Wenji Guo

Background: Breast cancer survivors face many health challenges, including tinnitus, hearing loss, and vertigo which will grow with an aging population and improved treatment outcomes. However, the prevalence of hearing/vestibular problems, racial differences, and relationships to physical function are poorly characterized in breast cancer survivors. Methods: Between July and September 2023, we surveyed the Chicago Multiethnic Epidemiologic Breast Cancer Cohort. Tinnitus, hearing loss, and vertigo were self-reported and verified through electronic health records. Physical function impairment was measured using the SF-36 10-item instrument. We fit logistic regression models for hearing/vestibular problems and linear regression models for physical function score, controlling for sociodemographic and clinical factors. Results: Of 1466 breast cancer survivors (mean [SD] age, 63.5 [11.8] years), 16.6%, 17.3%, and 8.6% reported experiencing tinnitus, hearing loss, and vertigo, respectively. Black survivors had lower odds of hearing loss (adjusted odds ratio [AOR] = 0.51; 95% confidence interval [CI] = 0.31 to 0.86) but greater odds of vertigo (AOR = 2.29; 95% CI = 1.34 to 3.89) than White survivors. Survivors with hearing/vestibular problems had higher average impairment scores (worse physical function) than those without. In the adjusted regression models, survivors who reported experiencing tinnitus (β = 0.76; 95% CI = 0.10 to 1.43), hearing loss (β = 0.73; 95% CI = 0.06 to 1.40), or vertigo (β = 1.70; 95% CI = 0.81 to 2.58) had a higher level of physical function impairment. Conclusions: This study demonstrates racial differences in hearing/vestibular problems and associations between these problems and physical function impairment. Survivorship programs should consider routine screening and interventions to improve hearing health and physical function among breast cancer survivors.

Polygenic risk score (PRS) models effectively predict breast cancer (BC) risk in European-ancestry women but have limited accuracy for African-ancestry women, particularly for aggressive subtypes. We developed PRS models for overall BC, estrogen receptor (ER)-positive, ER-negative and triple-negative BC (TNBC) in African-ancestry women using data from the African Ancestry Breast Cancer Genetics consortium (17,391 cases and 18,800 controls). We applied several PRS methods and integrated information across ancestries and BC subtypes. The best models for overall, ER-positive, ER-negative and TNBC showed an area under the receiving operating curve of 0.612, 0.621, 0.611 and 0.639, respectively, and maintained predictive accuracy in external validation studies with area under the receiving operating curves of 0.612, 0.640, 0.605 and 0.652. We further introduce a parsimonious 162-variant PRS for TNBC with comparable accuracy (0.626). These findings demonstrate markedly improved PRS accuracy for BC risk prediction in African-ancestry women. Using these PRS models for screening will help promote more equitable cancer prevention efforts.

Background: Previous studies suggest a protective role of physical activity in breast cancer risk, largely based on self-reported activity. We aimed to clarify this association by examining breast cancer risk in relation to self-reported physical activity, informed by accelerometer-based measures in a large subset of participants. Methods: We analysed data from 47,456 premenopausal and 126,704 postmenopausal women in UK Biobank followed from 2006 to 2014. Physical activity was self-reported at baseline, and at resurvey in a subsample of 6443 participants. Accelerometer data, measured from 2013 to 2015, were available in 20,785 women. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using multivariable-adjusted Cox regression. Results: A total of 3189 cases were diagnosed during follow-up (mean = 5.7 years). Women in the top compared with the bottom quartile of self-reported physical activity had a reduced risk of both premenopausal (RR 0.75; 95% CI 0.60–0.93) and postmenopausal breast cancer (RR 0.87; 95% CI 0.78–0.98), after adjusting for adiposity. In analyses utilising physical activity values assigned from accelerometer measurements, an increase of 5 milli-gravity was associated with a 21% (RR 0.79; 95% CI 0.66–0.95) reduction in premenopausal and a 16% (RR 0.84; 95% CI 0.73–0.96) reduction in postmenopausal breast cancer risk. Conclusions: Greater physical activity is associated with a reduction in breast cancer risk, which appears to be independent of any association it may have on risk through its effects on adiposity.

Objectives: Previous studies of the association between physical activity and adiposity are largely based on physical activity and body mass index (BMI) from questionnaires, which are prone to inaccurate and biased reporting. We assessed the associations of accelerometer-measured and questionnaire-measured physical activity with BMI, waist circumference and body fat per cent measured by bioelectrical impedance and dual-energy X-ray absorptiometry (DXA). Design: Cross-sectional analysis of UK Biobank participants. Setting: UK Biobank assessment centres. Participants: 78 947 UK Biobank participants (35 955 men and 42 992 women) aged 40–70 at recruitment, who had physical activity measured by both questionnaire and accelerometer. Main outcome measures: BMI, waist circumference and body fat per cent measured by bioelectrical impedance. Results: Greater physical activity was associated with lower adiposity. Women in the top 10th of accelerometer-measured physical activity had a 4.8 (95% CI 4.6 to 5.0) kg/m ² lower BMI, 8.1% (95% CI 7.8% to 8.3%) lower body fat per cent and 11.9 (95% CI 11.4 to 12.4) cm lower waist circumference. Women in the top 10th of questionnaire-measured physical activity had a 2.5 (95% CI 2.3 to 2.7) kg/m ² lower BMI, 4.3% (95% CI 4.0% to 4.5%) lower body fat per cent and 6.4 (95% CI 5.9 to 6.9) cm lower waist circumference, compared with women in the bottom 10th. The patterns were similar in men and also similar to body fat per cent measured by DXA compared with impedance. Conclusion: Our findings of approximately twofold stronger associations between physical activity and adiposity with objectively measured than with self-reported physical activity emphasise the need to incorporate objective measures in future studies.

Body size is an important modifiable risk factor for postmenopausal breast cancer. However, it remains unclear whether direct measures of fat mass are better indicators of risk than anthropometric measures, or whether central adiposity may contribute to risk beyond overall adiposity. We analyzed data from 162,691 postmenopausal women in UK Biobank followed from 2006 to 2014. Body size was measured by trained technicians. Multivariable‐adjusted Cox regression was used to estimate relative risks. Analyses were stratified by age at recruitment, region and socioeconomic status, and adjusted for family history of breast cancer, age at menarche, age at first birth, parity, age at menopause, previous hormone replacement therapy use, smoking, alcohol intake, height, physical activity and ethnicity. We observed 2,913 incident invasive breast cancers during a mean 5.7 years of follow‐up. There was a continuous increase in risk of postmenopausal breast cancer with increasing adiposity, across all measures. The point estimate, comparing women in the top (median 37.6 kg) to bottom (median 17.6 kg) quartile of body fat mass was 1.70 (95% confidence interval 1.52–1.90). The magnitudes of the associations between per SD increase in BMI and body fat mass with breast cancer risk were similar, suggesting impedance measures of fat were not substantially better indicators of risk than anthropometric measures. After adjusting for body fat mass, the associations between anthropometric measures of central adiposity and breast cancer risk were attenuated. The magnitude of risk, across all measures of adiposity, was greater in women who had been postmenopausal for 12 or more years.