Accounting for time-varying exposures and covariates in the relationship between obesity and diabetes: analysis using parametric g-formula.

BACKGROUND: Previous studies investigating the association between obesity and diabetes often did not consider the role of time-varying covariates affected by previous obesity status. This study quantified the association between obesity and diabetes using parametric g-formula. METHODS: We included 8924 participants without diabetes from the Korean Genome and Epidemiology Study-Ansan and Ansung study(2001-2002)-with up to the seventh biennial follow-up data from 2015 to 2016. Obesity status was categorised as normal (body mass index (BMI) <23.5 kg/m2), overweight (23.5-24.9 kg/m2), obese 1 (25.0-27.4 kg/m2) and obese 2 (≥27.5 kg/m2). Hazard ratios (HRs) comparing baseline or time-varying obesity status were estimated using Cox models, whereas risk ratio (RR) was estimated using g-formula. RESULTS: The Cox model for baseline obesity status demonstrated an increased risk of diabetes in overweight (HR 1.85; 95% CI=1.48-2.31), obese 1 (2.40; 1.97-2.93) and obese 2 (3.65; 2.98-4.47) statuses than that in normal weight status. Obesity as a time-varying exposure with time-varying covariates had HRs of 1.31 (1.07-1.60), 1.55 (1.29-1.86) and 2.58 (2.14-3.12) for overweight, obese 1 and obese 2 statuses. Parametric g-formula comparing if everyone had been in each obesity category versus normal over 15 years showed increased associations of RRs of 1.37 (1.34-1.40), 1.78 (1.76-1.80) and 2.42 (2.34-2.50). CONCLUSIONS: Higher BMI classification category was associated with increased risk of diabetes after accounting for time-varying covariates using g-formula. The results from g-formula were smaller than when considering baseline obesity status only but comparable with the results from time-varying Cox model.

Validation of self-reported morbidities of the Korean Atomic Bomb Survivor Cohort.

Objectives: This study aimed to evaluate the agreement of disease status collected through a survey of the Korean Atomic Bomb Survivor Cohort (K-ABC), compared with medical claim records from the Korean National Health Insurance Service (NHIS) database and the Korean Central Cancer Registry (KCCR). Methods: Data on the lifetime physician-diagnosed morbidities of 1,215 K-ABC participants were collected through an interviewer-administered questionnaire between 2020 and 2022. Survey data were linked to the NHIS and KCCR databases. Eleven diseases were included for validation. We evaluated the following indicators: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, the area under the curve (AUC), and the kappa coefficient. Results: The mean (standard deviation) age was 62.1 (18.7) years, and 42.6% of the participants were aged ≥70 years. Hypertension and cataracts showed the highest prevalence rates (33.8% and 28.8%, respectively). Hypertension, diabetes, and cancer demonstrated high sensitivity (>0.8) and specificity (>0.9), whereas diabetes, cancer, myocardial infarction, angina pectoris, and asthma exhibited high accuracy (>0.9). In contrast, arthritis, allergic rhinitis, and asthma showed low sensitivity (<0.4) and kappa values (<0.3). In the participants aged ≥70 years, the kappa value was ≥0.4 for all diseases except arthritis, allergic rhinitis, and asthma. Conclusion: The results from this initial analysis showed relatively high agreement between the survey and NHIS/KCCR databases, especially for hypertension, diabetes, and cancer. Our findings suggest that the information on morbidities collected through the questionnaires in this cohort was valid for both younger and older individuals.

Mammographic breast features and risk of cardiovascular diseases in korean women.

BACKGROUND: There is a growing amount of evidence on the association between cardiovascular diseases (CVDs) and breast calcification. Thus, mammographic breast features have recently gained attention as CVD predictors. OBJECTIVE: This study assessed the association of mammographic features, including benign calcification, microcalcification, and breast density, with cardiovascular diseases. METHODS: This study comprised 6,878,686 women aged ≥40 who underwent mammographic screening between 2009 and 2012 with follow-up until 2020. The mammographic features included benign calcification, microcalcification, and breast density. The cardiovascular diseases associated with the mammographic features were assessed using logistic regression. RESULTS: The prevalence of benign calcification, microcalcification, and dense breasts were 9.6 %, 0.9 % and 47.3 % at baseline, respectively. Over a median follow-up of 10 years, benign calcification and microcalcification were positively associated with an increased risk of chronic ischaemic heart disease whereas breast density was inversely associated with it; the corresponding aOR (95 % CI) was 1.14 (1.10-1.17), 1.19 (1.03-1.15), and 0.88 (0.85-0.90), respectively. A significantly increased risk of chronic ischaemic heart disease (IHD) was observed among women with benign calcifications (aHR, 1.14; 95 % CI 1.10-1.17) and microcalcifications (aOR, 1.19; 95 % CI 1.06-1.33). Women with microcalcifications had a 1.16-fold (95 % CI 1.03-1.30) increased risk of heart failure. CONCLUSIONS: Mammographic calcifications were associated with an increased risk of chronic ischaemic heart diseases, whereas dense breast was associated with a decreased risk of cardiovascular disease. Thus, the mammographic features identified on breast cancer screening may provide an opportunity for cardiovascular disease risk identification and prevention.

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.

Adiposity, Body Composition Measures, and Breast Cancer Risk in Korean Premenopausal Women.

Objective: To investigate the association between body composition parameters and breast cancer (BC) risk in premenopausal women. Design, Setting, and Participants: Prospective cohort study using data from the Kangbuk Samsung Cohort Study. Participants were women aged 20 to 54 years who were enrolled from 2011 to 2019 and followed up for BC development until December 31, 2020. Data were analyzed from June to August 2023. Exposures: Trained nurses conducted anthropometric measurements and assessed body composition using segmental bioelectric impedance analysis. The analysis encompassed adiposity measures such as body mass index (BMI), waist circumference, and body composition parameters, including muscle mass, fat mass, ratio of muscle mass to weight, ratio of fat mass to weight, and fat mass index. Main outcomes and measures: Adjusted hazard ratios (aHR) for BC during the follow-up period. Results: Among 125 188 premenopausal women, the mean (SD) age was 34.9 (6.3) years. During a mean (range) follow-up of 6.7 (0.5-9.9) years, 1110 incident BC cases were identified. The mean (SD) BMI and waist circumference were 21.6 (3.1) and 75.3 (8.2) cm, respectively. Higher BMI and waist circumference were associated with decreased risk, with an aHR of 0.89 (95% CI, 0.84-0.95) per SD increase in BMI and 0.92 (95% CI, 0.86-0.98) per SD increase in waist circumference. A higher ratio of fat mass to weight was associated with decreased BC risk (aHR, 0.92; 95% CI, 0.86-0.99 per SD increase), whereas the opposite trend was observed for the ratio of muscle mass to weight, with an aHR of 1.08 (95% CI, 1.02-1.15) per SD increase. The results remained consistent even after additional adjustments for height in the model. The fat mass index was also inversely associated with BC risk, with an HR of 0.90 (95% CI, 0.85-0.97) per SD increase. Conclusions and Relevance: In this cohort study of premenopausal women, a higher level of adiposity, represented by increased BMI, waist circumference, and fat mass, was consistently associated with decreased breast cancer risk. Conversely, muscle mass and its ratio to weight displayed opposite or inconsistent patterns. These findings suggest an inverse association between excess adiposity and the risk of BC in premenopausal women, confirming earlier findings that BMI is an indirect measure of adiposity.

Longitudinal Changes in Smoking Behaviors and Cancer-Related Mortality Risk in Middle-Aged Korean Women.

PURPOSE: This study investigated association between smoking habit change and cancer-related mortality risk in Korean women. MATERIALS AND METHODS: Study population were women aged ≥ 40 years who underwent two biennial cancer screenings during 2009-2012 and were followed up until 2020. Participants were grouped into sustained nonsmokers, sustained quitters, new quitters, relapsers/smoking initiators, and sustained smokers. Outcomes included all-cause and cancer-related deaths. Cox regression and competing risk analysis was used to assess association between smoking habit change and mortality risk. RESULTS: Of 2,892,590 women, 54,443 death cases were recorded (median follow-up of 9.0 years). Compared with sustained nonsmokers, mortality risk from all causes and cancer-related causes increased in all other smoking groups. Cancer-related risk increased 1.22-fold among sustained quitters (95% confidence interval [CI], 1.10 to 1.36), 1.56-fold (95% CI, 1.40 to 1.75) in new quitters, 1.40-fold (95% CI, 1.21 to 1.62) in relapsers/smoking initiators, and 1.61-fold (95% CI, 1.46 to 1.78) in sustained smokers compared with sustained nonsmokers. Women who were sustained smokers with higher smoking intensity had a higher mortality risk in terms of hazard ratios compared to nonsmokers (< 5 pack-years 2.12-fold, 5-10 pack-years 2.15-fold, and > 10 pack-years 2.27-fold). CONCLUSION: Quitting smoking earlier is critical for preventing death from all causes and cancer among female smokers.

Temporal Trend in Uptake of the National General Health Checkups and Cancer Screening Program among Korean Women with Breast Cancer.

PURPOSE: This study assessed the temporal trends of uptake of national general health and cancer screening among women with breast cancer in Korea between 2009 and 2016. MATERIALS AND METHODS: We retrospectively analyzed the claims data from the Korean National Health Insurance Service database. Participants included 101,403 breast cancer patients diagnosed between 2009 and 2016. Information on participation in national screening programs, including breast cancer screening, general health, and gastric, colorectal, and cervical cancers, up to 2020 was collected. Screening participation rates within the first 2 and 5 years postdiagnosis were calculated by diagnosis year and fitted with joinpoint regression models to assess temporal trends. RESULTS: Overall, the participation rate in breast cancer screening within 2 years postdiagnosis increased from 10.9% to 14.0% from 2009-2016, with an annual percentage change (APC) of 3.7% (p < 0.05). The participation rate in breast cancer screening was lower than that in general health checkup and screening for other cancers within 2 and 5 years postdiagnosis. A steady increase in screening trends was also observed for general health, gastric, colorectal, and cervical cancers, with APC of 5.3%, 5.7%, 6.9%, and 7.6% in the 2-year postdiagnosis rate, and APC of 3.6%, 3.7%, 3.7%, and 4.4% in 5-year postdiagnosis rate, respectively. The screening rate was highest among age groups 50-59 and 60-69 in 2009 and significant upward trends were observed in all age groups for general health checkup and gastric, colorectal, and cervical cancer screening. CONCLUSION: Among female breast cancer survivors in Korea, the uptake rate of screenings for general health and various cancers, including breast, gastric, colorectal, and cervical cancers, has shown a gradual increase in recent years.

Mammographic breast density and cardiovascular disease risk in women.

AIMS: We aimed to determine the predictive role of mammographic breast density in addition to the Framingham Risk Score (FRS) on subsequent CVD events in women. METHODS AND RESULTS: This cohort study included 4,268,579 women aged ≥40 years who underwent mammography screening between 2009 and 2010 with follow-up until 2020. Breast density was reported following the Breast Imaging Reporting and Data System. Primary outcomes included coronary heart disease, cerebrovascular disease, peripheral arterial disease, and heart failure. The incremental predictive ability of breast density added to the FRS model was assessed using the ROC and net reclassification index (NRI) among all women and strata based on FRS risk categories (<5% as low-risk, 5%-10% as moderate-risk, and ≥10% as high-risk). In total, 135,475 CVD events were recorded after a median follow-up of 10.9 years. A lower category of breast density was associated with a higher risk of CVD. Compared to the extremely dense breast group, the hazard ratios (95% CI) for CVDs were 1.12 (1.09-1.14), 1.19 (1.17-1.22), and 1.29 (1.26-1.32) in women with heterogeneously dense, scattered fibroglandular densities, and almost entirely fat breast density, respectively. Adding breast density to the FRS showed a slight improvement in AUROC but a modest improvement in NRI; the C-statistic difference was 0.083% (95% CI 0.069-0.096) with a 7.15% (6.85-7.69) increase in NRI, with the strongest improvement observed in the low-risk group. CONCLUSIONS: Mammographic breast density is an independent predictor of incident CVD among women. The addition of mammographic breast density to FRS improves the prediction of CVDs, especially in low-risk individuals.

Health-related quality of life in long-term early-stage breast cancer survivors compared to general population in Korea.

PURPOSE: This study assessed health-related quality of life (HRQoL) of long-term breast cancer (BC) survivors diagnosed at early stages and compare with cancer-free, age-matched women. METHODS: The study population included BC survivors diagnosed with ductal carcinoma in situ (DCIS) or breast cancer stages I-II, who had undergone lumpectomy/mastectomy, with time since diagnosis ranging from 9 to 16 years. Survey was conducted at two tertiary hospitals in 2020. Data for cancer-free female controls was randomly drawn from a population-based survey and age-, education-matched with 1 case: 3 controls ratio. Self-reported HRQoL was assessed using EQ-5D with five dimentions. EQ-5D utility index score was calculated. Difference in EQ-5D score was evaluated using the Tobit regression model with adjustment for other covariates. RESULTS: Of 273 survivors. 88% and 12% underwent mastectomy and lumpectomy, respectively. The mean (standard deviation, SD) age at survey was 57.3 (8.5) years old. BC survivors reported significantly more problems performing daily activities (11% vs. 5%, p < 0.001), pain/discomfort (46% vs. 23%, p < 0.001), and anxious/depressed feelings (44% vs. 8%, p < 0.001) relative to the controls. Difference in EQ-5D score between BC survivors and the general population was higher in older age groups. The overall EQ-5D score of BC survivors was statistically lower than that of the control subjects (adjusted [Formula: see text]=0.117, p < 0.001). CONCLUSION: Long-term BC survivors who survived beyond ten years post-diagnosis experience more pain, anxiety, and distress, leading to an overall poorer HRQoL. IMPLICATIONS FOR CANCER SURVIVORS: This study suggest the importance of follow-up care, particularly focusing on pain, anxiety, and distress management to enhance the HRQoL of long-term BC survivors.

Mammographic Breast Density and Risk of Ovarian Cancer in Korean Women.

BACKGROUND: This study aimed to investigate the potential association between mammographic breast density and ovarian cancer risk. METHODS: This retrospective cohort study included women ≥40 years of age who underwent a mammography screening from 2009 to 2014. Breast density was assessed using the Breast Imaging-Reporting and Data System. The primary outcome was ovarian cancer development, and the cases were recorded until 2020. Cox proportional hazards regression was used to assess the association between breast density and ovarian cancer development. Subgroup analyses stratified by age, menopausal status, and body mass index (BMI) were conducted. RESULTS: Of the 8,556,914 women included in this study, 9,246 ovarian cancer events were recorded during a median follow-up period of 10 years (interquartile range, 8.1-11.0 years). Compared with women with almost entirely fat density, those with scattered fibroglandular density, heterogeneous density, and extreme density had an increased risk of ovarian cancer with adjusted HRs of 1.08 [95% confidence interval (CI), 1.02-1.15], 1.16 (95% CI, 1.09-1.24), and 1.24 (95% CI, 1.15-1.34), respectively. The strongest association was observed in the ≥60 years age group; subgroup analysis indicated a significant increase in association between the higher-density category and ovarian cancer risk, regardless of BMI or menopausal status. CONCLUSIONS: Higher levels of breast density are associated with an increased risk of ovarian cancer. IMPACT: Breast density may have a relationship with ovarian cancer risk and could be used to assess future risk.

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.

Changes in metabolic syndrome and the risk of breast and endometrial cancer according to menopause in Korean women.

OBJECTIVES: This study investigated how changes in metabolic syndrome (MetS) are associated with the subsequent risk of breast and endometrial cancer according to menopausal status. METHODS: This cohort study, using data from the National Health Insurance Service database, included women aged ≥40 years who underwent 2 biennial cancer screenings (2009-2010 and 2011-2012) and were followed up until 2020. Participants were grouped into MetS-free, MetS-recovery, MetS-development, and MetS-persistent groups. Menopausal status (premenopausal, perimenopausal, and postmenopausal) was assessed at 2 screenings. Cox proportional hazard regression was used to assess the association between MetS changes and cancer risk. RESULTS: In 3,031,980 women, breast and endometrial cancers were detected in 39,184 and 4,298, respectively. Compared with the MetS-free group, those who recovered, developed, or had persistent MetS showed an increased risk of breast cancer, with adjusted hazard ratios (aHRs) of 1.05, 1.05, and 1.11, respectively (p<0.005). MetS persistence was associated with an increased risk of breast cancer in postmenopausal women (aHR, 1.12, 95% confidence interval [CI], 1.08 to 1.16) but not in premenopausal or perimenopausal women. MetS persistence was associated with an increased risk of endometrial cancer in premenopausal, perimenopausal, and postmenopausal women, with aHRs of 1.41 (95% CI, 1.17 to 1.70), 1.59 (95% CI, 1.19 to 2.12), and 1.47 (95% CI, 1.32 to 1.63), respectively. CONCLUSIONS: Increased breast cancer risk was associated with recovered, developed, and persistent MetS in postmenopausal women. Meanwhile, increased endometrial cancer risk was found in obese women who recovered from MetS or persistently had MetS, regardless of menopausal status, when compared to MetS-free women.

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.

Long-term trajectory of postoperative health-related quality of life in young breast cancer patients: a 15-year follow-up study.

PURPOSE: Breast cancer (BC) patients often experience various long-term sequelae due to aggressive treatment. We analyzed and illustrated long-term trajectory during different phases of treatment and survivorship. METHODS: Data were obtained from a cohort of 298 BC patients diagnosed between 2004 and 2006 and were followed up until 2020. We measured HRQoL using EORTC QLQ-C30, QLQ-BR23, and EuroQoL-5D questionnaires and conducted eight assessments right after initial diagnosis, during treatment, post-treatment, and during survivorship phases. Linear mixed model was used to assess changes in HRQoL. Overall HRQoL measured by EQ-5D index of long-term BC survivors were further compared with that of the age-matched general population. RESULTS: Of 298 participants, 246 women survived and 124 participated in the long-term follow-up survey (LTFU). Overall, HRQoL functions deteriorated during treatment but gradually improved between 1- and 3-year post-diagnosis and stabilized over LTFU measure. Significant recovery was observed in physical, role, emotional, social functions, and future perspectives (p < 0.05). Treatment-related acute symptoms were reported in the first year but diminished afterward, and treatment-related financial difficulties lessened. At LTFU, BC survivors reported a high level of insomnia, fatigue, and pain and appeared to have poorer overall HRQoL than the general population (mean difference, EQ-5D index: 0.073, p < 0.001). CONCLUSIONS: Through 15-year survivorship, BC survivors showed improvement in many aspects of HRQoL. However, some inferior aspects remain relevant for long-term survivors. Ongoing supportive programs concentrating on pain management, persistent cancer-related fatigue, and sleeping problems might aid enhance their HRQoL.

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.

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.

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.

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.