Conflicting conclusions have been published regarding breast cancer survival of BRCA1/2 mutation carriers. Here we provide an evidence-based systematic literature review.
Eligible publications were ...observational studies assessing the survival of breast cancer patients carrying a BRCA1/2 mutation compared to non-carriers or the general breast cancer population. We performed meta-analyses and best-evidence syntheses for survival outcomes taking into account study quality assessed by selection bias, misclassification bias and confounding.
Sixty-six relevant studies were identified. Moderate evidence for a worse unadjusted recurrence-free survival for BRCA1 mutation carriers was found. For BRCA1 and BRCA2 there was a tendency towards a worse breast cancer-specific and overall survival, however, results were heterogeneous and the evidence was judged to be indecisive. Surprisingly, only 8 studies considered adjuvant treatment as a confounder or effect modifier while only two studies took prophylactic surgery into account. Adjustment for tumour characteristics tended to shift the observed risk estimates towards a relatively more favourable survival.
In contrast to currently held beliefs of some oncologists, current evidence does not support worse breast cancer survival of BRCA1/2 mutation carriers in the adjuvant setting; differences if any are likely to be small. More well-designed studies are awaited.
To investigate the effects of different types of surgery on breast cancer prognosis in germline BRCA1/BRCA2 mutation carriers compared with noncarriers.
Although breast-conserving therapy ...(breast-conserving surgery followed by radiotherapy) has been associated with more local recurrences than mastectomy, no differences in overall survival have been found in randomized trials performed in the general breast cancer population. Whether breast-conservation can be safely offered to BRCA1/2 mutation carriers is debatable.
The study comprised a cohort of women with invasive breast cancer diagnosed <50 years and treated between 1970 and 2003 in 10 Dutch centers. Germline DNA for BRCA1/2 testing of most-prevalent mutations (covering ∼61%) was mainly derived from paraffin-blocks. Survival analyses were performed taking into account competing risks.
In noncarriers (N = 5820), as well as in BRCA1 (N = 191) and BRCA2 (N = 70) mutation carriers, approximately half of the patients received breast-conserving therapy. Patients receiving mastectomy followed by radiotherapy had prognostically worse tumor characteristics and more often received systemic therapy. After adjustment for these potential confounders, patients who received breast-conserving therapy had a similar overall survival compared with patients who received mastectomy, both in noncarriers (hazard ratio HR = 0.95, confidence interval CI = 0.85-1.07, P = 0.41) and BRCA1 mutation carriers (HR = 0.80, CI = 0.42-1.51, P = 0.50). Numbers for BRCA2 were insufficient to draw conclusions. The rate of local recurrences after breast-conserving therapy did not differ between BRCA1 carriers (10-year risk = 7.3%) and noncarriers (10-year risk = 7.9%).
Our results, together with the available literature, provide reassurance that breast-conserving therapy is a safe local treatment option to offer to BRCA1 mutation carriers with invasive breast cancer.
To determine prospectively overall and age-specific estimates of contralateral breast cancer (CBC) risk for young patients with breast cancer with or without BRCA1/2 mutations.
A cohort of 6,294 ...patients with invasive breast cancer diagnosed under 50 years of age and treated between 1970 and 2003 in 10 Dutch centers was tested for the most prevalent BRCA1/2 mutations. We report absolute risks and hazard ratios within the cohort from competing risk analyses.
After a median follow-up of 12.5 years, 578 CBCs were observed in our study population. CBC risk for BRCA1 and BRCA2 mutation carriers was two to three times higher than for noncarriers (hazard ratios, 3.31 95% CI, 2.41 to 4.55; P < .001 and 2.17 95% CI,1.22 to 3.85; P = .01, respectively). Ten-year cumulative CBC risks were 21.1% (95% CI, 15.4 to 27.4) for BRCA1, 10.8% (95% CI, 4.7 to 19.6) for BRCA2 mutation carriers and 5.1% (95% CI, 4.5 to 5.7) for noncarriers. Age at diagnosis of the first breast cancer was a significant predictor of CBC risk in BRCA1/2 mutation carriers only; those diagnosed before age 41 years had a 10-year cumulative CBC risk of 23.9% (BRCA1: 25.5%; BRCA2: 17.2%) compared with 12.6% (BRCA1: 15.6%; BRCA2: 7.2%) for those 41 to 49 years of age (P = .02); our review of published studies showed ranges of 24% to 31% before age 40 years (BRCA1: 24% to 32%; BRCA2:17% to 29%) and 8% to 21% after 40 years (BRCA1: 11% to 52%; BRCA2: 7% to 18%), respectively.
Age at first breast cancer is a strong risk factor for cumulative CBC risk in BRCA1/2 mutation carriers. Considering the available evidence, age-specific risk estimates should be included in counseling.
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.
Investigating Variation in Replicability Klein, Richard A.; Ratliff, Kate A.; Vianello, Michelangelo ...
Social psychology (Göttingen, Germany),
01/2014, Letnik:
45, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Although replication is a central tenet of science, direct replications are rare
in psychology. This research tested variation in the replicability of 13 classic and
contemporary effects across 36 ...independent samples totaling 6,344 participants. In the
aggregate, 10 effects replicated consistently. One effect - imagined contact reducing
prejudice - showed weak support for replicability. And two effects - flag priming
influencing conservatism and currency priming influencing system justification - did not
replicate. We compared whether the conditions such as lab versus online or US versus
international sample predicted effect magnitudes. By and large they did not. The results of
this small sample of effects suggest that replicability is more dependent on the effect itself
than on the sample and setting used to investigate the effect.
Prehospital risk stratification and triage are currently not performed in patients suspected of non-ST-segment elevation acute coronary syndrome (NSTE-ACS). This may lead to prolonged time to ...revascularisation, increased duration of hospital admission and higher healthcare costs. The preHEART score (prehospital history, ECG, age, risk factors and point-of-care troponin score) can be used by emergency medical services (EMS) personnel for prehospital risk stratification and triage decisions in patients with NSTE-ACS. The aim of the current study was to evaluate the effect of prehospital risk stratification and direct transfer to a percutaneous coronary intervention (PCI) centre, based on the preHEART score, on time to final invasive diagnostics or culprit revascularisation.
Prospective, multicentre, two-cohort study in patients with suspected NSTE-ACS. The first cohort is observational (standard care), while the second (interventional) cohort includes patients who are stratified for direct transfer to either a PCI or a non-PCI centre based on their preHEART score. Risk stratification and triage are performed by EMS personnel. The primary endpoint of the study is time from first medical contact until final invasive diagnostics or revascularisation. Secondary endpoints are time from first medical contact until intracoronary angiography (ICA), duration of hospital admission, number of invasive diagnostics, number of inter-hospital transfers and major adverse cardiac events at 7 and 30 days.
A total of 1069 patients were included. In the interventional cohort (n=577), time between final invasive diagnostics or revascularisation (42 (17-101) hours vs 20 (5-44) hours, p<0.001) and length of hospital admission (3 (2-5) days vs 2 (1-4) days, p=0.007) were shorter than in the observational cohort (n=492). In patients with NSTE-ACS in need for ICA or revascularisation, healthcare costs were reduced in the interventional cohort (€5599 (2978-9625) vs €4899 (2278-5947), p=0.02).
Prehospital risk stratification and direct transfer to a PCI centre, based on the preHEART score, reduces time from first medical contact to final invasive diagnostics and revascularisation, reduces duration of hospital admission and decreases healthcare costs in patients with NSTE-ACS in need for ICA or revascularisation.
NCT05243485.
Perspectives on scientific error van Ravenzwaaij, D; Bakker, M; Heesen, R ...
Royal Society open science,
07/2023, Letnik:
10, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Theoretical arguments and empirical investigations indicate that a high proportion of published findings do not replicate and are likely false. The current position paper provides a broad perspective ...on
which may lead to replication failures. This broad perspective focuses on reform history and on opportunities for future reform. We organize our perspective along four main themes: institutional reform, methodological reform, statistical reform and publishing reform. For each theme, we illustrate potential errors by narrating the story of a fictional researcher during the research cycle. We discuss future opportunities for reform. The resulting agenda provides a resource to usher in an era that is marked by a research culture that is less error-prone and a scientific publication landscape with fewer spurious findings.
The primary aim of the study was to investigate prognosis and long-term survival in young breast cancer patients with a BRCA1 or BRCA2 germline mutation compared with noncarriers. The secondary aim ...was to investigate whether differences in survival originate from associations with tumor characteristics, second cancers, and/or treatment response.
We established a cohort of invasive breast cancer patients diagnosed younger than age 50 years in 10 Dutch hospitals between 1970 and 2003. BRCA1/2 testing of most prevalent mutations was mainly done using DNA isolate from formalin-fixed paraffin-embedded nontumor tissue. Survival estimates were derived using Cox regression and competing risk models.
In 6478 breast cancer patients, we identified 3.2% BRCA1 and 1.2% BRCA2 mutation carriers. BRCA1 mutation carriers had a worse overall survival independent of clinico-pathological/treatment characteristics, compared with noncarriers (adjusted hazard ratio HR = 1.20, 95% confidence interval CI = 0.97 to 1.47), though only statistically significant in the first five years of follow-up (adjusted HR = 1.40, 95% CI = 1.07 to 1.84). A large part of the worse survival was explained by incidence of ovarian cancers. Breast cancer-specific, disease-free, and metastasis-free survival results were less pronounced and mostly statistically nonsignificant but in the same direction with those of overall survival. Overall survival was worse, although not statistically significantly, within the ER-negative or ER-positive, grade 3, and small tumor subgroups. The worse survival was most pronounced in non-chemotherapy-treated patients (adjusted HR = 1.54, 95% CI = 1.08 to 2.19). Power for BRCA2 mutation carriers was limited; only after five years' follow-up overall survival was worse (adjusted HR = 1.47, 95% CI = 1.00 to 2.17).
BRCA1/2 mutation carriers diagnosed with breast cancer before age 50 years are prone to a worse survival, which is partly explained by differences in tumor characteristics, treatment response, and second ovarian cancers.
Background
Minimally invasive esophagectomy (MIE) is a complex and technically demanding procedure with a long learning curve, which is associated with increased morbidity and mortality. To master ...MIE, training in essential steps is crucial. Yet, no consensus on essential steps of MIE is available. The aim of this study was to achieve expert consensus on essential steps in Ivor Lewis and McKeown MIE through Delphi methodology.
Methods
Based on expert opinion and peer-reviewed literature, essential steps were defined for Ivor Lewis (IL) and McKeown (McK) MIE. In a round table discussion, experts finalized the lists of steps and an online Delphi questionnaire was sent to an international expert panel (7 European countries) of minimally invasive upper GI surgeons. Based on replies and comments, steps were adjusted and rephrased and sent in iterative fashion until consensus was achieved.
Results
Two Delphi rounds were conducted and response rates were 74% (23 out of 31 experts) for the first and 81% (27 out of 33 experts) for the second round. Consensus was achieved on 106 essential steps for both the IL and McK approach. Cronbach’s alpha in the first round was 0.78 (IL) and 0.78 (McK) and in the second round 0.92 (IL) and 0.88 (McK).
Conclusions
Consensus among European experts was achieved on essential surgical steps for both Ivor Lewis and McKeown minimally invasive esophagectomy.
Abstract Importance Online prognostication tools such as PREDICT and Adjuvant! are increasingly used in clinical practice by oncologists to inform patients and guide treatment decisions about ...adjuvant systemic therapy. However, their validity for young breast cancer patients is debated. Objective To assess first, the prognostic accuracy of PREDICT's and Adjuvant! 10-year all-cause mortality, and second, its breast cancer–specific mortality estimates, in a large cohort of breast cancer patients diagnosed <50 years. Design Hospital-based cohort. Setting General and cancer hospitals. Participants A consecutive series of 2710 patients without a prior history of cancer, diagnosed between 1990 and 2000 with unilateral stage I–III breast cancer aged <50 years. Main outcome measures Calibration and discriminatory accuracy, measured with C-statistics, of estimated 10-year all-cause and breast cancer–specific mortality. Results Overall, PREDICT's calibration for all-cause mortality was good (predicted versus observed) meandifference : −1.1% (95%CI: −3.2%–0.9%; P = 0.28). PREDICT tended to underestimate all-cause mortality in good prognosis subgroups (range meandifference : −2.9% to −4.8%), overestimated all-cause mortality in poor prognosis subgroups (range meandifference : 2.6%–9.4%) and underestimated survival in patients < 35 by −6.6%. Overall, PREDICT overestimated breast cancer–specific mortality by 3.2% (95%CI: 0.8%–5.6%; P = 0.007); and also overestimated it seemingly indiscriminately in numerous subgroups (range meandifference : 3.2%–14.1%). Calibration was poor in the cohort of patients with the lowest and those with the highest mortality probabilities. Discriminatory accuracy was moderate-to-good for all-cause mortality in PREDICT (0.71 95%CI: 0.68 to 0.73), and the results were similar for breast cancer–specific mortality. Adjuvant!'s calibration and discriminatory accuracy for both all-cause and breast cancer–specific mortality were in line with PREDICT's findings. Conclusions Although imprecise at the extremes, PREDICT's estimates of 10-year all-cause mortality seem reasonably sound for breast cancer patients <50 years; Adjuvant! findings were similar. Prognostication tools should be used with caution due to the intrinsic variability of their estimates, and because the threshold to discuss adjuvant systemic treatment is low. Thus, seemingly insignificant mortality overestimations or underestimations of a few percentages can significantly impact treatment decision-making.
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