[News in breast oncology genetics for female and male population].

Objectives: Breast oncology genetics emerged almost 30 years ago with the discovery of the BRCA1 and BRCA2 genes. The evolution of analytical practices has progressively allowed access to tests whose results now have a considerable impact on the management of both female and male breast cancers. The Sénologie commission of the Collège national des gynécologues et obstétriciens français (CNGOF) asked five specialists in breast surgery, oncology and oncological genetics to draw up a summary of the oncogenetic testing criteria used and the clinical implications for the female and male population of the test results, with or without an identified causal variant.

[Place of breast self-examination in screening strategies. French College of Gynecologists and Obstetricians (CNGOF) recommendations for clinical practice].

Objectives: Breast cancer is the most common female cancer in the world. In France, over 60,000 new cases are currently diagnosed, and 12,000 deaths are attributed to it annually. Numerous studies have shown that the risk of metastatic disease increases with tumor volume.

Association and performance of polygenic risk scores for breast cancer among French women presenting or not a familial predisposition to the disease.

Background: Three partially overlapping breast cancer polygenic risk scores (PRS) comprising 77, 179 and 313 SNPs have been proposed for European-ancestry women by the Breast Cancer Association Consortium (BCAC) for improving risk prediction in the general population. However, the effect of these SNPs may vary from one country to another and within a country because of other factors.

Objective: To assess their associated risk and predictive performance in French women from (1) the CECILE population-based case-control study, (2) BRCA1 or BRCA2 (BRCA1/2) pathogenic variant (PV) carriers from the GEMO study, and (3) familial breast cancer cases with no BRCA1/2 PV and unrelated controls from the GENESIS study.

Iron deficiency screening is a key issue in chronic inflammatory diseases: A call to action.

Iron deficiency is frequent in patients with chronic inflammatory conditions (e.g., chronic heart failure, chronic kidney disease, cancers, and bowel inflammatory diseases).

Towards a Common Definition for the Diagnosis of Iron Deficiency in Chronic Inflammatory Diseases.

Iron deficiency (ID) in patients with chronic inflammatory diseases is frequent. However, under-diagnosis is also frequent due to the heterogeneity between guidelines from different medical societies. We applied a common definition for the diagnosis of ID to a large panel of patients with cancer, heart failure (HF), inflammatory bowel disease (IBD), and chronic kidney disease (CKD), where ID was defined as serum ferritin concentration <100 μg/L and/or a transferrin saturation (TSAT) index <20%.

[Techniques and complications of non-genetic risk reducing mastectomies: Guidelines of the National College of French Gynecologists and Obstetricians (CNGOF)].

Objective: Based on an updated review of the international literature covering the different surgical techniques and complications of risk reducing mastectomies (RRM) in non-genetic context, the Commission of Senology (CS) of the College National des Gynécologues Obstétriciens Français (CNGOF) aimed to establish recommendations on the techniques to be chosen and their implementation.

Design: The CNGOF CS, composed of 24 experts, developed these recommendations. A policy of declaration and monitoring of links of interest was applied throughout the process of making the recommendations.

Diagnostic chest X-rays and breast cancer risk among women with a hereditary predisposition to breast cancer unexplained by a BRCA1 or BRCA2 mutation.

Background: Diagnostic ionizing radiation is a risk factor for breast cancer (BC). BC risk increases with increased dose to the chest and decreases with increased age at exposure, with possible effect modification related to familial or genetic predisposition. While chest X-rays increase the BC risk of BRCA1/2 mutation carriers compared to non-carriers, little is known for women with a hereditary predisposition to BC but who tested negative for a BRCA1 or BRCA2 (BRCA1/2) mutation.

Iron deficiency in patients with cancer: a prospective cross-sectional study.

Background: Despite the deleterious consequences of iron deficiency (ID) in patients with cancer, underdiagnosis is frequent. The CARENFER study aimed to assess the prevalence of ID using both serum ferritin concentration and transferrin coefficient saturation (iron-saturation of transferrin, TSAT) index, as well as ID anaemia in patients with cancer.

Methods: This prospective cross-sectional study was conducted in 15 oncology units in France in 2019.

Actionability of HER2-amplified circulating tumor cells in HER2-negative metastatic breast cancer: the CirCe T-DM1 trial.

Background: In this prospective phase 2 trial, we assessed the efficacy of trastuzumab-emtansine (T-DM1) in HER2-negative metastatic breast cancer (MBC) patients with HER2-positive CTC.

Methods: Main inclusion criteria for screening were as follows: women with HER2-negative MBC treated with ≥ 2 prior lines of chemotherapy and measurable disease. CTC with a HER2/CEP17 ratio of ≥ 2.

The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With or Mutations.

Background: Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for and mutation carriers.

Methods: Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 and 3525 mutation carriers) and a prospective cohort (2276 and 1610 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort.

A novel machine learning-derived decision tree including uPA/PAI-1 for breast cancer care.

Background uPA and PAI-1 are breast cancer biomarkers that evaluate the benefit of chemotherapy (CT) for HER2-negative, estrogen receptor-positive, low or intermediate grade patients. Our objectives were to observe clinical routine use of uPA/PAI-1 and to build a new therapeutic decision tree integrating uPA/PAI-1. Methods We observed the concordance between CT indications proposed by a canonical decision tree representative of French practices (not including uPA/PAI-1) and actual CT prescriptions decided by a medical board which included uPA/PAI-1.

Familial breast cancer and DNA repair genes: Insights into known and novel susceptibility genes from the GENESIS study, and implications for multigene panel testing.

Pathogenic variants in BRCA1 and BRCA2 only explain the underlying genetic cause of about 10% of hereditary breast and ovarian cancer families. Because of cost-effectiveness, multigene panel testing is often performed even if the clinical utility of testing most of the genes remains questionable. The purpose of our study was to assess the contribution of rare, deleterious-predicted variants in DNA repair genes in familial breast cancer (BC) in a well-characterized and homogeneous population.

[The French Genetic and Cancer Consortium guidelines for multigene panel analysis in hereditary breast and ovarian cancer predisposition].

Introduction: Next generation sequencing allows the simultaneous analysis of large panel of genes for families or individuals with a strong suspicion of hereditary breast and/or ovarian cancer (HBOC). Because of lack of guidelines, several panels of genes potentially involved in HBOC were designed, with large disparities not only in their composition but also in medical care offered to mutation carriers. Then, homogenization in practices is needed.

[PALB2, a major susceptibility gene for breast cancer].

Objectives: About 5% of breast cancers are linked to an inherited predisposition, the two most known susceptibility genes being BRCA1 and BRCA2. Recently, new susceptibility genes, including PALB2, have been identified. The risk of breast cancer associated with a deleterious mutation of PALB2, the age of onset of these cancers, their prognosis and associated cancers have so far been the subject of controversy.

Guidelines for reporting secondary findings of genome sequencing in cancer genes: the SFMPP recommendations.

In oncology, the expanding use of multi-gene panels to explore familial cancer predisposition and tumor genome analysis has led to increased secondary findings discoveries (SFs) and has given rise to important medical, ethical, and legal issues. The American College of Medical Genetics and Genomics published a policy statement for managing SFs for a list of genes, including 25 cancer-related genes. Currently, there are few recommendations in Europe.

Clinical and pathologic characteristics of breast cancer patients carrying the c.3481_3491del11 mutation.

Tumor characteristics are used today to evaluate the possibility of mutation and to target mutation screening in families with high risk of breast and/or ovarian cancer. We studied the breast tumor profile associated to the c.3481_3491del11 French founder effect mutation on the BRCA1 gene to an attempt to identify any particularity or difference when comparing it to that related to other BRCA1 mutations.

Is there a genetic anticipation in breast and/or ovarian cancer families with the germline c.3481_3491del11 mutation?

The aim of the current analysis is to evaluate any differences of breast or ovarian cancer age at diagnosis between mothers and daughters carrying the c.3481_3491del11 mutation in the BRCA1 gene. A study cohort of 38 women carrying the c.

Prevalence and incidence of chronic pain with or without neuropathic characteristics in patients with cancer.

This prospective national multicenter study was carried out to estimate the prevalence and incidence of chronic pain with or without neuropathic characteristics in patients with cancer in France. All consecutive outpatients (n = 1885) seen over 2 weeks for cancer treatment in 12 oncology units were invited to participate in the study, and 1805 were included. Patients underwent a clinical examination during visit 1, and a questionnaire was completed to detect chronic pain (defined as daily pain for at least 3 months), and to characterize its intensity, location, and neuropathic characteristics (ie, DN4 score ≥4).

Use of iron sucrose and red blood cell transfusions in anaemic cancer patients in France (OncoFer study).

Purpose: This report describes the results of an observational, retrospective cohort study, evaluating the use of iron sucrose (IS) and red blood cell (RBC) transfusions in patients with cancer in routine clinical practice in France. A parallel investigated cohort treated with ferric carboxymaltose (FCM) has been reported earlier.

Methods: Data of patients with a solid tumour or haematological malignancy who have received IS or an RBC transfusion during 2010 from 3 months prior (M) to 3 months post first treatment (M) were analysed.