Abstract
Background
We aimed to explore the association between daily sitting time and breast cancer in obese women, and further examine the mitigating role of physical activity in this relationship.
Materials and methods
A secondary analysis of cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 1999–2020 were used. Subjects were divided into four groups based on the duration of daily sitting time (< 4, 4 to 6, 6 to 8, and > 8 h). Survey-based logistic regression models, smooth curve fitting, subgroup analysis and sensitivity analysis were conducted.
Results
A total of 9706 obese females (mean age 50.28 years) were included in the study. Breast cancer was reported by 271 (2.8%) individuals. In the fully adjusted model, compared with those with < 4 h of daily sitting time, ORs (95%CI) for breast cancer were 1.61 (95%CI: 1.41–5.33, p = 0.001) in group with 4 to 6 h of sitting, 1.86 (95%CI: 1.35 to 4.52) in group with 6 to 8 h, and 2.21 (95%CI: 1.36–4.95, p = 0.008) with > 8 h per day. Of note, the detrimental effects of prolonged sedentary behavior on increased prevalence of breast cancer were only found in physically inactive group, but not in physically active group. Smooth curve fitting showed a positive dose-response relationship between daily sitting time and breast cancer in total participants and physically inactive group. Furthermore, obese women aged 60 years or older, non-Hispanic white, and with more than a high school education, post-menopause, and with higher obesity levels were more likely to be affected by sedentary behavior.
Conclusion
Prolonged daily sitting time is associated with increased prevalence of breast cancer in obese women and being physically active may mitigate this association. Prospective studies are needed to further examine this association.
Clinical trial number
Not applicable.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12905-025-03894-x.
Keywords: Daily sitting time, Breast cancer, National health and nutrition examination survey (NHANES), Cross-sectional, Obesity, Physical activity
Introduction
According to the World Health Organization (WHO), obesity is defined as an excessive accumulation of body fat that causes a body mass index (BMI) to exceed the normal range, a BMI above 30 kg/m2 is defined as obesity [1]. More than 600 million people worldwide are obese [2, 3]. In most countries, obesity is more prevalent in women than in men [4]. Obesity is associated with altered prevalence of a variety of female reproductive diseases, including abnormal uterine bleeding, endometriosis, polycystic ovary syndrome (PCOS), infertility, and other related conditions [5]. A prospective cohort study found that the prevalence of early-onset colorectal cancer was almost doubled in obese women compared to women with a normal body mass index [6, 7]. Other studies have shown that obesity increases endometrial cancer incidence, all-cause mortality, and endometrial cancer-specific mortality [8, 9]. At present, among adult women in the world, breast cancer has replaced lung cancer as the world’s most prevalent diagnosed cancer [10–13]. Obesity may contribute to the development of breast cancer by influencing pathways such as hormone levels, inflammatory responses, and insulin resistance, leading to a significantly increased prevalence of breast cancer in obese women [14].
Sedentary behavior refers to any activity with energy expenditure below 1.5 metabolic equivalents (METs) [15, 16]. Sedentary behavior is not the same as physical inactivity, which is when an individual does not engage in moderate or vigorous physical activity, and even if a person is physically active for 300 min per week, they may still be sedentary for up to several hours a day at work or in leisure time [15–18]. Sedentary behavior, as a modifiable lifestyle, has a profound impact on health. Prolonged daily sitting time can lead to decreased cardiopulmonary function, insulin resistance, vascular dysfunction, decreased muscle activity, and reduced energy expenditure, which in turn increases the prevalence of obesity and metabolic syndrome [19, 20]. Excessive sedentary time is also associated with an increased incidence of cardiovascular disease and diabetes [17]. Of note, there is a positive link between prolonged sitting and the prevalence of breast cancer [21–25]. However, most of these studies recruited the general female population, although there is a heterogeneity regarding the prevalence of breast cancer among different subpopulation of women. Relatively few studies focused on specific female populations. Nomura, S.J.et al. conducted a cohort study of 46,734 women and found that sedentary lifestyles may increase the prevalence of breast cancer in African-American women [26, 27]. Pinto-Carbó et al. found that sedentary behavior increases the prevalence of breast cancer in women with low education [28, 29]. However, little is known about whether the prevalence of breast cancer in obese women is associated with prolonged sedentary time. While some studies have found that long sedentary time increases the prevalence of breast cancer in the overall female population, some studies revealed no significance [30–33]. In addition, there were some differences in design and sample size between studies, and some studies did not investigate exercise as a mitigating factor [22, 34, 35]. Therefore, the association between daily sitting time and female breast cancer needs to be further explored, especially in obese women, a high-prevalence population for breast cancer.
To fill the aforementioned gap of research, our study aims to explore the association between sedentary time and the prevalence of breast cancer in obese women using a nationally representative sample. Specifically, we investigate whether obese women with longer daily sitting time have an increased prevalence of breast cancer compared to those with lower sedentary levels, and whether this effect can be ameliorated by physical activity. Our findings may help guide the targeted prevention of breast cancer in obese women and provide evidence-based insights for public health policy-making.
Materials and methods
Study design and population
This study is a secondary analysis using the database of a population-based cross-sectional study. Our participants were recruited from the National Health and Nutrition Examination Survey (NHANES) 1999 ~ 2020, and this project is an ongoing health and nutrition status survey initiated by the National Center for Health Investigation in the United States, utilizing a stratified, multistage probability sampling design. A nationwide survey has been conducted on two-year cycles since 1999 to measure the health and nutritional status of the US population. The NHANES protocols got approval by the National Center for Health Statistics (NCHS) Research Ethics Review Board, and written informed consent was provided by every participant involved. All methods were performed in accordance with the relevant guidelines and regulations by NCHS. Data used in our work and design of NHANES can be downloaded in https://www.cdc.gov/nchs/nhanes/nhanes.htm. Our study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement guidelines.
The total sample of 123,182 cases was initially recruited in the wave of 1999–2020 NHANES study, and our inclusion criteria were: (1) female participants; (2) have cancer diagnosis information; (3) with assessment of sedentary time and physical activity; (4) BMI ≥ 30 kg/m2. According to the WHO standard, we defined women with a BMI ≥ 30 kg/m2 as obese women, and finally screened 9706 individuals for analysis (Fig. 1).
Fig. 1.
Flow diagram of participant screening. NHANES, National Health and Nutrition Examination Survey
Daily sitting time and physical activity
The assessment of daily sitting time and physical activity is derived from the Global Physical Activity Questionnaire (GPAQ), which evaluates the minutes of sedentary activity using the question “The following question is about sitting or reclining at work, at home, or at school. Include time spent sitting at a desk, sitting with friends, traveling in a car, bus, or train, reading, playing cards, watching television, or using a computer. Do not include time spent sleeping. How much time do you usually spend sitting or reclining on a typical day?”. Based on previous research [36–39], we calculated the number of sedentary hours per day for each participant, and divided participants into four groups based on the length sedentary time (< 4 h, 4 to 6 h, 6 to 8 h, and > 8 h). We used “In a typical week do you do any vigorous-intensity sports, fitness, or recreational activities that cause large increases in breathing or heart rate like running or basketball for at least 10 minutes continuously?” and “In a typical week do you do any moderate-intensity sports, fitness, or recreational activities that cause a small increase in breathing or heart rate such as brisk walking, bicycling, swimming, or volleyball for at least 10 minutes continuously?” to evaluate whether the subjects have engaged in vigorous or moderate physical exercise. If the answer was yes to either of these two questions, participants were defined as physically active. Otherwise, they were defined as physically inactive.
Breast cancer
The diagnosis of breast cancer is based on Medical Conditions assessment (MCQ), which is a self-report form that collects information about the subject’s previous disease diagnoses with quality assurance and quality control by NHANES [40, 41]. Specifically, we used the question “Have you ever been told by a doctor or other health professional that you had cancer or a malignancy of any kind?” to determine whether the subject had been diagnosed with cancer. In addition, “What kind of cancer was it?” was used to ascertain the type of cancer firstly diagnosed. Participants with breast cancer was defined by a previous diagnosis with cancer and breast cancer was the firstly diagnosed type.
Covariates
Based on previous research [36, 42], we included the following covariates for analyses: age, race, education level, marital status, ratio of family income to poverty, alcohol use, smoking-cigarette use, hypertension, diabetes, coronary heart disease, menopause status, pregnancy history, number of deliveries, female hormone use. The detailed assessment of covariates is provided in Supplementary Table 1.
Statistical analysis
We divided participants into four groups based on their sedentary time, and descriptive statistics were performed for each group and comparisons were made between groups. Categorical variables were expressed in frequency and percentage (%) and compared using Chi-square tests. Continuous data are presented as mean (± standard deviation [SD]) and compared using ANOVA tests or Wilcoxon test based on the distribution of the data. Then, we used three weighted logistic regression models to explore the relationship between daily sitting time and the prevalence of breast cancer in obese women. Model A did not adjust for any covariate (Crude model). Model B adjusted for age, race, education level, marital status, the ratio of family income to poverty, BMI, alcohol use, smoking-cigarette use, and physical activity. Model C further adjusted for hypertension, diabetes, coronary heart disease (CHD), menopause status, pregnancy history, number of deliveries, female hormone use based on Model B. The covariate selection followed a hierarchical adjustment strategy to progressively control for potential confounders while avoiding overadjustment [43]. Model A provided unadjusted estimates as reference. Model B adjusted for core demographic (age, race, education, marital status, income), metabolic (BMI), and lifestyle factors (alcohol, smoking, physical activity) known to influence breast cancer risk [44]. Model C further incorporated clinical/reproductive variables (hypertension, diabetes, CHD, menopause status, pregnancy history, deliveries, hormone use) to isolate the independent associations. This approach aligns with causal inference principles by first adjusting for socioeconomic/behavioral confounders before adding biological mediators, while ensuring covariates were selected based on established breast cancer risk factors from prior literature. The stepwise adjustment allows examination of how effect estimates change with increasing covariate control. Then, we repeated the three logistic regressions separately in physically active and inactive group to examine the mitigating effect of physical activity in the relationship between daily sitting time and the prevalence of breast cancer. We implemented penalized spline smooth curve fitting and weighted generalized additive model (GAM) regression analysis to explore the dose-response relationship between daily sitting time and breast cancer. Further, to explore the interaction between different covariates and sedentary time, we conducted a number of subgroup analyses according to the classification of different covariates. Specifically, we stratified the study population by age distribution (< 60 and ≥ 60 years), race (non-Hispanic white and other race), education level (less than high school, high school or above), marital status (married/living with partner, living alone, ), ratio of family income to poverty (< 1.3, 1.3 to 3.5, ≥ 3.5), alcohol use (yes, no), smoking-cigarette use (yes, no), hypertension (yes, no), diabetes(yes, no), coronary heart disease (yes, no), menopause (yes, no), and BMI (< 35, ≥ 35 kg/m2) [45]. Finally, we conducted sensitivity analysis to verify the robustness of our findings. We excluded participants with any missing covariate to exclude the effect of missing values. P-values in this study were two-sided, and p < 0.05 was considered statistically significant. All statistical analyses were performed using R (version 4.4.1).
Results
Population characteristics
A total of 9706 obese women was involved in our study, with a weighted population of 40,196,185 after taking into account the sample weights for NHANES. The mean age ± SD of all participants in this study was 50.28 ± 16.53 years, 66.3% of our participants were younger than 60 years old. 34.6% were non-Hispanic white, 31.3% were non-Hispanic black, 16.1% were Mexican-American, 11.2% were other Hispanic, and 6.9% other races. The comparison of demographic characteristics between our study participants and all women in the NHANES 1999–2020 databases were performed to ensure the representativeness of subsample, and no significant difference were observed between the subsample and overall females (Supplementary Table 2). Among all selected participants, 2,584 (26.6%) had a daily sitting time of less than 4 h, 2,175 (22.4%) sit for 4 to 6 h, 2,882 (29.7%) sit for 6 to 8 h, and 2,065 (21.3%) sit for more than 8 h. Breast cancer was diagnosed in 271 (2.8%) of all obese women. Significant differences were observed in the prevalence of breast cancer between different sitting time groups (p < 0.001). In addition, there were significant differences in age distribution, ethnicity, education level, marital status, household income-to-poverty ratio, smoking, alcohol consumption, physical activity, hypertension, diabetes, pregnancy history, menopause status, pregnancy history, number of deliveries, female hormone use and among obese women with different sedentary levels (all p < 0.05), and the specific baseline characteristics are shown in Table 1.
Table 1.
Baseline characteristics of study participants from NHANES 1999–2020 a
| Variables | Overall | Daily sitting time (hours/day) | p-Value | |||
|---|---|---|---|---|---|---|
| <4 | 4 to 6 | 6 to 8 | > 8 | |||
| (n = 9706) | (n = 2584) | (n = 2175) | (n = 2882) | (n = 2065) | ||
| Weighted sample size | 40,196,185 | 8,755,663 | 8,770,704 | 12,485,486 | 10,184,332 | |
| Age (years), mean ± SD | 50.28 ± 16.53 | 48.59 ± 15.39 | 50.35 ± 16.90 | 52.12 ± 17.11 | 49.77 ± 16.41 | < 0.001 |
| Age distribution (years), n (%) | < 0.001 | |||||
| <60 | 6439 (66.3) | 1837 (71.1) | 1403 (64.5) | 1755 (60.9) | 1444 (69.9) | |
| ≥60 | 3267 (33.7) | 747 (28.9) | 772 (35.5) | 1127 (39.1) | 621 (30.1) | |
| Race, n (%) | < 0.001 | |||||
| Mexican American | 1564 (16.1) | 663 (25.7) | 349 (16.0) | 354 (12.3) | 198 (9.6) | |
| Other Hispanic | 1088 (11.2) | 464 (18.0) | 243 (11.2) | 244 (8.5) | 137 (6.6) | |
| Non-Hispanic White | 3355 (34.6) | 614 (23.8) | 686 (31.5) | 1147 (39.8) | 908 (44.0) | |
| Non-Hispanic Black | 3034 (31.3) | 696 (26.9) | 732 (33.7) | 940 (32.6) | 666 (32.3) | |
| Other Race | 665 (6.9) | 147 (5.7) | 165 (7.6) | 197 (6.8) | 156 (7.6) | |
| Education level, n (%) | < 0.001 | |||||
| Less than high school | 2326 (24.0) | 940 (36.5) | 528 (24.3) | 612 (21.2) | 246 (11.9) | |
| High school or above | 7369 (76.0) | 1637 (63.5) | 1646 (75.7) | 2269 (78.8) | 1817 (88.1) | |
| Marital status, n (%) | < 0.001 | |||||
| Married | 4515 (46.6) | 3818 (53.5) | 1055 (48.6) | 1284 (44.6) | 895 (43.4) | |
| Widowed | 1801 (18.6) | 447 (17.3) | 407 (18.7) | 582 (20.2) | 365 (17.7) | |
| Divorced | 1629 (16.8) | 374 (14.5) | 355 (16.3) | 496 (17.2) | 404 (19.6) | |
| Separated | 282 (2.9) | 113 (4.4) | 49 (2.3) | 76 (2.6) | 44 (2.1) | |
| Never married | 1040 (10.7) | 232 (9.0) | 208 (9.6) | 328 (11.4) | 272 (13.2) | |
| Living with partner | 429 (4.4) | 132 (5.1) | 98 (4.5) | 115 (4.0) | 84 (4.1) | |
| Ratio of family income to poverty, n (%) | < 0.001 | |||||
| <1.3 | 3248 (37.3) | 1017 (45.2) | 781 (39.7) | 934 (36.0) | 516 (27.3) | |
| 1.3 to 3.5 | 3394 (39.0) | 911 (40.5) | 760 (38.7) | 991 (38.1) | 732 (38.7) | |
| ≥3.5 | 2063 (23.7) | 321 (14.3) | 424 (21.6) | 673 (25.9) | 645 (34.1) | |
| BMI (kg/m2), mean ± SD | 36.75 ± 5.96 | 35.73 ± 5.14 | 36.68 ± 5.84 | 37.01 ± 6.08 | 37.73 ± 6.65 | < 0.001 |
| Alcohol use, n (%) | < 0.001 | |||||
| Yes | 6277 (70.5) | 1506 (64.4) | 1426 (71.3) | 1882 (71.1) | 1463 (76.3) | |
| No | 2628 (29.5) | 834 (35.6) | 575 (28.7) | 764 (28.9) | 455 (23.7) | |
| Smoking—cigarette use, n (%) | < 0.001 | |||||
| Yes | 3539 (36.5) | 798 (30.9) | 775 (35.6) | 1130 (39.2) | 836 (40.5) | |
| No | 6163 (63.5) | 1785 (69.1) | 1400 (64.4) | 1751 (60.8) | 1227 (59.5) | |
| Physical activity, n (%) | 0.275 | |||||
| Active | 3743 (38.6) | 1009 (39.1) | 862 (39.6) | 1111 (38.6) | 761 (36.9) | |
| Inactive | 5960 (61.4) | 1574 (60.9) | 1313 (60.4) | 1769 (61.4) | 1304 (63.1) | |
| Hypertension, n (%) | < 0.001 | |||||
| Yes | 4611 (47.6) | 1097 (42.6) | 1043 (48.0) | 1496 (51.9) | 975 (47.2) | |
| No | 5084 (52.4) | 1480 (57.4) | 1131 (52.0) | 1384 (48.1) | 1089 (52.8) | |
| Diabetes, n (%) | < 0.001 | |||||
| Yes | 1841 (19.6) | 442 (17.5) | 404 (19.1) | 611 (22.0) | 384 (19.2) | |
| No | 7572 (80.4) | 2078 (82.5) | 1707 (80.9) | 2166 (78.0) | 1621 (80.8) | |
| Coronary heart disease, n(%) | 0.085 | |||||
| Yes | 265 (2.7) | 54 (2.1) | 59 (2.7) | 85 (3.0) | 67 (3.3) | |
| No | 9408 (97.3) | 2523 (97.9) | 2111 (97.3) | 2783 (97.0) | 1991 (96.7) | |
| Ever been pregnant, n(%) | < 0.001 | |||||
| Yes | 7745 (87.2) | 2136 (91.7) | 1730 (86.6) | 2278 (86.4) | 1601 (83.6) | |
| No | 1137 (12.8) | 194 (8.3) | 268 (13.4) | 360 (13.6) | 315 (16.4) | |
| Number of pregnancies, mean ± SD | 3.6 ± 2.1 | 3.8 ± 2.1 | 3.5 ± 2.1 | 3.5 ± 2.0 | 3.4 ± 2.0 | < 0.001 |
| Number of deliveries, mean ± SD | 2.8 ± 1.6 | 3.0 ± 1.7 | 2.8 ± 1.6 | 2.7 ± 1.5 | 2.5 ± 1.4 | < 0.001 |
| Female hormone use, n(%) | < 0.001 | |||||
| Yes | 265 (2.7) | 328 (14.1) | 390 (19.6) | 512 (19.5) | 348 (18.2) | |
| No | 9408 (97.3) | 1994 (85.9) | 1604 (80.4) | 2118 (80.5) | 1565 (81.8) | |
| Menopause, n(%) | 0.006 | |||||
| Yes | 3424 (38.6) | 881 (37.7) | 771 (38.7) | 1082 (41.0) | 690 (36.1) | |
| No | 5452 (61.4) | 1453 (62.3) | 1220 (61.3) | 1555 (59.0) | 1224 (63.9) | |
| Breast cancer, n(%) | < 0.001 | |||||
| Yes | 271 (2.8) | 39 (1.5) | 67 (3.1) | 96 (3.3) | 69 (3.3) | |
| No | 9435 (97.2) | 2545 (98.5) | 2108 (96.9) | 2786 (96.7) | 1996 (96.7) | |
Abbreviations: NHANES, National Health and Nutrition Examination Survey; BMI, body mass index. a All estimates accounted for sample weights and complex survey designs, and percentages and means were adjusted for survey weights of NHANES
Association between daily sitting time and breast cancer prevalence
In the crude model (model A), compared with the sitting group for less than 4 h, the OR (95%CI) for breast cancer in the groups with 4 to 6, 6 to 8 and > 8 h of sitting were 2.07 (95% CI: 1.40–3.12, p < 0.001), 2.25 (95% CI: 1.56–3.31, p < 0.001), 2.26 (95% CI: 1.53–3.38, p < 0.001), and p-trend < 0.001.
After adjusted for age, race, education level, marital status, the ratio of family income to poverty, BMI, alcohol use, smoking-cigarette use, and physical activity (Model B), the OR (95%CI) for breast cancer in participants with sedentary duration of 4 to 6 h, 6 to 8 h, and more than 8 h were 2.73 (95% CI: 1.50–5.28, p = 0.001), 2.68 (95% CI: 1.51–5.08, p = 0.001), 2.47 (95% CI: 1.32–4.87, p = 0.006), respectively, and p-trend = 0.035.
In addition, after further adjusted for hypertension, diabetes, and coronary heart disease, menopause status, pregnancy history, number of deliveries, female hormone uses on the basis of model B, the higher the sedentary time, the higher the prevalence of breast cancer in obese women, and the OR (95%CI) of breast cancer in subjects with sedentary time of 4 to 6, 6 to 8 and > 8 h were 1.61 (95% CI: 1.41–5.33, p = 0.001), 1.86 (95% CI: 1.35–4.52, p = 0.005), 2.21 (95% CI: 1.36–4.95, p = 0.008), and p-trend = 0.046. We further explored the impact of daily sitting time on breast cancer among obese women in physically active and inactive group separately. Of note, the above findings were only replicated in physically inactive group. (Table 2)
Table 2.
Associations between Daily Sitting Time and Self-reported Breast Cancer Diagnosis a
| Daily sitting time (hours) | Model A | Model B | Model C | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| OR | 95% CI | p-Value | OR | 95% CI | p-Value | OR | 95% CI | p-Value | ||
| Total | ||||||||||
| <4 | Reference | Reference | Reference | |||||||
| 4 to 6 | 2.07 | 1.40–3.12 | < 0.001 | 2.73 | 1.50–5.28 | 0.001 | 1.61 | 1.41–5.33 | 0.001 | |
| 6 to 8 | 2.25 | 1.56–3.31 | < 0.001 | 2.68 | 1.51–5.08 | 0.001 | 1.86 | 1.35–4.52 | 0.005 | |
| >8 | 2.26 | 1.53–3.38 | < 0.001 | 2.47 | 1.32–4.87 | 0.006 | 2.21 | 1.36–4.95 | 0.008 | |
| p-trend | < 0.001 | 0.035 | 0.046 | |||||||
| Physically active | ||||||||||
| <4 | Reference | Reference | Reference | |||||||
| 4 to 6 | 1.17 | 0.63–2.18 | 0.606 | 0.877 | 0.45–1.69 | 0.694 | 0.87 | 0.39–1.81 | 0.681 | |
| 6 to 8 | 1.13 | 0.63–2.04 | 0.686 | 0.717 | 0.37–1.38 | 0.315 | 0.71 | 0.29–1.52 | 0.352 | |
| >8 | 1.66 | 0.93–3.01 | 0.086 | 0.975 | 0.48–1.94 | 0.943 | 1.06 | 0.47–2.35 | 0.922 | |
| p-trend | 0.827 | 0.682 | 0.874 | |||||||
| Physically inactive | ||||||||||
| <4 | Reference | Reference | Reference | |||||||
| 4 to 6 | 3.14 | 1.84–5.58 | < 0.001 | 2.76 | 1.52–5.33 | 0.001 | 2.56 | 1.53–5.86 | 0.001 | |
| 6 to 8 | 3.56 | 2.16–6.18 | < 0.001 | 2.70 | 1.52–5.13 | 0.001 | 2.12 | 1.40–4.80 | 0.005 | |
| >8 | 2.95 | 1.72–5.26 | < 0.001 | 2.49 | 1.33–4.90 | 0.005 | 2.43 | 1.37–5.84 | 0.006 | |
| p-trend | 0.047 | 0.035 | 0.032 |
Abbreviations: CI, confidence interval; OR, odds ratio. a The associations between daily sitting time and the risks of breast cancer in women are presented as ORs (95% CI). Model A did not adjust for any covariates. Model B adjusted for age, race, education level, marital status, the ratio of family income to poverty, BMI, alcohol use, smoking—cigarette use, and physical activity. Model C further adjusted for hypertension, diabetes, coronary heart disease, menopause status, pregnancy history, number of deliveries, female hormone use based on Model B
According to smooth curve fitting analysis, a positive non-linear dose-response relationship between daily sitting time and breast cancer in total participants (Fig. 2A, p = 0.0433) and physically inactive group (Fig. 2C, p = 0.0102), but not in physically active group (Fig. 2B, p = 0.5115).
Fig. 2.
Dose-response relationship between daily sitting time and breast cancer among obese females. (A) Total population (B) Physically active group (C) Physically inactive group
Subgroup analysis
The results of subgroup analysis showed that among obese women aged ≥ 60 years, non-Hispanic whites, with high school education or above, family income to poverty ratio < 3, and with alcohol consumption, post-menopause, and with higher obesity levels, the effect of sedentary time on the prevalence of breast cancer was more pronounced. (Table 3)
Table 3.
Subgroup analysis of Associations between Daily Sitting Time and Self-reported Breast Cancer Diagnosis a
| Daily Sitting Time (hours/day) | ||||||
|---|---|---|---|---|---|---|
| <4 | 4 to 6 | 6 to 8 | > 8 | p for interaction | ||
| Age distribution (years) | ||||||
| <60 | Reference | 1.05 (0.30, 3.37) | 0.84 (0.24, 2.72) | 2.47 (0.91, 7.13) | 0.532 | |
| ≥60 | Reference | 4.17 (1.91, 10.40)*** | 3.89 (1.83,9.62)*** | 2.78 (1.19, 7.26)* | ||
| Race | 0.646 | |||||
| Non-Hispanic White | Reference | 6.55 (1.83, 41.8)* | 6.01 (1.78, 37.6)* | 5.40 (1.53, 34.3)* | ||
| Other Race | Reference | 2.24 (1.08, 4.84)* | 1.99 (0.95, 4.30) | 2.04 (0.84, 4.85) | ||
| Education level | 0.347 | |||||
| Less than high school | Reference | 2.52 (0.95, 7.06) | 2.16 (0.82, 6.06) | 3.14 (0.99, 9.90) | ||
| High school or above | Reference | 3.02 (1.36, 7.64)* | 3.02 (1.41, 7.48)** | 2.53 (1.13, 6.47)* | ||
| Ratio of family income to poverty | 0.039 | |||||
| <1.3 | Reference | 5.09 (1.82, 18.1)** | 3.44 (1.20, 12.4)* | 6.69 (2.18, 25.1)** | ||
| 1.3 to 3.5 | Reference | 1.79 (0.72, 4.66) | 2.36 (1.06, 5.83)* | 0.69 (0.21, 2.10) | ||
| ≥3.5 | Reference | 2.52 (0.59, 17.3) | 1.99 (0.50, 13.2) | 3.32 (0.85, 22.1) | ||
| Marital status | 0.694 | |||||
| Married/Living with partner | Reference | 2.64 (1.22, 6.22)* | 1.42 (0.62, 3.45) | 2.19 (0.91, 5.53) | ||
| Living alone | Reference | 2.78 (1.04, 8.07)* | 4.44 (1.86, 13.1)** | 2.94 (1.13, 9.13)* | ||
| Alcohol use | 0.294 | |||||
| Yes | Reference | 6.32 (2.33, 22.1)*** | 3.77 (1.36, 13.4)* | 5.24 (1.76, 19.3)** | ||
| No | Reference | 1.35 (0.61, 3.13) | 1.96 (0.97, 4.29) | 1.54 (0.70, 3.56) | ||
| Smoking—cigarette use | 0.449 | |||||
| Yes | Reference | 2.76 (1.03, 8.74)* | 2.47 (0.97, 7.57) | 2.15 (0.77, 6.94) | ||
| No | Reference | 2.62 (1.23, 6.09)* | 2.58 (1.24, 5.9)* | 2.68 (1.19, 6.45)* | ||
| Hypertension | 0.895 | |||||
| Yes | Reference | 2.38 (1.11, 5.55)* | 2.69 (1.33, 6.06)** | 2.23 (1.01, 5.33)* | ||
| No | Reference | 3.04 (1.13, 9.68)* | 2.08 (0.76, 6.67) | 2.45 (0.85, 8.12) | ||
| Diabetes | 0.793 | |||||
| Yes | Reference | 4.10 (1.04, 2.72)* | 5.21 (1.46, 33.3)* | 2.91 (0.65, 20.3) | ||
| No | Reference | 2.30 (1.17, 4.79)* | 1.99 (1.03, 4.11)* | 2.30 (1.14, 4.88)* | ||
| Coronary heart disease | 0.598 | |||||
| Yes | Reference | 0.60 (0.02, 16.6) | 1.45 (0.18, 30.3) | 0.20 (0.00, 5.93) | ||
| No | Reference | 2.88 (1.55, 5.69)** | 2.55 (1.40, 4.99)** | 2.66 (1.39, 5.40)** | ||
| Menopause | 0.647 | |||||
| Yes | Reference | 3.77 (2.01, 7.60)*** | 3.88 (1.91,6.53)*** | 3.91 (1.79,7.10)*** | ||
| No | Reference | 0.84 (0.40, 1.72) | 0.86 (0.43, 1.65) | 0.81 (0.39, 1.67) | ||
| BMI | 0.813 | |||||
| < 35 kg/m² | Reference | 2.09 (0.95, 3.81) | 1.77 (0.91, 3.22) | 1.35 (0.86, 3.11) | ||
| ≥35 kg/m² | Reference | 2.16 (1.04, 4.81)* | 2.29 (1.13, 5.05)* | 2.31 (1.17, 4.98)* | ||
Abbreviations: CI, confidence interval; OR, odds ratio; BMI, body mass index. a The associations between daily sitting time and the risks of breast cancer in women are presented as ORs (95% CI). Model adjusted for age, race, education level, marital status, the ratio of family income to poverty, BMI, alcohol use, smoking—cigarette use, and physical activity, hypertension, diabetes, and coronary heart disease, menopause status, pregnancy history, number of deliveries, female hormone use. *p < 0.05; **p < 0.01;***p < 0.001
Sensitivity analysis
After excluding participants with missing values of covariates, we found that the relationship between prolonged sedentary time and increased prevalence of breast cancer in obese women remained robust (Supplementary Table 3).
Discussion
In a large, nationally representative sample, we firstly explored the relationship between daily sitting time and the prevalence of breast cancer among obese women and further explored the role of physical activity in this association. Daily sedentary time of more than four hours was significantly associated with increased prevalence of breast cancer in this population. Notably, the detrimental effects of prolonged sedentary behavior on increased prevalence of breast cancer were only found in physically inactive group, which were verified with a positive dose-response relationship between daily sitting time and breast cancer in total participants and physically inactive group. In addition, the relationship was more pronounced in obese women aged ≥ 60 years, non-Hispanic whites, high school education or above, ratio of family income to poverty of < 3.3, alcohol consumption, non-smoking, with hypertension, without diabetes or coronary heart disease, and those after menopause and in higher obesity levels.
In this study, we observed a significantly increased prevalence of breast cancer in obese women who were sedentary for more than 4 h per day compared to obese women who spent less than 4 h a day. Of note, this finding has the potential to be generalized to other countries or regions as well, since a pooled analysis of seven British population cohorts indicated that sitting is linked to increased risk of cancer mortality [46]. Another prospective study in Japan also suggested that sitting time was associated with increased risk of multiple cancers [47]. Prolonged sedentary behavior contributes to a high risk of BC and poor outcomes, including obesity, insulin resistance, increased sex hormones, and chronic inflammation [48]. BC incidence is closely associated with sex hormone imbalance; therefore, lowering sex hormone levels with exercise lowers BC risk, increases anti-tumor immunity, which is consistent with lower cancer incidence and better prognosis [49]. Previous studies have found that obese women with less exercise are more likely to have breast inflammation, higher breast aromatase expression, and circulating metabolic inflammatory factor levels, which are associated with an increased prevalence of breast cancer [50, 51]. These mechanisms involve not only metabolic dysregulation of tumor cells, but also alterations in metabolic pathways of non-tumor cells in the tumor microenvironment. In addition, sedentary behavior may exacerbate hormone levels due to obesity, insulin resistance, and systemic inflammation, which are all factors associated with the development of breast cancer [14, 50, 52]. Although no studies have been conducted on the link between sedentary levels and breast cancer in obese women, the results of one systematic review showed that sedentary behavior was associated with a 15.5% increased prevalence of breast cancer in the overall female population [22]. Our results provide deeper insights into this field.
Another important finding of this study is that exercise can blunt the effect of sitting on an increased prevalence of breast cancer. Findings from the UK Biobank showed that women who are physically active may have a 20–25% lower prevalence of breast cancer than those who are physically inactive, suggesting that the overall prevalence of breast cancer decreases with more physical activity [50, 53]. The possible explanation are that exercise reduces visceral adipose tissue, has anti-inflammatory effects, regulates sex hormone levels, reduces insulin resistance and metabolic hormone levels, and these mechanisms together may help to reduce the incidence of breast cancer and improve the prognosis of breast cancer patients [54, 55]. On top of that, our work further substantiated that physical activity can ameliorate the increased prevalence associated with prolonged daily sitting time, which warrants further longitudinal study to help provide targeted intervention for cancer among obese females.
In addition, we found some heterogeneity in the association between prolonged sedentary and breast cancer prevalence in different subgroups of obese women. Prolonging sedentary behavior is closely related to the increased prevalence of breast cancer in older obese women. In contrast, no significant association was observed in young obese women, indicating that higher levels of physical activity or other unmeasured factors in this subgroup may have a potential buffering effect. Of note, > 40% of the affected breast cancer patients are currently > 65 of age and the incidence of breast cancer rises with age [11, 56]. We also observed that among postmenopausal women, sitting time is significantly associated with probabilities of breast cancer, which is in line with a high incidence of breast cancer in older women. Breast cancer incidence demonstrates a marked shift around menopausal transition. Premenopausal women (typically < 50 years) generally show lower incidence rates, which increase steadily with age until perimenopause [57]. This pattern reflects both hormonal mechanisms (estrogen-progesterone interplay) and cumulative lifetime exposure to risk factors [58]. In addition, the incidence of obesity in women increases with age, and obese elderly people sit for longer periods of time [62, 63]. Obese elderly women are particularly prone to metabolic dysfunction and functional limitations, leading to a vicious cycle of inactivity, further weight gain, and functional decline [64], which weakens the protective effect of physical activity on the harm of prolonged sitting in the elderly. Moreover, we found that women with higher levels obesity were more easily affected by increased sedentary behavior, potentially due to BMI by itself increases breast cancer risk due to increasing sex hormones levels at increasing BMI [59], through various mechanisms including altered adipokine balance, dysfunctional adipose tissue, dysregulated insulin signaling, and chronic inflammation contribute to tumorigenesis [60]. These findings have positive implications for preventing the occurrence of breast cancer: for obese women aged 60 and above, priority should be given to reducing sitting time to less than 4 h per day and engaging in endurance training to counteract metabolic imbalances. For young obese women, although sedentary behavior does not show a significant risk of cancer, maintaining physical activity is still crucial for obesity management. Future research should explore the molecular mediators (such as aging related cytokines) that link sedentary aging and breast cancer. In non-Hispanic white obese women, prolonged sittings have a significant effect on an increased prevalence of breast cancer. There is data showing a higher prevalence of overweight and severe obesity among non-Hispanic whites, which may exacerbate the prevalence of breast cancer [61]. In addition, studies have highlighted the effect of body mass index (BMI) on breast density in women of different races and ethnicities, and in non-Hispanic white women, an increase in BMI is associated with an increase in breast density, which may further increase the prevalence of breast cancer [62].
Among obese women with a high school education or higher, prolonged sedentary activities have a significant effect on an increased prevalence of breast cancer. Sitting for > 2 h per day is associated with breast cancer prevalence in women with low education [28], and our findings are not entirely consistent with the conclusions of this study, which may be due to the difference of the study design and the study participants of our study are obese. Obese women with higher levels of education have reproductive prevalence factors associated with breast cancer (e.g., nulliparous) and that women in this group are more likely to have a sedentary lifestyle and are more likely to attend a mammogram [63, 64]. In addition, obese women with low incomes tend to face more sedentary behaviors, which may be related to the nature of their work and socioeconomic status, as low-income women may have less access to healthy lifestyles and eating habits due to low health awareness or resource constraints, further increasing the prevalence of breast cancer [65–68]. In terms of alcohol consumption, studies have shown that the relative prevalence of breast cancer increases by 7% for every 10 g of alcohol intake increased, and there is a positive correlation between alcohol intake and breast cancer prevalence, which may increase breast cancer prevalence by affecting hormone levels such as estrogen [69, 70]. Alcohol consumption may affect an individual’s lifestyle choices and may cause an individual to be more inclined to choose sedentary activities such as watching television or playing video games rather than engaging in physical activity during their leisure time, and may also affect an individual’s self-control, making it more difficult to adhere to a healthy lifestyle including reducing sedentary time after drinking [71]. Thus, in obese women, alcohol consumption may make the effect of sitting for long periods of time on an increased prevalence of breast cancer more pronounced. The effect of smoking on the prevalence of breast cancer is controversial, and studies have shown that whether smoking increases the prevalence of breast cancer in women is affected by smoking-related factors (duration, intensity, years of quitting), population-related factors (fertility status) and breast cancer subtype, smoking can increase the occurrence of breast cancer in premenopausal, estrogen receptor-positive, and multiparous populations, but has no effect on postmenopausal, estrogen receptor-negative, and non-nulliparous people [72, 73]. In this study, the relationship between prolonged sedentary and breast cancer prevalence was more significant among obese women who did not smoke, and the specific mechanism needs to be further explored. In addition, we found a significant effect of prolonged sitting on an increased prevalence of breast cancer only in obese women without coronary heart disease. On the one hand, obese women with coronary heart disease often have long-term cardiovascular drug use, which makes the body’s inflammation level and hormone level interfere to a certain extent, so that the impact of long-term sedentary is not significant. On the other hand, obese women with coronary heart disease tend to be more likely to be sedentary, and these people tend to be sedentary for a long time, so the change in the length of sedentary time is relatively insensitive to the prevalence of breast cancer in these women.
Study limitations
First, the cross-sectional design of this study does not allow for direct causal inferences, and longitudinal studies of obese women are needed in the future to verify this finding. Although our analysis adjusted for key confounders, the cross-sectional design precludes determining whether prolonged sitting precedes breast cancer diagnosis or reflects post-diagnosis behavioral changes. Reverse causality remains plausible (e.g., women with undiagnosed cancer may reduce activity prior to diagnosis). Prospective cohorts are needed to clarify temporality. Second, we only included the US population, so the findings of this study cannot be generalized to populations in different countries around the world, and it is necessary to validate our findings in obese women in different countries. In addition, breast cancer diagnoses were self-reported and not validated against medical records or cancer registries, which may introduce misclassification bias, since no information is provided about cancer stage, type (e.g., hormone receptor status), or diagnostic verification. Future studies should incorporate registry linkages where possible. Emerging evidence suggests physical activity may preferentially influence hormone receptor-positive (luminal) breast cancer via obesity-related estrogen pathways [74]; conversely, triple-negative subtypes may be less associated with metabolic factors [75]. Unfortunately, subtype data were unavailable in our dataset. Future studies should examine subtype-specific associations with sedentary behavior to refine biological mechanisms.
Conclusion
This study explored for the first time in a large, nationally representative sample the relationship between daily sedentary time and the prevalence of breast cancer in obese women, and we found that sedentary time of more than four hours per day significantly increased the prevalence of breast cancer in obese women. We found that the detrimental effects of prolonged daily sitting time on increased prevalence of breast cancer could be mitigated by physical activity. Our results can help provide evidence-based guidance for cancer prevention program among obese women to reduce the burden of breast cancer.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Acknowledgements
We appreciate all every NHANES participant and staff for their invaluable efforts and contributions to our work.
Author contributions
L.Z. and T.X. contributed to the conception and design of the study, manuscript writing, and the statistics analysis; L.Z. and Z.W. reviewed manuscripts and analyzed data; C.L. and H.L. contributed to manuscript revision and data review. All authors have read and approved the manuscript.
Funding
This work was supported by the following funding: Meizhou People’s Hospital Cultivation Project (PY-C2021037).
Data availability
The data used in this study are openly available from the Centers for Disease Control and Prevention at https://www.cdc.gov/nchs/nhanes/.
Declarations
Ethics approval and consent to participate
The National Health and Nutrition Examination Survey (NHANES) has been approved by the National Center for Health Statistics Ethics Review Board, and all participants provided informed written consent at enrollment.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data used in this study are openly available from the Centers for Disease Control and Prevention at https://www.cdc.gov/nchs/nhanes/.