Background: Lung cancer screening (LCS) has the potential to reduce the risk of lung cancer death in healthy individuals, but the impact of coexisting chronic illnesses on LCS outcomes has not been well defined. Consideration of the complex relationship between baseline risk of lung cancer, treatment-related harms, and risk of death from competing causes is crucial in determining the balance of benefits and harms of LCS. Objectives: To summarize evidence, identify knowledge and research gaps, prioritize topics, and propose methods for future research on how best to incorporate comorbidities in making decisions regarding LCS. Methods: A multidisciplinary group of international clinicians and researchers reviewed available data on the effects of comorbidities on LCS outcomes, focusing on the juxtaposition of lung cancer risk and competing risks of death, consideration of benefits and risks in patients with chronic obstructive pulmonary disease, communication of risk, and treatment of screen-detected lung cancer. Results: This statement identifies gaps in knowledge regarding how comorbidities and competing causes of death impact outcomes in LCS, and we have developed questions to help guide future research efforts to better inform patient selection, education, and implementation of LCS. Conclusions: There is an urgent need for further research that can help guide clinical decision-making with patients who may not benefit from LCS owing to coexisting chronic illness. This statement establishes a research framework to address essential questions regarding how to incorporate and communicate risks of comorbidities into patient selection and decisions regarding LCS.

Evidence of the association between the first-degree family history and the risk of invasive breast cancer among women 65 years and older (hereafter referred to as older women) is limited. Although family history is a strong risk factor for breast cancer among younger women,^1,2 controversy exists about the magnitude of the association between family history and breast cancer among older women. While some studies indicate that the risk associated with family history may be minimal for women after the age of 60 years,³ other reports suggest that risk remains elevated among women 75 years or older.⁴ Moreover, a systematic review suggests that family history and breast cancer risk vary according to the first-degree relative’s age at diagnosis, especially whether it occurred before or after menopause.¹

Loss of muscle mass and waning in muscle strength are common in older adults, and inflammation may play a key role in pathogenesis. This study aimed to examine associations of C-reactive protein (CRP) and systemic immune-inflammation index (SII) with sarcopenia and sarcopenic obesity in older adults with chronic comorbidities. Cross-sectional data from the National Health and Nutrition Examination Survey (1999–2006) were obtained for participants aged ≥60 years. Sarcopenia was defined by a lean mass and body height (males < 7.26 kg/m², females < 5.45 kg/m²). Sarcopenic obesity was defined by the concurrent presence of sarcopenia and obesity (defined by relative fat mass). Logistic regression was used to assess the associations of CRP and SII with sarcopenia and sarcopenic obesity. The dose–response relationship was examined via restricted cubic splines. Of the participants (n = 2483), 23.1% (n = 574) and 7.7% (n = 190) had sarcopenia and sarcopenic obesity, respectively. The multivariable logistic regression models suggested a positive association of SII with sarcopenia and sarcopenic obesity, but a positive statistically significant association was not consistently observed for CRP. Dose–response curves suggested similar association patterns for these biomarkers. In clinical practice, measures to prevent sarcopenia and sarcopenic obesity are needed for older vulnerable people with high systemic inflammation.

Breast density, a potential intermediate phenotype in the molecular pathway of breast cancer, is a measure of the amount of radiopaque fibroglandular tissue in the breast that consists of epithelial tissue and stroma as opposed to surrounding fat tissue that appears radiolucent on mammography.^1,2 Evidence from the US Breast Cancer Surveillance Consortium (BCSC) estimates that approximately 27.6 million women (43.3%) aged 40 to 74 years in the US have dense breasts (heterogeneously or extremely dense), whereas the prevalence of dense breasts is only 28% among women aged 75 years or older.^3,4 A systematic review¹ comparing breast density among age groups concluded that breast density decreased in association with increasing age in both the premenopausal and postmenopausal period, with greater decreases observed in the postmenopausal period.

The objective of this study was to investigate the association of metabolic syndrome (MetS) with the risk of invasive breast cancer and molecular subtypes across race, menopause, and body mass index (BMI) groups. We examined the association of metabolic syndrome and its components with risk of invasive breast cancer among 94,555 female participants of the National Institute of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study, accounting for ductal carcinoma in situ as a competing risk. Cox proportional hazard regression with the Fine and Gray method was used to generate hazard ratios (HR) and 95% confidence intervals (CI) adjusting for baseline sociodemographic, behavioral, and clinical covariates. During a mean follow-up of 14 years, 5380 (5.7%) women developed breast cancer. Overall, MetS at baseline was associated with a 13% increased risk of breast cancer compared to women without MetS (HR: 1.13, 95% CI: 1.00, 1.27); similar estimates were obtained among postmenopausal women (HR: 1.14, 95% CI: 1.01, 1.29). MetS was associated with a slight but non-significantly increased risk of breast cancer among those with both normal weight and overweight/obesity, and those with estrogen receptor positive breast cancer subtype. In the NIH-AARP cohort, MetS was associated with an increased risk of breast cancer. Further studies are needed to definitively evaluate the association of MetS with triple negative breast cancer subtypes across all levels of BMI.

Background: Potential benefits of screening mammography among women ages 75 years and older remain unclear. Methods: We evaluated 10-year cumulative incidence of breast cancer and death from breast cancer and other causes by Charlson Comorbidity Index (CCI) and age in the Medicare-linked Breast Cancer Surveillance Consortium (1999–2010) cohort of 222 088 women with no less than 1 screening mammogram between ages 66 and 94 years. Results: During median follow-up of 107 months, 7583 were diagnosed with invasive breast cancer and 1742 with ductal carcinoma in situ; 471 died from breast cancer and 42 229 from other causes. The 10-year cumulative incidence of invasive breast cancer did not change with increasing CCI but decreased slightly with age: ages 66–74 years (CCI0 = 4.0% [95% CI = 3.9% to 4.2%] vs CCI ≥ 2 = 3.9% [95% CI = 3.5% to 4.3%]); ages 75–84 years (CCI0 = 3.7% [95% CI = 3.5% to 3.9%] vs CCI ≥ 2 = 3.4% [95% CI = 2.9% to 3.9%]); and ages 85–94 years (CCI0 = 2.7% [95% CI = 2.3% to 3.1%] vs CCI ≥ 2 = 2.1% [95% CI = 1.3% to 3.0%]). The 10-year cumulative incidence of other-cause death increased with increasing CCI and age: ages 66–74 years (CCI0 = 10.4% [95% CI = 10.3 to 10.7%] vs CCI ≥ 2 = 43.4% [95% CI = 42.2% to 44.4%]), ages 75–84 years (CCI0 = 29.8% [95% CI = 29.3% to 30.2%] vs CCI ≥ 2 = 61.7% [95% CI = 60.2% to 63.3%]), and ages 85 to 94 years (CCI0 = 60.3% [95% CI = 59.1% to 61.5%] vs CCI ≥ 2 = 84.8% [95% CI = 82.5% to 86.9%]). The 10-year cumulative incidence of breast cancer death was small and did not vary by age: ages 66–74 years = 0.2% (95% CI = 0.2% to 0.3%), ages 75–84 years = 0.29% (95% CI = 0.25% to 0.34%), and ages 85 to 94 years = 0.3% (95% CI = 0.2% to 0.4%). Conclusions: Cumulative incidence of other-cause death was many times higher than breast cancer incidence and death, depending on comorbidity and age. Hence, older women with increased comorbidity may experience diminished benefit from continued screening.