Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers

The clinical outcome of contralateral prophylactic mastectomy (CPM) in women with a BRCA1 or BRCA2 mutation and a personal history of invasive breast cancer is unknown. We identified a cohort of 148 female BRCA1 or BRCA2 mutation carriers (115 and 33, respectively) who previously were treated for unilateral invasive breast cancer stages I–IIIa. In all, 79 women underwent a CPM, while the other women remained under intensive surveillance. The mean follow-up was 3.5 years and started at the time of CPM or at the date of mutation testing, whichever came last, that is, on average 5 years after diagnosis of the first breast cancer. One woman developed an invasive contralateral primary breast cancer after CPM, whereas six were observed in the surveillance group (P<0.001). Contralateral prophylactic mastectomy reduced the risk of contralateral breast cancer by 91%, independent of the effect of bilateral prophylactic oophorectomy (BPO). At 5 years follow-up, overall survival was 94% for the CPM group vs 77% for the surveillance group (P=0.03), but this was unexpectedly mostly due to higher mortality related with first breast cancer and ovarian cancer in the surveillance group. After adjustment for BPO in a multivariate Cox analysis, the CPM effect on overall survival was no longer significant. Our data show that CPM markedly reduces the risk of contralateral breast cancer among BRCA1 or BRCA2 mutation carriers with a history of breast cancer. Longer follow-up is needed to study the impact of CPM on contralateral breast cancer-specific survival. The choice for CPM is highly correlated with that for BPO, while only BPO leads to a significant improvement in overall survival so far

Risk factors for cancer-related fatigue in adult childhood cancer survivors: A report from the CardioOnco study

Cancer-related fatigue (CRF) is a distressing late effect in childhood cancer survivors (CCS) with prevalence between 10-85% and little evidence on its risk factors. We aimed to describe the prevalence of CRF in adult CCS and assess its risk factors. As part of the CardioOnco study, we invited adult 5-year CCS treated at Inselspital Bern between 1976-2015 to a cardiooncological outpatient clinic and sent them questionnaires. We assessed fatigue with the Checklist Individual Strength subjective fatigue subscore (CIS, during last 2 weeks) and the Visual Analog Scale (VAS, at the current day). Increased fatigue was defined as CIS score 27-35 and VAS score ≥70. We collected information on previous cancer treatment and medical history and calculated mean CRF scores with ANCOVA adjusting for sex and age. We included 158 CCS (participation rate 29%) with median age at study of 33 years (IQR: 26-38). We found that 19% of CCS had increased fatigue with CIS and 11% with VAS. Mean CIS fatigue score was higher in women (21, CI 20-22) than men (18, CI 16-19, p = 0.001), in those treated with radiotherapy (22, CI 20-23 vs. 18, CI 17-19, p&lt;0.001), those with sleep disturbance (23, CI 21-24 vs. 18, CI 17-19, p&lt;0.001), and those with an endocrine abnormality (24, CI 22-25 vs. 18, CI 17-19, p&lt;0.001). We found that one fifth of adult CCS experiences increased fatigue. Female CCS with history of radiotherapy and suffering from endocrine or sleep problems would profit from screening for CRF and further counselling with a specialist

Impact of rapid genetic counselling and testing on the decision to undergo immediate or delayed prophylactic mastectomy in newly diagnosed breast cancer patients: findings from a randomized controlled trial

Background: Female breast cancer patients with a BRCA1/2 mutation have an increased risk of contralateral breast cancer. We investigated the effect of rapid genetic counselling and testing (RGCT) on choice of surgery. Methods: Newly diagnosed breast cancer patients with at least a 10% risk of a BRCA1/2 mutation were randomised to an intervention group (offer of RGCT) or a control group (usual care; ratio 2 : 1). Primary study outcomes were uptake of direct bilateral mastectomy (BLM) and delayed contralateral prophylactic mastectomy (CPM). Results: Between 2008 and 2010, we recruited 265 women. On the basis of intention-to-treat analyses, no significant group differences were observed in percentage of patients opting for a direct BLM (14.6% for the RGCT group vs 9.2% for the control group; odds ratio (OR) 2.31; confidence interval (CI) 0.92-5.81; P=0.08) or for a delayed CPM (4.5% for the RGCT group vs 5.7% for the control group; OR 0.89; CI 0.27-2.90; P=0.84). Per-protocol analysis indicated that patients who received DNA test results before surgery (59 out of 178 women in the RGCT group) opted for direct BLM significantly more often than patients who received usual care (22% vs 9.2%; OR 3.09, CI 1.15-8.31, P=0.03). Interpretation: Although the large majority of patients in the intervention group underwent rapid genetic counselling, only a minority received DNA test results before surgery. This may explain why offering RGCT yielded only marginally significant differences in uptake of BLM. As patients who received DNA test results before surgery were more likely to undergo BLM, we hypothesise that when DNA test results are made routinely available pre-surgery, they will have a more significant role in surgical treatment decisions

Joint effect of obesity and TNFA variability on asthma: two international cohort studies

Obesity is a risk factor for asthma. Adipose tissue expresses pro-inflammatory molecules including tumour necrosis factor (TNF), and levels of TNF are also related to polymorphisms in the TNF-a (TNFA) gene. The current authors examined the joint effect of obesity and TNFA variability on asthma in adults by combining two population-based studies. The European Community Respiratory Health Survey and the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults used comparable protocols, questionnaires and measures of lung function and atopy. DNA samples from 9,167 participants were genotyped for TNFA -308 and lymphotoxin-a (LTA) +252 gene variants. Obesity and TNFA were associated with asthma when mutually adjusting for their independent effects (odds ratio (OR) for obesity 2.4, 95% confidence interval (CI) 1.7–3.2; OR for TNFA -308 polymorphism 1.3, 95% CI 1.1–1.6). The association of obesity with asthma was stronger for subjects carrying the G/A and A/A TNFA -308 genotypes compared with the more common G/G genotype, particularly among nonatopics (OR for G/A and A/A genotypes 6.1, 95% CI 2.5–14.4; OR for G/G genotype 1.7, 95% CI 0.8–3.3). The present findings provide, for the first time, evidence for a complex pattern of interaction between obesity, a pro-inflammatory genetic factor and asthma