Establishing a Family Risk Assessment Clinic for Breast Cancer

Abstract:  Breast cancer is the most common cancer affecting European women and the leading cause of cancer-related death. A total of 15–20% of women who develop breast cancer have a family history and 5–10% a true genetic predisposition. The identification and screening of women at increased risk may allow early detection of breast cancer and improve prognosis. We established a family risk assessment clinic in May 2005 to assess and counsel women with a family history of breast cancer, to initiate surveillance, and to offer risk-reducing strategies for selected high-risk patients. Patients at medium or high risk of developing breast cancer according to NICE guidelines were accepted. Family history was determined by structured questionnaire and interview. Lifetime risk of developing breast cancer was calculated using Claus and Tyrer-Cuzick scoring. Risk of carrying a breast cancer-related gene mutation was calculated using the Manchester system. One thousand two hundred and forty-three patients have been referred. Ninety-two percent were at medium or high risk of developing breast cancer. Formal assessment of risk has been performed in 368 patients, 73% have a high lifetime risk of developing breast cancer, and 72% a Manchester score ≥16. BRCA1/2 mutations have been identified in 14 patients and breast cancer diagnosed in two. Our initial experience of family risk assessment has shown there to be a significant demand for this service. Identification of patients at increased risk of developing breast cancer allows us to provide individuals with accurate risk profiles, and enables patients to make informed choices regarding their follow-up and management.     

BRCA1/2 mutations and triple negative breast cancers

Identifying breast cancer patients at increased risk for carrying a mutation in the BRCA1 and BRCA2 genes is an important objective in clinical practice. Although age at diagnosis, family history of breast and/or ovarian cancer, and ethnicity are all essential parameters to consider when assessing risk, there are limitations as to how well such factors accurately predict BRCA1/2 status, even when quantitative risk models are applied. Integrating information about triple negative (TN) disease may help refine these estimates. Among newly diagnosed breast cancer patients, fewer than 10% have a mutation in the BRCA1 or BRCA2 genes, and up to 20% present However, among BRCA1 mutation carriers at least one-third have TN breast cancers. In this paper, we review key studies that have assessed breast cancer cases with a known BRCA1/2 status and triple marker data. We also discuss how integrating such information into qualitative and quantitative risk assessments of BRCA1/2 carrier probability may improve the ability to identify women who are appropriate candidates for genetic testing. Identifying women at increased risk is critical as knowledge of mutation status may impact surgical and systemic treatment in newly diagnosed patients, as well as recommendations for ovarian cancer risk management.     

Reasons for risk-reducing mastectomy versus MRI-screening in a cohort of women at high hereditary risk of breast cancer

Objective

To determine the reasons that motivate women in a cohort of women under intensive surveillance for breast cancer to undergo risk-reducing mastectomy (RRM).

Patients and methods

Women with a BRCA1 or BRCA2 mutation who were enrolled in an MRI-based breast screening study were eligible to participate in this survey. A self-administered questionnaire was given to women who did, and who did not terminate annual MRI-based surveillance in order to undergo RRM. The questionnaire included information on family history, risk perception and satisfaction with screening. In addition, women were asked to provide the principal reason for their choice of having preventive surgery or not, and were asked about their satisfaction with this choice.

Results

246 women without breast cancer participated in the study. Of these, 39 women (16%) elected to have RRM at some point after initiating screening. Although women who had a mother or sister with breast cancer were more likely to opt for RRM than were women with no affected first-degree relative (21% versus 10%) this did not reach statistical significance. Women who perceived their breast cancer risk to be greater than 50% were more likely to opt for RRM than were women who estimated their risk to be less than 50% (19% versus 6%). Fear of cancer was the most common reason cited for choosing to have RRM (38% of respondents) followed by having had a previous cancer, (25%), then concern over their children (16%).

Conclusion

Among women with a BRCA mutation who are enrolled in an MRI-based screening program, a high perception of personal breast cancer risk and a history of breast cancer in a first-degree relative are predictors of the decision to have RRM.     

Mammographic screening of the high-risk woman

Annual screening mammography beginning at age 40 is recommended for the general population. For some women at high risk for developing breast cancer at a younger age, annual screening may be appropriate starting at an earlier age. These women include those with a personal history of breast cancer, nontherapeutic radiation to the breasts especially for Hodgkin's disease, BRCA positive women, women with a family history of a first-degree relative with breast cancer at a young age, and women with a biopsy diagnosis of lobular carcinoma in situ or atypical ductal hyperplasia. Women with a biopsy diagnosis of atypical lobular hyperplasia develop breast cancer after age 40 and do not need earlier screening, unless they have a family history of breast cancer. Although increasing a woman's risk for breast cancer, radial scar does not increase risk for women younger than 40 years old and therefore does not require screening at a young age.     

A guide to establishing the risk for breast cancer in the plastic surgery patient

Plastic surgeons with a practice that includes breast augmentation, breast reduction, and breast reconstruction should have a working knowledge of both genetic and environmental breast cancer risk factors and of risk stratification of these patients. Specific tests to determine genetic susceptibility to certain cancers have become increasingly prevalent during recent years. Such testing is carried out by multidisciplinary teams, which may include plastic surgeons. Patients with a very strong family history of positive genetic testing for BRCA1 or BRCA2 may be offered prophylactic mastectomies. The authors present an overview of risk factors so that surgeons can stratify women appropriately with respect to their breast cancer risk. In addition to a brief literature review, the authors present 2 patients who represent the type of personal and family history of breast and/or ovarian cancer, and environmental risk factors that one would typically encounter in a plastic surgery patient population.     

Prophylactic Mastectomy

Abstract: Prophylactic mastectomy may be an appropriate treatment for several groups of women. These groups include women with a strong family history of breast cancer, especially those with known BRCA mutations, women with high risk pathologic changes found on previous breast biopsies, women with an immobilizing fear of developing breast cancer, and women with contralateral breast cancer. The effectiveness of prophylactic mastectomy is controversial although recent data suggests a possible gain in life expectancy for high risk women undergoing bilateral prophylactic mastectomy. Each woman should have a thorough discussion with her treatment team, which should include a oncologic surgeon, plastic surgeon, psychologist, and genetic counselor, to realistically assess her risk due to family history, genetic mutations, or high risk pathologic findings, as well as the expectations and limitations of prophylactic mastectomy.     

Breast cancer and ovarian cancer genetics

Breast and ovarian cancers are the second and fifth leading causes of cancer death, respectively, among women in the United States. Individuals with breast cancer have a 20--30% chance of having at least one relative with the disease. However, only 5--10% of the cases are a direct result of germline mutations in highly penetrable genes, such as BRCA1 and BRCA2 (BRCA1/2) as well as genes TP53 and PTEN. Since 1996, genetic testing for these mutations has been clinically available. A strategy for the management of women at increased familial risk of breast and ovarian cancers is described, which includes genetic assessment, chemoprevention, radiologic screening, and clinical and self-examination. Genetic testing should occur within a cancer genetic clinic after genetic counseling. A blood sample allows determination of the presence of the BRCA1 and BRCA2 genes, the TP53 gene, the PTEN gene, and the ATM gene. Tumor examination has identified a growth factor receptor gene, human epidermal growth factor receptor (HER-2).With regard to diet and lifestyle, women at increased risk of breast cancer could be advised to reduce dietary fat, avoid obesity, decrease alcohol consumption, and take regular exercise. Although chemoprotection is a valuable consideration, it is important to emphasize that the use of Tamoxifen in BRCA1 and BRCA2 mutation carriers is not established, nor is the optimum duration of benefit. An overview of the main outcomes of the current published studies confirms a 38% decrease in breast cancer incidence with Tamoxifen but recommends its use be restricted to women at high risk of breast cancer and low risk for potential side effects. The role of bilateral risk-reducing mastectomy or prophylactic mastectomy has been controversial for several reasons, including the psychosocial significance of the breast in Western cultures, the wide acceptance of breast conservation in surgery for early breast cancer, and the previous lack of data on its efficacy. The surgical procedure should aim to remove substantially all at-risk breast tissue. However, there is a balance between reduction of cancer risk and cosmetic outcome. Bilateral prophylactic oophorectomy can significantly decrease ovarian cancer risk in women who carry BCRA1 mutations. Oophorectomy lowers the risk of breast cancer, even in women who have previously used hormone replacement therapy. There are no published randomized controlled trials examining the effectiveness of mammographic screening in women under 50 years of age with a family history of breast cancer. However, the published studies do suggest that mammographic screening of a high-risk group of women under 50 years of age may detect cancer at a rate equivalent to that seen in women 10 years older with normal risk. Other initial studies also support MRI as having a greater sensitivity than mammography in high-risk women. Breast clinical and self-examination is often advocated, but its effectiveness is unproved, and only one randomized study has been undertaken in women at risk. On the basis of this study as well as one nonrandomized study, it can be concluded that clinical examination as well as mammography are essential in detecting breast cancer. under 50 years of age with a family history of breast cancer. However, the published studies do suggest that mammographic screening of a high-risk group of women under 50 years of age may detect cancer at a rate equivalent to that seen in women 10 years older with normal risk. Other initial studies also support MRI as having a greater sensitivity than mammography in high-risk women. Breast clinical and self-examination is often advocated, but its effectiveness is unproved, and only one randomized study has been undertaken in women at risk. On the basis of this study as well as one nonrandomized study, it can be concluded that clinical examination as well as mammography are essential in detecting breast cancer.     

Patient and medical barriers preclude uptake of tamoxifen preventative therapy in women with a strong family history

AimsTo assess the eligibility, uptake and impediments to tamoxifen use in high-risk women attending a risk management clinic due to family history.Patients and methodsAll patients with a germline mutation in a cancer predisposing gene or at high genetic risk (based on family history) attending a Breast and Ovarian cancer risk management clinic from February 2014 to May 2015 received both verbal and written evidence-based information on preventive therapy and were recommended to consider endocrine prevention if not contraindicated. Endocrine therapy initiation, use and cessation were captured. Patient eligibility was analysed and reasons for declining, ceasing or contraindications for medication use were recorded.ResultsDuring the study period, 237 women were seen over 305 consultations for breast surveillance and preventative therapy discussion. They comprised 38 BRCA1 and 42 BRCA2 mutation carriers, 4 with Peutz-Jegher syndrome, 153 with a strong family history. Their median age was 39.4 years. Endocrine preventative was considered and discussed with all but 19 women. Of the remaining 218, 34 chose bilateral prophylactic mastectomy, while endocrine preventative was not recommended in 50 women due to contraindications and 25 women declined treatment due to their intention to fall pregnant. In 118 patients who remained eligible, 18.6% (22) tried prevention and 9.4% (14) remained on therapy.ConclusionsPhysician-reluctance is not a dominant reason for poor uptake of endocrine prevention even by high-risk premenopausal women in a specialised risk management clinic. Many women are not eligible, and most elect for alternative options.     

Prevalence of family history of breast and ovarian cancer in a single primary care practice using a self-administered questionnaire

Women at high risk of hereditary breast and/or ovarian cancer require specific management strategies for cancer prevention and early detection. The goal of this study was to determine the prevalence of familial breast and ovarian cancer among patients in a primary care practice. Questionnaires were mailed to the 608 women less than 81 years of age in a single primary care practice. Additional mailings and phone calls were used for nonresponders. Data were analyzed by bloodline, the degree of relative, age of diagnosis and cancer type. Women were grouped into three categories of breast/ovarian family history: "no family history,"insignificant family history," and "significant potentially high-risk family history" (women with two or more relatives in a single bloodline with breast and/or ovarian cancer, a single individual with bilateral breast cancer or breast and ovarian cancer, or breast and/or ovarian cancer at less than 40 years of age). A pedigree analysis of women categorized as "significant potentially high-risk family history" further classified these women as to the likelihood of being at risk for hereditary cancer. Data were obtained from 567 women (93%); 27 patients with a personal diagnosis of breast and/or ovarian cancer were excluded. Of the 540 remaining respondents, 351 (65%) had no family history of cancer, 138 (25.6%) had an insignificant family history, and 51 (9.4%) had a significant family history. Based on pedigree analysis of these 51 patients, 19 were unlikely to be at high risk for hereditary cancer, and 32 (6%) were likely to be at significant risk and warrant intensive evaluation. The large proportion of women identified with a significant family history of breast and/or ovarian cancer has major implications regarding the magnitude of a population-based process to identify and manage high-risk individuals.     

Assessing the Knowledge and Attitudes Regarding Genetic Testing for Breast Cancer Risk in our Region of Southeastern Georgia

Abstract: Genetic testing for the breast cancer susceptibility genes, BRCA1 and BRCA2, has been available for over a decade. Positive test results carry significant medical, psychological, and social implications. Knowledge of the public’s awareness concerning BRCA testing, and perceived benefits and barriers to testing can help refine educational programs and identify subgroups needing additional support. Patients and their acquaintances with a breast complaint attending a surgical clinic or private office were asked to complete a questionnaire about their knowledge of breast cancer genes and their desire to be tested. Demographic information collected included ethnicity, education background, age, income, and personal and family history of breast cancer, knowledge of BRCA genes and testing, and their willingness to participate in genetic counseling. A total of 222 people completed the questionnaire that showed the majority of subjects in southeast Georgia believe breast cancer is inherited 26–50% of the time. Caucasians and those with advanced degrees are the most informed regarding awareness of BRCA genes (p < 0.05); the least informed groups include African Americans and those with no more than a college education. Participants with a family history of breast cancer were significantly more likely to know that genes had been identified that indicate an increased risk of breast cancer (p < 0.05). A history of breast cancer did not impact the degree of awareness (p > 0.05). Subjects aware of genetic testing are more willing to utilize counseling (p < 0.05). Perceptions of breast cancer inheritance, awareness of susceptibility genes, and availability of testing and counseling are not uniform among all population subgroups. In southeast Georgia, educational efforts should focus on the less educated and minority groups.     

Overestimation of hereditary breast cancer risk.

OBJECTIVE: To find out how women with breast or ovarian cancer rate their chances of carrying hereditary factors for these cancers and to determine the extent to which they overestimate their risk. SUMMARY BACKGROUND DATA: BRCA1 and BRCA2 are genes that cause breast and ovarian cancer when they are inherited in families. Testing for disease-associated mutations in these genes is now available commercially. Previous studies have shown that women overestimate their chances of carrying mutations. However, women's perceptions of risk have not been compared to objective estimates or to actual BRCA1 and BRCA2 testing results. METHODS: This study examines estimates of carrying BRCA1 and BRCA2 mutations among women participating in a randomized trial comparing alternative precounseling educational materials. Estimates were provided by participants in a baseline mailed survey. Estimates given by participants were compared to those given by an expert panel and by a statistical model. Testing was offered free of charge and was done in an academic laboratory using standard techniques. Baseline estimates of participating women were compared to the estimates of the expert panel, to the carrier probability provided by the statistical model, and to actual testing results. RESULTS: Women who have a personal history of breast or ovarian cancer significantly overestimate their risk of carrying hereditary factors for breast and ovarian cancer. Self-estimates exceeded the estimates of experts and a statistical model. One hundred women completed testing, and 21 mutations in BRCA1 or BRCA2 were found. Many test-negative women also overestimated their hereditary risk. Some women with a high carrier probability were negative for BRCA1 and BRCA2 mutations. CONCLUSIONS: Overestimation of hereditary factors is common among affected women with a family history of cancer. Pretest education and counseling should reduce these high-risk perceptions. Better estimates of carrier probability will direct more intensive clinical services and research.     

Family history of breast cancer,mammographic breast density and breast cancer risk: Findings from a cohort study of Korean women

BackgroundThis study investigated whether the association between family history of breast cancer in first-degree relatives and breast cancer risk varies by breast density.MethodsWomen aged 40 years and older who underwent screening between 2009 and 2010 were followed up until 2020. Family history was assessed using a self-reported questionnaire. Using Breast Imaging Reporting and Data System (BI-RADS), breast density was categorized into dense breast (heterogeneously or extremely dense) and non-dense breast (almost entirely fatty or scattered areas of fibro-glandular). Cox regression model was used to assess the association between family history and breast cancer risk.ResultsOf the 4,835,507 women, 79,153 (1.6%) reported having a family history of breast cancer and 77,238 women developed breast cancer. Family history led to an increase in the 5-year cumulative incidence in women with dense- and non-dense breasts. Results from the regression model with and without adjustment for breast density yielded similar HRs in all age groups, suggesting that breast density did not modify the association between family history and breast cancer. After adjusting for breast density and other factors, family history of breast cancer was associated with an increased risk of breast cancer in all three age groups (age 40–49 years: aHR 1.96, 95% confidence interval [CI] 1.85–2.08; age 50–64 years: aHR 1.70, 95% CI 1.58–1.82, and age ≥65 years: aHR 1.95, 95% CI 1.78–2.14).ConclusionFamily history of breast cancer and breast density are independently associated with breast cancer. Both factors should be carefully considered in future risk prediction models of breast cancer.     

The genetics of breast cancer

Breast cancer is the commonest cancer affecting women. A family history of breast cancer increases a woman’s lifetime risk of developing the disease. Most of the genetic risk is due to low-risk and moderate-risk susceptibility alleles rather than high-penetrance genes such as BRCA1 and BRCA2. Pathogenic variants in these two tumour suppressor genes only account for about 2% of all breast cancers. Female carriers of the BRCA gene pathogenic variants have a high lifetime risk of developing breast and ovarian cancer and male carriers have an increased risk of prostate and breast cancer.     

The genetics of breast cancer

Breast cancer is the commonest cancer affecting women. A family history of breast cancer increases a woman's lifetime risk of developing the disease. Most of the genetic risk is due to low-risk and moderate-risk susceptibility alleles rather than high-penetrance genes such as BRCA1 and BRCA2. Mutations in these two tumour suppressor genes only account for about 2% of all breast cancers. Female carriers of BRCA gene mutations have a high lifetime risk of developing breast and ovarian cancer and male carriers have an increased risk of prostate and breast cancer.     

Medical Management of newly diagnosed breast cancer in a BRCA1/2 mutation carrier

Germline BRCA1/2 mutations may be infrequent in unselected breast cancer population but are concentrated in those with triple‐negative breast cancer or high‐risk family history. Insight into the biology of BRCA mutation is now allowing a targeted therapeutic approach to these carriers with breast cancer. Functional BRCA genes play a critical role in DNA damage repair. Agents such as platinum salts and poly (ADP‐ribose) polymerase (PARP) inhibitors exploit this vulnerability of impaired DNA damage repair mechanism in BRCA mutant cancers to leverage therapeutic benefit. Research has demonstrated improved response rates to platinum salts in BRCA‐mutated compared with non‐BRCA‐mutated breast cancer, particularly in the metastatic setting. Additionally, clinical trials of single‐agent PARP inhibitors have shown encouraging response rates and progression‐free survival in patients with BRCA1/2‐mutated breast cancer. In this review, we summarize the medical management of BRCA‐associated breast cancer.     

Breast cancer risk in relation to alcohol consumption and BRCA gene mutations--a case-only study of gene-environment interaction

The variable penetrance of the BRCA1 and BRCA2 genes suggests that other genetic or environmental factors may interact with these mutations to modify breast cancer risk. The objective of this study was to measure departures from multiplicative effects of alcohol consumption and BRCA gene mutations. A cohort of French-Canadian breast cancer patients was tested for BRCA gene mutations and completed a food frequency questionnaire. The case-only odds ratio (COR) was calculated. A total of 857 women, including 10 BRCA1 and 33 BRCA2 mutation carriers, participated in the study. No significant interaction between alcohol consumption and BRCA1 mutations was detected, although the interaction with wine consumption suggested a sub-multiplicative effect (COR = 0.38, 95% CI: 0.08-1.81). Consumption of alcohol other than wine interacted significantly with BRCA2 mutations (COR = 2.15, 95% CI: 1.03-4.49). Consumption of wine may protect against BRCA1-associated tumors, while women with BRCA2 mutations may be at greater risk of alcohol-induced breast cancer.     

The breast surgeon's role in BRCA1 and BRCA2 testing

Five percent to 10% of all women who develop breast cancer carry a hereditary mutation in the genes BRCA1 or BRCA2. Genetic testing is now clinically available, and the results of such testing can dramatically alter a patient's risks for an ipsilateral or contralateral primary breast cancer and ovarian cancer. Therefore, genetic testing will become integral in tailoring surveillance, chemoprevention, and surgical management plans for patients at risk for hereditary cancer syndromes. Such results will also impact the cancer risks for the patient's nuclear and extended family members. Surgeons will play a pivotal role in eliciting personal and family histories from patients, determining which of those histories is suggestive of a germline mutation, facilitating referrals for genetic counseling and testing, and incorporating the results of genetic testing into the patient's short- and long-term management plans.     

Risk-reducing mastectomy

Breast cancer is a malignant proliferation of epithelial cells lining the ducts or lobules of the breast. Excluding skin cancer, breast cancer is the most common cancer in women. Only lung cancer accounts for more cancer deaths in women. Breast cancer may exist for a long period either as an invasive or noninvasive disease, but not as a nonmetastatic disease. Consequently, timely diagnosis and appropriate management are lifesaving. Approximately 10% of human breast cancers are linked to germline mutations, such BRCA1 and BRCA2. Correct staging of breast cancer patients is critical. It permits an accurate diagnosis, as well as in many cases, therapeutic decisions based largely on the TNM classification. Staging provides the most important prognostic variable. Second opinions of the staging of breast cancer by pathologic examination of the tissue is recommended. There are some variables in which the association with disease-free survival and overall survival seem clear and include estrogen and progesterone receptor cells, S-phase analysis using flow cytometry, histologic classification, molecular changes in the tumor as well as neovasculature semi-quantitative scoring systems. There are four objectives to risk-reducing mastectomy. First, risk-reducing mastectomy should reduce the incidence of breast cancer in high-risk women, for example, BRCA1 or BRCA2 carriers. It should reduce mortality from breast cancer in high-risk women. Moreover, it should have psychological benefits in relieving anxiety about developing breast cancer. Finally, there must be a balance in the reduction in risk against cosmetic outcome, with subsequent quality of life issues. Women should be offered risk reduction mastectomy only on the basis of a strict selection and management plan, like that used in Manchester protocol. This protocol involves a minimum of two sessions with a geneticist/oncologist, a session with a psychiatrist and two sessions with a plastic and reconstructive surgeon with the support of a breast care nurse. The surgical technique should aim at removing substantially all at-risk breast tissue. However, there is an obvious balance between reduction of cancer risk and cosmetic outcome. The surgical technique involves several operations to include the risk-reducing mastectomy as well as breast reconstructive procedures. Skin-sparing mastectomy represents a new surgical approach that allows a mastectomy, whereas preserving the natural skin envelope of the breast. Breast reconstruction will involve several operations, especially if the nipple areola complex is resected and is subsequently reconstructed. The contraindications to risk-reducing mastectomy include the following. The status of the family history or Munchausen's syndrome has not been confirmed. The risk-reducing mastectomy is not the women's own choice. The patient has a current psychiatric disorder including clinical depression, cancer phobia or body dysmorphic syndrome. If the co-morbidity outweighs the clinical benefits, surgery should not be undertaken. Finally, the patient must not have unrealistic expectations of the benefits of surgery. She must understand the subsequent risk-reducing mastectomy may significantly reduce, but not eliminate the risk of subsequent breast cancer.     

Limitations of the Gail model in the specialized breast cancer risk assessment clinic

The Gail model is a risk assessment tool that is accurate for general breast cancer risk screening. Because of the limited way that this model incorporates family history information, however, there are concerns that it may underestimate risk for many women attending specialized breast cancer risk assessment clinics. We collected comprehensive breast cancer risk factor information for 213 women attending a specialized breast cancer risk assessment clinic using a modified version of the CancerGene software. Breast cancer risk was calculated using the models of Gail and Claus as well as BRCAPRO and the tables of Bodian (for women with lobular neoplasia). Eighty-six percent of the women had a family history of breast cancer. Although 74% of women had risk factor histories that are thought to confound the Gail model (family history of breast cancer in second-degree relatives, family history of breast cancer before the age of 50, family history of bilateral breast cancer, family history of ovarian cancer, or personal history of lobular neoplasia), the inclusion of other models increased the risk level assignment in only 13% of the cases. We conclude that the Gail model is an appropriate risk assessment tool for most women attending specialized clinics, although the inclusion of models better able to account for family history information and personal history of lobular neoplasia is required to accommodate all women.     

Management of women at high risk for breast cancer: new imaging beyond mammography

The management of women with an increased lifetime risk of breast cancer is a difficult task. This is especially true for women with a documented mutation in a breast cancer susceptibility gene (BRCA), and also for those who tested negative for a mutation, but have a family history that is suggestive of familial breast cancer. Primary prevention by prophylactic mastectomy has been shown to reduce breast cancer incidence in these women, but this intervention is still not considered a "first-line" option in the majority of guidelines. Instead, secondary prevention (intensified surveillance) is recommended. However, due to the early onset of familial breast cancer, screening must start at a substantially younger age than in women at average risk. This, together with the fact that familial breast cancers may differ from sporadic cancers in many aspects, will have a significant impact on the design and on the success rates of surveillance protocols. This article describes the different management options that exist for women at increased genetic risk and provides a survey of the current evidence regarding mammographic and non-mammographic imaging techniques. The conclusion is that mammographic screening, with or without concomitant ultrasound and clinical breast examination, is probably not sufficient to ensure an early diagnosis of familial breast cancer. If MRI is integrated in surveillance programs, early diagnosis seems to be possible. Still, the efficacy of screening even with MRI is unclear in terms of morbidity and mortality, and this lack of evidence must be communicated to women at high genetic risk.