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1.
Screening and genetic counselling for relatives of patients with breast cancer in a family cancer clinic.
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R S Houlston L Lemoine E McCarter S Harrington K MacDermot J Hinton L Berger J Slack 《Journal of medical genetics》1992,29(10):691-694
Family history is the major risk factor in the aetiology of breast cancer. Breast screening is currently available to women from the age of 50 to 64 through the National Breast Screening Programme. There is, however, an equivalent risk of developing breast cancer below 50 for first degree relatives of women diagnosed with breast cancer premenopausally. We have estimated the risk of breast cancer for relatives of women affected at different ages and used these to establish a family cancer clinic offering breast screening based on individual risk. In three years we have seen 851 patients. Compliance for annual radiology was in excess of 83% over this period and of five cancers detected one had a lump at presentation, two developed interval breast lumps, and two were asymptomatic. 相似文献
2.
Evans DG Anderson E Lalloo F Vasen H Beckmann M Eccles D Hodgson S Møller P Chang-Claude J Morrison P Stoppa-Lyonnet D Steel M Haites N 《Disease markers》1999,15(1-3):148-151
Increasingly women at high risk of breast cancer are opting for prophylactic surgery to reduce their risks. Data from 10 European centres that offer a risk counselling and screening service to women at risk show different approaches to the option of preventive surgery, although most centres adhere to a protocol including at least two risk counselling sessions and a psychological assessment. Thus far the combined centres have data on 174 women who have undergone prophylactic mastectomy with in excess of 400 women years of follow up. Operations were carried out on women with lifetime risks of 25-80%, with an average annual expected incidence rate of 1% per women. No breast cancers have occurred in this cohort. Long term follow up on an extended group of women will be necessary to truly address the risk of subsequent breast cancer and the psychological sequelae. 相似文献
3.
The risk of breast cancer in first degree relatives of patients with breast cancer can be derived from family history and is dependent upon the age at diagnosis in the index patient. For the relatives of index patients older than 55, the relative risk is 1.57, if less than 55 the relative risk is 2.29, and 3.85 if less than 45 (95% confidence limits 0.83 to 2.68, 1.18 to 4.01, and 1.67 to 3.85, respectively). First degree relatives of patients with bilateral breast cancer have a 6.43-fold increase in risk (95% confidence limits 1.32 to 18.77). The genetic contribution to overall lifetime liability to breast cancer in the relatives declines rapidly with increasing age of onset of breast cancer in the index patient from 37% at 20 years to 8% by 45 years. This information can be used in clinical practice for counselling and the establishment of screening programmes. 相似文献
4.
The demand for genetic services by women with a family history of breast cancer has increased exponentially over the last few years. It is important that risks to women are accurately assessed and that processes are in place for appropriate counselling and management. The classification of risk into average, moderate, and high, depending upon the assessed lifetime risk of breast cancer, allows for the management of moderate risk women within cancer units and high risk women within the regional genetic centres. Management of high risk women includes discussion of options including screening, chemoprevention, and preventive surgery. The majority of these options are still unproven in the long term and continuing research is needed for their evaluation. Mutation screening and predictive testing are now a reality for a minority of families, allowing for a more informed basis for decisions regarding management options. 相似文献
5.
Casadei S Falcini F Naldoni C Amadori D Calistri D 《International journal of molecular medicine》2002,10(3):299-305
Assessment of family history is an important element in the identification of individuals and families likely to be at risk of hereditary cancers. It is based on the recognition of important features in the natural history of cancer syndromes. These include the occurrence of the same type of cancer in two or more close relatives, bilateral cancer in paired organs, multiple primaries in the same individual, early age at onset, a specific constellation of cancers or other physical findings associated with a known syndrome, and a mendelian pattern of inheritance. We set up a population-based screening program to identify women at increased risk of breast or ovarian cancer in a region of North-Central Italy. As a preliminary screening, 159 women with a family history of breast and ovarian cancer were recruited at the Cancer Prevention Unit of Pierantoni Hospital in Forli. Information on the number of affected individuals and the age at onset of breast or ovarian cancer in each woman's family was recorded. Thirty-nine women reported two or more first- or second-degree relatives with breast cancer under the age of 50 (25%) and 95 a single first- or second-degree relative with breast cancer under the age of 50 (60%) with or without other late onset breast cancers in the family. The remaining 25 women reported first- and second-degree relatives with breast cancer over the age of 50 (15%). There were five families with a history of ovarian cancer (3%), one of which comprised 3 affected members. Twenty-three families showed multiple cancers associated with breast cancer cases. Associated prostate and colorectal cancers were found in 5 and 4 families with a history of breast cancer, respectively. On the basis of these preliminary data, we aimed to extend the population-based screening to the whole of the Emilia-Romagna population, involving the Cancer Prevention Units of neighboring towns and adopting homogeneous family history evaluation and risk assessment criteria. 相似文献
6.
In this review we present an overview of recent developments in the management of hereditary ovarian cancer. Until recently, intensive screening of the ovaries was recommended to mutation carriers and their first-degree female relatives. However, since screening is not effective in detecting early-stage ovarian cancer, women are counselled for a prophylactic bilateral salpingo-oophorectomy (pBSO) shortly after child-bearing age (>35 years). Many mutation carriers already choose to undergo pBSO to reduce their cancer risks; however, the age of prophylactic surgery may interfere with reproductive and other important (psychosexual) issues in life. Due to the protective effect of oral contraceptives regarding ovarian cancer, we advise women at increased risk of ovarian cancer to use oral contraceptive pills for 3–5 years early in life (<25 years of age), when the absolute incidence of breast cancer is extremely low. A transient increased relative risk of breast cancer due to oral contraceptives at this age will result in a negligible increased absolute number of breast cancers, while the risk reduction of ovarian cancer remains for life. Research should aim at finding new molecular markers and screening strategies for detecting early-stage ovarian cancer in women with a hereditary ovarian cancer trait. 相似文献
7.
Halbert Ch Kessler L Collier A Paul Wileyto E Brewster K Weathers B 《Clinical genetics》2005,68(3):222-227
Despite attention to psychological issues during genetic counselling and testing for hereditary breast and ovarian cancer risk, limited information is available on cancer-specific distress among African American women being targeted for participation in counselling and testing. Therefore, the purpose of this study is to examine cancer-specific distress in African American women at an increased risk of hereditary breast and ovarian cancer and to identify factors having significant associations with distress in this population. Respondents were 141 African American women identified for participation in genetic counselling and testing for BRCA1/2 mutations. Overall, respondents reported moderate levels of cancer-specific distress. Younger age (coefficient=6.0, p=0.001), being unemployed (coefficient=-5.0, p=0.01), and having a personal history of cancer (coefficient=5.0, p=0.02) had significant associations with intrusion. Younger age was also associated significantly with greater avoidance (r=6.0, p=0.02). These results suggest that African American women aged 50 and younger, those who are unemployed and women with a personal history of breast or ovarian cancer may be the most vulnerable to experiencing elevated levels of distress during genetic counselling and testing. Greater attention to psychological issues, including concerns about cancer and cancer risks, may be needed during genetic counselling and testing for BRCA1/2 mutations with these women. 相似文献
8.
Incidence of cancer in 161 families affected by ataxia-telangiectasia 总被引:46,自引:0,他引:46
BACKGROUND. Ataxia-telangiectasia is an autosomal recessive syndrome in which cancers develop in affected homozygotes at a rate approximately 100 times higher than in unaffected age-matched subjects. Retrospective studies have shown that persons heterozygous for the ataxia-telangiectasia gene, who make up about 1 percent of the general population, also have an excess risk of cancer, particularly breast cancer in women. Patients with ataxia-telangiectasia and cells derived from homozygotes and heterozygotes are unusually sensitive to ionizing radiation. METHODS. Cancer incidence and mortality, mortality from ischemic heart disease, and mortality from all causes were compared prospectively for a mean of 6.4 years in 1599 adult blood relatives of patients with ataxia-telangiectasia and 821 of their spouses, who served as controls, in 161 families affected by ataxia-telangiectasia. In a case-control substudy, we compared documented occupational and fluoroscopic diagnostic exposures to radiation in the 19 female blood relatives in whom breast cancer was first diagnosed during the period of prospective observation with the exposures in 57 matched blood relatives who did not have breast cancer. RESULTS. Cancer rates were significantly higher in the group of blood relatives than in their spouses, specifically in the subgroup of 294 blood relatives who were known to be heterozygous for the ataxia-telangiectasia gene. The estimated risk of cancer of all types among heterozygotes as compared with noncarriers was 3.8 in men and 3.5 in women, and that for breast cancer in women was 5.1. Among the blood relatives, women with breast cancer were more likely to have been exposed to selected sources of ionizing radiation than controls without cancer (odds ratio = 5.8, P = 0.005). Male and female blood relatives also had 3-fold and 2.6-fold excess mortality from all causes, respectively, from the ages of 20 through 59 years. CONCLUSIONS. The ataxia-telangiectasia gene predisposes heterozygotes to cancer, particularly breast cancer in women. There is also excess mortality from all causes in adults under the age of 60. Diagnostic or occupational exposure to ionizing radiation probably increases the risk of breast cancer in women heterozygous for ataxia-telangiectasia. 相似文献
9.
Akbari MR Zhang S Fan I Royer R Li S Risch H McLaughlin J Rosen B Sun P Narod SA 《Journal of medical genetics》2011,48(11):783-786
Women who carry a pathogenic mutation in BRCA1 or BRCA2 have high risks of developing breast and ovarian cancers. The functional effect of many missense variants on BRCA1 and BRCA2 protein function is not known. Here, the authors construct a historical cohort of 4030 female first-degree relatives of 1345 unselected patients with ovarian cancer who have been screened for BRCA1 and BRCA2 mutations. The authors compared the risks by the age of 80 years for all cancers combined in female first-degree relatives of women with a pathogenic mutation, women with a variant of unknown significance (unclassified variant) and non-carriers. The cumulative risk of cancer among the relatives of patients with a pathogenic mutation was much higher than the risk in relatives of non-carriers (50.2% vs 28.5%; HR=2.87, p<10(-4)). In contrast, the cumulative risk of cancer among relatives of patients carrying an unclassified variant was similar to the risk of cancer for relatives of non-carriers (27.6% vs 28.5%; HR=1.08, p=0.79). The authors used three different algorithms to predict the pathogenicity of unclassified variants and compared their penetrance with non-carriers. In this sample, only Align Grantham Variation Grantham Deviation appeared to predict penetrance based on first-degree relatives. 相似文献
10.
The risk of contralateral breast cancer in daughters of women with and without breast cancer
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We aimed to estimate the 15‐year and lifetime risks of contralateral breast cancer in breast cancer patients according to the age of diagnosis of the first cancer and the history of breast cancer in the mother. The risks of contralateral breast cancer were estimated for all 78,775 breast cancer patients in the Swedish Family‐Cancer Database (age at diagnosis of first breast cancer <70 years). The risk of experiencing a contralateral breast cancer within 15 years of diagnosis was 8.4% [95% confidence interval (CI): 8.1–8.7%] for women with an unaffected mother, was 12% (95%CI: 11–13%) for a woman with a mother with unilateral breast cancer and was 13% (95%CI: 9.5–17%) for women with a mother with bilateral breast cancer. In early‐onset diagnosed women (<50 years) with an unaffected mother, the risk of contralateral breast cancer until age 80 was 23% (95%CI: 20–26%) and for late‐onset (50–69 years) diagnosed women it was 17% (95%CI: 14–21%). In a woman with a mother with an early‐onset unilateral breast cancer, risk of contralateral breast cancer by age 80 was 35% (95%CI: 25–46%). Women with a mother with early‐onset bilateral breast cancer had 31% (95%CI: 12–67%) lifetime risk of contralateral breast cancer. The risk of contralateral breast cancer is higher for daughters of breast cancer patients than for daughters of women without breast cancer. Maternal cancer history and age at onset of first breast cancer in women should be taken into account when counseling breast cancer patients about their risk of contralateral breast cancer. 相似文献
11.
Publicly organized population breast cancer screening is presently hotly debated. Indeed, population screening is poorly effective, induces harms in a healthy population and is costly. However, stopping all kind of screening of low- and average-risk women would be problematic as about 70% of breast cancers are diagnosed in those subgroups, and maintaining current population screening in high-risk women would be insufficient. We propose herein a review about the advantages and the inconvenients of individualized screening. The latter could be a more efficient strategy. The principles of individualized screening are (a) to start from the age at which the breast cancer risk is equal to that for an average women aged 50 years, (b) to stop when the risk of co-mortality exceeds the risk of breast cancer mortality, (c) to adapt the exams frequency and the imaging modalities to the individual risk and to the breast density, (d) to reassess regularly and individually the screening strategy, and (e) to discuss honestly with each woman in order to help her to decide if she participates or not. 相似文献
12.
Andersen MR Nelson J Peacock S Giedzinska A Dresher C Bowen D Urban N 《American journal of medical genetics. Part A》2004,(2):130-135
Several studies have described the characteristics of women at high-risk for ovarian cancer who are participating in registry studies and high-risk screening programs. These studies have found high-risk women to report high levels of perceived risk and worry about their risk for ovarian cancer. In contrast, population based studies have found that while high-risk women did report high levels of perceived risk, they did not report high levels of worry about their risk. In this study, we examine reports of perceived risk, worry about ovarian cancer, and use of screening by high-risk women recruited to participate in a survey from several recruitment sources. These sources include self-, physician-, and affected patient relative-referral, a fundraising mailer, and a mass mailing to a commercial mailing list. High-risk women recruited via mass mailing were less likely than those recruited via physicians or affected relatives to report either worry about their risk or use of ovarian cancer screening tests. 相似文献
13.
Lisa Kessler Aliya Collier Kiyona Brewster ChaChira Smith Benita Weathers E Paul Wileyto Chanita Hughes Halbert 《Genetics in medicine》2005,7(4):230-238
PURPOSE: To evaluate attitudes about the benefits, limitations, and risks of genetic testing for BRCA1 and BRCA2 (BRCA1/2) mutations and explore testing intentions in African American women at increased risk for hereditary breast cancer. METHODS: Attitudes and intentions were evaluated by telephone in African American women (n = 74) at moderate and high risk for having a BRCA1/2 mutation. RESULTS: Attitudes about the benefits of genetic testing were endorsed at a higher rate relative to limitations and risks; however, only 30% of respondents indicated that they would definitely have testing. In regression analysis, women most likely to be considering testing were those with fatalistic beliefs about cancer and those who believed they had a BRCA1/2 mutation. Women who had two or more affected relatives were also most likely to be considering testing. Women who had a personal history of cancer and those who believed they were at high risk for developing breast cancer were most likely to report greater limitations and risks. Pros scores were higher among women older than age 50 and those who were unemployed. CONCLUSION: Although African American women at moderate and high risk for BRCA1/2 mutations report favorable attitudes about genetic testing, interest in testing may be limited. Women affected with cancer and those who believe they are at a higher risk for developing breast cancer may be most concerned about the negative consequences of testing. Increased attention may need to be given to beliefs about genetic testing and testing motivations during genetic counseling with African American women. 相似文献
14.
A.M. Burton‐Chase S.R. Hovick C.C. Sun S. Boyd‐Rogers P.M. Lynch K.H. Lu S.K. Peterson 《Clinical genetics》2014,86(2):185-189
We evaluated knowledge of gynecologic cancer screening recommendations, screening behaviors, and communication with providers among women with Lynch syndrome (LS). Women aged ≥25 years who were at risk for LS‐associated cancers completed a semi‐structured interview and a questionnaire. Of 74 participants (mean age 40 years), 61% knew the appropriate age to begin screening, 75–80% correctly identified the recommended screening frequency, and 84% reported no previous screening endometrial biopsy. Women initiated discussions with their providers about their LS cancer risks, but many used nonspecific terms or relied on family history. Most were not offered high‐risk screening options. While many women were aware of risk‐appropriate LS screening guidelines, adherence was suboptimal. Improving communication between women and their providers regarding LS‐related gynecologic cancer risk and screening options may help improve adherence. 相似文献
15.
An evaluation of common breast cancer gene mutations in a population of Ashkenazi Jews. 总被引:1,自引:4,他引:1
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F Lalloo S Cochrane B Bulman J Varley R Elles A Howell D G Evans 《Journal of medical genetics》1998,35(1):10-12
OBJECTIVES: In view of the recent reports of recurrent mutations in BRCA1 and BRCA2 in the Ashkenazi Jewish population, we have undertaken to assess the frequency of these mutations in this population attending for genetic counselling and risk assessment of familial breast cancer. DESIGN: Mutation screening for the 185delAG and the 5382insC mutations in BRCA1 and the 6174delT mutation in BRCA2 was performed on DNA samples from either subjects affected by breast or ovarian cancer or obligate gene carriers. The likelihood of the cancers being hereditary in each family was calculated. SUBJECTS: Blood samples were obtained from 26 affected subjects or obligate gene carriers from 23 Ashkenazi Jewish families, all with a history of either early onset breast or ovarian cancers, or multiple cases of breast or ovarian cancer. RESULTS: Twelve mutations have been identified in the 23 families (52%) of which eight (67%) were the 185delAG mutation, three (25%) were the 6174delT mutation, and one (8%) was the 5382insC mutation. While the majority of these mutations were identified in families with a greater than 50% probability of being hereditary under the CASH segregation model, three mutations were identified in families with a 35% or less probability. CONCLUSIONS: Genetic screening of the recurrent mutations in Ashkenazi Jewish families will lead to the availability of predictive testing in a reasonably large proportion, even if the family history of breast/ovarian cancer is not particularly strong. In our view it is possible to reassure high risk unaffected members of these families, if the screening is negative for these mutations, even if a sample from an affected member of the family is unavailable for previous screening. 相似文献
16.
Women who carry a BRCA1 or BRCA2 mutation are at high risk of breast and ovarian cancer, and may be at moderately increased risk of other cancer types. This review examines studies to date that have evaluated the risk of BRCA1 and BRCA2 mutations for colorectal cancer. Accurate knowledge of colorectal cancer risk in BRCA1/2 carriers is important, because colonoscopy screening can prevent colorectal cancer through the removal of adenomatous polyps. Most studies that have identified an increased risk for colorectal cancer in BRCA1/2 mutation carriers were in high‐risk cancer families, while studies that found no association were conducted in specific populations and involved the analysis of founder mutations. A recent prospective study of 7015 women with a BRCA1 or BRCA2 mutation identified significant fivefold increased risk of colorectal cancer among BRCA1 mutation carriers younger than 50 years [standardized incidence ratio (SIR): 4.8; 95% CI: 2.2–9], but not in women with a BRCA2 mutation or in older women. Based on this evidence, women with BRCA1 mutations should be counseled about their increased risk for early‐onset colorectal cancer, and offered colonoscopy at 3‐ to 5‐year intervals between the ages of 40 and 50 years, and should follow population guidelines thereafter. 相似文献
17.
Lodder L Frets PG Trijsburg RW Klijn JG Seynaeve C Tilanus MM Bartels CC Meijers-Heijboer EJ Verhoog LC Niermeijer MF 《American journal of medical genetics. Part A》2003,(3):266-272
Genetic testing enables women at risk for hereditary breast and/or ovarian cancer to find out whether they have inherited the gene mutation, and if so, to opt for undergoing frequent surveillance and/or prophylactic surgery. However, the option to know about one's genetic status is not always seen as a benefit by women at risk. Motives for declining genetic testing were explored in 13 women at 25% or 50% risk to be a BRCA1/BRCA2 mutation carrier, who participated in a surveillance program for breast/ovarian cancer (the non-tested group). We hypothesized that high anxiety might be an important motive to decline testing. In addition, we investigated whether the non-tested group differed from a reference group of women who did undergo the test (tested group; n = 85) with regard to biographical factors, experience with cancer in relatives, and personality traits. Most non-tested women (10/13) were satisfied with participating in the surveillance program. Four reported to feel emotionally unprepared to cope with the consequences of testing. Compared with the tested group, the non-tested women had similar mean distress levels (which were not high), but a higher education level, they were more often childless, showed more reluctance towards prophylactic surgery, were younger when first confronted with a relative affected with breast/ovarian cancer, and were longer aware of the genetic nature of the disease. This study showed that women were more likely to have thoroughly reflected on their decision not to undergo genetic testing, than to deny the whole issue due to high anxiety. Being confronted at a relatively young age with breast/ovarian cancer in a relative, and being aware of the genetic risk for a many years, may have resulted in the risk for cancer becoming an integrated part of their lives. However, generalization of these results to women who neither underwent the test nor participated in a surveillance program should be considered with caution. 相似文献
18.
OBJECTIVE: The efficacy of population screening mammography for the age group of 50-74 years has been demonstrated. However, only limited data are available regarding women aged 75 and over, and recommendations for breast cancer screening in this age group vary in different countries. The aim of the current study is to review the evidence of the efficacy of breast cancer screening in women over the age of 74 years. METHODS: Studies published in English were retrieved by systematically searching MEDLINE (for papers published until August 2006), and by manually examining the references of the original articles and reviews retrieved. All studies that dealt with screening mammography over age 74 years were included. The studies were reviewed according to their outcomes and study design, focusing on breast cancer mortality and stage of breast cancer at diagnosis. RESULTS: Three studies focused on the relationship between breast cancer screening and mortality; in the 75-84 years age group, the risk of disease-specific mortality was approximately two-fold higher among women who did not perform screening mammography compared to women who did. Another four studies showed that women who underwent screening mammography had significantly smaller tumors and earlier disease stage at diagnosis. CONCLUSIONS: Regular mammography screening in older women may be associated with an earlier-stage disease and lower breast cancer mortality. These data support the use of screening mammography above age 75 years based on individual evaluations, rather than setting an upper age limit for breast cancer screening. 相似文献
19.
Bonadona V Sinilnikova OM Chopin S Antoniou AC Mignotte H Mathevet P Brémond A Martin A Bobin JY Romestaing P Raudrant D Rudigoz RC Léoné M Chauvin F Easton DF Lenoir GM Lasset C 《Genes, chromosomes & cancer》2005,43(4):404-413
The prevalence of BRCA1/2 germ-line mutations was assessed in a prospective population-based series of early-onset breast cancer (BC) patients in France, and the usefulness of a clinical assessment of hereditary BC risk, based on multiple criteria including pedigree structure, was evaluated. Through the Rhone region BC registry, 232 women diagnosed with BC before 46 years of age were included. They were tested for BRCA1/2 mutations an average of 10 months after diagnosis. All the women were classified according to their family history of cancer: high risk of hereditary breast cancer (HBC), low risk of HBC, isolated BC, and unknown HBC risk. Deleterious mutations were observed in 21 women (9.1%): 15 (6.5%) BRCA1 and 6 (2.6%) BRCA2. Mutations were more prevalent in women who developed BC before age 41 than in women who developed BC between ages 41 and 45 (12.8% versus 5.2%, respectively, P = 0.04). A high prevalence of BRCA1/2 mutations was found among women in the high-risk category with particular family features (i.e., small family size, predominantly male pedigree, specific cancers; 23.5%) and among women with isolated BC before age 41 and with five or fewer close adult female relatives (16.6%). According to the 10% probability level recommended by the American Society of Clinical Oncology guidelines for genetic testing of cancer, BRCA1/2 mutation screening should be considered for all women diagnosed before age 41, except for those with isolated BC in a large pedigree including multiple unaffected female relatives. The clinical assessment of HBC risk that we have developed should help in the decision to perform genetic testing. 相似文献
20.
Gronwald J Byrski T Huzarski T Cybulski C Stawicka M Szwiec M Debniak T Tulman A Sun P Oszurek O Lubinski J Narod SA 《Clinical genetics》2007,71(2):153-157
Among women with a BRCA1 mutation, the lifetime risks of breast and ovarian cancer are elevated. Several measures for reducing cancer risk in carriers of BRCA1 mutations have been proposed, including prophylactic surgery and tamoxifen chemoprevention. It is not yet known to what extent women with mutations have adopted these various preventive measures. We surveyed 414 Polish women with a BRCA1 mutation who had received counseling about various preventive strategies. Each woman completed a survey for a minimum of 18 months after receiving her genetic result. A high proportion of women reported having had an oophorectomy to reduce breast and ovarian cancer risk (49.1%). In contrast, only 11% had taken tamoxifen and only 5% had undergone a preventive mastectomy. Most of the women (81%) had a screening mammogram during the follow-up period. Oral contraceptives and breastfeeding are believed to protect against ovarian cancer, but only 9% of women had taken the birth control pill for 3 years or more and 27% had breastfed for 1 year or more. In summary, approximately one-half of Polish women with a BRCA1 mutation had taken an active step to reduce their risk of breast cancer within 18 months of receiving a positive result. A greater effort should be made to promote breastfeeding and use of oral contraceptive as risk-reducing measures. 相似文献