In France, breast cancer is the most common cancer among women and the leading cause of cancer deaths. Identifying women with a "high" or "very high" breast cancer risk, according the terminology of ...the Haute Autorité de Santé 2014 guidelines, is essential to offer them special cares in term of screening and prevention. Women genetically predisposed have a very high risk of breast cancer. During the oncogenetic specialist consultation, familial and personal history of cancer is taken into account to evaluate the risk of hereditary Breast/Ovarian syndrome and thus the need of a genetic screening. In 2017, a list of 13 genes involved in hereditary ovarian or breast cancer has been established in France (Genetic and Cancer Group - Unicancer). Women carrying a BRCA1, BRCA2, PALB2, TP53, CDH1, PTEN mutation have a higher risk of breast cancer and are considered as "high risk". Therefore, medical breast surveillance similar to carriers of BRCA1/BRCA2 mutation is recommended for these patients (INCa guidelines 2017). However a mutation in one of those genes is only identified in approximatively 10 % of the screened families. The oncogenetic specialist's assessment distinguishes families in which women remain at a "high" risk of breast cancer (HAS 2014 for screening) from those where women have a "very high" risk (INCa guidelines 2017 for screening and prevention).
Le cancer du sein est, en France, le plus fréquent des cancers chez la femme et la première cause de décès par cancer. L’identification des femmes, dont le niveau de risque de cancer du sein est ...« élevé » ou « très élevé » selon la terminologie de la Haute Autorité de Santé en 2014, est essentielle puisque leur prise en charge, en termes de dépistage et de prévention, pourra ainsi être adaptée.
Les femmes prédisposées génétiquement sont à risque très élevé de cancer du sein. La consultation d’oncogénétique a pour but d’étudier l’histoire personnelle et familiale de cancers de la patiente afin d’identifier les situations évocatrices d’une prédisposition héréditaire aux cancers du sein et/ou des ovaires et leur proposer des analyses de biologie moléculaire. Une liste de 13 gènes devant être étudiés face à ce risque héréditaire a été établie en France en 2017 (Groupe Génétique et Cancer – Unicancer).
La mise en évidence d’une mutation constitutionnelle délétère des gènes BRCA1, BRCA2, PALB2, TP53, CDH1, PTEN confère un niveau de risque de cancer du sein considéré comme « très élevé » chez les femmes porteuses. Elles se voient recommander une surveillance mammaire similaire aux femmes porteuses d’une mutation d’un des deux gènes BRCA1/BRCA2 (Référentiel INCa 2017).
Une mutation délétère sur un gène d’intérêt est identifiée dans environ 10 % des familles testées. Lorsque l’analyse est négative, l’évaluation faite par l’onco-généticien permet de distinguer les familles où les femmes restent à un risque « élevé » de cancer du sein (Référentiel HAS 2014 pour le dépistage) de celles où les femmes sont à un risque « très élevé » (Référentiel INCa 2017 pour le dépistage et la prévention).
In France, breast cancer is the most common cancer among women and the leading cause of cancer deaths. Identifying women with a “high” or “very high” breast cancer risk, according the terminology of the Haute Autorité de Santé 2014 guidelines, is essential to offer them special cares in term of screening and prevention.
Women genetically predisposed have a very high risk of breast cancer. During the oncogenetic specialist consultation, familial and personal history of cancer is taken into account to evaluate the risk of hereditary Breast/Ovarian syndrome and thus the need of a genetic screening. In 2017, a list of 13 genes involved in hereditary ovarian or breast cancer has been established in France (Genetic and Cancer Group – Unicancer).
Women carrying a BRCA1, BRCA2, PALB2, TP53, CDH1, PTEN mutation have a higher risk of breast cancer and are considered as “high risk”. Therefore, medical breast surveillance similar to carriers of BRCA1/BRCA2 mutation is recommended for these patients (INCa guidelines 2017).
However a mutation in one of those genes is only identified in approximatively 10 % of the screened families. The oncogenetic specialist's assessment distinguishes families in which women remain at a “high” risk of breast cancer (HAS 2014 for screening) from those where women have a “very high” risk (INCa guidelines 2017 for screening and prevention).
Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive use. Although the effects of using oral contraceptives in the general ...population are well established (approximately 50% risk reduction in ovarian cancer), the estimated risk reduction in mutation carriers is much less precise because of potential bias and small sample sizes. In addition, only a few studies on oral contraceptive use have examined the associations of duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer.
This study aimed to investigate in more detail the associations of various characteristics of oral contraceptive use and risk of ovarian cancer, to provide healthcare providers and carriers with better risk estimates.
In this international retrospective study, ovarian cancer risk associations were assessed using oral contraceptives data on 3989 BRCA1 and 2445 BRCA2 mutation carriers. Age-dependent–weighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as a covariate. To minimize survival bias, analyses were left truncated at 5 years before baseline questionnaire. Separate analyses were conducted for each aspect of oral contraceptive use and in a multivariate analysis, including all these aspects. In addition, the analysis of duration of oral contraceptive use was stratified by recency of use.
Oral contraceptives were less often used by mutation carriers who were diagnosed with ovarian cancer (ever use: 58.6% for BRCA1 and 53.5% BRCA2) than by unaffected carriers (ever use: 88.9% for BRCA1 and 80.7% for BRCA2). The median duration of use was 7 years for both BRCA1 and BRCA2 carriers who developed ovarian cancer and 9 and 8 years for unaffected BRCA1 and BRCA2 carriers with ovarian cancer, respectively. For BRCA1 mutation carriers, univariate analyses have shown that both a longer duration of oral contraceptive use and more recent oral contraceptive use were associated with a reduction in the risk of ovarian cancer. However, in multivariate analyses, including duration of use, age at first use, and time since last use, duration of oral contraceptive use proved to be the prominent protective factor (compared with <5 years: 5–9 years hazard ratio, 0.67; 95% confidence interval, 0.40–1.12; >10 years hazard ratio, 0.37; 95% confidence interval, 0.19–0.73; Ptrend=.008). The inverse association between duration of use and ovarian cancer risk persisted for more than 15 years (duration of ≥10 years; BRCA1 <15 years since last use hazard ratio, 0.24; 95% confidence interval, 0.14–0.43; BRCA1 >15 years since last use hazard ratio, 0.56; 95% confidence interval, 0.18–0.59). Univariate results for BRCA2 mutation carriers were similar but were inconclusive because of limited sample size.
For BRCA1 mutation carriers, longer duration of oral contraceptive use is associated with a greater reduction in ovarian cancer risk, and the protection is long term.
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.
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.
There is no consensual indication for surgical resection after diagnosis on per-cutaneous biopsy of borderline breast lesions (B3). We evaluate under-evaluation rate of per-cutaneous biopsy and ...predictive factors of under-evaluation. We analyze accuracy of reported decision-making tools.
We conduct a prospective multicentric study including, atypic-ductal hyperplasia (ADH), atypic-lobular hyperplasia (ALH), atypic-cylindro-cubic metaplasia (FEA), papilloma, radial scars (RS) and phyllod tumors. When several B3 lesions were associated, the more severe lesion was used to classify the lesion. We determined breast cancers (BC) rate and histologic type.
Among 478 patients, 518 B3 lesions were studied: 15.1% (78) FEA, 48.6% (252) ADH, 16.8% (n = 87) ALH, 5.4% (n = 28) RS, 12% (n = 62) papilloma, 0.8% (n = 4) phyllod tumors and 0,8% (n = 4) with a suspicious low grade DCIS. More than 1 lesion was identified in 31.9% (165) of cases.
A surgical resection was performed for 86.3% (447/518) lesions. Significant factors of surgical resection were: residual micro-calcification after biopsy (OR: 2.7) and type of B3 lesion.
Overall BC rate was 15.3% (68/445) with 79.4% (54) in-situ carcinomas. According to B3 lesions, BC rates were 12.9% for FEA, 20% for ADH, 11.6% for ALH, 3.7% for RS, 8.8% for papilloma and 25% for suspicious in-situ carcinoma.
A score has been calculated and patients were distributed in 3 groups. Patient's rates without BC were respectively: 100%, 80.4% and 80.6% (p = 0.029).
In conclusion, it could be suggested to avoided complementary surgical resection in case of good radio-pathologic concordance and low probability of BC.
•Among 518 B3 lesions a surgical resection was performed for 86.3%.•BC rate was 15.3% (79.4% in-situ carcinomas): 20%–3.7% according toB3 lesion type.•A score has been calculated with 3 groups.•Surgical resection with low probability of BC.
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