Observational data have shown that some cancer survivors develop chronic conditions like frailty, sarcopenia, cardiac dysfunction, and mild cognitive impairment earlier and/or at a greater burden than similarly aged individuals never diagnosed with cancer or exposed to systemic or targeted cancer therapies. In aggregate, cancer- and treatment-related physical, cognitive, and psychosocial late- and long-term morbidities experienced by cancer survivors are hypothesized to represent accelerated or accentuated aging trajectories. However, conceptual, measurement, and methodological challenges have constrained efforts to identify, predict, and mitigate aging-related consequences of cancer and cancer treatment. In July 2018, the National Cancer Institute convened basic, clinical, and translational science experts for a think tank titled “Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors.” Through the resulting deliberations, several research and resource needs were identified, including longitudinal studies to examine aging trajectories that include detailed data from before, during, and after cancer treatment; mechanistic studies to elucidate the pathways that lead to the emergence of aging phenotypes in cancer survivors; long-term clinical surveillance to monitor survivors for late-emerging effects; and tools to integrate multiple data sources to inform understanding of how cancer and its therapies contribute to the aging process. Addressing these needs will help expand the evidence base and inform strategies to optimize healthy aging of cancer survivors.

BackgroundLimited evidence, mostly from studies in Western populations, suggests that the prognostic effects of lifestyle-related risk factors may be molecular subtype-dependent. Here, we examined whether pre-diagnostic lifestyle-related risk factors for breast cancer are associated with clinical outcomes by molecular subtype among patients from an understudied Asian population.MethodsIn this population-based case series, we evaluated breast cancer risk factors in relation to 10-year all-cause mortality (ACM) and 5-year recurrence by molecular subtype among 3012 women with invasive breast cancer in Sarawak, Malaysia. A total of 579 deaths and 314 recurrence events occurred during a median follow-up period of ~ 24 months. Subtypes (luminal A-like, luminal B-like, HER2-enriched, triple-negative) were defined using immunohistochemical markers for hormone receptors and human epidermal growth factor receptor 2 (HER2) in conjunction with histologic grade. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between risk factors and ACM/recurrence were estimated in subtype-specific Cox regression models.ResultsWe observed heterogeneity in the relationships between parity/breastfeeding, age at first full-term pregnancy (FFP), family history, body mass index (BMI), and tumor subtype (p value < 0.05). Among luminal A-like patients only, older age at menarche [HR (95% CI) ≥15 vs ≤ 12 years = 2.28 (1.05, 4.95)] and being underweight [HRBMI < 18.5kg/m2 vs. 18.5–24.9kg/m2 = 3.46 (1.21, 9.89)] or overweight [HR25–29.9kg/m2 vs. 18.5–24.9kg/m2 = 3.14 (1.04, 9.50)] were associated with adverse prognosis, while parity/breastfeeding [HRbreastfeeding vs nulliparity = 0.48 (0.27, 0.85)] and older age at FFP [HR > 30 vs < 21 years = 0.20 (0.04, 0.90)] were associated with good prognosis. For these women, the addition of age at menarche, parity/breastfeeding, and BMI, provided significantly better fit to a prognostic model containing standard clinicopathological factors alone [LRχ2 (8df) = 21.78; p value = 0.005]. Overall, the results were similar in relation to recurrence.ConclusionsOur finding that breastfeeding and BMI were associated with prognosis only among women with luminal A-like breast cancer is consistent with those from previously published data in Western populations. Further prospective studies will be needed to clarify the role of lifestyle modification, especially changes in BMI, in improving clinical outcomes for women with luminal A-like breast cancer.

Elevated mammographic density (MD) is an established breast cancer risk factor. Studies examining relationships between MD and breast cancer risk factors are limited in China, where established breast cancer risk factors are less prevalent but dense breasts are more prevalent than Western countries. This study included 11,478 women (45-69 years; 36% premenopausal) participating in an ongoing national cancer screening program in 11 urban provinces in China and predicted as having high-risk for breast cancer. Polytomous logistic regression was performed to assess associations between MD and risk factors by comparing each higher Breast Imaging Reporting and Data System (BI-RADS) category (2, 3, or 4) to the lowest category (BI-RADS, 1). We found associations of increasing age, body mass index, weight, postmenopausal status, and parity with lower MD. Higher levels of education, increasing height, and later first birth were associated with higher MD. These associations did not vary by menopausal status. Additionally, the association between longer period of breastfeeding and lower MD was seen among postmenopausal women only (Pinteraction = 0.003). Having first-degree relatives with breast cancer diagnosed before 50 years was associated with lower MD only among premenopausal women (Pinteraction = 0.061). We found effects of established breast cancer risk factors on MD showed similar directions in Chinese and Western women, supporting the hypothesis that MD represents cumulative exposure to breast cancer risk factors over the life course. Our findings help to understand the biological basis of the association of MD with breast cancer risk and have implications for breast cancer prevention research in China.