Odds Of Breast Cancer Research Articles

Adherence to HEI-2010 and odds of breast cancer according to the menopause status: Evidence from Middle Eastern Country.

Majority of earlier studies have assessed the association between individual healthy eating index-2010 (HEI-2010) and the odds of breast cancer (BC). However, no study has been conducted on the effect of compliance with HEI-2010 and the odds of BC in the Iranian population with a large sample size. Therefore, we aimed to investigate the relationship between the HEI-2010 and the odds of BC in the Iranian population. This population-based case-control study included 350 newly diagnosed cases of BC and 700 healthy controls randomly selected from adult women. HEI-2010 was examined using validated questionnaires. The adherence to HEI-2010 among the participants was divided into four categories. The general characteristics of the participants in the quartiles of the HEI score for categorical variables and continuous variables were evaluated using chi-square and one-way analysis of variance, respectively. Also, using logistic regression analysis, dietary intakes were evaluated in HEI score quartiles. Also, confounding variables were adjusted in different models. People with the highest HEI score had 60% lower odds of BC (OR: 0.40; 95% CI: 0.27, 0.57) than those with the lowest score among post-menopause women. After controlling for age and energy intake, individuals with the highest HEI score were 78% less likely to have BC compared with those with the lowest score (OR: 0.22; 95% CI: 0.14, 0.33). Adjustments for other potential confounders including demographic factors made the association stronger (OR: 0.21; 95% CI: 0.13, 0.32). This association remained significant even after taking BMI into model (OR: 0.27; 95% CI: 0.17, 0.43). Finally, in this study we found an association between HEI-2010 and odds of breast cancer. This association was particularly seen in postmenopausal women. No significant association was found between adherence to HEI-2010 and odds of BC among pre-menopausal.

Are mammography image acquisition factors, compression pressure and paddle tilt, associated with breast cancer detection in screening?

To assess the associations between objectively measured mammographic compression pressure and paddle tilt and breast cancer (BC) detected at the same ("contemporaneous") screen, subsequent screens, or in-between screens (interval cancers). Automated pressure and paddle tilt estimates were derived for 80,495 mammographic examinations in a UK population-based screening programme. Adjusted logistic regression models were fitted to estimate the associations of compression parameters with BC detected at contemporaneous screen (777 cases).Nested case-control designs were used to estimate associations of pressure and tilt with: (a) interval cancer (148 cases/625 age-matched controls) and (b) subsequent screen-detected cancer (344/1436), via conditional logistic regression. Compression pressure was negatively associated with odds of BC at contemporaneous screen (odds ratio (OR) for top versus bottom third of the pressure distribution: 0.74; 95% CI 0.60, 0.92; P-for-linear-trend (Pt) = 0.007). There was weak evidence that moderate pressure at screening was associated with lower odds of interval cancer (OR for middle versus bottom third: 0.63; 95% CI 0.38, 1.05; p = 0.079), but no association was found between pressure and the odds of BC at subsequent screen. There was no evidence that paddle tilt was associated with the odds of contemporaneous, subsequent screen or interval cancer detection. Findings are consistent with compression pressure, but not paddle tilt, affecting the performance of mammographic screening by interfering with its ability to detect cancers. Inadequate or excessive compression pressure at screening may contribute to a reduced ability to detect cancers, resulting in a greater number of interval cancer cases.

Diet-dependent acid load and the risk of breast cancer: A case–control study

Dietary acid load causes metabolic acidosis, which leads to inflammation and cell change, both of which are related to cancer development. Even though a high acid load has been associated with an increased risk of breast cancer (BC), epidemiologic evidence correlating diet-dependent acid load and cancer risk, particularly for BC, is still lacking. As a result, we intend to investigate its potential role. The potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores were calculated in this case-control study using the dietary intake of individuals as determined by a verified FFQ. Logistic regression was used to calculate odds ratios (ORs), which were adjusted for probable confounders. Using multivariate logistic regression models, the odds ratios (OR) of BC according to quartiles of PRAL and NEAP scores revealed that neither PRAL (P-trend=0.53) nor NEAP (P-trend=0.19) scores were significantly associated with BC risk. Multiple logistic regressions remained non-significant after controlling for covariates, indicating no significant relationships between PRAL (P-trend=0.96) and NEAP (trend=0.45) scores and the odds of BC. According to the findings of our study, there is no relation between DAL and the risk of BC in Iranian women.

Association between diabetes risk reduction diet score and risk of breast cancer: A case–control study

Purpose To assess the association between the diabetes risk reduction diet score (DRRD) and the odds of breast cancer (BC). Methods During this hospital-based case-control study we included 149 newly diagnosed cases of BC and 150 controls matched by age. All cases were patients with pathologically confirmed BC, with no history of any form of other cancers. The controls were randomly selected from visitors and families of non-cancer patients in other wards of the same hospital who had no health issues including BC. The dietary intakes were evaluated by a validated 147-item semi-quantitative FFQ. DRRD score was calculated from 9 dietary components published before, with a better score resembling a higher adherence to DRRD. Results A negative association was found between the chances of BC and DRRD after adjusting for potential confounders, but it was not statistically significant (OR, 0.47;95%CI, 0.11-2.08; P=0.531). Also, there were no significant associations between DRRD and therefore the odds of BC in the crude model and also in post-menopausal (OR, 0.45;95%CI, 0.10-1.99; P=0.505) and pre-menopausal women (OR, 0.52;95%CI, 0.18-1.40; P=0.097) in our study, after adjusting for potential confounders. Conclusion Adherence to a diet with a high DRRD score was not associated with the reduced risk of BC in Iranian adults.

Healthy Lifestyle and Breast Cancer Risk in Palestinian Women: A Case-Control Study

The aim of this study was to investigate the association between a combined healthy lifestyle score and the risk of breast cancer (BC) in Palestinian women. A hospital-based case-control study compared 237 BC cases with confirmed diagnoses to 237 healthy controls. Women’s lifestyle components were assessed using a validated questionnaire. A healthy lifestyle index (HLI) has been developed. We used logistic regression models to investigate the relationship between combined lifestyle scores and BC odds. The results revealed that HLI was significantly higher in the control group than in the study group. A higher HLI score was associated with a lower risk of BC in the multivariate analysis. The adjusted odds ratios (AOR) were 0.19 for all women, 0.15 for postmenopausal women, and 0.23 for premenopausal women when the HLI highest and lowest tertiles were compared. HLI score increases of one point resulted in a 41% reduction in the risk of BC for all women, a 42% reduction for postmenopausal and premenopausal women, and a 39% reduction for postmenopausal women. Women who live a healthy lifestyle, according to our findings, have a lower risk of breast cancer. BC prevention programs must promote long-term healthy food and lifestyle choices.

Association of lipid profile biomarkers with breast cancer by molecular subtype: analysis of the MEND study

There is conflicting evidence on the role of lipid biomarkers in breast cancer (BC), and no study to our knowledge has examined this association among African women. We estimated odds ratios (ORs) and 95% confidence intervals (95% CI) for the association of lipid biomarkers—total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides—with odds of BC overall and by subtype (Luminal A, Luminal B, HER2-enriched and triple-negative or TNBC) for 296 newly diagnosed BC cases and 116 healthy controls in Nigeria. Each unit standard deviation (SD) increase in triglycerides was associated with 39% increased odds of BC in fully adjusted models (aOR: 1.39; 95% CI: 1.03, 1.86). Among post-menopausal women, higher total cholesterol (aOR: 1.65; 95% CI: 1.06, 2.57), LDL cholesterol (aOR: 1.59; 95% CI: 1.04, 2.41), and triglycerides (aOR: 1.91; 95% CI: 1.21, 3.01) were associated with increased odds of BC. Additionally, each unit SD increase in LDL was associated with 64% increased odds of Luminal B BC (aOR 1.64; 95% CI: 1.06, 2.55). Clinically low HDL was associated with 2.7 times increased odds of TNBC (aOR 2.67; 95% CI: 1.10, 6.49). Among post-menopausal women, higher LDL cholesterol and triglycerides were significantly associated with increased odds of Luminal B BC and HER2 BC, respectively. In conclusion, low HDL and high LDL are associated with increased odds of TN and Luminal B BC, respectively, among African women. Future prospective studies can definitively characterize this association and inform clinical approaches targeting HDL as a BC prevention strategy.

Substitution of dietary macronutrients and their sources in association with breast cancer: results from a large-scale case-control study.

To evaluate the association between dietary replacement of carbohydrates, proteins, fats, and their sources and odds of developing breast cancer (BC). This hospital-based large-scale case-control study recruited 464 women with confirmed BC within the past year and 500 apparently healthy controls matched in terms of age and residential place. Dietary data as well as other variables were collected by trained interviewers. After adjustment for all possible confounders, substituting every 50kcal of energy from dietary carbohydrates for the same amount of energy from total fats was associated with lower odds for developing BC among all participants [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.95-0.99] as well as premenopausal women (OR 0.96, 95% CI 0.94-0.99). Replacing protein intake with fat was associated with a higher likelihood of BC among postmenopausal women (OR 1.11, 95% CI 1.03-1.20). Replacement of carbohydrates with MUFAs might be associated with a decreased odds of BC and replacement of dietary carbohydrates with PUFAs might be associated with an increased odds of BC in all participants as well as postmenopausal women (P < 0.05). The same association was shown for protein only in postmenopausal women. Substituting MUFAs for saturated (SFAs) and PUFAs was associated with a significant decreased odds of BC in the whole population (P < 0.05). The same association was observed for replacing MUFAs for PUFAs in postmenopausal women. Substitution of dietary carbohydrates for total fats and PUFAs might reduce the odds of breast cancer. Also, substituting MUFAs for carbohydrates, SFAs and PUFAs might lower the disease risk. Future prospective investigations are highly recommended.

Dietary carbohydrate quality and risk of breast cancer among women

BackgroundA few studies have examined the relationship between carbohydrate quality index (CQI) and risk of breast cancer (BC) among women in Middle Eastern countries. We studied the associations between carbohydrate quality index and the risk of BC in overall and by menopausal status.MethodsIn this case-control study, dietary intake of 461 women with pathologically confirmed BC within the past year were examined. The same information were collected for 495 apparently healthy controls using a 168-item validated FFQ. Carbohydrate quality was determined by considering four criteria including: ratio of solid carbohydrates to total carbohydrates, dietary fiber intake, GI and the ratio of whole grains to total grains.ResultsMean GI and GL of participants were totally 57.5 ± 7.2 and 245.7 ± 64.7, respectively. A trend toward significant association was seen between GI and odds of BC in the whole population; such that after stratifying analysis by menopausal status, premenopausal women in the highest quartile of GI were 1.85 times higher likely to have BC than those in the lowest quartile (95% CI: 1.12, 3.07, P = 0.01). We found that women with the greatest CQI had lower odds for BC, compared with those with the lowest CQI (0.63; 95% CI: 0.43–0.94, P = 0.03). This association was remained after stratifying analysis by menopausal status in premenopausal (0.55; 95% CI: 0.34–0.90, P = 0.04).ConclusionWe found that GI was directly and CQI inversely associated with odds of BC. In order to determine the effects of dietary carbohydrate quality prospective cohort studies are needed.

Association between dietary fat and fat subtypes with the risk of breast cancer in an Iranian population: a case-control study

AimTo examine the relationship between dietary fat intake and breast cancer (BC) development.MethodThis case-control study included 473 women with breast cancer (pathologically confirmed) and 501 healthy subjects matched by age and residency. Dietary intakes of different types and sources of fatty acids were assessed using a validated food frequency questionnaire. The association between dietary fats and odds of BC was assessed using a logistic regression model in crude and multivariable-adjusted models. P values below 0.05 were regarded as statistically significant.ResultsParticipants’ age and body mass index were 44.0 ± 10.8 years and 28.4 ± 5.6 kg/m2, respectively. Individuals with the highest quartile of total fat intake and polyunsaturated fatty acid (PUFA) intake were 1.50 times more at risk to develop BC than others. A positive significant association was observed between animal fat (Q4 vs. Q1, OR = 1.89, 95 % CI = 0.93–3.81), saturated fatty acid (SFA) (Q4 vs. Q1, OR = 1.70, 95 % CI = 0.88–3.30), monounsaturated fatty acid (MUFA) (Q4 vs. Q1 OR = 1.85, 95 % CI = 0.95–3.61) and PUFA intake (Q4 vs. Q1, OR = 2.12, 95 % CI = 1.05–4.27) with BC risk in postmenopausal women. However, there was no association in premenopausal women.ConclusionsTotal dietary fat and its subtypes might increase the risk of BC, especially in postmenopausal women. This observational study confirms the role of dietary fat in breast cancer development. Intervention studies involving different estrogen receptor subgroups are needed.

Association of body composition with odds of breast cancer by molecular subtype: analysis of the Mechanisms for Established and Novel Risk Factors for Breast Cancer in Nigerian Women (MEND) study

BackgroundThe association between obesity and breast cancer (BC) has been extensively studied among US, European and Asian study populations, with often conflicting evidence. However, despite the increasing prevalence of obesity and associated conditions in Africa, the continent with the highest age-standardized BC mortality rate globally, few studies have evaluated this association, and none has examined in relation to molecular subtypes among African women. The current analysis examines the association between body composition, defined by body mass index (BMI), height, and weight, and BC by molecular subtype among African women.MethodsWe estimated odds ratios (ORs) and 95% confidence intervals (95% CI) for the association between measures of body composition and BC and molecular subtypes among 419 histologically confirmed cases of BC and 286 healthy controls from the Mechanisms for Established and Novel Risk Factors for Breast Cancer in Women of Nigerian Descent (MEND) case-control study.ResultsHigher BMI (aOR: 0.79; 95% CI: 0.67, 0.95) and weight (aOR: 0.83; 95% CI: 0.69, 0.98) were associated with reduced odds of BC in adjusted models, while height was associated with non-statistically significant increased odds of BC (aOR: 1.07, 95% CI: 0.90, 1.28). In pre/peri-menopausal, but not post-menopausal women, both higher BMI and weight were significantly associated with reduced odds of BC. Further, higher BMI was associated with reduced odds of Luminal A, Luminal B, and HER2-enriched BC among pre/peri-menopausal women, and reduced odds of triple-negative BC among post-menopausal women.ConclusionsHigher BMI and weight were associated with reduced odds of BC overall and by molecular subtype among West African women. Larger studies of women of African descent are needed to definitively characterize these associations and inform cancer prevention strategies.

The association between adherence to MIND diet and risk of breast cancer: A case-control study.

Recently, a new eating pattern called "Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND)" has been coined. This study was aimed to examine the association between adherence to the MIND diet and risk of breast cancer (BC) among Iranian women. In this hospital-based case-control study, 150 newly diagnosed BC cases and 150 age-matched controls were included. All cases were pathologically confirmed BC patients, with no history of any type of other pathologically confirmed cancers. Controls were selected from visitors, relatives and friends of non-cancer patients in other wards, which had no family relationship with cases. Dietary intakes of study participants were assessed using a validated 147-item semi-quantitative food frequency questionnaire (FFQ). The MIND diet score was computed based on participants' dietary intakes obtained from FFQ, Regression logistic models were used to examine the association between the MIND diet score and BC. Examining the whole study population, we found no significant association between the MIND diet score and odds of BC, either before (ORs for comparing T3 vs. T1: 0.818; 95% CI: 0.469-1.42, P-trend=.48) or after controlling for potential confounders (ORs for T3 vs. T1: 1.32; 95% CI: 0.31-5.64, P-trend=.633). This was also the case for pre-menopausal and post-menopausal when analyzed separately. We also failed to find any significant association between the MIND diet score and odds of BC after controlling for potential confounders in both pre-menopausal and post-menopausal. In conclusion, we found that adherence to the MIND diet was not associated with odds of BC in this case-control study. Further studies are required to confirm these findings.

Association of high-sensitivity C-reactive protein and odds of breast cancer by molecular subtype: analysis of the MEND study.

Breast cancer (BC) in Nigeria is characterized by disproportionately aggressive molecular subtypes. C-reactive protein (CRP) is associated with risk and aggressiveness for several types of cancer. We examined the association of high-sensitivity CRP (hsCRP) with odds of BC by molecular subtype among Nigerian women. Among 296 newly diagnosed BC cases and 259 healthy controls, multivariable logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the association between hsCRP and odds of BC overall and by molecular subtype (luminal A, luminal B, HER2-enriched and triple-negative or TNBC). High hsCRP (> 3 mg/L) was observed in 57% of cases and 31% of controls and was associated with 4 times the odds of BC (aOR: 4.43; 95% CI: 2.56, 7.66) after adjusting for socio-demographic, reproductive, and clinical variables. This association persisted regardless of menopausal status and body mass index (BMI) category. High hsCRP was associated with increased odds of TNBC (aOR: 3.32; 95% CI: 1.07, 10.35), luminal A BC (aOR: 4.03; 95% CI: 1.29, 12.64), and HER2-enriched BC (aOR: 6.27; 95% CI: 1.69, 23.25). Future studies are necessary in this population to further evaluate a potential role for CRP as a predictive biomarker for BC.

Dietary Insulin Index and Insulin Load in Relation to Breast Cancer: Findings from a Case–Control Study

BackgroundNo data are available on the association between dietary insulin index (DII) and dietary insulin load (DIL) and the risk of breast cancer (BC). Patients and MethodsThis hospital-based case–control study enrolled 150 newly diagnosed cases of BC and 150 age-matched controls. All cases were patients with pathologically confirmed BC, with no history of any type of other pathologically confirmed cancers. Controls were selected from visitors, relatives, and friends of non-cancer patients in other wards who had no family relationships with the cases. We assessed the dietary intakes of study participants using a validated 147-item semiquantitative food frequency questionnaire. DII and DIL were obtained from previously published data. ResultsA significant positive association was found between DII and BC (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.02-3.25), such that after considering energy intake and age, participants in the highest tertile of DII had 1.86 times greater risk of BC than those in the lowest tertile (OR, 1.86; 95% CI, 1.03-3.35). However, this association became non-significant after controlling for further potential risk factors (OR, 3.26; 95% CI, 0.9-11.7). Furthermore, we observed a significant positive association between DIL and BC (OR, 1.9; 95% CI, 1.06-3.40). The association remained significant even after controlling for age and energy intake. Further controlling for other potential confounders resulted in the disappearance of the association (OR, 3.06; 95% CI, 0.87-10.6). ConclusionAdherence to a diet with high DII and DIL was not associated with odds of BC after controlling for potential confounders.

Abstract PO-174: Racial and socioeconomic disparities in height and body size in adolescence and risk for breast cancer subtypes in the Young Women’s Health History Study

Abstract The etiology of breast cancer (BC) appears to vary by tumor subtypes and currently, in the United States, non-Hispanic White (NHW) women are at an increased risk for luminal A BC and non-Hispanic-Black (NHB) women are at an increased risk for triple negative (TN) BC. Adolescence is a sensitive time for breast development, and childhood overweight/obesity and short height are associated with lower risk of premenopausal BC. The role of adolescent body size on BC risk by subtype, however, has not been well-studied. Relative to NHW girls and girls with higher socioeconomic position (SEP), NHB girls and those with lower SEP are at increased risk of overweight/obesity throughout life. We examined the association between height and body size in adolescence and odds of BC subtypes and the distribution of these factors by self-reported race and SEP. Data are from the Young Women’s Health History Study, a population-based case-control (case n=1812; control n=1381) study of invasive BC among NHB and NHW women aged 20-49 years. BC was diagnosed in Metro Detroit and Los Angeles County SEER registries, 2010-2015. Tumors were classified as luminal A, luminal B, HER2-type, or TN based on estrogen, progesterone, and HER2 receptor status and tumor grade. Area-based controls were frequency matched to cases on site, race and age. During in-home interviews, participants recalled body size at age 12 years with somatotypes (6 levels), weight at age 18 years (used to calculate body mass index (BMI)), and both measured and recalled adult height (&amp;lt;64, 65-66, &amp;gt;67 inches). Data were also collected on self-reported race, adult SEP (household percent poverty (HHP)), and established BC risk factors to evaluate confounding. Adjusted weighted logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) of BC subtype (vs controls). We also examined potential interactions with race and SEP. Among controls, NHB women and women with lower SEP (&amp;lt;150% HHP) were more likely to report a higher age 12 somatotype (SEP X2 p=0.02; race X2 p=0.08) and age 18 BMI (SEP X2 p&amp;lt;0.01; race X2 p&amp;lt;0.01); height did not vary by race or SEP. For age 12 somatotype a trend for reduced odds with increased somatotype was observed for Luminal B BC (p=0.05) and potentially TN (p=0.08). Women with age 18 BMI &amp;gt;30 vs 18.5-&amp;lt;25 kg/m2 had lower odds of luminal A (OR=0.43, 95% CI 0.22, 0.87); women with age 18 BMI &amp;lt;18.5 vs 18.5-&amp;lt;25 kg/m2 had increased odds of HER2-type BC (OR=1.85, 95% CI 1.03, 3.32). Taller height (&amp;gt;67 vs 65-66 inches), was associated with increased odds of all BC subtypes, most strongly for HER2-type (OR=1.80, 95% CI: 1.07, 3.03) and TN (OR=1.42, 95% CI: 0.98, 2.07) BC. The effect of these three body size measures on BC subtype risk did not vary by race or SEP. Body size in adolescence appears to be associated with risk for some BC subtypes, perhaps through hormonal mechanisms, and may partially contribute to explanations for racial and SEP disparities. Citation Format: Lydia R. Marcus, Dorothy P. Pathak, Ann S. Hamilton, Kendra L. Schwartz, Richard Houang, Dan A. Sanfelippo, Ellen M. Velie. Racial and socioeconomic disparities in height and body size in adolescence and risk for breast cancer subtypes in the Young Women’s Health History Study [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-174.

Association between Adherence to “Dietary Approaches to Stop Hypertension” Eating Plan and Breast Cancer

Despite the favorable association of components of “dietary approaches to stop hypertension (DASH)” diet and breast cancer (BC), limited data are available linking the whole DASH diet to BC. The aim of the present study was to examine the association between adherence to DASH eating plan and odds of BC in Iranian women. This population-based case-control study was conducted among women aged ≥30 years, who were residing in Isfahan, Iran. Cases were 350 patients with newly diagnosed stage I-IV breast cancer, for whom in-situ or invasive status of BC was confirmed by physical examination and mammography. Controls were 700 age-matched apparently healthy individuals who were randomly selected from general population. Dietary data were collected using a validated 106-item Willett-format semi-quantitative dish-based food frequency questionnaire. To investigate participants’ adherence to DASH diet, we created DASH scores based on foods and nutrients emphasized or minimized in the DASH diet. After controlling for potential confounders, individuals in the highest quartile of the DASH diet score had 85% lower odds of breast cancer than women in the bottom quartile (OR: 0.15; 95% CIs: 0.09–0.24). Stratified analysis by menopausal status revealed such association in postmenopausal women (OR: 0.11; 95% CI: 0.06–0.19), but not in premenopausal women (OR: 0.60; 95% CI: 0.14–2.59). In addition, when stratified by BMI status, we found statistically significant inverse association between adherence to the DASH eating pattern and odds of breast cancer among normal-weight (OR for comparing extreme quartiles: 0.13; 95% CI: 0.07–0.24; P-trend < 0.001) and obese women (0.13; 0.05–0.34; P-trend < 0.001). In conclusion, our findings indicated an inverse association between adherence to the DASH eating plan and odds of breast cancer among Iranian women. Further, prospective studies are required to confirm our findings.

Family history of breast cancer in non-BRCA male breast cancer: A case-control study.

e13032 Background: Approximately 85% of male breast cancer (MBC) patients test negative for a BRCA mutation, and the role of genetic predisposition is unclear. Cancer risk counseling for unaffected relatives of BRCA-negative MBC patients relies on accurate cancer risk estimates, but there is limited data on the risk of breast cancer (BC) for relatives of these men. We characterized the association between MBC and family history of BC in patients who test negative for BRCA mutations in order to facilitate cancer risk counseling and to explore the possibility of unidentified MBC susceptibility alleles. Methods: We performed a case-control study of patients who had full length sequencing and large-rearrangement analysis for germline mutations in BRCA1/2 or the mismatch repair (MMR) genes at a commercial laboratory from 2006-2012. Cases were MBC patients who tested negative for a BRCA1/2 mutation (n = 3,647); controls were male colon cancer patients who tested negative for mutations in MMR genes (n = 4,269). Information on family history of BC was ascertained from test request forms completed by the ordering healthcare provider at the time of testing. Unconditional multivariable logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) for associations between family history of BC in first- (FDR) and second-degree relatives (SDR) and MBC with adjustment for potential confounders (age, ethnicity, year of testing). Results: Compared to controls, MBC cases had higher odds of BC in a FDR or SDR (OR = 4.7; 95% CI 4.1, 5.3). Associations were strongest for family history of BC in 1 female FDR (OR = 3.9; 95% CI: 3.3, 4.6), ≥2 female FDR (OR = 7.5; 95% CI 5.0, 11.4), BC in a FDR &lt; 45 years old (for cases diagnosed &lt; 45, OR = 6.9; 95% CI 3.9, 12.4), a male FDR or SDR with BC (OR = 17.9; 95% CI 7.6, 42.1), and both a male and female FDR or SDR with BC (OR = 15.7; 95%CI 4.4, 55.3). Conclusions: MBC patients who test negative for a BRCA mutation have significantly higher odds of reporting family members affected by breast cancer, particularly with affected FDR &lt; 45 years old, multiple affected relatives, and male relatives with BC. This data can guide risk counseling in MBC families, and suggests the existence of unidentified MBC susceptibility alleles.

Abstract 2394: The role of DNA repair in breast cancer risk and recurrence

Abstract BACKGROUND: Breast cancer (BC) is a complex disease that is caused by multiple factors. Deficits in DNA repair capacity (DRC) are known to cause certain familial BC, and dysregulation of DRC develops with progressive carcinogenesis. However, the effect of DRC on carcinogenesis of sporadic breast tumors has not been well characterized_and the factors associated with DRC variability are still poorly understood. DNA repair is integral to maintain genomic integrity, and carcinogenesis occurs when efficient, effective DNA repair is impaired. Our laboratory has just finished the recruitment of nearly 1,200 women in a seven-year molecular epidemiology study focused on the role of DRC as a risk factor for BC. OBJECTIVE: Our aim is to present key findings on the role of DRC as a risk factor for BC and its potential association with BC recurrence. METHODS: A personal interview was conducted for soliciting information on BC risk factors. Among the 493 BC cases and 683 controls the DRC was measured in lymphocytes using a host cell reactivation assay with a luciferase reporter gene. We stratified the women with BC using the median of the DRC level and selected 70 women with a low DRC level (&amp;lt;2.8%) who had been enrolled in the study for at least 5 years in order to assess the BC recurrence. RESULTS: Our 7 year study of DRC of female cohorts in Puerto Rico has shown that women with BC have a DRC that, on average, is 51% lower than women without BC (P &amp;lt; 0.001, Mann Whitney U-test). Women with low DRC have 6.8 (95%CI 5.2, 9.0) times the odds for BC when compared with women with high DRC level. So far, the overall BC recurrence was 17% and the 5-year mortality was 10%. Recurrence was primarily in the lung, liver, bone, or occurred as generalized metastatic disease. CONCLUSIONS: Using a large sample size (n=1,183 participants), we show that women with BC had on an average a 51% lower DRC than controls (P&amp;lt;0.001). We also present the first data on the potential between a low DRC and risk of BC recurrence. With a larger sample size, we will test the hypothesis that low DRC can predict risk of BC recurrence. Supported by grants from the NCI Center to Reduce Health Disparities through the NIH-MBRS Program grants S06 GM008239-20, 9SC1CA182846-04 to PSMHS through JM and MBRS-RISE GM082406 through CO. Citation Format: Jaime L. Matta, Erick Suarez, Wanda Vargas, Carmen Ortiz, Manuel Bayona, Luisa Morales. The role of DNA repair in breast cancer risk and recurrence. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2394. doi:10.1158/1538-7445.AM2014-2394

P4-11-22: Familial History of Cancer among Breast Cancer Women under 36 yr. in Rio De Janeiro, Brazil.

Abstract Background. Antecedents of familial history of cancer (FHC) have been reported as an important feature observed among young women with breast cancer (BC). Objective. To explore the distribution of FHC in a sample of young women with BC in Brazil. Methods. Antecedents of FHC were obtained by a face to face interview carried out with 224 BC cases 20–35 yr., and 246 age-frequency matched controls, enrolled in a hospital-based case control study carried out along 1996–2006 in Rio de Janeiro, Brazil. Unconditional logistic regression was performed and BC odds ratios adjusted for age and education (adj. OR) were obtained according to FHC characteristics (parenthood degree, age of diagnosis and amount of relatives with cancer). Results. BC antecedents among 1 st degree relatives was 5.4% among BC cases and 1.2% of controls (p=0.01). The adj. OR for BC among 1st degree relatives was 4.3, 95% CI 1.2−15.8. Comparatively to families without BC antecedents, an adj. OR =2.4, 95% CI 1.4−4.1 was observed for those with 1 reported BC case, and an adj. OR = 3.7, 95% CI 1.0–14.0 for those with 2 or more BC cases (p trend =0.0002). A similar trend was verified according to all other cancer sites (p-trend &amp;lt; 0.0001). The reported median age of BC diagnosis in the 1st generation (proband grand-mothers) was 76 yr., being 45 yr. at the 2nd generation (proband mothers), and 38,4 yr. at the 3rd (proband sisters). A similar trend along generations was also verified for other cancer sites among case relatives, respectively, 69 yr., 58 yr. ***, and 45 yr. The mean age of diagnosis among the cases offspring was 6.7 yr. (standard deviation, SD = 0.6) and 12.0 yr. (SD = 1.4) among the controls descents (p&amp;lt; 0.01). Brain cancer reported among case relatives was 6.0 fold higher than among control relatives (3.7 fold higher for ovarian cancer, and 3.2 higher for skin cancer). Discussion. The observed results reveal that cancer risks among relatives of young women with BC are either higher for BC or other selected cancer sites. The observed decline along successive generations on the age at diagnosis of BC and other tumors is suggestive of recent genetic-environmental interaction in the studied sample of young women with BC in Brazil. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-22.