IntroductionIn recent years, primary surgical treatment of older women with non-metastatic breast cancer has decreased in favor of primary endocrine therapy (PET). PET can be considered in women... Show moreIntroductionIn recent years, primary surgical treatment of older women with non-metastatic breast cancer has decreased in favor of primary endocrine therapy (PET). PET can be considered in women with a remaining life expectancy of less than five years. The aim of this study was to (1) assess the risk of distant metastases and other cause mortality over ten years in women aged 65 and older with stage I-III breast cancer treated with PET, (2) whether this was associated with geriatric characteristics and comorbidities and to (3) describe the reasons on which the choice for PET was made.MethodsWomen were included from the retrospective FOCUS cohort, which comprises all incident women diagnosed with breast cancer aged 65 or older between January 1997 and December 2004 in the Comprehensive Cancer Center Region West in the Netherlands. We selected women (N = 257) with stage I-III breast cancer and treated with PET from this cohort. Patient characteristics (including comorbidity, polypharmacy, walking, cognitive and sensory impairment), treatment and tumor characteristics were retrospectively extracted from charts. Outcomes were distant metastasis and other cause mortality. Cumulative incidences were calculated using the Cumulative Incidence for Competing Risks method (CICR); and subdistribution hazard ratios (SHR) were tested between groups based on age, geriatric characteristics and comorbidity with the Fine and Gray model.ResultsWomen treated with PET were on average 84 years old and 41% had one or more geriatric characteristics. Other cause mortality exceeded the cumulative incidence of distant metastasis over ten years (83 versus 5.6%). The risk of dying from another cause further increased in women with geriatric characteristics (SHR 2.06, p < 0.001) or two or more comorbidities (SHR 1.72, p < 0.001). Often the reason for omitting surgery was not recorded (52.9%), but if recorded surgery was omitted mainly at the patient's request (18.7%).DiscussionThis study shows that the cumulative incidence of distant metastasis is much lower than other cause mortality in older women with breast cancer treated with PET, especially in the presence of geriatric characteristics or comorbidities. This confirms the importance of assessment of geriatric characteristics to aid counseling of older women. Show less
This thesis describes to which extent the skin reflects the aging process, with a specific focus on cellular senescence. Since the first descriptions of the growth arrested state of... Show more This thesis describes to which extent the skin reflects the aging process, with a specific focus on cellular senescence. Since the first descriptions of the growth arrested state of fibroblasts upon multiple replication rounds, cellular senescence has now emerged as a promising target to regulate the aging process in vivo as well. Here, we study whether fibroblast senescence in vitro is associated with in vivo donor characteristics such as chronological age and prevalence of disease. We further describe in this thesis whether senescence in skin tissue (in situ) is associated with other histological skin characteristics and with in vivo donor characteristics. Show less
Cellular senescence is a defense mechanism in response to molecular damage which accumulates with aging. Correspondingly, the number of senescent cells has been reported to be greater in older than... Show moreCellular senescence is a defense mechanism in response to molecular damage which accumulates with aging. Correspondingly, the number of senescent cells has been reported to be greater in older than in younger subjects and furthermore associates with age-related pathologies. Inter-individual differences exist in the rate at which a person ages (biological age). Here, we studied whether younger biological age is related to fewer senescent cells in middle-aged individuals with the propensity for longevity, using p16INK4a as a marker for cellular senescence. We observed that a younger biological age associates with lower levels of p16INK4a positive cells in human skin. Show less
The effect of chronological age on skin characteristics is readily visible, and its underlying histological changes have been a field of study for several years. However, the effect of biological... Show moreThe effect of chronological age on skin characteristics is readily visible, and its underlying histological changes have been a field of study for several years. However, the effect of biological age (i.e. a person's rate of ageing compared to their chronological age) on the skin has so far only been studied in facial photographs. Skin biopsies obtained from middle-aged offspring of nonagenarian siblings that are genetically enriched for longevity were compared to their partners who represent the general Dutch population. Though of the same chronological age, the offspring were previously observed to be of a younger biological age than their partners. The biopsies were analysed on several aspects epidermal and elastic fibre morphology. We investigated whether these skin characteristics were dependent on chronological age, familial longevity (the difference between the offspring and partners) and Framingham heart risk scores, adjusted for external stressors. A decreased thickness and flattening of the epidermis as well as an increased amount of elastic fibres in the reticular dermis were observed with chronological age (P < 0.001, P < 0.001 and P = 0.03, respectively), but no effect of familial longevity was found. The Framingham heart risk score was associated with some skin characteristics. A slower rate of skin ageing does not mark offspring from nonagenarian siblings. Epidermal and elastic fibre morphometric characteristics are not a potential marker for familial longevity in middle-aged subjects enriched for familial longevity. Show less
