Risk Of Advanced Breast Cancer Research Articles

Abstract B080: Advancing Breast Cancer Risk Prediction: Introducing the Gabbi Risk Assessment Model (GRAM)

Abstract Introduction: Advanced breast cancer risk models hold promise in implementing more effective and accurate screening strategies, facilitating early detection while minimizing screening-related harm compared to current guidelines. However, integrating machine learning risk models into clinical practice requires essential steps to be taken, including continual refinement to enhance their accuracy, validation across diverse populations, and demonstrating their ability to optimize clinical workflows. Gabbi Risk Assessment Model (GRAM), an innovative machine learning model, is a binary classifier based on medical claims developed to provide personalized breast cancer risk prediction. GRAM efficiently estimates risk and utilizes potentially missing risk factor information. Furthermore, it offers easy integration into EMR systems, thus optimizing its practical application. Methods: Construction of the GRAM utilized a medical claims dataset of 500k members from IQVIA carefully sampled from the entire IQVIA population (IQVIA acquires ~94% of the US claims data) with 4 years of history. The information extracted from the dataset included demographics, and medical history in the form of diagnostic and treatment codes, laboratory tests, and medications. The dataset consisted of 250k women aged 18-70 with a breast cancer diagnosis and a random sample of 250k women aged 18-70 without a known breast cancer diagnosis. For the selected cohorts, a 4-year history before the first breast cancer diagnosis was obtained. The control group was carefully chosen to possess similar statistical properties as the group with breast cancer. All women had a minimum enrollment period of 4 years before diagnosis with the same insurance provider. The GRAM was developed with 4 main steps: 1) member selection - members with breast cancer based on selection criteria defined above were in the test group, members without in the control group; 2) feature engineering to ensure that GRAM learns from medical history before a first diagnosis; 3) model development & testing - training/fine tuning using the ensemble methods and neural network, followed by hyperparameter tuning using a held out validation dataset; and 4) model performance on the held out validation set and identification of key risk factors contributing to the breast cancer risk. Results and Conclusion: By addressing these challenges and harnessing the potential of machine learning, GRAM has the capacity to revolutionize breast cancer risk estimation. Its integration into clinical practice can lead to more targeted and efficient screening strategies, resulting in earlier detection and improved patient outcomes. Preliminary results have shown that the GRAM surpasses the current standard of care models (GAIL and Tyrer Cusick) by at least 20% in sensitivity, and AUC ROC with no decline in specificity. GRAM achieved 91% AUC ROC (balanced data), 86% sensitivity, and 80% specificity on a held out dataset. As research progresses, continuous refinement and validation, the GRAM model holds promise to make significant contributions in the fight against breast cancer and identifying the correlated risk factors. Citation Format: Priyanshi Jain, Shaleen K Theiler, Kaitlin Christine. Advancing Breast Cancer Risk Prediction: Introducing the Gabbi Risk Assessment Model (GRAM) [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B080.

Breast cancer risk characteristics of women undergoing whole-breast ultrasound screening versus mammography alone.

There are no consensus guidelines for supplemental breast cancer screening with whole-breast ultrasound. However, criteria for women at high risk of mammography screening failures (interval invasive cancer or advanced cancer) have been identified. Mammography screening failure risk was evaluated among women undergoing supplemental ultrasound screening in clinical practice compared with women undergoing mammography alone. A total of 38,166 screening ultrasounds and 825,360 screening mammograms without supplemental screening were identified during 2014-2020 within three Breast Cancer Surveillance Consortium (BCSC) registries. Risk of interval invasive cancer and advanced cancer were determined using BCSC prediction models. High interval invasive breast cancer risk was defined as heterogeneously dense breasts and BCSC 5-year breast cancer risk ≥2.5% or extremely dense breasts and BCSC 5-year breast cancer risk ≥1.67%. Intermediate/high advanced cancer risk was defined as BCSC 6-year advanced breast cancer risk ≥0.38%. A total of 95.3% of 38,166 ultrasounds were among women with heterogeneously or extremely dense breasts, compared with 41.8% of 825,360 screening mammograms without supplemental screening (p<.0001). Among women with dense breasts, high interval invasive breast cancer risk was prevalent in 23.7% of screening ultrasounds compared with 18.5% of screening mammograms without supplemental imaging (adjusted odds ratio,1.35; 95% CI, 1.30-1.39); intermediate/high advanced cancer risk was prevalent in 32.0% of screening ultrasounds versus 30.5% of screening mammograms without supplemental screening (adjusted odds ratio,0.91; 95% CI, 0.89-0.94). Ultrasound screening was highly targeted to women with dense breasts, but only a modest proportion were at high mammography screening failure risk. A clinically significant proportion of women undergoing mammography screening alone were at high mammography screening failure risk.

Association of Screening With Digital Breast Tomosynthesis vs Digital Mammography With Risk of Interval Invasive and Advanced Breast Cancer

Digital breast tomosynthesis (DBT) was developed with the expectation of improving cancer detection in women with dense breasts. Studies are needed to evaluate interval invasive and advanced breast cancer rates, intermediary outcomes related to breast cancer mortality, by breast density and breast cancer risk. To evaluate whether DBT screening is associated with a lower likelihood of interval invasive cancer and advanced breast cancer compared with digital mammography by extent of breast density and breast cancer risk. Cohort study of 504 427 women aged 40 to 79 years who underwent 1 003 900 screening digital mammography and 375 189 screening DBT examinations from 2011 through 2018 at 44 US Breast Cancer Surveillance Consortium (BCSC) facilities with follow-up for cancer diagnoses through 2019 by linkage to state or regional cancer registries. Breast Imaging Reporting and Data System (BI-RADS) breast density; BCSC 5-year breast cancer risk. Rates per 1000 examinations of interval invasive cancer within 12 months of screening mammography and advanced breast cancer (prognostic pathologic stage II or higher) within 12 months of screening mammography, both estimated with inverse probability weighting. Among 504 427 women in the study population, the median age at time of mammography was 58 years (IQR, 50-65 years). Interval invasive cancer rates per 1000 examinations were not significantly different for DBT vs digital mammography (overall, 0.57 vs 0.61, respectively; difference, -0.04; 95% CI, -0.14 to 0.06; P = .43) or among all the 836 250 examinations with BCSC 5-year risk less than 1.67% (low to average-risk) or all the 413 061 examinations with BCSC 5-year risk of 1.67% or higher (high risk) across breast density categories. Advanced cancer rates were not significantly different for DBT vs digital mammography among women at low to average risk or at high risk with almost entirely fatty, scattered fibroglandular densities, or heterogeneously dense breasts. Advanced cancer rates per 1000 examinations were significantly lower for DBT vs digital mammography for the 3.6% of women with extremely dense breasts and at high risk of breast cancer (13 291 examinations in the DBT group and 31 300 in the digital mammography group; 0.27 vs 0.80 per 1000 examinations; difference, -0.53; 95% CI, -0.97 to -0.10) but not for women at low to average risk (10 611 examinations in the DBT group and 37 796 in the digital mammography group; 0.54 vs 0.42 per 1000 examinations; difference, 0.12; 95% CI, -0.09 to 0.32). Screening with DBT vs digital mammography was not associated with a significant difference in risk of interval invasive cancer and was associated with a significantly lower risk of advanced breast cancer among the 3.6% of women with extremely dense breasts and at high risk of breast cancer. No significant difference was observed in the 96.4% of women with nondense breasts, heterogeneously dense breasts, or with extremely dense breasts not at high risk.

The efficacy of continuing nursing interventions on intraoperative pressure ulcer-related complications in breast cancer patients: systematic review and meta-analysis.

This study systematically reviewed the effects of continuous nursing intervention on intraoperative pressure ulcers (PUs) and related complications in breast cancer patients. The effectiveness of continuous nursing intervention for intraoperative pressure ulcers related complications in breast cancer patients is highly controversial. Therefore, it is necessary to systematically review and address this issue by means of meta-analysis. By searching the Cochrane Library, PubMed, Web of Science, Embase, and Chinese Biomedical Literature Database (CBM) were screened. Quality evaluation and data extraction were performed for the included studies, and meta-analysis was performed for the included RCTs using Review Manager 5.2 software. Literature was included in strict compliance with the PICOS principle, and bias risk was analyzed by t-test and funnel plot. A total of 1,431 patients were enrolled in 9 studies, and meta-analysis showed that there was a significant statistical difference between the experimental group and the control group in the incidence of PUs [odds ratio (OR) =0.18, 95% confidence interval (95% CI): 0.13-0.24, P<0.00001], the Braden pressure ulcer risk score after nursing [mean difference (MD) =2.64, 95% CI: 1.47-3.81, P<0.0001], and the quality of life after nursing (MD =9.76, 95% CI: 6.82-12.69, P<0.00001). Continuous care can reduce the incidence of PUs in patients with advanced breast cancer, reduce the severity of wounds in the healing process of PUs, and improve the knowledge of PUs in patients with advanced breast cancer risk.

Cumulative Advanced Breast Cancer Risk Prediction Model Developed in a Screening Mammography Population.

Estimating advanced breast cancer risk in women undergoing annual or biennial mammography could identify women who may benefit from less or more intensive screening. We developed an actionable model to predict cumulative 6-year advanced cancer (prognostic pathologic stage II or higher) risk according to screening interval. We included 931 186 women aged 40-74 years in the Breast Cancer Surveillance Consortium undergoing 2 542 382 annual (prior mammogram within 11-18 months) or 752 049 biennial (prior within 19-30 months) screening mammograms. The prediction model includes age, race and ethnicity, body mass index, breast density, family history of breast cancer, and prior breast biopsy subdivided by menopausal status and screening interval. We used fivefold cross-validation to internally validate model performance. We defined higher than 95th percentile as high risk (>0.658%), higher than 75th percentile to 95th or less percentile as intermediate risk (0.380%-0.658%), and 75th or less percentile as low to average risk (<0.380%). Obesity, high breast density, and proliferative disease with atypia were strongly associated with advanced cancer. The model is well calibrated and has an area under the receiver operating characteristics curve of 0.682 (95% confidence interval = 0.670 to 0.694). Based on women's predicted advanced cancer risk under annual and biennial screening, 69.1% had low or average risk regardless of screening interval, 12.4% intermediate risk with biennial screening and average risk with annual screening, and 17.4% intermediate or high risk regardless of screening interval. Most women have low or average advanced cancer risk and can undergo biennial screening. Intermediate-risk women may consider annual screening, and high-risk women may consider supplemental imaging in addition to annual screening.

Income Disparity in Breast Cancer Incidence and Stage at Presentation: A National Population Study of South Korea.

This study aims to explore income-based disparities in breast cancer (BC) incidence and stage at presentation in a national population in South Korea, where a National Cancer Screening Program (NCSP) has been implemented. In 2007, new patients with BC were identified using the Korea Central Cancer Registry database. We calculated adjusted odds ratios (aORs) to evaluate the association between individual income level and the risk of distant stage BC at presentation, adjusting for women's age, body mass index, disability registration, employment, region of residence, and year of diagnosis. The cumulative age-standardized incidence of BC in the 11 years was highest among women in the richest quintile (2,040 per 100,000 women for 11 years), whereas the proportion of distant stage at presentation was the highest (10.2%) among the medical aid beneficiaries. The aOR of distant stage diagnosis at presentation was higher for lower-income quintiles, and the risk was the highest in the medical aid beneficiaries (aOR, 2.25; 95% confidence interval, 1.97-2.58) than in the richest quintile. The income-based gradient in aORs for distant stage did not differ between younger (< 40 years) and older patients. A higher risk of distant stage BC at presentation among the lower-income and medical aid groups in the context of a NCSP was observed. A more focused approach toward women in lower-income groups is necessary to alleviate the disparity in the risk of advanced BC.

Exposure to airborne cadmium and breast cancer stage, grade and histology at diagnosis: findings from the E3N cohort study

Molecular studies suggest that cadmium due to its estrogenic properties, might play a role in breast cancer (BC) progression. However epidemiological evidence is limited. This study explored the association between long-term exposure to airborne cadmium and risk of BC by stage, grade of differentiation, and histological types at diagnosis. A nested case–control study of 4401 cases and 4401 matched controls was conducted within the French E3N cohort. A Geographic Information System (GIS)-based metric demonstrated to reliably characterize long-term environmental exposures was employed to evaluate airborne exposure to cadmium. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. There was no relationship between cadmium exposure and stage of BC. Also, no association between cadmium exposure and grade of differentiation of BC was observed. However, further analyses by histological type suggested a positive association between cadmium and risk of invasive tubular carcinoma (ITC) BC [ORQ5 vs Q1 = 3.4 (95% CI 1.1–10.7)]. The restricted cubic spline assessment suggested a dose–response relationship between cadmium and ITC BC subtype. Our results do not support the hypothesis that airborne cadmium exposure may play a role in advanced BC risk, but suggest that cadmium may be associated with an increased risk of ITC.

XPF -673C>T variation is associated with the susceptibility to breast cancer

PurposeXPF variations might decrease the DNA repair capacity and further contribute to cancer development. This study aimed to investigate the association of XPF polymorphisms with risk of developing breast cancer. MethodsTCGA, the Human Protein Atlas and Kaplan-Meier plotter were used to analyze the expression of XPF in breast cancer tissues and its effect on the survival of breast cancer patients. The expression of XPF in breast cancer tissues was detected by qRT-PCR. This case-control study included 467 breast cancer patients and 467 healthy controls. The genotype of genetic variation was detected by polymerase chain reaction restriction fragment length polymorphism. Odds ratios and 95 % confidence intervals were calculated. Correlations between XPF variation and clinicopathological parameters were assessed through Kendall’s Tau-b test. The relationship between XPF gene function variation and XPF gene expression was analyzed by GTEx. ResultsThe expression of XPF in breast cancer tissues is higher than that in normal tissues. Breast cancer patients with high XPF expression have a higher relapse free survival rate (HR = 0.88, 95 % CI = 0.80−0.97), but have no effect on the overall survival rate (logrank P = 0.28). XPF -673C > T variant can reduce the risk of breast cancer patients (OR = 0.35, 95 %CI = 0.20−0.63 for codominant mode; OR = 0.66, 95 %CI = 0.51−0.85 for dominant model; OR = 0.40, 95 %CI = 0.23−0.70 for recessive model). The XPF 11985 GG genotype reduced the risk of early breast cancer (OR = 0.49, 95 %CI = 0.24−0.97), but not the risk of advanced breast cancer (OR = 1.20, 95 % CI = 0.58−2.48). XPF 11985A > G variant can also reduce the risk of ERBB2 expression in patients (OR = 0.50, 95 %CI = 0.27−0.94). There is no correlation between XPF -673C > T/XPF11985A > G variants and ER and PR. XPF -673C > T variant can reduce XPF expression (P < 0.05). ConclusionsGenetic variations of XPF gene may affect its expression and the risk of breast cancer in the Chinese population.

Relationship between insurance status and outcomes for patients with breast cancer in Missouri.

The cancer stage at diagnosis, treatment delays, and breast cancer mortality vary with insurance status. Using the Missouri Cancer Registry, this analysis included 31,485 women diagnosed with invasive breast cancer from January 1, 2007, to December 31, 2015. Odds ratios (ORs) of a late-stage (stage III or IV) diagnosis and a treatment delay (>60 days after the diagnosis) were calculated with logistic regression. The hazard ratio (HR) of breast cancer mortality was calculated with Cox proportional hazards regression. Mediation analysis was used to quantify the individual contributions of each covariate to mortality. The OR of a late-stage diagnosis was higher for patients with Medicaid (OR, 1.72; 95% confidence interval [CI], 1.56-1.91) or no insurance (OR, 2.30; 95% CI, 1.91-2.78) in comparison with privately insured patients. Medicare (OR, 1.21; 95% CI, 1.10-1.37), Medicaid (OR, 1.60; 95% CI, 1.37-1.85), and uninsured patients (OR, 1.58; 95% CI, 1.18-2.12) had higher odds of a treatment delay. The HR of breast cancer-specific mortality was significantly increased in the groups with public insurance or no insurance and decreased after sequential adjustments for sociodemographic factors (HR, 2.39; 95% CI, 1.96-2.91), tumor characteristics (HR, 1.28; 95% CI, 1.05-1.56), and treatment (HR, 1.23; 95% CI, 1.01-1.50). Late-stage diagnoses accounted for 72.5% of breast cancer mortality in the uninsured. Compared with the privately insured, women with public or no insurance had a higher risk for advanced breast cancer, a >60-day treatment delay, and death from breast cancer. Particularly for the uninsured, Medicaid expansion and increased funding for education and screening programs could decrease breast cancer disparities.

Strategies to Identify Women at High Risk of Advanced Breast Cancer During Routine Screening for Discussion of Supplemental Imaging

Federal legislation proposes requiring that screening mammography reports to practitioners and women incorporate breast density information and that women with dense breasts discuss supplemental imaging with their practitioner given their increased risk of interval breast cancer. Instead of discussing supplemental imaging with all women with dense breasts, it may be more efficient to identify women at high risk of advanced breast cancer who may benefit most from supplemental imaging. To identify women at high risk of advanced breast cancer to target woman-practitioner discussions about the need for supplemental imaging. This prospective cohort study assessed 638 856 women aged 40 to 74 years who had 1 693 163 screening digital mammograms taken at Breast Cancer Surveillance Consortium (BCSC) imaging facilities from January 3, 2005, to December 31, 2014. Data analysis was performed from October 10, 2018, to March 20, 2019. Breast Imaging Reporting and Data System (BI-RADS) breast density and BCSC 5-year breast cancer risk. Advanced breast cancer (stage IIB or higher) within 12 months of screening mammography; high advanced cancer rates (≥0.61 cases per 1000 mammograms) defined as the top 25th percentile of advanced cancer rates, and discussions per potential advanced cancer prevented. A total of 638 856 women (mean [SD] age, 56.5 [8.9] years) were included in the study. Women with dense breasts (heterogeneously or extremely dense) accounted for 47.0% of screened women and 60.0% of advanced cancers. Low advanced cancer rates (<0.61 per 1000 mammograms) occurred in 34.5% of screened women with dense breasts. High advanced breast cancer rates occurred in women with heterogeneously dense breasts and a 5-year risk of 2.5% or higher (6.0% of screened women) and those with extremely dense breasts and a 5-year risk of 1.0% or higher (6.5% of screened women). Density-risk subgroups at high advanced cancer risk comprised 12.5% of screened women and 27.1% of advanced cancers. Density-risk subgroups had the fewest supplemental imaging discussions per potential advanced cancer prevented compared with a strategy based on dense breasts (1097 vs 1866 discussions). Women with heterogeneously dense breasts and a 5-year risk less than 1.67% (21.7% of screened women) had high rates of false-positive short-interval follow-up recommendation without undergoing supplemental imaging. The findings suggest that breast density notification should be combined with breast cancer risk so women at highest risk for advanced cancer are targeted for supplemental imaging discussions and women at low risk are not. BI-RADS breast density combined with BCSC 5-year risk may offer a more efficient strategy for supplemental imaging discussions than targeting all women with dense breasts.

Novel sequence variants in the TLR6 gene associated with advanced breast cancer risk in the Saudi Arabian population.

Herein, we evaluated the association of the Toll-like receptor 6 (TLR6) single nucleotide polymorphisms (SNPs) rs3796508 (Val327Met) and rs5743810 (Ser249Pro) with breast cancer (BC) susceptibility in Saudi Arabian women, using in silico analysis. We found no significant differences in genotypic and allelic frequencies for rs3796508 between the BC patients (n = 127) and healthy individuals (n = 116). However, 86% of the BC patients, versus 98% of the healthy controls, carried the rs5743810 Pro allele (OR = 0.103, CI = 0.036–0.293, P = 0.00001). Advanced analysis based on the comparison of the estrogen receptor (ER)-positive and -negative patients with the healthy controls indicated a significant association between rs5743810 allelic frequency and BC risk protection (OR = 0.100, CI = 0.034–0.297, P = 0.00001 for ER+ BC cases; OR = 0.102, CI = 0.033–0.318, P = 0.00001 for ER−BC cases). Furthermore, rs5743810 was associated with BC risk protection at either above or below 48 years of age at diagnosis (OR = 0.101, CI = 0.022–0.455, P = 0.00037 for age ≤48 years; OR = 0.120, CI = 0.028–0.519, P = 0.00087 for age >48 years). Such associations were not found for rs3796508. In silico analysis indicated that these SNPs had neutral effects within the TLR6 structure, confirming the protective role of rs5743810. Our findings therefore suggest a strong association between rs5743810 and protection against BC risk in Saudi Arabian women. Importantly, the rs5743810 Pro allele could be a potential BC diagnostic biomarker in this ethnic population.

Geographical differences in risk of advanced breast cancer: Limited evidence for reductions over time, Queensland, Australia 1997–2014

BackgroundReducing geographical inequalities in breast cancer stage remains a key focus of public health policy. We explored whether patterns of advanced breast cancer by residential accessibility and disadvantage in Queensland, Australia, have changed over time. MethodsPopulation-based cancer registry study of 38,706 women aged at least 30 years diagnosed with a first primary invasive breast cancer of known stage between 1997 and 2014. Multilevel logistic regression was used to examine temporal changes in associations of area-level factors with odds of advanced disease after adjustment for individual-level factors. ResultsOverall 19,401 (50%) women had advanced breast cancer. Women from the most disadvantaged areas had higher adjusted odds (OR = 1.23 [95%CI 1.13, 1.32]) of advanced disease than those from least disadvantaged areas, with no evidence this association had changed over time (interaction p = 0.197). Living in less accessible areas independently increased the adjusted odds (OR = 1.18 [1.09, 1.28]) of advanced disease, with some evidence that the geographical inequality had reduced over time (p = 0.045). Sensitivity analyses for un-staged cases showed that the original associations remained, regardless of assumptions made about the true stage distribution. ConclusionsBoth geographical and residential socioeconomic inequalities in advanced stage diagnoses persist, potentially reflecting barriers in accessing diagnostic services. Given the role of screening mammography in early detection of breast cancer, the lack of population-based data on private screening limits our ability to determine overall participation rates by residential characteristics. Without such data, the efficacy of strategies to reduce inequalities in breast cancer stage will remain compromised.

Reduction in advanced breast cancer after introduction of a mammography screening program in Tyrol/Austria

BackgroundWe analysed all female breast cancer (BC) cases in Tyrol/Austria regarding the shift in cancer characteristics, especially the shift in advanced BC, for the group exposed to screening as compared to the group unexposed to screening. MethodsThe analysis was based on all BC cases diagnosed in women aged 40–69 years, resident in Tyrol, and diagnosed between 2009 and 2013. The data were linked to the Tyrolean mammography screening programme database to classify BC cases as “exposed to screening” or “unexposed to screening”. Age-adjusted relative risks (RR) were estimated by relating the exposed to the unexposed group. ResultsIn a total of about 145,000 women aged 40–69 years living in Tyrol during the study period, 1475 invasive BC cases were registered. We estimated an age-adjusted relative risk (RR) for tumour size ≥ 21 mm of 0.72 (95% confidence interval (CI) 0.60 to 0.86), for metastatic BC of 0.27 (95% CI 0.17 to 0.46) and for advanced BC of 0.83 (95% CI 0.71 to 0.96), each comparing those exposed to those unexposed to screening, respectively. ConclusionIn our population-based registry analysis we observed that participation in the mammography screening programme in Tyrol is associated with a 28% decrease in risk for BC cases with tumour size ≥ 21 mm and a 17% decrease in risk for advanced BC. We therefore expect the Tyrolean mammography programme to show a reduction in BC mortality.

Abstract 135: Coffee consumption increases risk of advanced breast cancer among Singapore Chinese women.

Abstract Background: There is experimental evidence supporting a dual role of coffee-related compounds on breast cancer development. Although reports from prospective epidemiologic studies do not support a relationship between coffee intake and breast cancer risk overall, there is support for an adverse effect among population subgroups defined by body size and stage of disease. Objective: Using data from a prospective cohort of Chinese women in Singapore, we examined the relationship between coffee intake and breast cancer risk. Methods: At baseline, between 1993 and 1998, we collected information on dietary history from 35,303 Singaporean Chinese women aged 45 to 74 years. Using Cox regression models, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for potential confounders. Stratified analysis by menopausal status and body mass index (BMI) were conducted to evaluate potential effect modification. Results: After a mean follow-up of 10 years, 629 women developed breast cancer. Average intake among coffee drinkers (80% of the study population) was 1.5 cups/day (interquartile range = 0.8, 2.3). Women consuming ≥2 cups of coffee per day had a statistically borderline significant increase in risk of breast cancer compared with coffee nondrinkers or monthly drinkers (HR=1.23; 95% CI: 0.98, 1.54; Ptrend=0.11). The positive association strengthened and became statistically significant when the analysis was restricted to advanced breast cancer (n=272) (HR=1.90; 95% CI: 1.30, 2.77; Ptrend&amp;lt;0.01). A similar association was observed for intake of total caffeine; HR was 2.23 (95% CI: 1.52, 3.26) the highest relative to the lowest of caffeine intake (Ptrend&amp;lt;0.01). The associations between coffee and caffeine intake and advanced disease did not differ by menopausal status. In stratified analyses by BMI, the adverse effect of coffee intake on the development of advanced breast cancer was present only among heavier women (BMI &amp;gt; median, 23 kg/m2) (HR=2.35; 95% CI: 1.51, 3.66; P for interaction=0.02). Similar patterns of association were observed with caffeine intake and advanced breast cancer risk by levels of BMI. There was no association with either coffee or caffeine intake and localized breast cancer risk. Conclusion: We provide the first prospective evidence among an Asian population for the adverse effect of coffee at relatively low levels of intake on the development of advanced breast cancer. Our data suggest that a larger body size may influence the adverse effect of coffee on breast cancer development. Citation Format: Lei Zhu, Lesley M. Butler, Renwei Wang, Woon-Puay Koh, Mimi C. Yu, Jian-Min Yuan. Coffee consumption increases risk of advanced breast cancer among Singapore Chinese women. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 135. doi:10.1158/1538-7445.AM2013-135

Trends in incidence and detection of advanced breast cancer at biennial screening mammography in The Netherlands: a population based study

IntroductionThe aims of this study were to determine trends in the incidence of advanced breast cancer at screening mammography and the potential of screening to reduce it.MethodsWe included a consecutive series of 351,009 screening mammograms of 85,274 women aged 50-75 years, who underwent biennial screening at a Dutch breast screening region in the period 1997-2008. Two screening radiologists reviewed the screening mammograms of all advanced screen detected and advanced interval cancers and determined whether the advanced cancer (tumor > 20 mm and/or lymph node positive tumor) had been visible at a previous screen. Interval cancers were breast cancers diagnosed in women after a negative screening examination (defined as no recommendation for referral) and before any subsequent screen. Patient and tumor characteristics were compared between women with advanced cancer and women with non-advanced cancer, including ductal carcinoma in situ.ResultsA total of 1,771 screen detected cancers and 669 interval cancers were diagnosed in 2,440 women. Rates of advanced cancer remained stable over the 12-year period; the incidence of advanced screen-detected cancers fluctuated between 1.5 - 1.9 per 1,000 screened women (mean 1.6 per 1,000) and of advanced interval cancers between 0.8 - 1.6 per 1,000 screened women (mean 1.2 per 1,000). Of the 570 advanced screen-detected cancers, 106 (18.6%) were detected at initial screening; 265 (46.5%) cancers detected at subsequent screening had been radiologically occult at the previous screening mammogram, 88 (15.4%) had shown a minimal sign, and 111 (19.5%) had been missed. Corresponding figures for advanced interval cancers were 50.9% (216/424), 24.3% (103/424) and 25.1% (105/424), respectively. At multivariate analysis, women with a ≥ 30 months interval between the latest two screens had an increased risk of screen-detected advanced breast cancer (OR 1.63, 95%CI: 1.07-2.48) and hormone replacement therapy increased the risk of advanced disease among interval cancers (OR 3.04, 95%CI: 1.22-7.53).ConclusionWe observed no decline in the risk of advanced breast cancer during 12 years of biennial screening mammography. The majority of these cancers could not have been prevented through earlier detection at screening.

Geographic remoteness, area-level socio-economic disadvantage and advanced breast cancer: a cross-sectional, multilevel study

BackgroundReducing disparities in cancer outcomes is a major priority for cancer-control agencies. The authors examine the relationships between geographic remoteness, area disadvantage and risk of advanced breast cancer among women.MethodsMultilevel...

Vitamin D Receptor Polymorphisms and Breast Cancer Risk: Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

Vitamin D is hypothesized to lower the risk of breast cancer by inhibiting cell proliferation via the nuclear vitamin D receptor (VDR). Two common single nucleotide polymorphisms (SNP) in the VDR gene (VDR), rs1544410 (BsmI), and rs2228570 (FokI), have been inconsistently associated with breast cancer risk. Increased risk has been reported for the FokI ff genotype, which encodes a less transcriptionally active isoform of VDR, and reduced risk has been reported for the BsmI BB genotype, a SNP in strong linkage disequilibrium with a 3'-untranslated region, which may influence VDR mRNA stability. We pooled data from 6 prospective studies in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium to examine associations between these SNPs and breast cancer among >6,300 cases and 8,100 controls for each SNP using conditional logistic regression. The odds ratio (OR) for the rs2228570 (FokI) ff versus FF genotype in the overall population was statistically significantly elevated [OR, 1.16; 95% confidence interval (95% CI), 1.04-1.28] but was weaker once data from the cohort with previously published positive findings were removed (OR, 1.10; 95% CI, 0.98-1.24). No association was noted between rs1544410 (BsmI) BB and breast cancer risk overall (OR, 0.98; 95% CI, 0.89-1.09), but the BB genotype was associated with a significantly lower risk of advanced breast cancer (OR, 0.74; 95% CI, 0.60-0.92). Although the evidence for independent contributions of these variants to breast cancer susceptibility remains equivocal, future large studies should integrate genetic variation in VDR with biomarkers of vitamin D status.

Obesity, Mammography Use and Accuracy, and Advanced Breast Cancer Risk

Being overweight or obese is associated with increased breast cancer risk and disease severity among postmenopausal women, but whether extent of mammography use and accuracy modify this association and further contribute to increases in disease severity at diagnosis among overweight and obese women is unclear. We prospectively collected data during 1996-2005 on 287,115 postmenopausal women not using hormone therapy (HT) who underwent 614,562 mammography examinations; 4,446 women were diagnosed with breast cancer within 12 months of a mammography examination. We calculated rates per 1,000 mammography examinations of large (>15 mm), advanced-stage (IIb, III, or IV), high-grade (3 or 4), estrogen receptor (ER)-positive and -negative, and screen-detected and non-screen-detected breast cancer across body mass index (BMI, kg/m(2)) groups defined as normal (18.5-24.9), overweight (25.0-29.9), obese class I (30.0-34.9), and obese class II/III (> or =35.0), adjusting for age, race/ethnicity, and mammography registry and use. All statistical tests were two-sided. Adjusted rates per 1000 mammography examinations of overall breast cancer increased across BMI groups (6.6 normal, 7.4 overweight, 7.9 obese I, 8.5 obese II/III; P(trend) < .001), as did rates of advanced disease, including large invasive (2.3 normal, 2.6 overweight, 2.9 obese I, 3.2 obese II/III; P(trend) < .001), advanced-stage (0.8 normal, 0.9 overweight, 1.3 obese I, 1.5 obese II/III; P(trend) < .001), and high nuclear grade (1.5 normal, 1.7 overweight, 1.7 obese I, 1.9 obese II/III; P(trend) = .10) tumors. Rates of ER-positive tumors increased across BMI groups (P(trend) < .001); rates of ER-negative tumors did not. Rates of screen-detected cancers were higher among overweight and obese women than normal and underweight women, but rates of non-screen-detected (false-negative) cancers were similar. Rates of advanced breast cancer increased across BMI groups regardless of extent of mammography use. Patterns of mammography use and mammography accuracy are not the primary reasons for higher rates of advanced breast cancer among overweight and obese postmenopausal women not using HT; thus, biologic differences in breast tumor development and/or progression may be important.

Women with large breasts are at an increased risk of advanced breast cancer

BackgroundThe risk of nodal metastasis is higher in women with bigger breast. It is not clear if this increase is due to the size of the breast (largely related to obesity) or is the result of larger tumour size at presentation (due to delayed diagnosis). It is hypothesised that women with large breasts are more likely to have node positive disease mainly attributable to their breast size.Patients and methodsOne hundred and twenty consecutive patients who underwent mastectomy during the year 2004 and 2005 for primary breast cancers in a large Teaching Hospital were included in the study. Patient's variable and tumour variable were collected and analysed by SPSS® computer programme.ResultsIt was found that big breasted women (those patients with mastectomy weight greater than 800 g) had a significantly greater tumour size than those with smaller breasts (p = 0.019, Mann-Whitney test) but there was no significant difference in grade (Kendall's tau-b = 0.055, p = 0.57) or lymph node positivity (Kendall's tau-b = 0.011, p = 0.93) between the two groups. Although, the tumour size was significantly greater in those with lymph node metastases (p < 0.001) but mastectomy weight was not found to be significantly greater in those with lymph node metastases (p = 0.11). For patients with similar tumour sizes mastectomy weight was not significantly greater in those patients with lymph node metastases (p = 0.28).ConclusionIt is concluded that increased incidence of lymph node positivity at presentation big-breasted women is because of larger size of the primary tumour and not due to the size of the breast alone.

Sun Exposure, Vitamin D Receptor Gene Polymorphisms, and Breast Cancer Risk in a Multiethnic Population

Considerable evidence indicates that vitamin D may reduce the risk of several cancers, including breast cancer. This study examined associations of breast cancer with sun exposure, the principal source of vitamin D, and vitamin D receptor gene (VDR) polymorphisms (FokI, TaqI, BglI) in a population-based case-control study of Hispanic, African-American, and non-Hispanic White women aged 35-79 years from the San Francisco Bay Area of California (1995-2003). In-person interviews were obtained for 1,788 newly diagnosed cases and 2,129 controls. Skin pigmentation measurements were taken on the upper underarm (a sun-protected site that measures constitutive pigmentation) and on the forehead (a sun-exposed site) using reflectometry. Biospecimens were collected for a subset of the study population (814 cases, 910 controls). A high sun exposure index based on reflectometry was associated with reduced risk of advanced breast cancer among women with light constitutive skin pigmentation (odds ratio = 0.53, 95% confidence interval: 0.31, 0.91). The association did not vary with VDR genotype. No associations were found for women with medium or dark pigmentation. Localized breast cancer was not associated with sun exposure or VDR genotype. This study supports the hypothesis that sunlight exposure reduces risk of advanced breast cancer among women with light skin pigmentation.