Objective To estimate the risk of breast cancer associated with diagnostic radiation in carriers of BRCA1/2 mutations. Design Retrospective cohort study (GENE-RAD-RISK).Setting Three nationwide studies (GENEPSO, EMBRACE, HEBON) in France, United Kingdom, and the Netherlands, Participants 1993 female carriers of BRCA1/2 mutations recruited in 2006-09.Main outcome measure Risk of breast cancer estimated with a weighted Cox proportional hazards model with a time dependent individually estimated cumulative breast dose, based on nominal estimates of organ dose and frequency of self reported diagnostic procedures. To correct for potential survival bias, the analysis excluded carriers who were diagnosed more than five years before completion of the study questionnaire.Results In carriers of BRCA1/2 mutations any exposure to diagnostic radiation before the age of 30 was associated with an increased risk of ConclusionIn this large European study among carriers of BRCA1/2 mutations, exposure to diagnostic radiation before age 30 was associated with an increased risk of breast cancer at dose levels considerably lower than those at which increases have been found in other cohorts exposed to radiation. The results of this study support the use of non-ionising radiation imaging techniques (such as magnetic resonance imaging) as the main tool for surveillance in young women with BRCA1/2 mutations. IntroductionExposure to ionising radiation is an established risk factor for breast cancer in the general population, with exposures in childhood and adolescence conferring a greater risk than exposure in adulthood. 1 As BRCA1 and BRCA2 are involved in the repair of DNA double strand breaks, 2-6 which can be caused by ionising radiation, it has been hypothesised that carriers of BRCA1/2 mutations might have increased radiosensitivity. Results of the few studies 7-10 conducted so far on diagnostic radiation and risk of breast cancer among carriers have been inconsistent. Explanations for this inconsistency include differences in age at exposure and study limitations such as the investigation of a single type of diagnostic procedure (such as only chest radiography 7 8 or only mammography 9 10 ), a retrospective design with potential recall and/or survival bias, [7][8][9][10] or sometimes relatively small numbers. 8 9 In some countries the screening protocol for BRCA1/2 mutation carriers now recommends the avoidance of mammographic screening before age 30 and advises the use of non-ionising radiation imaging techniques (such as magnetic resonance imaging (MRI)) as the main tool for surveillance at young ages.We report on the BRCA1/2 mutation carrier study arm of the GENE-RAD-RISK project, a large European cohort study designed to examine whether variations in specific DNA repair genes increase the risk of breast cancer associated with radiation. Although the present study has a retrospective design, the association between diagnostic radiation and breast cancer risk in BRCA1/2 mutation carriers is unlikely to be investigated p...

Obesity is an established risk factor for postmenopausal breast cancer in the general population. However, it is still unclear whether this association also exists in BRCA1/2 mutation carriers. We investigated the association between self-reported anthropometric measures and breast cancer risk in a nationwide retrospective cohort study, including 719 BRCA1/2 carriers, of whom 218 had been diagnosed with breast cancer within 10 years prior to questionnaire completion. All time-varying Cox proportional hazards analyses were stratified by menopausal status. For premenopausal breast cancer, no statistically significant associations were observed for any of the anthropometric measures. The association between body mass index (BMI) at age 18 and premenopausal breast cancer risk suggested a trend of decreasing risk with increasing BMI 123Breast Cancer Res Treat (2011) 126:193-202 DOI 10.1007/s10549-010-1120 5 kg or more, and a relative adult weight gain of 20% or more were all non-significantly associated with a 50-60% increased risk of postmenopausal breast cancer [HR = 1.46 (0.86-2.51), HR = 1.56 (95% CI = 0.85-2.87), and HR = 1.60 (95% CI = 0.97-2.63), respectively], when compared with having a healthy or stable weight. No associations for body weight or BMI at age 18 were observed. In conclusion, menopausal status seemed to modify the association between body weight and breast cancer risk among BRCA1/2 carriers. We observed no clear association between body weight and premenopausal breast cancer, while overweight and weight gain increased postmenopausal breast cancer risk. Carriers may reduce their risk of postmenopausal breast cancer by maintaining a healthy body weight throughout life.

BRCA1/2 mutation carriers have a high lifetime risk of developing breast cancer. Differences in penetrance indicate that this risk may be influenced by lifestyle factors. Because physical activity is one of the few modifiable risk factors, it may provide a target to add to breast cancer prevention in this high-risk population. We examined the association between self-reported lifetime sports activity and breast cancer risk in a nationwide retrospective cohort study, including 725 carriers, of whom 218 had been diagnosed with breast cancer within 10 years prior to questionnaire completion. We found a nonsignificantly decreased risk for ever engaging in sports activity (HR = 0.84, 95%CI = 0.57-1.24). Among women who had participated in sports, a medium versus low level of intensity and duration (i.e., between 11.0 and 22.7 mean MET hours/week averaged over a lifetime) reduced the risk of breast cancer (HR = 0.59, 95%CI = 0.36-0.95); no dose-response trend was observed. For mean hours/week of sports activity, a nonsignificant trend was observed (HR low versus never = 0.93, 95%CI = 0.60-1.43; HR medium versus never = 0.81, 95%CI = 0.51-1.29; HR high versus never = 0.78, 95%CI = 0.48-1.29; p trend overall = 0.272; p trend active women = 0.487). For number of years of sports activity no significant associations were found. Among women active in sports before age 30, mean MET hours/week showed the strongest inverse association of all activity measures (HR medium versus low = 0.60, 95%CI = 0.38-0.96; HR high versus low = 0.58, 95%CI = 0.35-0.94; p trend = 0.053). Engaging in sports activity after age 30 was also inversely associated with breast cancer risk (HR = 0.63, 95%CI = 0.44-0.91). Our results indicate that sports activity may reduce the risk of breast cancer in BRCA1/2 mutation carriers.

BACKGROUND: Physical activity has been related to improved breast cancer outcomes. Especially in the older breast cancer population, physical activity may be important because old age is associated with comorbidities and decreased physical function. The purpose of this study was to investigate the relation between physical activity and overall survival, breast cancer-specific survival, and recurrence in several age groups of postmenopausal breast cancer patients. METHODS: The Tamoxifen Exemestane Adjuvant Multinational Lifestyle study was a side study of the Tamoxifen Exemestane Adjuvant Multinational trial and prospectively investigated lifestyle habits of postmenopausal, hormone receptor-positive breast cancer patients. The relations between prediagnosis and postdiagnosis physical activity and overall survival, breast cancer-specific survival, and recurrence-free survival were assessed with Cox regression and competing risk regression models. RESULTS: Among 521 patients, high levels of physical activity before and after the diagnosis were associated with better overall survival (the multivariate hazard ratios were 0.50 [95% confidence interval 5 0.26-0.98] and 0.57 (95% confidence interval 5 0.26-1.40] for patients who were very active before and after the diagnosis, respectively, in comparison with inactive patients). This was most evident in patients who were 65 years old or older. Physical activity was not significantly associated with breast cancer-specific survival or the relapse-free period. CONCLUSIONS: Overall survival was better for patients who were active before and after the diagnosis. In contrast with previous studies, breast cancer survival and the risk of recurrence were not significantly associated with physical activity. These findings confirmed the need for more studies investigating the use of physical activity to supplement breast cancer treatment in older patients. Cancer 2014;120:2847-54.

Severe burn injury causes local and systemic immune responses that can persist up to months, and can lead to systemic inflammatory response syndrome, organ damage and long-term sequalae such as hypertrophic scarring. To prevent these pathological conditions, a better understanding of the underlying mechanisms is essential. In this longitudinal study, we analyzed the temporal peripheral blood immune profile of 20 burn wound patients admitted to the intensive care by flow cytometry and secretome profiling, and compared this to data from 20 healthy subjects. The patient cohort showed signs of systemic inflammation and persistently high levels of pro-inflammatory soluble mediators, such as IL-6, IL-8, MCP-1, MIP-1β, and MIP-3α, were measured. Using both unsupervised and supervised flow cytometry techniques, we observed a continuous release of neutrophils and monocytes into the blood for at least 39 days. Increased numbers of immature neutrophils were present in peripheral blood in the first three weeks after injury (0.1–2.8 × 106/ml after burn vs. 5 × 103/ml in healthy controls). Total lymphocyte numbers did not increase, but numbers of effector T cells as well as regulatory T cells were increased from the second week onward. Within the CD4+ T cell population, elevated numbers of CCR4+CCR6- and CCR4+CCR6+ cells were found. Altogether, these data reveal that severe burn injury induced a persistent innate inflammatory response, including a release of immature neutrophils, and shifts in the T cell composition toward an overall more pro-inflammatory phenotype, thereby continuing systemic inflammation and increasing the risk of secondary complications.

Scar formation is an important adverse consequence of burns. How patients appraise their scar quality is often studied shortly after sustaining the injury, but information in the long‐term is scarce. Our aim was, therefore, to evaluate long‐term patient‐reported quality of burn scars. Adults with a burn center admission of ≥1 day between August 2011 and September 2012 were invited to complete a questionnaire on long‐term consequences of burns. We enriched this sample with patients with severe burns (>20% total body surface area [TBSA] burned or TBSA full thickness >5%) treated between January 2010 and March 2013. Self‐reported scar quality was assessed with the Patient Scale of the Patient and Observer Scar Assessment Scale (POSAS). Patients completed this scale for their—in their opinion—most severe scar ≥5 years after burns. This study included 251 patients with a mean %TBSA burned of 10%. The vast majority (91.4%) reported at least minor differences with normal skin (POSAS item score ≥2) on one or more scar characteristics and 78.9% of the patients’ overall opinion was that their scar deviated from normal skin. Patients with severe burns had higher POSAS scores, representing worse scar quality, than patients with mild/intermediate burns, except for color, which was high in both groups. A longer hospital stay predicted reduced scar quality (both mean POSAS and mean overall opinion of the scar) in multivariate analyses. In addition, female gender was also associated with a poorer overall opinion of the scar. In conclusion, this study provides new insights in long‐term scar quality. Scars differed from normal skin in a large part of the burn population more than 5 years after burns, especially in those with severe burns. Female gender is associated with a poorer patients’ overall opinion of their scar, which may be an indication of gender differences in perception of scar quality after burns.

The results of our study support the view that phytoestrogens have a protective effect on the risk of atherosclerosis and arterial degeneration through an effect on arterial walls, especially among older women.

To study whether or not there is an adverse effect of early chest X-rays on breast cancer risk in breast cancer susceptibility gene 1 (BRCA1) carriers, we compared the histories of chest X-ray exposures before age 30 in 138 BRCA1 carriers with breast cancer with 158 age-matched women with breast cancer, but without a BRCA1 mutation. All cases were drawn from a national breast cancer research registry. Affected carriers reported more frequent chest X-ray use before age 20 than affected non-carriers (0.6 vs. 0.3; P = 0.01). Affected carriers had, on average, 1.8 chest X-rays before age 30 compared to an average of 1.0 for affected non-carriers (P = 0.002). The odds ratio for ever having had a chest X-ray below age 30, given a BRCA1 mutation, was 1.8 [95% confidence interval (CI) = 1.2-2.9; P = 0.01]. These observations support the hypothesis that early radiation exposure may be a risk factor for breast cancer in BRCA1 carriers.