Abstract
Background
Linking independent sources of data describing the same individuals enable innovative epidemiological and health studies but require a robust record linkage approach. We describe ...a hybrid record linkage process to link databases from two independent ongoing French national studies, GEMO (Genetic Modifiers of
BRCA1
and
BRCA2
), which focuses on the identification of genetic factors modifying cancer risk of
BRCA1
and
BRCA2
mutation carriers, and GENEPSO (prospective cohort of
BRCAx
mutation carriers), which focuses on environmental and lifestyle risk factors.
Methods
To identify as many as possible of the individuals participating in the two studies but not registered by a shared identifier, we combined probabilistic record linkage (PRL) and supervised machine learning (ML). This approach (named “PRL + ML”) combined together the candidate matches identified by both approaches. We built the ML model using the gold standard on a first version of the two databases as a training dataset. This gold standard was obtained from PRL-derived matches verified by an exhaustive manual review. Results
The Random Forest (RF) algorithm showed a highest recall (0.985) among six widely used ML algorithms: RF, Bagged trees, AdaBoost, Support Vector Machine, Neural Network.
Therefore, RF was selected to build the ML model since our goal was to identify the maximum number of true matches. Our combined linkage PRL + ML showed a higher recall (range 0.988–0.992) than either PRL (range 0.916–0.991) or ML (0.981) alone. It identified 1995 individuals participating in both GEMO (6375 participants) and GENEPSO (4925 participants).
Conclusions
Our hybrid linkage process represents an efficient tool for linking GEMO and GENEPSO. It may be generalizable to other epidemiological studies involving other databases and registries.
This study aims to estimate the pathologic complete response (pCR) rate after neo‐adjuvant chemotherapy and to compare disease‐free survival (DFS) and overall survival (OS) between pCR and non‐pCR ...groups of patients with triple‐negative breast cancer (TNBC) and deleterious BRCA1 or BRCA2 mutation. We carried out a retrospective analysis of 53 patients including 46 BRCA1, 6 BRCA2, and 1 combined BRCA1 and BRCA2 mutation. All patients had been diagnosed with triple‐negative breast cancer (TNBC) between 1997 and 2014. Neo‐adjuvant therapy consisted of regimens that were based on anthracycline or an anthracycline‐taxane doublet. DFS included any relapse or second cancer. The Kaplan‐Meier method and the log‐rank test were used to compare pCR and non‐pCR groups. A pCR was observed in 23 (42.6% 95% CI, 29.2%‐56.8%) of the TNBC included. The pCR rate was 38.3% 95% CI, 26%‐55% among BRCA1 mutation carriers, and 66% among the 6 BRCA2 mutation carriers. Median follow‐up was 4.4 years (range 0.62‐16.2 years) and did not differ between the groups (P = .25). Fifteen relapses and six second cancers were recorded during the follow‐up period. Eleven deaths occurred, all of which were in the non‐pCR group. DFS (P < .01) and OS (P < .01) were significantly better in the pCR group than the non‐pCR group. This study shows a high pCR rate after neo‐adjuvant therapy in BRCA‐mutated triple‐negative breast cancer, and the survival results confirm the prognostic value of pCR in this group. These outcomes should be considered as a basis of comparison to be used by future studies about new therapies in this domain.
Objective
Genetic counseling in at‐risk families is known to improve cancer prevention. Our study aimed to determine the rate of uptake of genetic counseling among adult children of BRCA1/2 mutation ...carriers and to identify the potential psychosocial factors associated with uptake of genetic counseling.
Methods
A self‐reported questionnaire was mailed to 328 BRCA1/2 mutation carriers 10 years after BRCA1/2 test disclosure. Of the 233 carriers who returned the questionnaire (response rate = 71%), 135 reported having children over age 18 years and were therefore included in the analysis. Generalized estimating equations models were used to identify the factors associated with uptake of genetic counseling among adult children of mutation carriers.
Results
Data were gathered for a total of 296 children (46% male, 54% female). The vast majority were informed about the familial mutation (90.9%) and 113 (38%; 95% CI, 32%‐44%) underwent genetic counseling. This percentage exceeded 80% in women over 40 years. In the multivariate model, female sex, advanced age, mutation in the father, diagnosis of cancer in the mutation‐carrying parent after genetic testing, and good family relationships were all factors associated with higher uptake of genetic counseling.
Conclusions
Adult children of BRCA1/2 mutation carriers in France do not undergo genetic counseling sufficiently often. Further studies should be conducted on the psychosocial factors that hinder the uptake of genetic counseling among adult children of BRCA1/2 mutation carriers.
Background
Although greater attention is currently being paid to participants in research, no studies have dealt so far with the issue of returning aggregate psychosocial results to cohort ...participants.
Objective
(i) To explore participants’ views about disclosure of the aggregate results of a French national psychosocial cohort survey on the epidemiology of preventive behaviour in women from families with a hereditary breast cancer risk. (ii) To assess whether it is worth consulting participants before designing the disclosure process.
Design
A qualitative study using semi‐structured face‐to‐face interviews and a thematic analysis based on Grounded Theory methods.
Participants
Nineteen interviews were conducted with cancer‐free female BRCA mutation carriers/non‐carriers aged 31–79 who had participated in a cohort survey by answering self‐administered questionnaires.
Results
Participants showed considerable interest in the issue of result disclosure. The preferences expressed about disclosure were rarely relevant to the topic investigated, however, as they often focused on medical knowledge about BRCA and not on the psychosocial findings obtained. This confusion may have been due to the participants’ experience of the survey procedures, including its longitudinal nature, the occurrence of very few interactions with the investigators and the wide range of topics addressed in the questionnaires.
Conclusion
Investigators should ascertain participants’ expectations and preferences by consulting them before disclosing the results obtained. Although the disclosure process may not meet participants’ expectations completely, consultation is the key to preventing them from having irrealistic expectations about the information they are going to receive.
Preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND) practices for inherited predisposition to cancer are heterogeneous in industrialized countries. In France, permission to perform ...PGD/PND must be obtained from registered Multidisciplinary Prenatal Diagnosis Teams (MPDTs). The aim of this study was to determine French professionals' attitudes about the acceptability of PGD and PND for inherited predisposition to cancer.
A cross-sectional survey was performed, involving self-administered questionnaires mailed to all registered cancer geneticists (CGs; n = 123) and MPDTs (n = 47) in France.
The response rates of CGs and MPDTs were 62% and 64%, respectively; 59% and 50% of the CGs had at least discussed PGD and PND, respectively, with their consultees during the previous year. When severe cancer is liable to occur in childhood with a high penetrance and no effective methods of prevention/treatment exist, high rates of acceptability of PGD/PND were recorded (> 80%). When cancer is liable to occur before the age of 50 years but not in childhood and some form of prevention/treatment is available that preserves quality of life, PGD was rated as acceptable by one MPDT (3.3%) and 10 CGs (13.2%), and PND was rated acceptable by nine CGs (11.8%). Most respondents agreed that the acceptability of PND/PGD depends on patients' family history of cancer and their reproductive history.
With the most severe forms of inherited cancer, no differences were observed between the acceptability to practitioners of PND and PGD, but with late-onset syndromes, there is still much uncertainty. Guidelines would help to standardize the practices of professionals handling these reproductive issues.
To assess the impact of BRCA1/2 test results on carriers' reproductive decision-making and the factors determining their theoretical intentions about preimplantation genetic diagnosis (PGD) and ...prenatal diagnosis (PND).
Unaffected BRCA1/2 mutation carriers of childbearing age (N = 605; 449 women; 151 men) were included at least 1 year after the disclosure of their test results in a cross-sectional survey nested in a national cohort. Multivariate adjustment was performed on the data obtained in self-administered questionnaires.
Response rate was 81.0%. Overall, 32.5% and 50% said that they would undergo PGD/PND, respectively, at a theoretical next pregnancy, whereas only 12.1% found termination of pregnancy (TOP) acceptable. Theoretical intentions toward PGD did not depend on gender/age, but were higher among those with no future childbearing plans (adjusted odds ratio (AOR) 95% confidence interval (CI): 3.5 (1.9-6.4)) and those having fewer relatives with cancer (AOR 1.5 95% CI (1.0-2.3)). Greater TOP acceptability was observed among males and those with lower educational levels; 85.4% of respondents agreed that information about PGD/PND should be systematically delivered with the test results.
The closer to reproductive decision-making BRCA1/2 carriers are, i.e., when they are more likely to be making future reproductive plans, the less frequently they intend to have PGD. Carriers' theoretical intentions toward PND are discussed further.
Previous qualitative and intentions surveys have shown that the disclosure of a
BRCA1
/
2
mutation might deter young women from becoming pregnant. However, to our knowledge, no comparative studies ...have ever documented the possibility that positive genetic test results might affect these women’s future reproductive rates. Our aim was therefore to quantify the impact of
BRCA1
/
2
mutation disclosure on long-term relationships between partners and childbearing rates. Participants were cancer-free women belonging to families in which a deleterious
BRCA1
/
2
mutation had been identified, who had attended one of the 29 participating cancer genetic clinics for
BRCA1
/
2
testing between 2000 and 2006. Logistic regression models were used to determine predictors of the 5-year self-reported parenthood rate. The sample consisted of 271 women aged 18–45 years (126
BRCA1
/
2
mutation carriers and 145 non-carriers). Couples had separated more frequently among
BRCA1
/
2
carriers than non-carriers (10 vs. 3 %,
p
= .040), especially among nulliparous carriers (13 %). Among the 104 women who were childless at disclosure, disclosure of a
BRCA1
/
2
mutation was not significantly associated with childbearing during the 5-year follow-up period adjusted odds ratio .64, 95 % confidence interval (CI) (.26, 1.57),
p
= .334. Among the 167 women with at least one child at disclosure of a
BRCA1
/
2
mutation had no conspicuous effect on the childbearing trends adjOR .88, 95 % CI (.35, 2.21),
p
= .787. The disclosure of a
BRCA1
/
2
mutation might impact couples’ relationships and future mothering rates, particularly among nulliparous women. Studies on larger populations are now required to confirm these findings.
Mutations in BRCA1/2 confer a high risk of breast cancer, but literature values of this risk vary. A genotype-phenotype correlation has been found in both genes, and the effect of reproductive ...factors differs according to mutation location. Therefore, we hypothesize that such a variation may exist for other factors related to estrogen exposure.
We used a weighted Cox regression model to assess variation in breast cancer risk with these factors using location of mutation in homogeneous breast cancer risk region of BRCA1/2 in the GENEPSO study.
We found that late age at menarche reduced breast cancer risk by 31% and that among BRCA1 carriers, a long or a short menstrual cycle increased risk (by 65% and 73%, respectively). Among premenopausal women, overweight was associated with a 45% decrease in risk whereas underweight was associated with an increased risk (HR, 2.40). A natural menopause, mainly after age 50, was associated with a high breast cancer risk (HR, 2.46), and a significant interaction between menopause status and the location of mutations was found leading up to 10% variation in absolute risk according to the age at menopause.
As observed in the general population, a late menarche, a long or a short menstrual cycle, over- or underweight, and being postmenopausal were associated with breast cancer risk in BRCA1/2 carriers. The association with the menopause was observed only when the mutation was located in the "high-risk" zones.
Taking into account modifier factors, location of mutation might be important for the clinical management of BRCA1/2 mutation carriers.
This study aimed to measure patients' smoking patterns for 5 years after BRCA1/2 test result disclosure.
A national cohort consisting of 621 French cancer-free women from families with BRCA1/2 ...mutations (mean age (SD): 40.5 years (11.5 years)) were included from December 1999 to January 2006, before disclosure of genetic test results, and followed for 5 years. They completed self-administered questionnaires about their cigarette smoking behaviors before receiving their test results (baseline) and 6, 12, 24, and 60 months after disclosure. Multivariate statistical analyses of the changes in participants' smoking behaviors were performed using a zero-inflated Poisson mixed model.
Baseline smoking was found to depend on age, educational level, marital status, alcohol consumption, body mass index, and cancer risk perception. The zero-inflated part of the model showed the occurrence of no significant changes in the percentage of smokers during the 5 years after disclosure of the BRCA1/2 test results; however, daily smoking among BRCA1/2 carriers decreased significantly compared with that of noncarriers (adjusted hazard ratio = 0.83; (95% confidence interval: 0.69-0.99); P = 0.04) after adjusting for baseline smoking behavior.
It would be worth investigating the possibility of counseling women during the genetic testing process about the multiple risk factors involved in cancer, such as genetic and lifestyle factors.
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