Breast Cancer In First-degree Relatives Research Articles

Association between melanocytic nevi and risk of breast diseases: The French E3N prospective cohort.

While melanocytic nevi have been associated with genetic factors and childhood sun exposure, several observations also suggest a potential hormonal influence on nevi. To test the hypothesis that nevi are associated with breast tumor risk, we explored the relationships between number of nevi and benign and malignant breast disease risk. We prospectively analyzed data from E3N, a cohort of French women aged 40-65 y at inclusion in 1990. Number of nevi was collected at inclusion. Hazard ratios (HRs) for breast cancer and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Associations of number of nevi with personal history of benign breast disease (BBD) and family history of breast cancer were estimated using logistic regression. Over the period 15 June 1990-15 June 2008, 5,956 incident breast cancer cases (including 5,245 invasive tumors) were ascertained among 89,902 women. In models adjusted for age, education, and known breast cancer risk factors, women with "very many" nevi had a significantly higher breast cancer risk (HR = 1.13, 95% CI = 1.01-1.27 versus "none"; ptrend = 0.04), although significance was lost after adjustment for personal history of BBD or family history of breast cancer. The 10-y absolute risk of invasive breast cancer increased from 3,749 per 100,000 women without nevi to 4,124 (95% CI = 3,674-4,649) per 100,000 women with "very many" nevi. The association was restricted to premenopausal women (HR = 1.40, ptrend = 0.01), even after full adjustment (HR = 1.34, ptrend = 0.03; phomogeneity = 0.04), but did not differ according to breast cancer type or hormone receptor status. In addition, we observed significantly positive dose-response relationships between number of nevi and history of biopsy-confirmed BBD (n = 5,169; ptrend<0.0001) and family history of breast cancer in first-degree relatives (n = 7,472; ptrend = 0.0003). The main limitations of our study include self-report of number of nevi using a qualitative scale, and self-reported history of biopsied BBD. Our findings suggest associations between number of nevi and the risk of premenopausal breast cancer, BBD, and family history of breast cancer. More research is warranted to elucidate these relationships and to understand their underlying mechanisms.

Risk Factors for Premenopausal Breast Cancer: A Case-control Study in Uruguay

In order to thoroughly analyze risk factors of breast cancer (BC) in premenopausal Uruguayan women, a case-control study was carried out at the Pereira Rossell Women's Hospital, Montevideo, where 253 incident BC cases and 497 frequency-matched healthy controls were interviewed on menstrual and reproductive story, were administered a short food frequency questionnaire and undertook a series of body measurements necessary to calculate body composition and somatotype. Odds ratio (OR) coefficients were taken as estimates of relative risk derived from unconditional logistic regression. Among the classical risk factors, only the family history of BC in first degree relatives was significantly associated with risk of premenopausal BC (OR=2.20, 95% CI 1.33-3.62). Interestingly, this risk factor was found to be stronger in women of ages >40 (OR=4.05, 95% CI 2.10-7.81), late menarche (OR= 2.39, 95% CI 1.18-4.85), early age for their first delivery (OR=3.02, 95% CI 1.26-7.22), short time between menarche and first delivery (OR=3.22, 95% CI 1.29-8.07), and with high parity (OR=4.10, 95% CI 1.79-9.36), although heterogeneity was detected only for age and parity. High consumption of red meat was positively associated with the disease risk (OR=2.20, 95% CI 1.35-3.60), in the same way as fried foods (OR=1.79, 95% CI 1.12-2.84). Conversely, a high intake of plant foods displayed a protective effect (OR=0.41, 95% CI 0.26-0.65). Except for hypertension (OR=1.55, 95% CI 1.03-2.35), none of the analyzed components of metabolic syndrome were associated to BC risk. Particular increases of risk for premenopausal BC were found for family history in first degree relatives in certain subsets derived from the menstrual-reproductive history. Preventive strategies could broaden their scope if new studies confirm the present results, in view of the limited prevention measures that premenopausal BC currently has.

Abstract PR-08: The willingness to accept chemoprevention strategies by women at increased risk of breast cancer

Abstract Background: Women who are at increased risk of breast cancer (BC), are largely not accepting of chemoprevention therapies (CPTs). Further, proven behavioral constructs were not employed in previous studies that assessed the correlates of acceptance of CPTs. Thus, we used the Breast Cancer Risk Reduction Health Belief scale, a validated instrument for assessing the health-seeking behavior of women who were at increased risk of BC with respect to being willing to accept risk assessment, CPTs counseling, or the therapies. Methods: Using the data from the Acceptance of Breast Cancer Chemoprevention Therapies Project, a cross-sectional telephone survey, we assessed the association of the sociodemographic, socioeconomic, knowledge of BC prevention and care strategies, health care access or utilization characteristics, and the factor-derived Health Belief Model constructs with the endpoints mentioned above (i.e. that had 5-point Likert style response options), in 265 consecutively recruited Caucasian (n=83), Latinas (n=73), African American (n=103) or unknown (n=6) women, who were of diverse socioeconomic backgrounds, and at increased risk of BC. Student's t tests, chi square, or multiple linear regression analyses were used to compare the covariates with the respective endpoints. Results: Most participants were in the 50-69 years age group (66.4%), of African American race/ethnicity (39.8%), single (58%), or of lower socioeconomic status (i.e., they had a high school education or less [65.3%], earned &amp;lt; $30,000 per annum before taxation [75.2%], etc). A slight majority had only publicly sponsored health insurance (50.5%), most had a regular physician (87.5%), had had a mammogram (98.8%), or screened annually (60%). Following multiple linear regression analyses, being willing to accept risk assessment, correlated positively with perceived susceptibility to BC (p=.03), or having higher knowledge test scores (p&amp;lt;.01), and negatively with being an African American with only elementary education (p&amp;lt;.001). Being willing to accept CPTs counseling correlated positively with being highly motivated based on self efficacy, perceived benefits and positive family-related cues (p&amp;lt;.001), or perceiving BC as life threatening (p&amp;lt;.01), and negatively with being of African American race/ethnicity (p=.02), being high school educated (p=.01), having a history of BC in first-degree relatives (p=.03), or ≥3 current medications (p=.05). Being willing to accept CPTs correlated positively being highly motivated based on self efficacy, perceived benefits, and positive family-related cues (p&amp;lt;.0001), and negatively with having a regular physician (p&amp;lt;.01), a history of other cancer (p&amp;lt;.01), being of African American race/ethnicity (p=.01), current age (p=.02), or having annual mammograms (p=.05). Conclusions: The correlates of the willingness to accept chemoprevention strategies differed by the specific strategies. Further, future interventions should be targeted towards not just the eligible women, but also their families, and their physicians, and should take into consideration pertinent behavioral constructs, personal and health care-related characteristics. Impact: Through our results, we have laid a firm foundation for future tailored interventions to enhance informed decision making about BC CPTs. Citation Information: Cancer Prev Res 2010;3(12 Suppl):PR-08.

Family history of breast cancer in first-degree relatives and triple-negative breast cancer risk

Triple-negative breast cancer accounts for less than 20% of breast cancers overall, but is the predominant subtype among carriers of mutations in BRCA1. However, few studies have assessed the association between breast cancer family history and risk of triple-negative breast cancer. We examined the relationship between having a family history of breast cancer in first-degree relatives and risk of triple-negative breast cancer, and risk of two other breast cancer subtypes defined by tumor marker expression. We evaluated data collected by the Breast Cancer Surveillance Consortium from 2,599,946 mammograms on 1,054,466 women, among whom 15% reported a first-degree family history of breast cancer. Using Cox regression in this cohort, we evaluated subtype-specific associations between family history and risk of triple-negative (N = 705), estrogen receptor-positive (ER+, N = 10,026), and hormone receptor-negative/HER2-expressing (ER-/PR-/HER2+, N = 308) breast cancer among women aged 40-84 years. First-degree family history was similarly and significantly associated with an increased risk of all the subtypes [hazard ratio (HR) = 1.73, 95% confidence interval (CI): 1.43-2.09, HR = 1.62, 95% CI: 1.54-1.70, and HR = 1.56, 95% CI: 1.15-2.13, for triple-negative, ER+, and ER-/PR-/HER2+, respectively]. Risk of all the subtypes was most pronounced among women with at least two affected first-degree relatives (versus women with no affected first-degree relatives, HR(triple-negative) = 2.66, 95% CI: 1.66-4.27, HR(ER+) = 2.05, 95% CI: 1.79-2.36, HR(ER)-(/PR)-(/HER2+) = 2.25, 95% CI: 0.99-5.08). Having a first-degree family history of breast cancer was associated with an increased risk of triple-negative breast cancer with a magnitude of association similar to that for the predominant ER+ subtype and ER-/PR-/HER2+ breast cancer.

A constant risk for familial breast cancer? A population-based family study

IntroductionThe incidence of breast cancer in the unaffected breast of women with previous breast malignancy remains constant after the first diagnosis. We investigated whether there is a similar pattern in the breast cancer incidence in first-degree relatives of breast cancer patients. We studied the risk for breast cancer in mothers at ages older than their daughter's age at diagnosis.MethodsWe analyzed a Swedish population-based cohort with complete family links and calculated incidence rates of breast cancer in mothers of 48,259 daughters diagnosed with breast cancer.ResultsThe risk for breast cancer in mothers of breast cancer patients is elevated relative to the background population at all ages. Mothers have an overall incidence of 0.34%/year at ages older than a daughter's age at diagnosis. This rate is not affected to any large extent by the daughter's age at diagnosis. A constant incidence rate of 0.40%/year from age 35 years onward is seen in mothers of breast cancer patients diagnosed before 35 years of age. For mothers of daughters diagnosed at age 35 to 44 years the incidence pattern is less clear, with the rate being stable for approximately 20 years after the daughter's age at diagnosis and rising thereafter. Older age at a daughter's diagnosis (≥ 45 years) appears to confer an age-dependent increase in incidence in the mother.ConclusionsIncidence of familial breast cancer in first-degree relatives may increase to a high and constant level by a predetermined age that is specific to each family. This phenomenon appears inconsistent with accepted theories of malignant transformation.

Age-Specific Incidence of Breast Cancer in Breast Cancer Survivors and Their First-Degree Relatives

The incidence rate of breast cancer in first-degree relatives of women with breast cancer has been hypothesized to become constant at a predetermined age in accordance with observations of a high, roughly constant incidence rate of contralateral breast cancer by age. We attempted to test this hypothesis in the Danish population with cancer registry data. We determined the age-specific incidence rates of contralateral breast cancer in Danish women who had a first breast cancer before they were 50 years of age and the rates of breast cancer among their first-degree female relatives during 1943 to 1999. The observed rates were tested for trends chi test or evaluated in Cox proportional hazard models. A high incidence rate of contralateral breast cancer was observed in women aged 25-44 years, followed by a decreasing rate, which reached a level corresponding to the rate per breast in the general female population at age 65. At ages older than the index patients age at diagnosis, their first-degree female relatives showed significantly increasing incidence rates of breast cancer by age, with a relatively constant absolute difference of 187 breast cancers per 100,000 person-years between the observed rates and the expected rates. The rate of contralateral breast cancer is particular high at young ages but the excess ebbs as the cohort ages, perhaps due to elimination of predisposed individuals at early ages from the cohort of survivors. First-degree relatives seem to share breast cancer susceptibility genes with the family proband resulting in a constant excess rate of breast cancer throughout life.

Epidemiology, genetics, and risk evaluation of postmenopausal women at risk of breast cancer

Breast cancer risk factors have been studied for the past three decades, and the single most important risk factor is age. Hormonally linked adult reproductive and anthropometric risk factors contribute to the etiology of postmenopausal breast cancer. The risk of breast cancer increases among women older than 50 years of age who have benign breast disease, especially those with atypical ductal or lobular hyperplasia. Lobular carcinoma in situ increases risk significantly, as do a family history of breast cancer in first-degree relatives and the presence of BRCA1 or BRCA2 mutations. Diet, exercise, and environmental factors play a very small role in overall risk. Mammographic breast density increases relative risk fivefold among women with the highest density, and breast cancer risk is two to three times greater in women with elevated serum levels of estradiol or testosterone. Multivariate risk models allow determination of composite relative risks and cumulative lifetime risk, although improved models for African American women are required. For postmenopausal women, newer risk models are being developed and validated that include age, breast density, race, ethnicity, family history of breast cancer, a previous breast biopsy, body mass index, age at onset of natural menopause, hormone therapy, and previous false-positive mammography. A simpler model that includes only age, breast cancer in first-degree relatives, and previous breast biopsy performs well for estrogen receptor-positive breast cancer in postmenopausal women. As many as 10 million women in the United States are at increased risk, and clinicians are obligated to identify these women and manage their risk appropriately.

Population-based estimates of the relation between breast cancer risk, tumor subtype, and family history

Many studies that have estimated the breast cancer risk attributable to family history have been based on data collected within family units. Use of this study design has likely overestimated risks for the general population. We provide population-based estimates of breast cancer risk and different tumor subtypes in relation to the degree, number, and age at diagnosis of affected relatives. Cox Proportional Hazards to calculate risks (hazard ratios; 95% confidence interval) of breast cancer and tumor subtypes for women with a family history of breast cancer relative to women without a family history among a cohort of 75,189 women age >or=40 years of whom 1,087 were diagnosed with breast cancer from June 1, 2001-December 31, 2005 (median follow-up 3.16 years). Breast cancer risk was highest for women with a first-degree family history (1.54; 1.34-1.77); and did not differ substantially by the affected relative's age at diagnosis or by number of affected first-degree relatives. A second-degree family history only was not associated with a significantly increased breast cancer risk (1.15; 0.98-1.35). There was a suggestion that a positive family history was associated with risk of triple positive (Estrogen+/Progesterone+/HER2+) and HER2-overexpressing tumors. While a family history of breast cancer in first-degree relatives is an important risk factor for breast cancer, gathering information such as the age at diagnosis of affected relatives or information on second-degree relative history may be unnecessary in assessing personal breast cancer risk among women age >or=40 years.

Active screening allowing to compare breast cancer staging and its impact at population survival between Brazil and developed countries

Women with a family history of breast cancer are at increased risk of the disease, but no study has been large enough to characterise reliably how, over women's lives, this risk is influenced by particular familial patterns of breast cancer. This report, on the relevance of breast cancer in first-degree relatives, is based on combined data from 52 epidemiological studies.Individual data on breast cancer in first-degree relatives (mothers, sisters, and daughters) of 58 209 women with breast cancer and of 101 986 controls were collected, checked, and analysed centrally. Risk ratios for breast cancer were calculated by conditional logistic regression, stratified by study, age, menopausal status, number of sisters, parity, and age when the first child was born. Breast-cancer incidence and mortality rates for particular family histories were calculated by applying age-specific risk ratios to breast-cancer rates typical for more-developed countries.Altogether 7496 (12·9%) women with breast cancer and 7438 (7·3%) controls reported that one or more first-degree relatives had a history of breast cancer: 12% of women with breast cancer had one affected relative and 1% had two or more. Risk ratios for breast cancer increased with increasing numbers of affected first-degree relatives: compared with women who had no affected relative, the ratios were 1·80 (99% CI 1·69–1·91), 2·93 (2·36–3·64), and 3·90 (2·03–7·49), respectively, for one, two, and three or more affected first-degree relatives (p<0·0001 each). The risk ratios were greatest at young ages, and for women of a given age, were greater the younger the relative was when diagnosed. The results did not differ substantially between women reporting an affected mother (9104) or sister (6386). Other factors, such as childbearing history, did not significantly alter the risk ratios associated with a family history of breast cancer. For women in more-developed countries with zero, one, or two affected first-degree relatives, the estimated cumulative incidence of breast cancer up to age 50 was 1·7%, 3·7%, and 8·0%, respectively; corresponding estimates for incidence up to age 80 were 7·8%, 13·3%, and 21·1%. Corresponding estimates for death from breast cancer up to age 80 were 2·3%, 4·2%, and 7·6%. The age when the relative was diagnosed had only a moderate effect on these estimates.Eight out of nine women who develop breast cancer do not have an affected mother, sister, or daughter. Although women who have first-degree relatives with a history of breast cancer are at increased risk of the disease, most will never develop breast cancer, and most who do will be aged over 50 when their cancer is diagnosed. In countries where breast cancer is common, the lifetime excess incidence of breast cancer is 5·5% for women with one affected first-degree relative and 13·3% for women with two.

Higher levels of central adiposity in healthy premenopausal women with family histories of premenopausal breast cancer

Research strongly suggests that lower overall adiposity and higher central adiposity are independent risk factors for premenopausal breast cancer in the general population. We aimed to test the possibility that these factors may contribute to familial risk of premenopausal breast cancer. A convenience sample of healthy women, ages 25-49, was recruited to yield three study groups: (1) Women with first-degree family histories of premenopausal breast cancer, operationally defined as being diagnosed prior to age 50 (Group FH < 50, n = 39); (2) Women with first-degree family histories of postmenopausal breast cancer, operationally defined as being diagnosed at age 50 or after (Group FH > or = 50, n = 33); and (3) Women without a history of breast cancer in first-degree relatives (Group FH-, n = 132). Multinomial logistic regression analyses, including possible confounders, waist circumference, and BMI, revealed a lower BMI among FH < 50 compared to either FH- (OR = 0.72; 95% CI = 0.59-0.87), or FH > or = 50 women (OR = 0.75; 95% CI = 0.60-0.95), and higher waist circumferences in FH < 50 compared to either FH- (OR = 1.15; 95% CI = 1.06-1.25), or FH > or = 50 women (OR = 1.16; 95% CI = 1.05-1.28). No group differences were seen for waist skinfold measures. These results support the possibility that differences in patterns of adiposity may contribute to familial risk of premenopausal breast cancer, and suggest the importance of conducting large scale, population-based studies of the link between body size characteristics and familial breast cancer risk.

Predicting Risk of Breast Cancer in Postmenopausal Women by Hormone Receptor Status

Strategies for estrogen receptor (ER)-positive breast cancer risk reduction in postmenopausal women require screening of large populations to identify those with potential benefit. We evaluated and attempted to improve the performance of the Breast Cancer Risk Assessment Tool (i.e., the Gail model) for estimating invasive breast cancer risk by receptor status in postmenopausal women. In The Women's Health Initiative cohort, breast cancer risk estimates from the Gail model and models incorporating additional or fewer risk factors and 5-year incidence of ER-positive and ER-negative invasive breast cancers were determined and compared by use of receiver operating characteristics and area under the curve (AUC) statistics. All statistical tests were two-sided. Among 147,916 eligible women, 3236 were diagnosed with invasive breast cancer. The overall AUC for the Gail model was 0.58 (95% confidence interval [CI]=0.56 to 0.60). The Gail model underestimated 5-year invasive breast cancer incidence by approximately 20% (P<.001), mostly among those with a low estimated risk. Discriminatory performance was better for the risk of ER-positive cancer (AUC = 0.60, 95% CI = 0.58 to 0.62) than for the risk of ER-negative cancer (AUC = 0.50, 95% CI = 0.45 to 0.54). Age and age at menopause were statistically significantly associated with ER-positive but not ER-negative cancers (P=.05 and P=.04 for heterogeneity, respectively). For ER-positive cancers, no additional risk factors substantially improved the Gail model prediction. However, a simpler model that included only age, breast cancer in first-degree relatives, and previous breast biopsy examination performed similarly for ER-positive breast cancer prediction (AUC=0.58, 95% CI= 0.56 to 0.60); postmenopausal women who were 55 years or older with either a previous breast biopsy examination or a family history of breast cancer had a 5-year breast cancer risk of 1.8% or higher. In postmenopausal women, the Gail model identified populations at increased risk for ER-positive but not ER-negative breast cancers. A model with fewer variables appears to provide a simpler approach for screening for breast cancer risk.

Breast Cancer in First-degree Relatives and Risk of Lung Cancer: Assessment of the Existence of Gene–Sex Interactions

Previous studies have shown the sex differences in lung cancer and the associations between estrogen-related genes and non-small cell lung cancer. In the present study, we assumed the existence of shared candidate genes that are common in lung and breast cancers, and examined whether women with a family history of breast cancer are at increased risk of lung cancer compared with men, especially adenocarcinoma, in a case-only study. This case-only study was conducted based on the Lung Cancer Database Project at the National Cancer Center Hospital East. A total of 1566 patients with newly diagnosed primary lung cancer were consecutively recruited between 1999 and 2003. Information on their family history of cancer and smoking habit was obtained from a self-administered questionnaire. To assess an interactions between two factors, odds ratios for interaction (ORis) and 95% confidence intervals (CIs) were calculated by case-only contingency table. A statistically significant ORi was observed between a family history of breast cancer in first-degree relatives (parent and siblings, not including children) and the sex of a patient (ORi: 2.22, 95% CI: 1.02-4.81). A stratified analysis by histologic subtypes showed a statistically significant ORi only for adenocarcinoma (ORi: 3.27, 95% CI: 1.19-8.98). No other family history of cancer, such as stomach, colon and lung cancer, showed a statistically significant ORi. This study suggests the possibility of gene-sex interaction in lung cancer.

Association between family history of prostate and breast cancer among African-American men with prostate cancer

Objectives To explore the familial aggregation of prostate and breast cancer using data from a population-based case-control study of African-American men participating in the Flint Men’s Health Study. Methods A detailed family history questionnaire was administered to 121 African-American men with prostate cancer and 179 African-American male controls. The family history data of prostate and breast cancer in first-degree relatives were compared between men with and without prostate cancer using standard statistical methods. Results In the Flint Men’s Health Study, men with prostate cancer were more likely than controls to report having a brother with prostate cancer (age-adjusted odds ratio 4.80, 95% confidence interval 2.01 to 11.44) or a sister with breast cancer (age-adjusted odds ratio 3.80, 95% confidence interval 1.57 to 9.22). Conclusions Although a family history of prostate cancer is a recognized prostate cancer risk factor consistent across different races, few studies have examined the co-clustering of breast and prostate cancer within African-American families. Future studies should focus on racially heterogeneous populations to further explore the observation from the Flint Men’s Health Study that having a brother with prostate cancer or a sister with breast cancer may be associated with prostate cancer occurrence. This research may have implications for both gene identification and early detection strategies.

Cancer incidence in first-degree relatives of a population-based set of cases of early-onset breast cancer

Reliable determination of familial risks for cancer is important for clinical counselling, cancer prevention and understanding cancer aetiology. Family-based gene identification efforts may be targeted if the risks are well characterised and the mode of inheritance is identified. Early-onset breast cancer in a family member is a risk indicator for cancer among first-degree relatives; however, the familial risk pattern has not been assessed fully in population-based incidence studies. We estimated the risks for cancers of the breast, ovary and other sites among the first-degree relatives of 8868 patients in whom breast cancer was diagnosed before they reached the age of 50 years (diagnosed during the period 1943–1999). Population registers and parish records were used to identify 31,235 first-degree relatives, who were followed up to 31 December 2002 for occurrence of cancer by linkage to the Danish Cancer Registry. The observed incidence rates were compared with national rates adjusted for age, sex and calendar period. Overall, 39% of the 674 cases of breast cancer and 43% of the 143 cases of ovarian cancer among relatives were associated with a diagnosis of early-onset breast cancer in a family member. Among relatives under 50 years of age, the proportions were 56% and 58%, respectively, and among relatives 50 years or above the proportions were approximately 30% and 10%. In addition, a slightly but significantly increased risk for cancer of the cervix uteri was observed among relatives, and among those under 50 years of age, we found significantly increased risks for cancers of the colon and gall-bladder. In conclusion, the excess risk for breast cancer in first-degree relatives is large and remains sizable in the subgroup of female relatives aged 50 years or older, and that mutations in BRCA1/ 2 seem to explain only half of breast cancer cases attributable to family history.

Higher risk of breast cancer in first-degree relatives of patients with Crohn's disease

Higher risk of breast cancer in first-degree relatives of patients with Crohn's disease

Increased risk of breast cancer in first-degree relatives of Crohn's disease patients: An IG-IBD study

Background Increased rates of colorectal cancer have been reported in patients with ulcerative colitis as well as with Crohn's colitis. This risk could be the result of shared genetic susceptibility and could be co-inherited rather than being just secondary to a long-standing, extensive mucosal inflammation. Aim. To assess the prevalence of all malignancies in first-degree relatives of Crohn's disease patients in order to establish whether any association exists. Patients and methods A total of 632 outpatients with a diagnosis of Crohn's disease and 632 control subjects were recruited. Information concerning the presence of malignancies was collected in 3292 first-degree relatives of Crohn's disease patients and in 3303 first-degree relatives of controls. Results Two hundred and fourteen (6.5%) subjects were found to be affected by malignancy in the first-degree relatives of Crohn's disease patients and 180 (5.5%) in the first-degree relatives of controls. Forty-seven (7.4%) of Crohn's disease patients had a first-degree relative with IBD, but none of them had cancer. The frequency of extra-intestinal malignancies was higher in first-degree relatives of Crohn's disease patients than in those of controls ( p = 0.011). Frequency of breast cancer in female relatives of Crohn's disease patients, mainly in mothers, was two-fold higher than that in controls (0.91% versus 0.42%; odds ratio = 2.16; 95% confidence interval = 1.14–4.08; p = 0.015). The presence of breast cancer showed no association with any specific phenotype of disease in Crohn's patients. Conclusions These results did not corroborate the hypothesis about a common genetic susceptibility between Crohn's disease and colorectal cancer. An unexpected finding was the more frequent occurrence of extra-digestive malignancies. The prevalence of breast cancer in first-degree relatives of Crohn's disease patients, in particular the mothers, was more than double than in those of controls. This association, if confirmed, would suggest that there may exist common genetic and/or environmental factors for Crohn's disease and breast cancer.

The A−336C Insulin-Like Growth Factor Binding Protein-3 Promoter Polymorphism Is Not a Modulator of Breast Cancer Risk in Caucasian Women

The A−336C Insulin-Like Growth Factor Binding Protein-3 Promoter Polymorphism Is Not a Modulator of Breast Cancer Risk in Caucasian Women

Relative frequency of BRCA2 versus BRCA1 mutations in Spanish families with hereditary breast/ovarian cancer

9687 Background: BRCA 1 and BRCA 2 have been identified as the genes responsible of hereditary breast/ovarian cancer in many families. Initial publications reported BRCA 1 germline mutations to be more frequent than those involving BRCA 2. We want to assess the relative frequency of BRCA 1 versus BRCA 2 mutations in families with hereditary breast/ovarian cancer from the region of Aragón, Spain. Methods: All patients attending the family cancer clinic of the University Hospital of Zaragoza, Spain, who fullfilled the following criteria: (1) At least 3 cases of breast/ovarian cancer in more than 2 generations and at least one case < 45 years old or/and (2) male breast cancer associated with female breast cancer in first-degree relatives, were offered BRCA 1 & BRCA 2 testing. BRCA 1 was performed first. Results: In 40 families tested for BRCA 1, 3 germline mutations were identified (7.5%). BRCA 2 testing is complete in 27 of these families. 6 BRCA 2 mutations (22.2%) were identified. Clinical features of families harbouring BRCA 1 vs BRCA 2 mutation will be presented. Conclusions: BRCA 2 mutations are significantly more frequent than those involving BRCA 1 in families with breast/ovarian cancer from the region of Aragon, Spain. No significant financial relationships to disclose.

Relative frequency of BRCA2 versus BRCA1 mutations in Spanish families with hereditary breast/ovarian cancer

9687 Background: BRCA 1 and BRCA 2 have been identified as the genes responsible of hereditary breast/ovarian cancer in many families. Initial publications reported BRCA 1 germline mutations to be more frequent than those involving BRCA 2. We want to assess the relative frequency of BRCA 1 versus BRCA 2 mutations in families with hereditary breast/ovarian cancer from the region of Aragón, Spain. Methods: All patients attending the family cancer clinic of the University Hospital of Zaragoza, Spain, who fullfilled the following criteria: (1) At least 3 cases of breast/ovarian cancer in more than 2 generations and at least one case < 45 years old or/and (2) male breast cancer associated with female breast cancer in first-degree relatives, were offered BRCA 1 & BRCA 2 testing. BRCA 1 was performed first. Results: In 40 families tested for BRCA 1, 3 germline mutations were identified (7.5%). BRCA 2 testing is complete in 27 of these families. 6 BRCA 2 mutations (22.2%) were identified. Clinical features of families harbouring BRCA 1 vs BRCA 2 mutation will be presented. Conclusions: BRCA 2 mutations are significantly more frequent than those involving BRCA 1 in families with breast/ovarian cancer from the region of Aragon, Spain. No significant financial relationships to disclose.

Advances in Screening, Diagnosis, and Treatment of Breast Cancer

Advances in Screening, Diagnosis, and Treatment of Breast Cancer