sample of non-neoplastic breast tissue was collected for immunohistochemical evaluation of estrogen and progesterone receptors. Comparison between the mean percentages of stained nuclei in the three groups was performed by analysis of variance and multiple comparisons, using Tukey’s method to compare pairwise means, with significance established at P < 0.05. Exposition to tamoxifen or raloxifene resulted in a significant and similar reduction in the mean percentage of stained nuclei for estrogen and progesterone receptors (P < 0.0001). Tamoxifen and raloxifene reduce progesterone and estrogen receptor alpha expression significantly and to a similar extent in the non-neoplastic breast tissue of women of reproductive age.     

A <Emphasis Type="Italic">CYP19</Emphasis> (aromatase) polymorphism is associated with increased premenopausal breast cancer risk

Due to the established association between estrogen levels and breast cancer risk, polymorphic variation in genes regulating estrogen levels is thought to be related to breast cancer risk. Aromatase, the protein product of the CYP19 gene, is involved in the production of endogenous estrogens via androgen conversion. We examined whether polymorphic variation in CYP19 associated with increased breast cancer risk in a population based case-control study. We examined two single nucleotide polymorphisms (SNP), rs1008805 (A/G) and rs730154 (C/T), which have been shown to tag SNPs within two different haplotype blocks in CYP19. Among premenopausal women, the presence of at least one G allele at rs1008805 was significantly associated with an increase in the risk of breast cancer (OR = 1.72 [95% CI, 1.20–2.49]), especially with estrogen and progesterone receptor negative breast cancer (OR = 3.89 [1.74–8.70] and OR = 2.52 [1.26–5.05], respectively). No association was observed among postmenopausal women (OR = 1.06 [0.82–1.36]). There was no significant association between rs730154 and breast cancer, regardless of menopausal status. Our results suggest that premenopausal women carrying the G allele at CYP19 rs1008805 have increased risk of breast cancer. The finding supports the potential role of variation in estrogen biosynthesis genes in premenopausal breast cancer risk.     

Lysophosphatidic acid (LPA)—a perspective marker in ovarian cancer

To compare plasma lysophosphatidic acid (LPA) levels in ovarian cancer patients in women with benign ovarian tumors and in women with no ovarian pathology. We correlated clinico-pathological parameters with plasma LPA levels. Capillary electrophoresis with indirect ultraviolet detection was used to analyze the plasma LPA levels of 159 patients (81 patients with ovarian cancer, 27 women without ovarian or uterine pathologies, and 51 patients with benign ovarian tumors) during a 5-year period. Patients with ovarian cancer had a significantly higher plasma LPA level (n = 81; median (med), 11.53 μmol/l; range, 1.78–43.21 μmol/l) compared with controls with no ovarian pathology (n = 27; med, 1.86 μmol/l; range, 0.94–9.73 μmol/l), and patients with benign ovarian tumor (n = 51; med, 6.17 μmol/l; range, 1.12–25.23 μmol/l; P < 0.001). We found that plasma LPA levels were associated with the International Federation of Gynecology and Obstetrics stage. The histological subtype and grade of ovarian cancer did not influence the plasma LPA levels in this study. The plasma LPA level can be a useful marker for ovarian cancer, particularly in the early stages of the disease.     

Genetic Polymorphisms of Paraoxonase 1 (PON1) Gene: Association Between L55M or Q192R with Breast Cancer Risk and Clinico-Pathological Parameters

The aim of the present study was to evaluate the association between the paraoxonase 1 (PON1) L55M and Q192R polymorphisms and breast cancer risk as well as clinico-pathological characteristics of the patients. Genotyping of these polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Malaysian population. Peripheral blood samples were collected from 387 breast cancer patients and 252 normal and healthy women who had no history of any malignancy. The genotype (P = 0.023) and allele (P = 0.008) frequencies of L55M polymorphism were significantly different between the breast cancer cases and normal individuals. However, the distribution of genotype (P = 0.333) and allele (P = 0.163) frequencies of Q192R polymorphism showed lack of statistical significance. Women who were MM homozygotes (OR = 2.229; 95% CI, 1.219–4.075) and carriers of M allele genotype (OR = 1.429; 95% CI, 1.035–1.974) or M allele (OR = 1.397; 95% CI, 1.093–1.785) were associated with increased risk of breast cancer. However, women who were heterozygous (OR = 0.793; 95% CI, 0.567–1.110) or homozygous (OR = 0.746; 95% CI, 0.407–1.370) for R allele or carriers of R allele (OR = 0.838; 95%, 0.654–1.074) were not associated with breast cancer risk. The M allele genotype was significantly associated with estrogen receptor negativity (P = 0.046) and nodal involvement (P = 0.004) but R allele genotype was not associated with any of the clinico-pathological characteristics. In conclusion, our findings suggest that the polymorphic variant of L55M polymorphism could be a useful genetic marker for tumor prognosis and to identify women who might be at greater risk of developing breast cancer in a hospital-based Malaysian population.     

Predicted cardiovascular mortality and reported cardiovascular morbidity in testicular cancer survivors

Introduction  We examined if testicular cancer (TC) treatment is associated with any risk for cardiovascular morbidity or predicted mortality according to the SCORE model, in which a 10-year future risk of ≥5% for developing a fatal cardiovascular event qualify for high-risk status. Methods  One thousand one hundred thirty-four TC survivors treated 1980–1994 participated in this study (1998–2002). Patients were categorised in four treatment groups: surgery (n = 225), radiotherapy (n = 445), and two chemotherapy groups: cumulative cisplatin dose ≤850 mg (n = 375) and >850 mg (cis>850, n = 89). Patients with cardiovascular disease, diabetes or SCORE ≥5% constituted a high-risk group, and those with SCORE >1% an intermediate/high risk group. Results  Age-adjusted mean SCORE was 0.93% for the surgery group. In comparison, chemotherapy treated patients had significantly higher SCORE (1.07%, p = 0.01). Only 15% of patients were scored to be at high-risk, while 53% qualified for the intermediate/high risk group. Patients in the cis>850 group had increased odds for having intermediate/high risk, compared with the surgery group (OR 3.4, 95% CI 1.3–8.7). Only 23 cardiovascular events had occurred since the testicular cancer diagnosis. Conclusion  The SCORE model indicates that patients treated with cisplatin-based chemotherapy have a significantly increased future risk of a fatal cardiovascular event. Implications for cancer survivors  TC survivors should be followed regularly with respect to cardiovascular risk profile beyond the routine 10-year clinical follow-up.