Genetic counseling for prostate cancer risk

Major risk factors for developing prostate cancer, including positive family history and African-American ethnicity, can be quantified for genetic counseling. Factors increasing familial risk for prostate cancer are closer degree of kinship, number of affected relatives, and early age of onset (< 50 years) among the affected relatives. Genetic testing may be useful for modification of risk, but currently should be performed only within the context of a well-designed research study that will determine penetrance and genotype-phenotype correlation of specific mutations. Even in the absence of genetic testing, African-American men and men with a strong family history of prostate cancer may opt to initiate screening by prostate specific antigen (PSA) and digital rectal exam (DRE) screening at age 40.     

Breast cancer risk with postmenopausal hormonal treatment

This review was designed to determine from the best evidence whether there is an association between postmenopausal hormonal treatment and breast cancer risk. Also, if there is an association, does it vary according to duration and cessation of use, type of regimen, type of hormonal product or route of administration; whether there is a differential effect on risk of lobular and ductal cancer; and whether hormone treatment is associated with breast cancers that have better prognostic factors? Data sources for the review included Medline, the Cochrane Database of Systematic Reviews (Cochrane Library, 2005) and reference lists in the identified citations. Eligible citations addressed invasive breast cancer risk among postmenopausal women and involved use of the estrogen products with or without progestin that are used as treatment for menopausal symptoms. Abstracted data were demographic groupings, categories of hormone use, categories of breast cancer, two-by-two tables of exposure and outcome and adjusted odds ratios, relative risks (RRs) or hazard rates. Average estimates of risk were weighted by the inverse variance method, or if heterogeneous, using a random effects model. The average risk of invasive breast cancer with estrogen use was 0.79 [95% confidence interval (95% CI) = 0.61-1.02] in four randomized trials involving 12 643 women. The average breast cancer risk with estrogen-progestin use was 1.24 (95% CI = 1.03-1.50) in four randomized trials involving 19 756 women. The average risks reported in recent epidemiological studies were higher: 1.18 (95% CI = 1.01-1.38) with current use of estrogen alone and 1.70 (95% CI = 1.36-2.17) with current use of estrogen-progestin. The association of breast cancer with current use was stronger than the association with ever use, which includes past use. For past use, the increased breast cancer risk diminished soon after discontinuing hormones and normalized within 5 years. Reasonably adequate data do not show that breast cancer risk varies significantly with different types of estrogen or progestin preparations, lower dosages or different routes of administration, although there is a small difference between sequential and continuous progestin regimens. Epidemiological studies indicate that estrogen-progestin use increases risk of lobular more than ductal breast cancer, but the number of studies and cases of lobular cancer remains limited. Among important prognostic factors, the stage and grade in breast cancers associated with hormone use [corrected] do not differ significantly from those in non-users, but breast cancers in estrogen-progestin users are significantly more likely to be estrogen receptor (ER) positive. In conclusion, valid evidence from randomized controlled trials (RCTs) indicates that breast cancer risk is increased with estrogen-progestin use more than with estrogen alone. Epidemiological evidence involving more than 1.5 million women agrees broadly with the trial findings. Although new studies are unlikely to alter the key findings about overall breast cancer risk, research is needed, however, to determine the role of progestin, evaluate the risk of lobular cancer and delineate effects of hormone use on receptor presence, prognosis and mortality in breast cancer.     

Breast cancer risk associated with ovulation-stimulating drugs

BACKGROUND: Despite the recognized role of hormones in the aetiology of breast cancer, there has been little evaluation of hormonal preparations used to treat infertility. METHODS: A retrospective cohort study of 12,193 women evaluated for infertility between 1965 and 1988 at five clinical sites identified 292 in situ and invasive breast cancers in follow-up through 1999. Standardized incidence ratios (SIRs) compared breast cancer risks with those of the general population. Analyses within the cohort estimated rate ratios (RRs) associated with medications after adjustment for other breast cancer predictors. RESULTS: Infertile patients had a significantly higher breast cancer risk than the general population [SIR = 1.29, 95% confidence interval (CI) 1.1-1.4]. Analyses within the cohort showed adjusted RRs of 1.02 for clomiphene citrate and 1.07 for gonadotrophins, and no substantial relationships to dosage or cycles of use. Slight and non-significant elevations in risk were seen for both drugs after > or = 20 years of follow-up (RRs = 1.39 for clomiphene and 1.54 for gonadotrophins). However, the risk associated with clomiphene for invasive breast cancers was statistically significant (RR = 1.60, 95% CI 1.0-2.5). CONCLUSIONS: Although there was no overall increase in breast cancer risk associated with use of ovulation-stimulating drugs, long-term effects should continue to be monitored.     

Psychological and social determinants of women's decisions to undergo genetic counseling and testing for breast cancer

This study examined the demand for breast cancer genetic testing and counseling among Canadian women diagnosed with breast cancer under the age of 50, together with some of the factors predicting both their intentions to be tested and the degree to which they act on their intentions. Participants were 110 women under the age of 50 and comprised of two groups: 1) women diagnosed with breast cancer (BC, n = 60): and 2) an index group of unaffected women from the general population (GP, n = 50). All participants completed a survey that addressed family history of breast and other cancers, demographic variables, knowledge and attitudes about breast cancer, and genetic testing. Members of the BC group were offered genetic counseling and testing for BRCA1 and BRCA2 free of charge. Overall, 60% of participants indicated they would like the test, and 40% either did not want it or were uncertain. Seventy-two percent of women in the BC group wanted to be tested. Of these, only 49% had actually contacted the genetic counselor about testing at follow-up 3-15 months later. Intention to be tested was associated with presence of breast cancer, greater perceived benefits of testing, fewer perceived 'costs' of testing, and higher levels of concern about the risk of relatives developing breast cancer. Actual arranging to meet with the genetic counselor among women in the BC group was associated with fewer perceived costs of having the test. Results suggest a moderate level of interest in gene testing, though intention to be tested may not translate into actual uptake. Women who do choose to have the test may believe the potential 'costs' of using this new genetic technology to be relatively few. This has implications for genetic counselors in terms of providing balanced and complete information to women considering genetic testing for breast cancer susceptibility.     

Breast cancer: hormones and other risk factors

In North America and Northern Europe, breast cancer incidence rates begin increasing in the early reproductive years and continue climbing into the late seventies, whereas rates plateau after menopause in japan and less developed countries. Female gender, age and country of birth are the strongest determinants of disease risk. Family history and mutations in the BRCA1 and BRCA2 genes are important correlates of lifetime risk. Genetic polymorphisms associated with estrogen synthesis and metabolism are currently under study. Atypical hyperplasia and molecular alterations in benign breast lesions appear to be involved in the pathogenesis of invasive carcinoma. In postmenopausal women, increased breast density on mammograms increases risk. Bone density and breast cancer are associated, presumably through the mechanism of endogenous estrogen levels. Serum estrogen levels are higher in breast cancer cases than controls. Many established risk factors for breast cancer may function through and endocrine mechanism. Current use of oral contraceptives and prolonged, current or recent use of hormone replacement therapy moderately increase risk. Tamoxifen and possibly other selective estrogen receptor modulators reduce breast cancer risk in high risk women. Relationships between various dietary micro and macronutrients and breast cancer have been suggested but require evaluation in clinical trials. Whereas alcohol consumption is associated with increased risk, most environmental factors, including polychlorinated compounds and electromagnetic fields, are not. Conclusion: Breast cancer etiology is becoming clearer through the study of molecular alterations in germline and somatic cell genes, and the interaction of these genes with steroid hormones and relevant growth factors. This knowledge should be useful for breast cancer prevention.     

Highly active antiretroviral therapy improves neurocognitive functioning

Although the effects of highly active antiretroviral therapy (HAART) have resulted in substantial improvements in the systemic health of patients with HIV infection, concerns remain that these medications, which cross the blood-brain barrier poorly, may have a less beneficial effect on nervous system function. This raises the possibility that there may be a progressive long-term decline in neurologic function in patients with adequate systemic response. In a prospective longitudinal study, subjects were evaluated immediately before instituting HAART. Forty-eight subjects underwent ultrasensitive HIV RNA quantitative evaluation of both plasma and cerebrospinal fluid as well as neurologic and neuropsychological examinations. They were reevaluated 6 months after treatment initiation while receiving stable HAART. Both plasma and cerebrospinal fluid viral levels significantly declined after treatment. There was significant improvement in neurologic and neuropsychological functioning after HAART. These results indicate that despite the poor central nervous system penetration of most of these agents, there is satisfactory short-term improvement in both central nervous system viral burden and nervous system function with HAART. However, because treatment failure is increasingly likely over time, continued longitudinal evaluation of this group of subjects is required.     

Breast cancer risk assessment in socioeconomically disadvantaged urban communities

During 2005, a risk assessment tool based on the Gail model was used to calculate the five-year risk of developing breast cancer for 445 women who live in socioeconomically disadvantaged urban communities in western Pennsylvania and who attended health fairs and other community-sponsored activities. This tool allowed us to evaluate each woman and advise her of her risks in a process lasting 15-20 minutes. Of the 445 women, 71.7% were black and 21.6% had a higher than average risk. The proportion of white women at high risk was significantly greater than the proportion of black women at high risk (33.3% vs. 16.9%; P < 0.01). The Gail model assessment tool for use in low-income and minority populations holds promise because it is noninvasive, is easy to use and provides immediate data about risk. This risk communication may help encourage minority and low-income women to receive screening mammography. It has the potential to improve breast cancer screening rates.     

Outcomes from intensive training in genetic cancer risk counseling for clinicians.

PURPOSE: Genetic cancer risk assessment is an emerging interdisciplinary practice that requires knowledge of genetics and oncology and specialized patient and family counseling skills. There is a growing need for cancer risk assessment practitioners, but most clinicians have inadequate cross-disciplinary training. An interdisciplinary course was developed to promote practitioner-level competency in cancer risk assessment to community-based clinicians. METHODS Participants were competitively selected from a pool of board-certified/eligible genetic counseling, masters-trained advanced practice nursing and physician applicants. Preference was given to clinicians with strong institutional backing practicing in underserved regions. The Continuing Medical Education/Continuing Education Unit-accredited course included didactic lectures, workshops, counseling practicum, and case conferences. Pre- and postcourse knowledge tests measured cancer genetics knowledge. Six month and one-year postcourse practice outcome surveys measured the impact of the program on professional self-efficacy and continued professional development. RESULTS/CONCLUSIONS: Forty clinicians completed the course (23 genetic counselors, 14 nurses, and three physicians). There was a significant overall increase of 22.6% in postcourse knowledge scores (P < 0.001). Thirty-five (88%) completed prescribed practice development activities. Of 29 respondents to 1-year postcourse survey, 76% reported increased professional self-efficacy; 66% reported increase in number of patients seen, and virtually all indicated interest in additional training. Outcomes demonstrate the value and efficacy of interdisciplinary training in genetic cancer risk assessment targeted to motivated community-based clinicians. Courses such as this can help address the need for competent cancer risk assessment services in communities outside the academic health center.     

Breast augmentation: a risk factor for breast cancer?

BACKGROUND. A relation between breast augmentation and the subsequent risk of breast cancer has been postulated. Since an estimated 2 million women in the United States alone have received breast implants, even a small increase in the risk of breast cancer could have considerable public health consequences. METHODS. We performed a population-based nonconcurrent cohort-linkage study. All women in Alberta, Canada, who underwent cosmetic breast augmentation from 1973 through 1986 were included in the implant cohort (n = 11,676). This cohort was compared with the cohort of all women in Alberta in whom a first primary breast cancer was diagnosed (n = 13,557). The expected number of breast-cancer cases in the implant cohort was estimated by applying age-specific and calendar year--specific incidence rates of breast cancer (obtained from the Alberta Cancer Registry) to the implant cohort. Standardized incidence ratios were calculated by dividing the observed by the expected number of breast-cancer cases in the implant cohort. RESULTS. Forty-one patients with implants were subsequently found to have breast cancer. The expected number was 86.2. The standardized incidence ratio was thus 47.6 percent, significantly lower than expected (P less than 0.01). The average length of follow-up in the implant cohort was 10.2 years, and the average length of time from breast augmentation to the diagnosis of breast cancer was 7.5 years. CONCLUSIONS. Women who undergo breast augmentation with silicone implants have a lower risk of breast cancer than the general population. This finding suggests that these women are drawn from a population already at low risk and that the implants do not substantially increase the risk.     

Results of a randomized study of telephone versus in-person breast cancer risk counseling

OBJECTIVE: Women of all risk levels have reported high interest in obtaining genetic testing for breast cancer risk. Breast cancer risk counseling may help women to learn about their risk and appropriate options of testing. This study measured the effects of an intervention in-person and by telephone, compared to a control group. METHODS: Participants were 340 women, recruited through a network of primary care physicians. They received a baseline questionnaire in the mail, were randomized to one of the three study arms, and completed a follow-up survey 3 months later. RESULTS: Both types of counseling were very well received. The counseling decreased women's cancer worry, risk perceptions, and intentions to pursue genetic testing. There were similar effects for both in-person and telephone counseling. CONCLUSION: Genetic counseling can be used to inform women at all risk levels about their breast cancer risk. PRACTICE IMPLICATIONS: Breast cancer risk counseling can be done in-person and by telephone--thereby reaching women in remote areas.     

Breast cancer screening in women at high risk using MRI

A series of prospective comparative studies have demonstrated that MRI has approximately twice the sensitivity of X‐ray mammography for screening women at high familial risk of breast cancer. In these studies, lesions have often been detected at an early stage, with disease being small and predominantly node negative. The diagnostic features in relation to risk and the biological behaviour of disease with risk category and age are being evaluated. The results of these studies have resulted in revised recommendations for screening for women at high risk of breast cancer. In this article, the results of the UK Magnetic Resonance Imaging in Breast Cancer Screening (MARIBS) study of MRI screening are described, and compared with results from other studies. Risk factors identifying women who would benefit from MRI screening are discussed, MRI measurement methods are described, and the results of studies evaluating MRI and mammographic lesions in different risk groups are reviewed. Recommendations for screening women at high risk of breast cancer published by the American Cancer Society and from the National Institute for Health and Clinical Excellence (NICE) in the UK are summarised. Copyright © 2008 John Wiley & Sons, Ltd.     

Results of a randomized study of telephone versus in-person breast cancer risk counseling

ObjectiveWomen of all risk levels have reported high interest in obtaining genetic testing for breast cancer risk. Breast cancer risk counseling may help women to learn about their risk and appropriate options of testing. This study measured the effects of an intervention in-person and by telephone, compared to a control group.MethodsParticipants were 340 women, recruited through a network of primary care physicians. They received a baseline questionnaire in the mail, were randomized to one of the three study arms, and completed a follow-up survey 3 months later.ResultsBoth types of counseling were very well received. The counseling decreased women's cancer worry, risk perceptions, and intentions to pursue genetic testing. There were similar effects for both in-person and telephone counseling.ConclusionGenetic counseling can be used to inform women at all risk levels about their breast cancer risk.Practice implicationsBreast cancer risk counseling can be done in-person and by telephone – thereby reaching women in remote areas.     

Breast cancer survivors' attitudes about communication of breast cancer risk to their children

Perceptions of breast cancer survivors regarding educating their children about hereditary breast cancer risk are underexplored. This study examined attitudes of early-onset breast cancer survivors concerning whether, at what age, and how their children should be educated about potential risk for hereditary breast cancer. Women with breast cancer diagnosed < age 50 years between 1994 and 1997 were recruited from 34 Virginia hospitals. Participants responded to two surveys. The Family History Questionnaire permitted participant classification into two groups based on risk for hereditary disease, as determined by personal and family history. The Knowledge, Attitudes and Beliefs Questionnaire addressed participants' concerns regarding their children's breast cancer risk, perceptions of their children's concerns about their own risk, and whether, at what age, and from what source their children should be informed about their own risk. Among 267 participants, the average age was 47.5 years; 90% were Caucasian, 7% were African American; 52% had suspected hereditary breast cancer. Of participants with children, 81% indicated concern about their children's breast cancer risk; 55% reported that their children had expressed concern about their own risk. Seventy-one percent of participants believed the age for informing children about hereditary breast cancer risk to be before 18 years. Eighty-four percent cited the child's parents and 65% cited health professionals as a preferred information source. No differences in responses between participants with suspected hereditary breast cancer versus presumed sporadic breast cancer were noted. These data establish the need for educational resources regarding hereditary breast cancer for children of early-onset breast cancer survivors.     

Initiating contact with a women's counseling service: Some correlates of help-utilization

Questionnaire and personality data were collected from a sample of 23 women who responded to four different letters and subsequently joined a women's counseling service group, and from a sample of 31 nonresponding women. Respondents who joined groups reported significantly lower self-acceptance scores, higher educational levels, and more positive attitudes towards the women's movement than did non-respondents. Of the 50 women who telephoned in response to a letter, 27 did not eventually join a group. Responses for the subgroup of 23 joiners as well as total responses for all 50 who telephoned were evenly distributed among the four letter treatments. However, women who responded and joined groups after receiving the two letters which indicated that their problems were “common to most women” scored higher on the FIRO-B “inclusion” scales than did women who joined groups after responding to the two other letters. Implications of these data for using multiple vs. single appeals to reach potential service users were discussed.     

Breast cancer risk factors in Queensland women attending population-based mammography screening

Objective

To investigate the prevalence of established modifiable and non-modifiable risk factors associated with breast cancer in Queensland (Australia) women.

Study design

Cross-sectional prevalence study of 9792 women (58% of women sent the questionnaire) attending BreastScreen Queensland Screening and Assessment Services between November 2008 and February 2009. Prevalence and 95% confidence intervals were calculated for each risk factor, stratified by age-group (45–49 years, 50–59 years, 60–69 years, ≥70 years).

Main outcome measures

First-degree family history (FH) of breast cancer (mother, sister, daughter), reproductive history, behavioural factors, co-morbidities, use of hormone replacement therapy (HRT) and alternatives, and socio-demographic factors.

Results

The prevalence of first-degree FH of breast cancer was 16% and a previous diagnosis of breast cancer was 3.5%; both are considered major risk factors for breast cancer. The prevalence of modifiable breast cancer risk factors of moderate risk were: current HRT use (12%), HRT use within the past 5 years (7%), overweight [body mass index 25–29] (33%) or obesity [BMI > 30] (27%), alcohol consumption [≥11 drinks/week] (10%), sedentary behaviour (70%), and low fruit (34%) and vegetable consumption (69%). These risk factors tended to be higher in younger women (45–49 years) compared to older women (>50 years).

Conclusion

Prevalence of risk factors in Queensland women were largely consistent with other Australian and international studies. Hormone therapy use is lower than previously reported estimates in Australia and internationally. The comparatively high prevalence of modifiable lifestyle factors which have been shown to be moderately associated with breast cancer are potential targets for reducing the public health burden of breast cancer.     

Increased genetic counseling support improves communication of genetic information in families

PurposeTo determine whether the provision of additional genetic counseling support could improve the uptake of genetic services by “at-risk” relatives of probands.MethodsThe Tasmanian Clinical Genetics Service implemented a specific counseling intervention to a cohort of patients who were diagnosed with a genetic condition with familial implications and compared this with a control cohort who had not experienced the specific counseling intervention. The study involved 150 family members in 19 different kindreds across the two cohorts. The principal outcome measure was the proportion of at-risk relatives who had made contact with the clinical genetics service within 2 years of the diagnosis in the index patient.ResultsThe proportion of at-risk relatives who made contact with the genetics service was 61% in the intervention cohort compared with 36% in the control cohort (P = 0.01). After controlling for the gender of the at-risk relatives, relatives in the intervention cohort were 2.6 times more likely to make contact with the genetics service (P = 0.02).ConclusionsThe provision of increased genetic counseling support significantly increased the proportion of at-risk relatives who made contact with the genetic service. This suggests that the communication of genetic information within families can be enhanced by the provision of increased genetic counseling support.