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Biomedical subjects

C Lerman

Publications and source records attributed to C Lerman.

At least 37 records · Page 2Linked to original sources
PubMed2000

Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study. Hereditary Breast Cancer Clinical Study Group.

BACKGROUND: Women with a mutation in BRCA1 or BRCA2 have a high risk of developing breast cancer and of contralateral cancer after the initial diagnosis of breast cancer. Tamoxifen protects against contralateral breast cancer in the general population, but whether it protects against contralateral breast cancer in BRCA1 or BRCA2 mutation carriers is not known. METHODS: We compared 209 women with bilateral breast cancer and BRCA1 or BRCA2 mutation (bilateral-disease cases), with 384 women with unilateral disease and BRCA1 or BRCA2 mutation (controls) in a matched case-control study. Age and age at diagnosis of breast cancer (range 24-74 years) were much the same in bilateral-disease cases and controls, and both groups had been followed up for the same time for a second primary breast cancer. History of tamoxifen use for first breast cancer was obtained by interview, or by self-administered questionnaire. FINDINGS: The multivariate odds ratio for contralateral breast cancer associated with tamoxifen use was 0.50 (95% CI 0.28-0.89). Tamoxifen protected against contralateral breast cancer for carriers of BRCA1 mutations (odds ratio 0.38, 95% CI 0.19-0.74) and for those with BRCA2 mutations (0.63, 0.20-1.50). In women who used tamoxifen for 2-4 years, the risk of contralateral breast cancer was reduced by 75%. A reduction in risk of contralateral cancer was also seen with oophorectomy (0.42, 0.22-0.83) and with chemotherapy (0-40, 0.26-0.60). INTERPRETATION: Tamoxifen use reduces the risk of contralateral breast cancer in women with pathogenic mutations in the BRCA1 or BRCA2 gene. The protective effect of tamoxifen seems independent of that of oophorectomy.

Adult↗
PubMed2000

Psychosocial factors predicting BRCA1/BRCA2 testing decisions in members of hereditary breast and ovarian cancer families.

Although BRCA1/2 testing has increasingly entered clinical practice, much is to be learned about the most effective ways to provide counseling to persons potentially interested in receiving test results. The purpose of this study was to identify factors affecting genetic testing decisions in a cohort of hereditary breast and ovarian cancer (HBOC) families presented with the choice to undergo testing. Relatives in these families are known to carry BRCA1 or BRCA2 mutations. Sociodemographics, personality traits, and family functioning were self-assessed using validated psychometric instruments at baseline. Among 172 individuals who participated in pretest education and counseling, 135 (78%) chose to undergo genetic testing and 37 (22%) chose not to be tested. Individuals who chose to undergo genetic testing were more likely to be older (> or =40 years), to have lower levels of optimism, and to report higher levels of cohesiveness in their families. A better understanding of factors that influence interest in predictive testing may help to inform the counseling that occurs prior to genetic testing.

Adolescent↗
PubMed2000

Prophylactic surgery decisions and surveillance practices one year following BRCA1/2 testing.

BACKGROUND: Although genetic testing for breast cancer risk is clinically available, its impact on health-related behaviors is unknown. This study examined prophylactic surgery and surveillance behavior during the year following BRCA1/2 gene testing. METHODS: Participants were female members (n = 216) of hereditary breast-ovarian cancer families (84 mutation carriers, 83 noncarriers and 49 test decliners). In this prospective observational study, utilization of prophylactic surgery and surveillance behavior were assessed 1-year following BRCA1/2 testing. RESULTS: Only 3% of the unaffected carriers obtained prophylactic mastectomy during the 1-year follow-up period. Among the remaining females, carriers had significantly higher rates of mammography (68%) than noncarriers (44%); (OR = 7.1; C.I. = 1.36-37.1; P = 0.02). However, the adherence rate in carriers was unchanged from baseline, suggesting that this difference is attributable to a reduction in screening among noncarriers. Women ages 25-39 years were significantly less likely to obtain mammograms than those aged 40 years and older. Cancer-related distress had a positive but nonsignificant (P < 0.07) association with adherence in bivariate but not multivariate analysis. With regard to ovarian risk, only 13% of carriers obtained prophylactic oophorectomy; of the remaining female carriers, only 21% reported a CA125 and 15% reported a transvaginal ultrasound. CONCLUSION: The vast majority of BRCA1/2 carriers may not opt for prophylactic surgery, and many do not adhere to surveillance recommendations. Greater attention to risk communication and medical decision-making is warranted.

Adult↗
PubMed2000

Adoption of a health education intervention for family members of breast cancer patients.

BACKGROUND: Relatives of breast cancer patients often face substantial uncertainty and psychological stress regarding their own health risks and optimal strategies for prevention and early detection. Efficacious educational and counseling interventions are rarely evaluated for their potential adoption and use in medical practice settings. This study evaluates a health education program for first-degree relatives of breast cancer patients based on the program's potential for being adopted and used by medical practices affiliated with cancer centers. METHODS: A randomized, controlled trial was implemented in four community hospital-based medical practices. After 9 months, clinical and administrative staff at each practice were given self-administered surveys. Of 90 staff members recruited to respond, useable responses were received from 60 (67%), including 13 physicians (31%), 43 nurses (98%), and four program managers (100%). Participants made self-reports of program awareness, program support, perceived program performance, likelihood of program adoption and use, and barriers to adoption. RESULTS: A strong majority of respondents (80%) reported that all or most staff agreed with the need for the program. Perceived program performance in meeting goals was generally favorable but varied across sites and across staff types. Overall, 56% of respondents indicated that their practices were likely or highly likely to adopt the program in full. The likelihood of adoption varied substantially across sites and across program components. CONCLUSIONS: Evaluating the potential for program adoption offers insight for tailoring preventive health interventions and their implementation strategies to improve diffusion in the field of practice.

Adult↗
PubMed2000

Interacting effects of the serotonin transporter gene and neuroticism in smoking practices and nicotine dependence.

Individual differences in propensity to nicotine dependence appear to be mediated, in part, by genetic factors.1 The serotonin transporter gene has a functional polymorphism (5-HTTLPR) which modulates gene transcription and reuptake.2,3 A possible role in nicotine dependence is suggested by a link between 5-HTTLPR and neuroticism,4 a personality trait which has been related to smoking practices.5 In a cross-sectional study of 185 smokers, we utilized multiple linear regression modeling to examine the interacting effects of the 5-HTTLPR and neuroticism on smoking practices and nicotine dependence. Genotype was classified according to the presence or absence of the short (s) allele vs the long (l) allele of 5-HTTLPR (ie, s/s or s/l vs l/l). Models controlled for gender, age, race, and alcohol use. The 5-HTTLPR by neuroticism interaction effect was statistically significant in the models of nicotine intake (P = 0.05), nicotine dependence (P = 0.001), and smoking motivations (smoking to reduce negative mood (P = 0.01); smoking for stimulation (P = 0.01)). The results suggested that neuroticism was positively associated with these smoking practices among smokers with 5-HTTLPR S genotypes (s/s or s/l), but not among smokers with the L genotype (l/l). The 5-HTTLPR may modify the effects of neuroticism on smoking motivations and nicotine dependence. Assessment of 5-HTTLPR genotype and neuroticism may help to identify smokers who are more responsive to psychotropic medications, such as selective serotonin reuptake inhibitors (SSRIs), which are being used in smoking cessation treatment.

Adult↗
PubMed2000

Spiritual faith and genetic testing decisions among high-risk breast cancer probands.

Despite widespread access to genetic testing for the BRCA1 and BRCA2 breast cancer susceptibility genes, little is known about rates or predictors of test use among individuals from newly ascertained high-risk families who have self-referred for genetic counseling/testing. The objective of this study was to examine rates of test use within this population. In addition, we sought to determine whether spiritual faith and psychological factors influenced testing decisions. Participants were 290 women with familial breast cancer. All were offered genetic counseling and testing for alterations in the BRCA1 and BRCA2 genes. Baseline levels of spiritual faith, cancer-specific distress, perceived risk, and demographic factors were examined to identify independent predictors of whether participants received versus declined testing. The final logistic model revealed statistically significant main effects for spiritual faith [odds ratio (OR), 0.2; 95% confidence intervals (CIs), 0.1 and 0.5] and perceived ovarian cancer risk (OR, 2.4; 95% CIs, 1.3 and 4.7) and a statistically significant spiritual faith by perceived risk interaction effect. Among women who perceived themselves to be at low risk of developing breast cancer again, those with higher levels of spiritual faith were significantly less likely to be tested, compared with those with lower levels of faith (OR, 0.2; 95% CIs, 0.1 and 0.5). However, among women with high levels of perceived risk, rates of test use were high, regardless of levels of spiritual faith (OR, 1.2; 95% CIs, 0.4 and 3.0). These results highlight the role that spirituality may play in the decision-making process about genetic testing.

Adult↗
PubMed2000

Intention to be tested for prostate cancer risk among African-American men.

This study was conducted to identify factors associated with intention to be tested for prostate cancer risk among African-American men. Participants in this study included African-American men (n = 548) who were patients at the University Health Service at the University of Chicago, were 40 to 70 years of age, and did not have a personal history of prostate cancer. Baseline telephone survey data were collected for 413 (75%) men. Respondents were asked if they intended to have a blood test to assess prostate cancer risk. Univariate and multivariate analyses of intention to be tested for risk were performed. Eighty-six percent of the men said that they intended to be tested. Multivariate analysis results show that belief in the efficacy of prostate cancer screening [odds ratio (OR) = 3.6; 95% confidence interval (CI) = 1.4, 9.1] and intention to undergo a prostate cancer-screening (i.e., digital rectal examination and prostate-specific antigen testing; OR = 2.8; 95% CI = 1.3, 6.3) were positively associated with intention to be tested for prostate cancer risk. Being older (OR = 0.4; 95% CI = 0.2, 0.9), having had a prostate cancer-screening examination in the past year (OR = 0.5; 95% CI = 0.2, 1.0), perceiving one's prostate cancer susceptibility to be high (OR = 0.4; 95% CI = 0.2, 0.8), and being fatalistic about prostate cancer prevention (OR = 0.3; 95% CI = 0.2, 0.7) were negatively associated with intention to be tested for risk. Intention to be tested for prostate cancer risk was high among men in the study. Past screening, perceived susceptibility, and beliefs related to early detection might influence receptivity to genetic testing for prostate cancer risk.

Adult↗
PubMed1999

Clinical impact of molecular genetic diagnosis, genetic counseling, and management of hereditary cancer. Part II: Hereditary nonpolyposis colorectal carcinoma as a model.

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is the most common hereditary form of colorectal carcinoma (CRC) and may account for 5-10% of the total CRC burden. The discovery of DNA mismatch repair (MMR) genes, inclusive of hMSH2, hMLH1, hPMS2, and hMSH6, has enabled the identification of who has and who does not have inordinately increased susceptibility to CRC as well as a litany of extracolonic cancers. Mutation testing has focused on hMSH2 and hMLH1, the most common mutations in HNPCC. The protocol for DNA testing and DNA-based genetic counseling is described in Part I of this study. One hundred ninety-nine bloodline relatives were tested and counseled from five hMLH1 and two hMSH2 families. Their major reason for seeking genetic counseling and DNA testing was to inform their children and other loved ones of their mutation status. Those who sought counseling overestimated their risk for inheriting the mutation and showed a high rate of interest in prophylactic surgery, and many were greatly concerned about insurance discrimination. Knowledge about HNPCC, its molecular genetic diagnosis, surveillance and management opportunities, and genetic counseling implications are still emerging, all in the face of a greater need for physician education regarding all facets of hereditary cancer.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Pregnancy and risk of early breast cancer in carriers of BRCA1 and BRCA2.

BACKGROUND: Early age at first full-term pregnancy and increasing parity are associated with a reduced risk of breast cancer. However, whether pregnancy decreases the risk of early-onset hereditary breast cancer is unknown. There is concern that pregnancy may increase breast-cancer risk in carriers of BRCA1 and BRCA2 germline mutations. We aimed to establish whether pregnancy is a risk factor for hereditary breast cancer. METHODS: We did a matched case-control study of breast cancer in women who carry deleterious BRCA1 or BRCA2 mutations. Cases were carriers who developed breast cancer by age 40 years, and controls were carriers of the same age without breast cancer, or who were diagnosed with breast cancer after age 40 years. Women who had undergone preventive mastectomy, hysterectomy, or oophorectomy, or who were diagnosed with ovarian cancer before the age at which breast cancer was diagnosed in the matched case were excluded. Information about pregnancies and pregnancy outcome was derived from a questionnaire completed by women in the course of genetic counselling. FINDINGS: A higher proportion of cases than controls had had a full term pregnancy (173/236 vs 146/236; odds ratio 1.71 [95% CI 1.13-2.62], p=0.01). The mean number of births was also greater for cases than for controls (1.62 vs 1.38, p=0.04). The risk increased with the number of births and did not diminish with time since last pregnancy. There were no significant differences in age at first birth or age at last birth between cases and controls. INTERPRETATION: Carriers of the BRCA1 and BRCA2 mutations who have children are significantly more likely to develop breast cancer by age 40 than carriers who are nulliparous. Each pregnancy is associated with an increased cancer risk. An early first pregnancy does not confer protection for carriers of BRCA1 or BRCA2 mutations.

Adult↗
PubMed1999

Genetic testing in families with hereditary nonpolyposis colon cancer.

CONTEXT: Genetic testing for hereditary nonpolyposis colon cancer (HNPCC) is available, but the rates of acceptance of testing or barriers to participation are not known. OBJECTIVE: To investigate rates and predictors of utilization of genetic testing for HNPCC. DESIGN: Cohort study conducted between July 1996 and July 1998. SETTING: Hereditary nonpolyposis colon cancer family registry. PARTICIPANTS: Adult male and female members (n = 208) of 4 extended HNPCC families contacted for a baseline telephone interview. INTERVENTIONS: Family education and individual genetic counseling. MAIN OUTCOME MEASURE: Participant acceptance of HNPCC test results. RESULTS: Of the 208 family members, 90 (43%) received test results and 118 (57%) declined. Of 139 subjects (67%) who completed a baseline telephone interview, 84 (60%) received test results and 55 (40%) declined. Of the 84 subjects who received test results, 35 (42%) received information indicating that they had HNPCC-associated mutations and 49 (58%) that they did not. Test acceptors had higher education levels (odds ratio [OR], 3.74; 95% confidence interval [CI], 2.49-5.61) and were more likely to have participated in a previous genetic linkage study (OR, 4.30; 95% CI, 1.84-10.10). The presence of depression symptoms significantly reduced rates of HNPCC test use (OR, 0.34; 95% CI, 0.17-0.66). Although rates of test use were identical among men and women, the presence of depression symptoms resulted in a 4-fold decrease in test use among women (OR, 0.25; 95% CI, 0.08-0.80) and a smaller, nonsignificant reduction among men (OR, 0.49; 95% CI, 0.19-1.27). CONCLUSIONS: Despite having significantly elevated risks of developing colon cancer, a relatively small proportion of HNPCC family members are likely to use genetic testing. Barriers to test acceptance may include less formal education and the presence of depression symptoms, especially among women. Additional research is needed to generalize these findings to different clinical settings and racially diverse populations.

Adult↗
PubMed1999

Bilateral prophylactic mastectomy decision making: A vignette study.

BACKGROUND: Little is known about the perception of bilateral prophylactic mastectomy (BPM), and whether perceptions are influenced by a family history of breast cancer. It is also unclear what factors may play a role in selecting BPM for follow-up care. METHODS: Samples of predominantly Caucasian, well-educated women with (n = 129) and without (n = 104) family histories of breast cancer were provided a vignette of a woman at increased risk. They selected one of two follow-up options: (1) clinical breast examination, breast self exam, and annual mammography or (2) BPM. RESULTS: The samples did not differ on the decision to select BPM (29.5% vs 22.1%). The family history sample reported worry about breast cancer as a problem (34.4%) more often than women with no history (15.7%). Multivariate analysis found worry and estimated 10-year risk of the woman in the vignette as significant predictors of selecting BPM. CONCLUSIONS: Approximately 25% of our sample selected BPM as the preferred option. The majority supported the need to discuss BPM among women at increased risk. Finally, both factors associated with the selection of BPM (worry, risk assessment) are potentially amenable to psychosocial or educational approaches. There is a clear need for assessment of worry and risk perception prior to surgical decision making.

Adult↗
PubMed1999

An update on DNA-based BRCA1/BRCA2 genetic counseling in hereditary breast cancer.

The identification of BRCA1 and BRCA2 mutations has enabled physicians to identify persons at high risk for carcinoma of the breast and ovary in hereditary breast-ovarian cancer (HBOC) families. Many physicians have limited knowledge about the effective translation of these new discoveries into clinical practice settings. This problem is further confounded by the limited number of genetic counselors who have experience with cancer genetics. Genetic counseling about DNA test results was provided to 420 patients from 37 HBC/HBOC families. Descriptive data were collected and recorded about their responses to questions posed immediately before and after test results were disclosed. Findings disclosed a significant tendency of patients to overestimate rather than underestimate their risk (P < .001) prior to receiving results. The chief reason for declining to receive results was fear of insurance discrimination. The primary reason that patients sought test results was for their children. Most women reported that, if testing identified them as mutation carriers, they would consider lifetime surveillance and prophylactic surgery. Responses to DNA test results were varied and often unpredictable. Counseling by an appropriately educated and skilled professional is essential to assist people in making decisions regarding testing and health management.

Adult↗
PubMed1999

Evidence suggesting the role of specific genetic factors in cigarette smoking.

Twin studies suggest that propensity to smoke and ability to quit smoking are influenced by genetic factors. As a means of investigating the risk of smoking associated with genetic polymorphisms in the dopamine transporter (SLC6A3) and the D2 dopamine receptor (DRD2) genes, a case-control study of 289 smokers and 233 nonsmoking controls and a case series analysis of smokers were conducted. A significant effect for SLC6A3 and a significant gene-gene interaction were found in a logistic regression model, indicating that individuals with SLC6A3-9 genotypes were significantly less likely to be smokers, especially if they also had DRD2-A2 genotypes. Smokers with SLC6A3-9 genotypes were also significantly less likely to have started smoking before 16 years of age and had prior smoking histories indicating a longer period of prior smoking cessation. This study provides preliminary evidence that the SLC6A3 gene may influence smoking initiation and nicotine dependence.

Adult↗
PubMed1999

Intron variants of the p53 gene are associated with increased risk for ovarian cancer but not in carriers of BRCA1 or BRCA2 germline mutations.

Two biallelic polymorphisms in introns 3 and 6 of the p53 gene were analysed for a possible risk-modifying effect for ovarian cancer. Germline DNA was genotyped from 310 German Caucasian ovarian cancer patients and 364 healthy controls. We also typed 124 affected and 276 unaffected female carriers with known deleterious BRCA1 or BRCA2 germline mutation from high-risk breast-ovarian cancer families. Genotyping was based on PCR and high-resolution gel electrophoresis. German ovarian cancer patients who carried the rare allele of the MspI restriction fragment length polymorphism (RELP) in intron 6 were found to have an overall 1.93-fold increased risk (95% confidence internal (CI) 1.27-2.91) which further increased with the age at diagnosis of 41-60 years (odds ratio (OR) 2.71, 95% CI 1.10-6.71 for 41-50 and OR 2.44, 95% CI 1.12-5.28 for 51-60). The 16 bp duplication polymorphism in intron 3 was in a strong linkage to the MspI RFLP. In BRCA1 or BRCA2 mutation carriers, no difference in allele frequency was observed for carriers affected or unaffected with ovarian cancer. Our data suggest that intronic polymorphisms of the p53 gene modify the risk for ovarian cancer patients but not in carriers with BRCA1 or BRCA2 mutations.

Adolescent↗
PubMed1999

Risk communication in genetic testing for cancer susceptibility.

Risk communication is an integral part of genetic counseling and testing for cancer susceptibility. This paper reviews the emerging literature on this topic. Three relevant aspects of risk communication are addressed: communication of individual risk, communication of the risks inherent in genetic testing, and family communications related to risk. These studies suggest that (a) most individuals with some family history of cancer, including those at low to moderate risk, overestimate their personal cancer risk; (b) awareness of the risks of genetic testing is limited; (c) decision making about genetic testing is influenced strongly by exaggerated perceptions of personal cancer risk and less so by perceptions of the risks of genetic testing; (d) perceptions of personal risk of cancer are resistant to standard education and counseling approaches; (e) psychologic distress and coping processes influence the processing of risk information and subsequent decision making in genetic testing; and (f) family influences play an important role in risk awareness, genetic testing decisions, and outcomes. To study these issues further, new theoretical models and measures of risk perceptions need to be developed. Both observational and experimental methods should be used to examine both the content and process of risk communication in cancer genetic counseling and testing. Emotional, familial, and sociocultural influences on the risk communication process require special attention.

Communication↗
PubMed1999

Patterns of breast cancer screening among lesbians at increased risk for breast cancer.

BACKGROUND: Women with a family history of breast cancer (i.e., in a mother, sister or daughter) are at increased risk for this disease. Previous data also suggest that lesbians are at increased risk for breast cancer. While the screening behaviors of women with a family history have been described, little is known about factors that influence screening behaviors of lesbians with the same risk factor profile. PURPOSE: The purpose of this study was to characterize the perceptions of susceptibility to breast cancer and describe factors that influence adherence to breast cancer screening guidelines in a sample of lesbians with a first-degree relative with a diagnosis of breast cancer. METHODS: Structured telephone interviews were conducted on a sample of 139 self-identified lesbians who had a first-degree relative with a diagnosis of breast cancer, were between the ages of 35 to 75 and had no previous history of cancer. Cross-sectional data obtained, included socio-demographics, breast cancer risk factors, breast cancer screening patterns, breast cancer perceptions, worries, and knowledge, and barriers and access to health care factors. Individual subject characteristics were examined for their association with adherence to mammography guidelines followed by a multivariate analysis to evaluate the most important combinations of factors. Outcome measures were age-specific adherence to ACS guidelines for both mammography and overall adherence (i.e., mammography, clinical breast examination and breast self-examination). RESULTS: The 139 lesbians interviewed for this study were young (mean age = 43), almost exclusively white (94%), highly educated (78% = college graduate and beyond), and partnered (68%). In the bivariate analysis of individual factors, being employed and reporting breast cancer worries were significantly and positively associated with adherence to mammography guidelines. Higher income and insurance type were significantly associated with mammography adherence. No factors were significantly associated with overall adherence. Multivariate logistic regression analyses revealed that only income level and degree of breast cancer worries were significantly and positively associated with mammography adherence. However, since there was a high correlation between income level and employment status, a regression model with employment status and worry was also significantly related to mammography adherence. CONCLUSIONS: In lesbians who are at an increased risk for breast cancer because of family history, breast cancer worries may motivate, rather than deter, adherence for mammography use. High income levels also appear to enable adherence in this population. IMPLICATIONS: Additional studies are needed to validate these findings, identify the prevalence of lesbians in general samples of women at increased risk for breast cancer, and prospectively test lesbian sensitive educational intervention strategies designed to facilitate adherence to mammography screening guidelines in this population.

Adult↗
PubMed1999

A randomized trial of breast cancer risk counseling: the impact on self-reported mammography use.

OBJECTIVES: We evaluated the impact of individualized breast cancer risk counseling on mammography use among women at risk for breast cancer. METHODS: Participants (n = 508) were randomized to the breast cancer risk counseling intervention or a general health education control intervention, and 85% completed follow-up. RESULTS: In multivariate modeling, a significant group-by-education interaction demonstrated that among less-educated participants, breast cancer risk counseling led to reduced mammography use. There was no intervention effect among the more-educated participants. CONCLUSIONS: These results suggest that standard breast cancer risk counseling could have an adverse impact on the health behaviors of less-educated women.

Adult↗