Risk Factors and Mortality Among Women With Interval Breast Cancer vs Screen-Detected Breast Cancer.

Importance: The risk factors for interval breast cancer (IBC) compared with those for screen-detected breast cancer (SBC) and their association with mortality outcomes have not yet been evaluated among Korean women. Objective: To evaluate risk factors associated with IBC and survival among Korean women with IBC compared with those with SBC. Design, Setting, and Participants: This retrospective cohort study used data from the Korean National Health Insurance Service Database. Women who participated in a national mammographic breast cancer screening program between January 1, 2009, and December 31, 2012, were included. Mortality outcomes were calculated from the date of breast cancer diagnosis to the date of death or December 31, 2020. Data were analyzed from March 1 to June 30, 2023. Exposure: Breast cancer diagnosed within 6 to 24 months after a negative screening result (ie, IBC) or within 6 months after a positive screening result (ie, SBC). Main Outcomes and Measures: Risk factors and survival rates for IBC and SBC. Results: This study included 8702 women with IBC (mean [SD] age, 53.3 [8.6] years) and 9492 women with SBC (mean [SD] age, 54.1 [9.0] years). Compared with SBC, the probability of IBC decreased as mammographic density increased. Lower body mass index, menopausal status, hormone replacement therapy (HRT) use, and lack of family history of breast cancer were associated with a higher likelihood of IBC. When stratified by detection time, younger age at breast cancer diagnosis and family history of breast cancer were associated with an increased likelihood of IBC diagnosed at 6 to 12 months but a decreased likelihood of IBC diagnosed at 12 to 24 months. Overall mortality of IBC was comparable with SBC, but total mortality and cancer-related mortality of IBC diagnosed between 6 and 12 months was higher than that of SBC. Conclusions and Relevance: The findings of this cohort study suggest that breast density, obesity, and HRT use were associated with IBC compared with SBC. These findings also suggest that higher supplemental breast ultrasound use among Korean women, especially those with dense breasts, could be attributed to a lower incidence of IBC among women with dense breasts compared with women with SBC, due to greater detection. Finally, overall mortality of IBC was comparable with that of SBC.

Increased risk of cancer and cancer-related mortality in middle-aged Korean women with prediabetes and diabetes: a population-based study.

OBJECTIVES: This study investigated the risk of developing and dying from all types of cancer, as well as cancer-specific mortality, in women diagnosed with prediabetes and diabetes. METHODS: We included women aged ≥40 years who underwent cancer screening from 2009 to 2014 with follow-up until 2020. Diabetes status was determined based on fasting plasma glucose levels, self-reported history of diabetes, and the use of antidiabetic medication. We quantified the risk of cancer and mortality in the prediabetes and diabetes groups, relative to the normoglycemia group, by calculating adjusted hazard ratios (aHRs). RESULTS: The study included 8,309,393 participants with a mean age of 52.7±9.7 years. Among these participants, 522,894 cases of cancer and 193,283 deaths were detected. An increased risk of cancer was observed in both the prediabetes group (aHR, 1.03; 95% confidence interval [CI], 1.02 to 1.04) and the diabetes group (aHR, 1.13; 95% CI, 1.12 to 1.14). The highest risk was identified in those with diabetes who developed liver (aHR, 1.72; 95% CI, 1.66 to 1.79), pancreatic (aHR, 1.68; 95% CI, 1.60 to 1.76), and gallbladder cancer (aHR, 1.43; 95% CI, 1.36 to 1.51). Women with prediabetes and diabetes exhibited a 1.07-fold (95% CI, 1.05 to 1.08) and 1.38-fold (95% CI, 1.36 to 1.41) increased risk of death from cancer, respectively. CONCLUSIONS: Both prediabetes and diabetes were associated with an elevated risk of cancer, as well as an increased risk of death from cancer, in middle-aged Korean women. However, the degree of risk varied depending on the specific site of the cancer.

Increased risk of pancreatic, thyroid, prostate and breast cancers in men with a family history of breast cancer: A population-based study.

The association between a family history of breast cancer (FHBC) in female first-degree relatives (FDRs) and cancer risk in men has not been evaluated. This study aimed to compare the risks of overall and site-specific cancers in men with and without FHBC. A population-based study was conducted with 3 329 106 men aged ≥40 years who underwent national cancer screening between 2013 and 2014. Men with and without FHBC in their female FDRs were age-matched in a 1:4 ratio. Men without FHBC were defined as those without a family history of any cancer type in their FDRs. Data from 69 124 men with FHBC and 276 496 men without FHBC were analyzed. The mean follow-up period was 4.7 ± 0.9 years. Men with an FHBC in any FDR (mother or sister) had a higher risk of pancreatic, thyroid, prostate and breast cancers than those without an FHBC (adjusted hazard ratios [aHRs] (95% confidence interval [CI]): 1.35 (1.07-1.70), 1.33 (1.12-1.56), 1.28 (1.13-1.44) and 3.03 (1.130-8.17), respectively). Although an FHBC in any one of the FDRs was not associated with overall cancer risk, FHBC in both mother and sibling was a significant risk factor for overall cancer (aHR: 1.69, 95% CI:1.11-2.57) and increased the risk of thyroid cancer by 3.41-fold (95% CI: 1.10-10.61). FHBC in the mother or sister was a significant risk factor for pancreatic, thyroid, prostate and breast cancers in men; therefore, men with FHBC may require more careful BRCA1/2 mutation-related cancer surveillance.

Association between Age at Helicobacter pylori Eradication and the Risk of Gastric Cancer Stratified by Family History of Gastric Cancer: A Nationwide Population-Based Study.

INTRODUCTION: This study compares the risk of GC according to age at H. pylori eradication, stratified based on the presence of family history of GC using a population-based large cohort. METHOD: We analyzed individuals who underwent GC screening between 2013 and 2014 and received H. pylori eradication therapy before screening. RESULTS: Among 1,888,815 H. pylori-treated patients, 2610/294,706 and 9332/1,594,109 patients with and without a family history of GC, respectively, developed GC. After adjusting for confounders, including age at screening, the adjusted hazard ratios (95% confidence intervals) for GC comparison, 70-74, 65-69, 60-64, 55-59, 50-54, 45-49, and <45 years with ≥75 years at H. pylori eradication were 0.98 (0.79-1.21), 0.88 (0.74-1.05), 0.76 (0.59-0.99), 0.62 (0.44-0.88), 0.57 (0.36-0.90), 0.38 (0.22-0.66), and 0.34 (0.17-0.67), respectively, among patients with a family history of GC (p < 0.001) and 1.01 (0.91-1.13), 0.95 (0.86-1.04), 0.86 (0.75-0.98), 0.67 (0.56-0.81), 0.56 (0.44-0.71), 0.51 (0.38-0.68), and 0.33 (0.23-0.47), respectively, among patients without a family history of GC (p < 0.001). CONCLUSION: In patients with and without a family history of GC, young age at H. pylori eradication was significantly associated with a reduced risk of GC, suggesting that the early treatment of H. pylori infection can maximize GC prevention.

Association of Breast Cancer Family History With Breast Density Over Time in Korean Women.

Importance: Evidence suggests that women with a family history of breast cancer (FHBC) in first-degree relatives have a higher level of breast density; however, studies of premenopausal women remain limited. Objective: To investigate the association between FHBC and mammographic breast density and breast density changes among premenopausal women. Design, Setting, and Participants: This retrospective cohort study used population-based data obtained from the National Health Insurance Service-National Health Information Database of Korea. We included premenopausal women aged 40 to 55 years who underwent mammography for breast cancer screening once between January 1, 2015, and December 31, 2016 (n = 1 174 214), and women who underwent mammography twice (first in 2015-2016 and again between January 1, 2017 and December 31, 2018) (n = 838 855). Exposures: Family history of breast cancer was assessed using a self-reported questionnaire, which included information on FHBC in the mother and/or sister. Main Outcomes and Measures: Breast density, based on the Breast Imaging Reporting and Data System, was categorized as dense (heterogeneously or extremely dense) and nondense (almost entirely fat or scattered fibroglandular areas). Multivariate logistic regression was used to assess the association among FHBC, breast density, and changes in breast density from the first to second screening. Data analysis was performed from June 1 to September 31, 2022. Results: Of the 1 174 214 premenopausal women, 34 003 (2.4%; mean [SD] age, 46.3 [3.2] years) reported having FHBC among their first-degree relatives, and 1 140 211 (97.1%; mean [SD] age, 46.3 [3.2] years) reported no FHBC. Odds of having dense breasts was 22% higher (adjusted odds ratio [aOR], 1.22; 95% CI, 1.19-1.26) in women with FHBC than in women without FHBC, and the association varied by affected relatives: mother alone (aOR, 1.15; 95% CI, 1.10-1.21), sister alone (aOR, 1.26; 95% CI, 1.22-1.31), and both mother and sister (aOR, 1.64; 95% CI, 1.20-2.25). Among women with fatty breasts at baseline, the odds of developing dense breasts was higher in women with FHBC than in those without FHBC (aOR, 1.19; 95% CI, 1.11-1.26), whereas among women with dense breasts, higher odds of having persistently dense breasts were observed in women with FHBC (aOR, 1.11; 95% CI, 1.05-1.16) than in those without FHBC. Conclusions and Relevance: In this cohort study of premenopausal Korean women, FHBC was positively associated with an increased incidence of having increased or persistently dense breasts over time. These findings suggest the need for a tailored breast cancer risk assessment for women with FHBC.

Association of Longitudinal Mammographic Breast Density Changes with Subsequent Breast Cancer Risk.

Background Although Breast Imaging Reporting and Data System (BI-RADS) density classification has been used to assess future breast cancer risk, its reliability and validity are still debated in literature. Purpose To determine the association between overall longitudinal changes in mammographic breast density and breast cancer risk stratified by menopausal status. Materials and Methods In a retrospective cohort study using the Korean National Health Insurance Service database, women aged at least 40 years without a history of cancer who underwent three consecutive biennial mammographic screenings in 2009-2014 were followed up through December 2020. Participants were divided according to baseline breast density: fatty (BI-RADS categories a, b) versus dense (BI-RADS categories c, d) and then into subgroups on the basis of changes from the first to second and from second to third screenings. Women without change in breast density were used as the reference group. Main outcomes were incident breast cancer events, both invasive breast cancer and ductal carcinoma in situ. Cox proportion hazard regression was used to calculate the hazard ratio (HR) with adjustment for other covariables. Results Among 2 253 963 women (mean age, 59 years ± 9) there were 22 439 detected breast cancers. Premenopausal women with fatty breasts at the first screening had a higher risk of breast cancer as density increased in the second and third screenings (fatty-to-dense HR, 1.45 [95% CI: 1.27, 1.65]; dense-to-fatty HR, 1.53 [95% CI: 1.34, 1.74]; dense-to-dense HR, 1.93 [95% CI: 1.75, 2.13]). In premenopausal women with dense breasts at baseline, those in whom density continuously decreased had a 0.62-fold lower risk (95% CI: 0.56, 0.69). Similar results were observed in postmenopausal women, remaining significant after adjustment for baseline breast density or changes in body mass index (fatty-to-dense HR, 1.50 [95% CI: 1.39, 1.62]; dense-to-fatty HR, 1.42 [95% CI: 1.31, 1.53]; dense-to-dense HR, 1.62 [95% CI: 1.51, 1.75]). Conclusion In both premenopausal and postmenopausal women undergoing three consecutive biennial mammographic screenings, a consecutive increase in breast density augmented the future breast cancer risk whereas a continuous decrease was associated with a lower risk. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kataoka et al in this issue.

Microcalcifications, mammographic breast density, and risk of breast cancer: a cohort study.

BACKGROUND: Breast density and microcalcifications are strongly associated with the risk of breast cancer. However, few studies have evaluated the combined association between these two factors and breast cancer risk. We investigated the association between breast density, microcalcifications, and risk of breast cancer. METHODS: This cohort study included 3,910,815 women aged 40-74 years who were screened for breast cancer between 2009 and 2010 and followed up until 2020. The National Health Insurance Service database includes national health-screening results from the national breast cancer screening program, which is an organized screening program provided every 2 years for all women aged 40 years or older. Breast density was assessed based on the Breast Imaging Reporting and Data System (BI-RADS) 4th edition, mostly through visual assessment by radiologists. The presence or absence of microcalcifications was obtained from the mammographic results. Cox proportional hazard regression for breast cancer risk was used to estimate hazard ratios (aHRs) adjusted for breast cancer risk factors. RESULTS: A total of 58,315 women developed breast cancer during a median follow-up of 10.8 years. Women with breast cancer had a higher proportion of microcalcifications than women without breast cancer (0.9% vs. 0.3%). After adjusting for breast density, women with microcalcification had a 3.07-fold (95% confidence interval [CI] 2.82-3.35) increased risk of breast cancer compared to women without microcalcification. The combined association between microcalcification and breast density dramatically increased the risk of breast cancer, corresponding to a higher level of breast density. Among postmenopausal women, the highest risk group was women with BI-RADS 4 and microcalcification. These women had more than a sevenfold higher risk than women with BI-RADS 1 and non-microcalcification (aHR, 7.26; 95% CI 5.01-10.53). CONCLUSION: Microcalcification is an independent risk factor for breast cancer, and its risk is elevated when combined with breast density.

Association between A Family History of Colorectal Cancer and the Risk of Colorectal Cancer: A Nationwide Population-Based Study.

Large-scale Asian studies on this topic are lacking. We evaluated the CRC risk associated with family history in the Korean population. We analyzed the data of participants aged ≥40 years who underwent national cancer screening between 2013 and 2014. During a mean follow-up of 4.7 ± 0.8 years, 0.43% of the 292,467 participants with family history and 0.28% of the 1,169,868 participants without family history developed CRC. Participants with a family history in any FDR, parents only, and siblings only had a higher risk of CRC than those without family history; adjusted hazard ratios (HRs) were 1.53, 1.46, and 1.61, respectively. Participants with a family history comprising both parents and siblings had an even higher risk of CRC than those without a family history (HR, 2.34). The HRs for CRC in the 40−49, 50−59, 60−69, 70−79, and ≥80 age groups with family history were 1.72, 1.74, 1.50, 1.30, and 0.78, respectively (p < 0.001). A family history of CRC in any FDR and both parents and siblings was associated with an approximately 1.5- and 2.3-fold increased risk of CRC. The effect of family history was relatively greater in the younger than the older age group.

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

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

Longitudinal Changes in Smoking Habits in Women and Subsequent Risk of Cancer.

INTRODUCTION: This study investigated the association between longitudinal smoking habit changes and cancer risk in a cohort of Korean women. METHODS: Study population included women aged ≥40 years who underwent 2 biennial cancer screenings (2009-2010 and 2011-2012) and were followed up until 2020. This analysis was conducted in 2021. On the basis of changes in smoking habits, participants were grouped into sustained nonsmokers, sustained quitters, new quitters, relapsers, smoking initiators, and sustained smokers. Outcomes included incident cancer cases, smoking-related cancers, and specific cancer sites. RESULTS: Of 3,051,946 women, the mean age was 54.8 years, and the median follow-up was 8.9 years. Compared with sustained nonsmokers, other groups had a significantly increased risk of cancer and smoking-related cancers: sustained quitters (adjusted hazard ratio=1.05; 95% CI=1.01, 1.09), new quitters (adjusted hazard ratio=1.12; 95% CI=1.07, 1.17), and sustained smokers (adjusted hazard ratio=1.14; 95% CI=1.09, 1.19). A significantly increased risk of lung, stomach, liver, and pancreas cancers was found in sustained smokers and new quitters. Relapsers/smoking initiators showed a higher risk of liver, lung, and breast cancer than sustained nonsmokers, but the strength of their corresponding adjusted hazard ratio was generally lower than that of sustained smokers. The hazard ratio of cancer risk was 0.92 (95% CI=0.87, 0.97) among sustained quitters and 0.97 (95% CI=0.91, 1.03) among new quitters relative to that among sustained smokers. CONCLUSIONS: This study found a significant association between changes in smoking behavior and cancer risk. These findings suggest that smoking cessation is critical for cancer prevention in women.

Consecutive gain and loss in body weight and waist circumference with risk of subsequent breast cancer in Korean women.

BACKGROUND: This study investigated the association between longitudinal changes in weight and waist circumference and breast cancer risk according to menopausal status. METHODS: This retrospective cohort study used data from the population-based Korean National Health Insurance Service (NHI) database. The study population included women aged ≥40 years who consecutively underwent three biennial breast cancer screenings between 2009-2014 and were followed up until 2020. The percentage changes in weight and waist circumference during the three screenings were calculated and categorized into five groups based on the level of increase or decrease in these two factors. Hazard ratios (HRs) and 95% confidence intervals (95% CI) for breast cancer risk were calculated and adjusted for other factors. RESULTS: Of 691,253 premenopausal and 1,519,211 postmenopausal women, 9485 and 12,553 breast cancer cases were identified, respectively, during a median 6.9 follow-up years. Postmenopausal women with two consecutive weight gains had an increased risk of breast cancer risk (HR = 1.11, 95% CI = 1.01 to 1.22); meanwhile, consecutive weight loss was associated with a decreased risk (HR = 0.84, 95% CI = 0.76 to 0.93). Single time and continuous decreases in waist circumference were associated with a decreased risk (HR = 0.91, 95% CI = 0.85 to 0.98, and HR = 0.84, 95% CI = 0.76-0.93), while single time and continuous increases were associated with an increased risk (HR = 1.08, 95% CI = 1.01 to 1.15, and HR = 1.13, 95% CI = 1.04 to 1.22). Single weight gain was associated with the increased breast cancer risk in premenopausal women (HR = 1.07, 95% CI = 1.01 1.13). CONCLUSIONS: Our findings suggest a dose-response relationship between weight, waist circumference change, and the risk of future breast cancer.

Association between Micronutrient Intake and Breast Cancer Risk According to Body Mass Index in South Korean Adult Women: A Cohort Study.

This study investigated the association between micronutrient intake and breast cancer risk in South Korean adult women. This association was stratified according to body mass index (BMI) categories. Data from the Korean Genome and Epidemiology Study (KoGES) and the Health Examinee Study were analyzed. Altogether, 63,337 individuals (aged ≥40 years) completed the baseline and first follow-up surveys; 40,432 women without a history of cancer at baseline were included in this study. The association between micronutrient intake and breast cancer was determined by estimating the hazard ratio (HR) and 95% confidence interval (CI) using the Cox proportional hazard regression model. A stratified analysis by BMI (<25 kg/m2 and ≥25 kg/m2) was performed. The an analysis of 15 micronutrients and breast cancer risk revealed that none of the micronutrients were associated with breast cancer risk after adjusting for covariates. In obese women, the risk of breast cancer was significantly reduced in the group that consumed vitamin C more than the recommended level (HR = 0.54, 95% CI: 0.31−0.93) and vitamin B6 levels above the recommended level (HR = 0.48, 95% CI: 0.25−0.89). In obese women, exceeding the recommended daily intake levels of vitamin C and vitamin B6 was associated with a lower risk of breast cancer. However, other micronutrients were not associated with breast cancer risk in these women.

Mammographic Breast Density, Benign Breast Disease, and Subsequent Breast Cancer Risk in 3.9 Million Korean Women.

Background Mammographic breast density and benign breast disease are strong risk factors for breast cancer. Accordingly, women with both risk factors may have a markedly high risk for developing breast cancer. Purpose To investigate the risk of breast cancer associated with the combination of mammographic density and benign breast disease in Korean women, where population-based mammographic breast cancer screening is provided for all women aged at least 40 years. Materials and Methods This is a retrospective analysis of data from a nationwide breast cancer screening program linked with the national cancer registry. The study included Korean women between 40-74 years of age screened for breast cancer between January 2009 and December 2010 and observed up to December 2020 (median follow-up of 10.6 years). Benign breast disease and breast density were extracted from mammography screening results. Cox proportional hazard regression analysis was used to calculate adjusted hazard ratios (HRs) for breast cancer risk. Results In this study, 3 911 348 women (mean age, 53 years ± 9 [SD]) were analyzed. During follow-up (median, 10.6 years), 58 321 women developed breast cancer. At screening, 10 729 (18.4%) cases of benign breast disease were detected among women who developed breast cancer. Women with extremely dense breasts (Breast Imaging Reporting and Data System [BI-RADS] density category D) and benign breast disease had a greater risk of breast cancer when compared with women presenting with fatty breast (BI-RADS density category A) and those without benign breast disease (HR, 2.75; 95% CI: 2.63, 2.88; P < .001). Women with benign breast disease and fatty breasts (HR, 1.49; 95% CI: 1.40, 1.58; P < .001) and women with extremely dense breasts and without benign breast disease (HR, 2.28; 95% CI: 2.20, 2.35; P < .001) also had an elevated breast cancer risk compared with women with fatty breast tissue. Conclusion Women with dense breasts and benign breast disease at screening mammography had an elevated risk of future breast cancer. © RSNA, 2022 Online supplemental material is available for this article.

Mammographic breast density, body mass index and risk of breast cancer in Korean women aged 75 years and older.

Mammographic breast density and body mass index (BMI) are strong risk factors of breast cancer, but few studies have investigated these factors in older women. Our study assessed the association between breast density, BMI and the breast cancer risk among women aged ≥75 years. We included women who underwent breast cancer screening between 2009 and 2014 and were followed up until 2020. Breast density was measured using Breast Imaging Reporting and Data System. BMI was classified into three groups: <23, 23 to <25 and ≥25. Cox proportional hazards models were used to estimate the association of breast density and BMI with breast cancer risk. In 483 564 women, 1885 developed breast cancer. The 5-year incidence increased with an increase in breast density and BMI. Increase in breast density was associated with an increased breast cancer risk in all BMI categories: among women with BMI <23, those with heterogeneous/extreme density had a 2.98-fold (95% CI: 2.23-3.80) increased risk of breast cancer compared to those with entirely fatty breasts. An increase in BMI was associated with increased breast cancer risk in women with the same breast density in all density categories. When the combined associations of breast density and BMI on the risk of breast cancer were considered, women with a BMI ≥25 and heterogeneous/extreme breast density had a 5.35-fold (95% CI: 4.26-6.72) increased risk of breast cancer compared to women with a BMI <23 and fatty breasts. Women aged ≥75 years, with dense breasts, regardless of BMI status, might benefit from a tailored screening strategy for early detection of breast cancer.