Traditional Breast Cancer Risk Factors Research Articles

Breast cancer risk factors in relation to molecular subtypes in breast cancer patients from Kenya

BackgroundFew studies have investigated risk factor heterogeneity by molecular subtypes in indigenous African populations where prevalence of traditional breast cancer (BC) risk factors, genetic background, and environmental exposures show marked differences compared to European ancestry populations.MethodsWe conducted a case-only analysis of 838 pathologically confirmed BC cases recruited from 5 groups of public, faith-based, and private institutions across Kenya between March 2012 to May 2015. Centralized pathology review and immunohistochemistry (IHC) for key markers (ER, PR, HER2, EGFR, CK5-6, and Ki67) was performed to define subtypes. Risk factor data was collected at time of diagnosis through a questionnaire. Multivariable polytomous logistic regression models were used to determine associations between BC risk factors and tumor molecular subtypes, adjusted for clinical characteristics and risk factors.ResultsThe median age at menarche and first pregnancy were 14 and 21 years, median number of children was 3, and breastfeeding duration was 62 months per child. Distribution of molecular subtypes for luminal A, luminal B, HER2-enriched, and triple negative (TN) breast cancers was 34.8%, 35.8%, 10.7%, and 18.6%, respectively. After adjusting for covariates, compared to patients with ER-positive tumors, ER-negative patients were more likely to have higher parity (OR = 2.03, 95% CI = (1.11, 3.72), p = 0.021, comparing ≥ 5 to ≤ 2 children). Compared to patients with luminal A tumors, luminal B patients were more likely to have lower parity (OR = 0.45, 95% CI = 0.23, 0.87, p = 0.018, comparing ≥ 5 to ≤ 2 children); HER2-enriched patients were less likely to be obese (OR = 0.36, 95% CI = 0.16, 0.81, p = 0.013) or older age at menopause (OR = 0.38, 95% CI = 0.15, 0.997, p = 0.049). Body mass index (BMI), either overall or by menopausal status, did not vary significantly by ER status. Overall, cumulative or average breastfeeding duration did not vary significantly across subtypes.ConclusionsIn Kenya, we found associations between parity-related risk factors and ER status consistent with observations in European ancestry populations, but differing associations with BMI and breastfeeding. Inclusion of diverse populations in cancer etiology studies is needed to develop population and subtype-specific risk prediction/prevention strategies.

Risks and protective factors for triple negative breast cancer with a focus on micronutrients and infections.

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer (BC) with a poor prognosis. Second, patients cannot benefit from targeted therapy, except for those with BRCA1/2 mutations, for whom poly (ADP-ribose) polymerase (PARP) inhibition therapy using olaparib has recently been approved. As global priorities continue to be epidemiological analysis of BC risk factors and early diagnosis, this review focuses on the risks and protective factors associated with TNBC. A PubMed keyword search for new knowledge on the risks and protective factors for TNBC was carried out. We also found statistical information from current online databases concerning the estimated incidence, prevalence and mortality worldwide of this cancer. Traditional risk factors for BC and TNBC are those related to reproduction such as the age of menarche, age of first birth, parity, breastfeeding and age at menopause. Attention needs to be paid to familial BC, weight control, alcohol consumption and regular physical activity. Epidemiological studies on TNBC provide evidence for protective factors such as regular consumption of soya, seafood, green tea, folic acid and vitamin D. Potential risk factors may include night work and viral infectious agents like human papillomavirus (HPV) and Epstein-Barr virus (EBV). Droplet digital methylation-specific PCR (ddMSP) is a possible new screening method for detection of BC including TNBC. Further research is necessary to validate these new factors.

Breast cancer risk in a screening cohort of Asian and white British/Irish women from Manchester UK

BackgroundThe differences between breast cancer risk factors in white British/Irish and Asian women attending screening in the UK are not well documented.MethodsBetween 2009-15 ethnicity and traditional breast cancer risk factors were self-identified by a screening cohort from Greater Manchester, with follow up to 2016. Risk factors and incidence rates were compared using age-standardised statistics (European standard population).ResultsEight hundred and seventy-nine Asian women and 51,779 unaffected white British/Irish women aged 46-73 years were recruited. Asian women were at lower predicted breast cancer risk from hormonal and reproductive risk factors than white British/Irish women (mean 10 year risk 2.6% vs 3.1%, difference 0.4%, 95%CI 0.3-0.5%). White British/Irish women were more likely to have had a younger age at menarche, be overweight or obese, taller, used hormone replacement therapy and not to have had children.. However, despite being less overweight Asian women had gained more weight from age 20 years and were less likely to undertake moderate physical activity. Asian women also had a slightly higher mammographic density. Asian age-standardised incidence was 3.2 (95%CI 1.6-5.2, 18 cancers) per thousand women/year vs 4.5 (95%CI 4.2-4.8, 1076 cancers) for white British/Irish women.ConclusionsAsian women attending screening in Greater Manchester are likely to have a lower risk of breast cancer than white British/Irish women, but they undertake less physical activity and have more adult weight gain.

Abstract 2600: Improving breast cancer risk prediction models: the addition of a genetic risk score, mammographic density, and endogenous hormones

Abstract Background: Risk prediction models have important public health implications for targeted disease prevention by identifying women at higher risk who would most likely benefit from screening, chemoprevention, or other risk-reducing regimens. Among such models, the Gail and Rosner-Colditz models have been well validated and used to identify high-risk women. Each of these models generally includes only traditional breast cancer risk factors (e.g., parity and family history of breast cancer). No prior study has examined the joint contribution of a genetic risk score (GRS), mammographic density (MD), and postmenopausal endogenous hormone levels to these models. Method: We conducted a nested-case control study within the Nurses’ Health Study (NHS, follow-up 1990-2010) and NHS II (1997-2009). We created a breast cancer GRS based on 67 single-nucleotide polymorphism (SNPs). We measured percent MD as well as circulating testosterone, estrone sulfate, and prolactin levels in prediagnostic plasma samples. Using receiver-operating-characteristic curve analyses, we calculated the area under the curve (AUC), adjusting for age, as a measure of discrimination for the 5-year risk of invasive breast cancer and estrogen receptor (ER) and progesterone receptor (PR) positive disease (ER+PR+) by menopausal status, after adding GRS, MD, and/or circulating hormones to the modified Gail and Rosner-Colditz models. Results: We documented 11,880 women (4,006 cases/7,874 controls; age range: 34-80 yr) for Gail model and 8,210 women (2,665 cases/5,455 controls) for Rosner-Colditz model analyses. In both models, about 45% women were premenopausal, 25% were postmenopausal women not using postmenopausal hormone (HT), and 30% were postmenopausal women using HT at blood draw. The AUC was statistically significantly improved by 7.0 units in premenopausal women (Gail+GRS+MD), 11.8 units in postmenopausal women not using HT (Gail+GRS+MD+hormones), and 6.1 units in postmenopausal women using HT (Gail+GRS+MD+prolactin, all p-value<0.001). For the Rosner-Colditz model, the corresponding AUC improved by 5.4 units, 7.9 units, and 5.4 units (all p-value<0.001). For ER+PR+ tumors specifically, among postmenopausal women not using HT, the AUC was improved by 13.2 units for the Gail model and 9.9 units for the Rosner-Colditz model (all p-values<0.001). Conclusion: While each of genetic markers, percent MD, and hormones independently improved risk prediction for invasive breast cancer and ER+PR+ disease, incorporating all of these factors simultaneously improved models the most, especially among postmenopausal women not using HT. If validated in independent populations, our findings could help identify women at a higher risk, who would most benefit from chemoprevention, other risk-reducing regimens or screening. Citation Format: Xuehong Zhang, Megan Rice, Shelley S. Tworoger, Bernard A. Rosner, A. Heather Eliassen, Rulla M. Tamimi, Jing Qian, Graham A. Colditz, Walter C. Willett, Susan E. Hankinson. Improving breast cancer risk prediction models: the addition of a genetic risk score, mammographic density, and endogenous hormones. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2600.

Breast Cancer Diagnosis from Screening in Trinidad and Tobago: Opportunities for Cancer Prevention

Trinidad and Tobago (TT) experiences the highest breast cancer mortality in the Caribbean; the distribution of traditional breast cancer risk factors in this population has not been analyzed. Data on women who underwent breast cancer screening at the TT Cancer Society between January 2009-December 2011(N = 2,689) were retrospectively collected. The screening detected 131 incident breast cancers; variables significantly associated with breast cancer diagnosis were, a positive family history of breast cancer (adjusted odds ratio [ORadj]: 1.55; 95% CI 1.00-2.41), presence of symptoms (ORadj: 1.91; 95% CI 1.25-2.92), and previous breast surgery (ORadj: 1.67; 95% CI 0.97-2.88). Breast cancer was significantly associated with increased breast density. Among healthy women, breast density was positively associated with nulliparity (ORadj: 1.46, 1.37, 2.52 respectively for density level 2, 3 and 4 vs. 1) and previous breast surgeries (ORadj: 2.27, 3.09 and 4.13 respectively for density level 2, 3 and 4 vs. 1). This analysis confirms that breast density is an important predictor of newly diagnosed breast cancer in this Caribbean population. Screening is still a diagnostic tool rather than a preventive measure in TT.

Association between common risk factors and molecular subtypes in breast cancer patients

BackgroundBreast cancer is the most commonly diagnosed cancer in women worldwide and characterized its by molecular and clinical heterogeneity. Gene expression profiling studies have classified breast cancers into five subtypes: luminal A, luminal B, HER-2 overexpressing, basal-like, and normal breast-like. Although clinical differences between subtypes have been well described in the literature, etiologic heterogeneity have not been fully studied. The aim of this study was to assess the associations between several hormonal and nonhormonal risk factors and molecular subtypes of breast cancer. MethodsThis cross-sectional study consisted of 1884 invasive breast cancer cases. Variables studied included family history, age at first full-term pregnancy, number of children, duration of lactation, menstruation history, menopausal status, blood type, smoking, obesity, oral contraceptive use, hormone replacement therapy and in vitro fertilization. The odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariate logistic regression analysis. ResultsThousand two-hundred and forty nine patients had luminal A, 234 had luminal B, 169 had HER-2 overexpressing and 232 had triple negative breast cancer. The age of ≥40 years was found to be a risk factor for luminal A (OR 1.41 95% CI 1.15–1.74; p=0.001) and HER-2 overexpressing subtype (OR: 1.51, 95% CI: 1.01–2.25; p=0.04). Women who were nulliparous (OR 1.48, 95% CI 1.03–2.13; p=0.03) or who had their first full-term pregnancy at age 30 years or older (OR 1.25 95% CI 0.83–1.88; p=0.04) were at increased risk of luminal breast cancer, whereas women with more than two children had a decreased risk (OR 0.68, 95% CI 0.47–0.97; p=0.03). Breast-feeding was also a protective factor for luminal subtype (OR 0.74, 95% CI 0.53–1.04; p=0.04) when compared to non-luminal breast cancer. We found increased risks for postmenopausal women with HER-2 overexpressing (OR 2.20, 95% CI 0.93–5.17; p=0.04) and luminal A (OR 1.87, 95% CI 0.93–3.90, p=0.02) breast cancers, who used hormone replacement therapy for 5 years or more. Overweight and obesity significantly increased the risk of triple negative subtype (OR 1.89 95% CI 1.06–3.37; p=0.04 and OR 1.90 95% CI 1.00–3.61; p=0.03), on the contrary, decreased the risk of luminal breast cancer (OR 0.63 95% CI 0.43–0.95; p=0.02 and OR 0.50 95% CI 0.32–0.76; p=0.002, respectively) in premenopausal women. There were no significant differences between risk of breast cancer subtypes and early menarche, late menopause, family history, postmenopausal obesity, oral contraseptive use, smoking, in vitro fertilization, blood groups and use of hands. ConclusionsReproductive and hormonal characteristics (breastfeeding, parity, age at first full-term birth, hormone replacement therapy) were associated with luminal subtype, compared to non-luminal breast cancer, as consistent with previous studies. Obesity and overweight increased the risk of triple negative subtype, particularly in premenopausal women. Older age and use of hormone replacement therapy were related to the risk of HER-2 overexpressing breast cancer. Our data suggest a significant heterogeneity in association of traditional breast cancer risk factors and tumor subtypes.

Birth Weight, Breast Cancer and the Potential Mediating Hormonal Environment

BackgroundPrevious studies have shown that woman’s risk of breast cancer in later life is associated with her infants birth weights. The objective of this study was to determine if this association is independent of breast cancer risk factors, mother’s own birth weight and to evaluate association between infants birth weight and hormonal environment during pregnancy. Independent association would have implications for understanding the mechanism, but also for prediction and prevention of breast cancer.Methods and FindingsRisk of breast cancer in relation to a first infant’s birth weight, mother’s own birth weight and breast cancer risk factors were evaluated in a prospective cohort of 410 women in the Framingham Study. Serum concentrations of estriol (E3), anti-estrogen alpha-fetoprotein (AFP), and pregnancy-associated plasma protein-A (PAPP-A) were measured in 23,824 pregnant women from a separate prospective cohort, the FASTER trial. During follow-up (median, 14 years) 31 women (7.6 %) were diagnosed with breast cancer. Women with large birth weight infants (in the top quintile) had a higher breast cancer risk compared to other women (hazard ratio (HR), 2.5; 95% confidence interval (CI), 1.2–5.2; P = 0.012). The finding was not affected by adjustment for birth weight of the mother and traditional breast cancer risk factors (adjusted HR, 2.5; 95% CI, 1.2–5.6; P = 0.021). An infant’s birth weight had a strong positive relationship with the mother’s serum E3/AFP ratio and PAPP-A concentration during pregnancy. Adjustment for breast cancer risk factors did not have a material effect on these relationships.ConclusionsGiving birth to an infant with high birth weight was associated with increased breast cancer risk in later life, independently of mother’s own birth weight and breast cancer risk factors and was also associated with a hormonal environment during pregnancy favoring future breast cancer development and progression.

A Review of Cancer in U.S. Hispanic Populations

There are compelling reasons to conduct studies of cancer in Hispanics, the fastest growing major demographic group in the United States (from 15% to 30% of the U.S. population by 2050). The genetically admixed Hispanic population coupled with secular trends in environmental exposures and lifestyle/behavioral practices that are associated with immigration and acculturation offer opportunities for elucidating the effects of genetics, environment, and lifestyle on cancer risk and identifying novel risk factors. For example, traditional breast cancer risk factors explain less of the breast cancer risk in Hispanics than in non-Hispanic whites (NHW), and there is a substantially greater proportion of never-smokers with lung cancer in Hispanics than in NHW. Hispanics have higher incidence rates for cancers of the cervix, stomach, liver, and gall bladder than NHW. With respect to these cancers, there are intriguing patterns that warrant study (e.g., depending on country of origin, the five-fold difference in gastric cancer rates for Hispanic men but not Hispanic women). Also, despite a substantially higher incidence rate and increasing secular trend for liver cancer in Hispanics, there have been no studies of Hispanics reported to date. We review the literature and discuss study design options and features that should be considered in future studies.

221: Does antepartum additional iron supplementation to standard prenatal vitamins decrease anemia at delivery?

standard prenatal vitamins decrease anemia at delivery? Samantha Boreland, Clones Lans, Chaur-Dong Hsu, Vinette Greenland, Elsi Santana-Fox, Maggie Tetrokalashvili, Scott Stanislawski, Joshua Fogel Nassau University Medical Center, OBGYN, East Meadow, NY OBJECTIVE: To investigate whether the addition of iron supplementation to the standard prenatal vitamins, improve hemoglobin/hematocrit levels, at delivery. STUDY DESIGN: This is a retrospective review of 300 medical charts of women delivered at our medical health system from January 2009 to December 2009. The patients were divided equally in 2 groups: group 1 consisted of patients who had prenatal care at Hospital Medical Center (HMC) obstetric clinic and received only standard prenatal vitamins, and group 2 consisted of patients followed at the outreach obstetric clinics of Federal Qualified Health Centers (FQHC) affiliated to HMC and received ferrous sulfate in addition to the standard prenatal vitamins. The hemoglobin and hematocrit levels at the first prenatal visit were compared to those at delivery for both groups. ANOVA, Chi-square test, McNemar test and ANCOVA were used for statistical analysis. Data were expressed as mean standard deviation. RESULTS: There were no significant differences for any of the baseline laboratory variables between the two groups. The mean comparisons for the laboratory variables at delivery showed both hemoglobin and hematocrit had significantly lower mean values for the HMC group as compared to FQHC group (Hemoglobin: 11.9 1.26 vs. 12.2 1.26 g/dL, p 0.0001; hematocrit: 34.9% vs. 35.8%, p 0.01). In analyses comparing within each of the two groups, hematocrit significantly decreased (p 0.001) from the first prenatal visit (35.9 3.02%) to delivery (34.9 3.53%) and hemoglobin significantly decreased (p 0.001) from the first prenatal visit (12.3 1.05g/dL) to delivery (11.9 1.26 g/dL). In categorical variable comparisons, there was significant increase of anemia percentage in HMC group from the first prenatal visit to delivery. In the FQHC group, both hematocrit and hemoglobin did not significantly differ from the first prenatal visit to delivery. CONCLUSION: Our data suggests that additional iron supplementation from antepartum at the first prenatal visit to delivery can benefit woman by keeping their hemoglobin/hematocrit levels stable prior to delivery. 222 Birth weight, breast cancer and the potential mediating hormonal environment Radek Bukowski, Rowan Chlebowski, Inger Thune, Anne-Sofie Furberg, Gary Hankins, Fergal Malone, Mary D’Alton University of Texas Medical Branch, Department of Obstetrics and Gynecology, Galveston, TX, Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, Oslo University Hospital, Department of Oncology, Oslo, Norway, University of Troms, Faculty of Health Sciences, Department of Community Medicine, Troms, Norway, The University of Texas Medical Branch, Obsterics & Gynecology, Galveston, TX, Royal College of Surgeons in Ireland, Obstetrics and Gynaecology, Dublin, Ireland, Columbia University, Department of Obstetrics and Gynecology, New York, NY OBJECTIVE: A womans breast cancer risk is proportional to her birth weight and the birth weight of her children. The relative contributions of these factors and their mediating mechanisms are not known. STUDY DESIGN: Risk of breast cancer in relation to a mothers birth weight and her first infants birth weight were evaluated in a prospective cohort of 410 women in the Framingham Study. Serum concentrations of estriol (E3), anti-estrogen alpha-fetoprotein (AFP), and pregnancy-associated plasma protein-A (PAPP-A) were measured in 23,824 pregnant women from a separate perspective cohort, the FASTER trial. RESULTS: During follow-up (median, 14 years) 31 women (7.6%) were diagnosed with breast cancer. Women with large birth weight infants (in the top quintile) had a higher breast cancer risk compared to other women (hazard ratio (HR), 2.5; 95% confidence interval (CI), 1.2-5.2; P 0.012). The finding was not affected by adjustment for birth weight of the mother and traditional breast cancer risk factors (adjusted HR, 2.6; 95% CI, 1.2-5.7; P 0.016). An infants birth weight had a strong positive relationship with the mothers serum E3/AFP ratio and PAPP-A concentration during pregnancy. Adjustment for breast cancer risk factors did not have a material effect on these relationships. CONCLUSION: Maternal risk of breast cancer was associated with giving birth to an infant with high birth weight, independent of a mothers own birth weight and traditional breast cancer risk factors. Having an infant with high birth weight was also associated with a hormonal environment during pregnancy favoring breast cancer development and progression.

Traditional breast cancer risk factors in relation to molecular subtypes of breast cancer

At least four major categories of invasive breast cancer have been reproducibly identified by gene expression profiling: luminal A, luminal B, HER2-type, and basal-like. These subtypes have been shown to differ in their outcome and response to treatment. Whether this heterogeneity reflects the evolution of these subtypes through distinct etiologic pathways has not been clearly defined. We evaluated the association between traditional breast cancer risk factors and risk of previously defined molecular subtypes of breast cancer in the Nurses' Health Study. This analysis included 2,022 invasive breast cancer cases for whom we were able to obtain archived breast cancer tissue specimens. Tissue microarrays (TMAs) were constructed, and slides were immunostained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor (EGFR). Using immunostain results in combination with histologic grade, cases were grouped into molecularly defined subtypes. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We observed differences in the association between risk factors and subtypes of breast cancer. In general, many reproductive factors were most strongly associated with the luminal A subtype, although these differences were not statistically significant. Weight gain since age 18 showed significant differences in its association with molecular subtypes (P-heterogeneity = 0.05) and was most strongly associated with the luminal B subtype (P-trend 0.001). Although there was not significant heterogeneity for lactation across subtypes, an inverse association was strongest for basal-like tumors (HR = 0.6, 95% CI 0.4-0.8; P-heterogeneity = 0.88). These results support the hypothesis that different subtypes of breast cancer have different etiologies and should not be considered as a single group. Identifying risk factors for less common subtypes such as luminal B, HER2-type and basal-like tumors has important implications for prevention of these more aggressive subtypes.

Breast Cancer Risk 55+ Years After Irradiation for an Enlarged Thymus and Its Implications for Early Childhood Medical Irradiation Today

Radiotherapy during childhood increases long-term cancer risk, but the risk from radiation as a result of relatively higher dose diagnostic procedures remains less well known. This study, which evaluates breast cancer incidence in a cohort treated with "lower dose" chest radiotherapy over 50 years ago, can assist with estimating lifetime breast cancer risk in young children exposed to radiation from procedures such as chest computed tomography (CT) or treatment with recent "lower dose" chest radiotherapy protocols. A population-based, longitudinal cohort of subjects exposed to thymic irradiation during infancy from 1926 to 1957 and of their unexposed siblings was re-established. Previously followed until 1987, we resurveyed cohort members from 2004 to 2008. Poisson regression models compared breast cancer incidence rates between women in the cohort by treatment and dose category groups. Breast cancer occurred in 96 treated (mean breast dose, 0.71 Gy) and 57 untreated women during 159,459 person-years of follow-up. After adjusting for attained age and treatment/birth cohort, the rate ratio was 3.01 (2.18-4.21). The adjusted excess relative risk per Gy was 1.10 (95% confidence interval, 0.61-1.86). Traditional breast cancer risk factors did not contribute significantly to multivariate model fit. Our results show that at radiation doses between those received by the breast from chest CT and cancer therapy during early childhood, breast cancer incidence rates remain elevated >50 years after exposure. This implies that increased breast cancer risk will remain a lifelong concern in females treated during childhood with currently reduced radiotherapy doses and for infants receiving multiple chest CTs.

Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors

IntroductionThe aim of this study was to describe breast tumor subtypes by common breast cancer risk factors and to determine correlates of subtypes using baseline data from two pooled prospective breast cancer studies within a large health maintenance organization.MethodsTumor data on 2544 invasive breast cancer cases subtyped by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (Her2) status were obtained (1868 luminal A tumors, 294 luminal B tumors, 288 triple-negative tumors and 94 Her2-overexpressing tumors). Demographic, reproductive and lifestyle information was collected either in person or by mailed questionnaires. Case-only odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for age at diagnosis, race/ethnicity, and study origin.ResultsCompared with luminal A cases, luminal B cases were more likely to be younger at diagnosis (P = 0.0001) and were less likely to consume alcohol (OR = 0.74, 95% CI = 0.56 to 0.98), use hormone replacement therapy (HRT) (OR = 0.66, 95% CI = 0.46 to 0.94), and oral contraceptives (OR = 0.73, 95% CI = 0.55 to 0.96). Compared with luminal A cases, triple-negative cases tended to be younger at diagnosis (P ≤ 0.0001) and African American (OR = 3.14, 95% CI = 2.12 to 4.16), were more likely to have not breastfed if they had parity greater than or equal to three (OR = 1.68, 95% CI = 1.00 to 2.81), and were more likely to be overweight (OR = 1.82, 95% CI = 1.03 to 3.24) or obese (OR = 1.97, 95% CI = 1.03 to 3.77) if premenopausal. Her2-overexpressing cases were more likely to be younger at diagnosis (P = 0.03) and Hispanic (OR = 2.19, 95% CI = 1.16 to 4.13) or Asian (OR = 2.02, 95% CI = 1.05 to 3.88), and less likely to use HRT (OR = 0.45, 95% CI = 0.26 to 0.79).ConclusionsThese observations suggest that investigators should consider tumor heterogeneity in associations with traditional breast cancer risk factors. Important modifiable lifestyle factors that may be related to the development of a specific tumor subtype, but not all subtypes, include obesity, breastfeeding, and alcohol consumption. Future work that will further categorize triple-negative cases into basal and non-basal tumors may help to elucidate these associations further.

Breast cancer risk factors and mammographic breast density in women over age 70

Breast density is a strong risk factor for breast cancer, but little is known about factors associated with breast density in women over 70. Percent breast density, sex hormone levels and breast cancer risk factor data were obtained on 239 women ages 70-92 recruited from 1986 to 1988 in the United States. Multivariable linear regression was used to develop a model to describe factors associated with percent density. Median (range) percent density among women was 23.7% (0-85%). Body mass index (beta=-0.345, p<0.001 adjusted for age and parity) and parity (beta=-0.277, p<0.001 adjusted for age and BMI) were significantly and inversely associated with percent breast density. After adjusting for parity and BMI, age was not associated with breast density (beta=0.05, p=0.45). Parous women had lower percent density than nulliparous women (23.7 versus 34.7%, p=0.005). Women who had undergone surgical menopause had greater breast density than those who had had a natural menopause (33.4 versus 24.8%, p=0.048), as did women who were not current smokers (26.0 versus 17.3% for smokers, p=0.02). Breast density was not associated with age at menarche, age at menopause, age at first birth, breastfeeding, estrogen levels or androgen levels. In a multivariable model, 24% of the variance in percent breast density was explained by BMI (beta=-0.35), parity (beta=-0.29), surgical menopause (beta=0.13) and current smoking (beta=-0.12). Factors associated with breast density in older, post-menopausal women differ from traditional breast cancer risk factors and from factors associated with breast density in pre-menopausal and younger post-menopausal women.

IGF1 CA repeat polymorphisms, lifestyle factors and breast cancer risk in the Long Island Breast Cancer Study Project

Insulin-like growth factor I (IGF-I) is an important regulator of growth and differentiation and is a potent mitogen for human breast cancer cells. Recent investigations suggest an association between cytosine-adenine dinucleotide (CA)n repeat polymorphisms of the IGF1 gene and IGF-I levels and further evidence indicates that genotype may influence breast cancer risk. We assessed the relation between IGF1 (CA)n repeats and breast cancer, and evaluated modification of genotype effects according to traditional breast cancer risk factors in 1028 breast cancer cases and 1086 controls. An increased risk of breast cancer was seen for genotypes that included alleles with fewer than (CA)19 repeats when compared to (CA)19 repeat carriers, an association that was particularly strong among premenopausal women [odds ratio (OR)=3.31; 95% confidence interval (CI)=1.47, 7.48]. No significant association was observed between an IGF1 genotype with no (CA)19 repeat compared to (CA)19 repeat genotypes in either pre- or postmenopausal women overall. However, when traditional breast cancer risk factors were considered, premenopausal women with genotypes that lacked a (CA)19 repeat had a nearly 60% increased risk of breast cancer among those who had ever used hormonal birth control, while never users had a significantly reduced risk (Pinteraction=0.01). Among postmenopausal women, those with genotypes lacking a (CA)19 repeat allele had significantly increased breast cancer risk among subjects with a lower than median body mass index (BMI) (OR=1.77 95% CI=1.09, 2.87), while no association for IGF1 genotype was seen among women with a higher than median BMI (Pinteraction=0.04). Our results demonstrate a role for alleles with fewer than (CA)19 repeats as a risk factor for breast cancer and also suggest that several traditional breast cancer risk factors modify the association of the IGF1 (CA)19 repeat genotype.

Exogenous hormone use and the risk of postmenopausal breast cancer: results from the Netherlands Cohort Study

The association between the use of exogenous hormones as either oral contraceptives (OC) or hormone replacement therapy (HRT) in relation to postmenopausal breast cancer incidence was examined in the Netherlands Cohort Study (NLCS) among 62,573 women aged 55 to 69 years. Information on these types of exogenous hormone use and other risk factors was collected by mailed questionnaire. During 3.3 years of follow-up, 471 incident breast cancer cases were identified. After adjustment for traditional breast cancer risk factors, the relative risk (RR) of breast cancer was 1.09 (95 percent confidence interval [CI]=0.79–1.48) for women who ever used OCs cf women who never used OCs. The relative rates (with CIs) for women who used OCs for a period < 5 years, 5–9 years, 10–14 years, and 15+ years were 0.97 (0.61–1.55), 1.20 (0.69–2.07), 1.03 (0.60–1.77), and 1.96 (0.99–3.89), respectively. The test for trend was not significant (P=0.13). There was no evidence of any association between the number of years between the first and the last use of OCs and breast cancer incidence. In the subgroup of women with first-degree relatives with breast cancer, the RR for breast cancer associated with ever use of OCs was 1.51 (CI=0.67–3.41), whereas in the remaining women, the RR was 0.97 (CI=0.73–1.27). Ever-use of HRT compared with never-use was not associated with an increase in breast cancer risk in the multivariate analysis (RR=0.99, CI=0.68–1.43). Also, the number of years of HRT use was not associated with an increased breast cancer risk (trend P=0.83), nor was the number of years between the first and the last use of HRT and breast cancer incidence. One subgroup of women in which the use of HRT seemed associated (but not significantly) with an increase in breast cancer risk was women with an induced menopause (RR=1.72, CI=0.95–3.12). The RR of breast cancer for women who had ever used both OCs and HRT, compared with women who never used these exogenous hormones was 1.00 (CI=0.51–1.94). From this study, it cannot be concluded that the use of exogenous hormones is a strong risk factor for the development of postmenopausal breast cancer. Since the acceptance of this paper, two other papers have been published on HRT and breast cancer. For HRT (estrogen alone), one supports our finding of no association (Stanford et al, JAMA 1995; 274: 137–42) and one did find a positive association for current use (Colditz et al, New Engl J Med 1995; 332: 1589–93), most pronounced in older women with longer durations of use. With regard to use of combined estrogen-progestin HRT, the results in both papers were comparable to those for estrogen alone. More research on (combinations of) types of hormones is needed.

Exogenous hormone use and the risk of postmenopausal breast cancer: results from The Netherlands Cohort Study.

The association between the use of exogenous hormones as either oral contraceptives (OC) or hormone replacement therapy (HRT) in relation to postmenopausal breast cancer incidence was examined in the Netherlands Cohort Study (NLCS) among 62,573 women aged 55 to 69 years. Information on these types of exogenous hormone use and other risk factors was collected by mailed questionnaire. During 3.3 years of follow-up, 471 incident breast cancer cases were identified. After adjustment for traditional breast cancer risk factors, the relative risk (RR) of breast cancer was 1.09 (95 percent confidence interval [CI] = 0.79-1.48) for women who ever used OCs cf women who never used OCs. The relative rates (with CIs) for women who used OCs for a period < 5 years, 5-9 years, 10-14 years, and 15+ years were 0.97 (0.61-1.55), 1.20 (0.69-2.07), 1.03 (0.60-1.77), and 1.96 (0.99-3.89), respectively. The test for trend was not significant (P = 0.13). There was no evidence of any association between the number of years between the first and the last use of OCs and breast cancer incidence. In the subgroup of women with first-degree relatives with breast cancer, the RR for breast cancer associated with ever use of OCs was 1.51 (CI = 0.67-3.41), whereas in the remaining women, the RR was 0.97 (CI = 0.73-1.27). Ever-use of HRT compared with never-use was not associated with an increase in breast cancer risk in the multivariate analysis (RR = 0.99, CI = 0.68-1.43).(ABSTRACT TRUNCATED AT 250 WORDS)