Validation of QTL for resistance to Aphanomyces euteiches in different pea genetic backgrounds using near-isogenic lines.

KEY MESSAGE: Marker-assisted backcrossing was used to generate pea NILs carrying individual or combined resistance alleles at main Aphanomyces resistance QTL. The effects of several QTL were successfully validated depending on genetic backgrounds. Quantitative trait loci (QTL) validation is an important and often overlooked step before subsequent research in QTL cloning or marker-assisted breeding for disease resistance in plants. Validation of QTL controlling partial resistance to Aphanomyces root rot, one of the most damaging diseases of pea worldwide, is of major interest for the future development of resistant varieties. The aim of this study was to validate, in different genetic backgrounds, the effects of various resistance alleles at seven main resistance QTL recently identified. Five backcross-assisted selection programs were developed. In each, resistance alleles at one to three of the seven main Aphanomyces resistance QTL were transferred into three genetic backgrounds, including two agronomically important spring (Eden) and winter (Isard) pea cultivars. The subsequent near-isogenic lines (NILs) were evaluated for resistance to two reference strains of the main A. euteiches pathotypes under controlled conditions. The NILs carrying resistance alleles at the major-effect QTL Ae-Ps4.5 and Ae-Ps7.6, either individually or in combination with resistance alleles at other QTL, showed significantly reduced disease severity compared to NILs without resistance alleles. Resistance alleles at some minor-effect QTL, especially Ae-Ps2.2 and Ae-Ps5.1, were also validated for their individual or combined effects on resistance. QTL × genetic background interactions were observed, mainly for QTL Ae-Ps7.6, the effect of which increased in the winter cultivar Isard. The pea NILs are a novel and valuable resource for further understanding the mechanisms underlying QTL and their integration in breeding programs.

[Lipofilling in the management of breast cancer: An update based on a literature review and national and international guidelines]. / Le lipomodelage du sein dans un contexte cancérologique : mise au point à partir d'une revue de littérature actualisée et des référentiels nationaux et internationaux.

BACKGROUND: Lipomodelling (LM) is an increasingly used technique to reconstruct or correct an aesthetic defect linked to a loss of substance. In France, the Haute Autorité de santé (HAS) published recommendations in 2015 and 2020 concerning the conditions of use of LM on the treated and contralateral breast. These appear to be inconsistently followed. METHODS: Twelve members of the Senology Commission of the Collège national des gynécologues-obstétriciens français (French College of Gynecologists and Obstetricians) reviewed the carcinological safety of LM and the clinical and radiological follow-up of patients after breast cancer surgery, based on French and international recommendations and a review of the literature. The bibliographic search was conducted via Medline from 2015 to 2022, selecting articles in French and English and applying PRISMA guidelines. RESULTS: A total of 14 studies on the oncological safety of LM, 5 studies on follow-up and 7 guidelines were retained. The 14 studies (6 retrospective, 2 prospective and 6 meta-analyses) had heterogeneous inclusion criteria and variable follow-up, ranging from 38 to 120 months. Most have shown no increased risk of locoregional or distant recurrence after LM. A retrospective case-control study (464 LMs and 3100 controls) showed, in patients who had no recurrence at 80 months, a subsequent reduction in recurrence-free survival after LM in cases of luminal A cancer, highlighting the number of lost to follow-up (more than 2/3 of luminal A cancers). About follow-up after LM, the 5 series showed the high frequency after LM of clinical mass and radiological images (in » of cases), most often corresponding to cytosteatonecrosis. Most of the guidelines highlighted the uncertainties concerning oncological safety of LM, due to the lack of prospective data and long-term follow-up. DISCUSSION AND PERSPECTIVES: The members of the Senology Commission agree with the conclusions of the HAS working group, in particular by advising against LM "without cautionary periods", excessively, or in cases of high risk of relapse, and recommend clear, detailed information to patients before undergoing LM, and the need for postoperative follow-up. The creation of a national registry could address most questions regarding both the oncological safety of this procedure and the modalities of patient follow-up.

[Techniques and complications of non-genetic risk reducing mastectomies: Guidelines of the National College of French Gynecologists and Obstetricians (CNGOF)]. / Modalités et morbidité des mastectomies de réduction de risque en dehors du risque avéré de prédisposition héréditaire : recommandations du Collège national des gynécologues et obstétriciens français (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. Similarly, the development of these recommendations did not benefit from any funding from a company marketing a health product. The CS adhered to and followed the AGREE II (Advancing guideline development, reporting and evaluation in healthcare) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method to assess the quality of the evidence on which the recommendations were based. The potential drawbacks of making recommendations in the presence of poor quality or insufficient evidence were highlighted. METHODS: The CS considered 6 questions in 4 thematic areas, focusing on oncologic safety, risk of complications, aesthetic satisfaction and psychological impact, and preoperative modalities. RESULTS: The application of the GRADE method resulted in 7 recommendations, 6 with a high level of evidence (GRADE 1±) and 1 with a low level of evidence (GRADE 2±). CONCLUSION: There was significant agreement among the CS members on recommendations for preferred surgical techniques and practical implementation.

Management of postmenopausal women: Collège National des Gynécologues et Obstétriciens Français (CNGOF) and Groupe d'Etude sur la Ménopause et le Vieillissement (GEMVi) Clinical Practice Guidelines.

AIM: The aim of these recommendations is to set forth an individualized approach to the management of early postmenopausal women (i.e., within the first 10 years after natural menopause) covering all aspects of lifestyle and therapeutic management, with or without menopause hormone therapy (MHT). MATERIALS AND METHODS: Literature review and consensus of French expert opinion. Recommendations were graded according to the HAS methodology and levels of evidence derived from the international literature, except when there was no good-quality evidence. SUMMARY RECOMMENDATIONS: The beginning of menopause is an ideal time for each woman to evaluate her health status by assessing her bone, cardiovascular, and cancer-related risk factors that may be amplified by postmenopausal estrogen deficiency and by reviewing her lifestyle habits. Improving lifestyle, including nutrition and physical activity, and avoiding risk factors (notably smoking), should be recommended to all women. MHT remains the most effective treatment for vasomotor symptoms but it could be also recommended as first-line treatment for the prevention of osteoporosis in early postmenopausal women at low to moderate risk for fracture. The risks of MHT differ depending on its type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used. There is reasonable evidence that using transdermal estradiol in association with micronized progesterone or dydrogesterone may limit both the venous thromboembolic risk associated with oral estrogens and the risk of breast cancer associated with synthetic progestins. Treatment should be individualized to each woman, by using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of its benefit-risk balance. For bothersome genitourinary syndrome of menopause (GSM) symptoms, vaginal treatment with lubricants and moisturizers is recommended as first-line treatment together with low-dose vaginal estrogen therapy, depending on the clinical course. No recommendation of an optimal duration of MHT can be made, but it must take into consideration the initial indication for MHT as well as each woman's benefit-risk balance. Management of gynecological side-effects of MHT is also examined. These recommendations are endorsed by the Groupe d'Etude sur la Ménopause et le Vieillissement hormonal (GEMVI) and the Collège National des Gynécologues-Obstétriciens Français (CNGOF).

[Non-hormonal alternatives for the management of menopausal hot flushes. Postmenopausal women management: CNGOF and GEMVi clinical practice guidelines]. / Alternatives non hormonales de prise en charge des bouffées vasomotrices post-ménopausiques. RPC Les femmes ménopausées du CNGOF et du GEMVi.

One of the major symptoms of climacteric syndrome is hot flushes (HF). They are most often experienced as very disabling. Estrogen therapy is the most effective treatment. However, it may be contraindicated in some women. The aim of this article is to provide a review of the scientific literature on pharmacological and non-pharmacological alternatives in this context. Only randomized trials and meta-analyses of randomized trials were considered. This review shows that some treatments usually used in non-gynecological or endocrinological disease have significant effect in reducing the frequency and/or severity of HF. Hence, some selective serotonin reuptake inhibitors (paroxetine, citalopram and escitalopram), serotonin and norepinephrine reuptake inhibitors (venlafaxine, desvenlafaxine) gabapentin, pregabalin and clonidine have a statistically effect as compared with placebo in reducing, the frequency and/or severity of HF. Some phytoestrogens, such as genistein, may also reduce the frequency of HF. Regarding non-pharmacological interventions, hypnosis, acupuncture or yoga have been analyzed with significant beneficial results, even if their evaluation is difficult by the absence of a good placebo group in most trials. By contrast, other approaches, both pharmacological or non-pharmacological, appear to be ineffective in the management of HT. These include homeopathy, vitamin E, alanine, omega 3, numerous phytoestrogens (red clover, black cohosh…), primrose oil, physical activity. In women suffering from breast cancer, several additional problems are added. On the one hand because all phytoestrogens are contraindicated and on the other hand, in patients using tamoxifen, because the molecules, that interact with CYP2D6, are to be formally avoided because of potential interaction with this anti-estrogen treatment. In conclusion, several pharmacological and non-pharmacological alternatives have significant efficacy in the management of severe HF.

[Mammographic density: a valid risk factor for breast cancer?]. / La densité mammaire: un facteur établi de risque de cancer du sein?

Whether estimated or measured, mammographic or breast density, which may be subject to physiological and therapeutic variations, is widely viewed in the literature as an important factor of increased risk for breast cancer. A high breast density, the causes of which are being refined, would increase the relative risk of breast cancer four to six fold, even though some authors direct critics at methodological flaws supporting these results. Three-dimensional imaging will confirm or refute the available results. Meanwhile, radiologists and clinicians must remain vigilant in patients with high breast density.

[Levonorgestrel-releasing intrauterine device (Mirena) and breast cancer: what do we learn from literature for clinical practice?]. / Dispositif intra-utérin au lévonorgestrel (Mirena) et cancer du sein: que nous apporte la littérature pour la pratique quotidienne?

Annual occurrence of breast cancer is constantly increasing in France. In 2000, the number of breast cancer cases for women of 30-49 years was estimated at 9,918, which represents 23.7% of all breast cancer cases diagnosed that year. The levonorgestrel-releasing intrauterine device (IUD LNG) is one of the most frequently used coils in France. Because contraception is an important matter for women whose ovarian function survived cancer treatments, the question of whether to use such device on a woman with breast cancer has become a frequent and controversial gynaecological issue. With the review of available literature as a basis, we have tried to answer the following questions. First, whether the use of IUD LNG increases the risk of breast cancer: there is at the moment no "A" level answer available. According to the only study published, which may be considered "C" level, there is no such increase. Second, whether the use of IUD LNG counterbalances the endometrial effects of Tamoxifene: based on a limited level of evidence via a single randomised controlled trial on a small number of patients for one year only, this device appears to be able to prevent benign endometrial modifications. However, there is no conclusive study regarding its effectiveness on the prevention of endometrium adenocarcinoma caused by Tamoxifene. In addition, there are numerous uncertainties as to whether levonorgestrel presence in the plasma would have a systemic prejudicial impact. Third, whether a woman with a personal antecedent of breast cancer can safely use DIU LNG: it is necessary to remove it promptly upon suspicion or diagnosis, to dissuade its use in case of current cancer, and, in the event of cancer remission for more than 5 years, to generally avoid this contraceptive method except on a case by case basis and with a regular medical follow-up. In the latter situation, the use of IUD LNG can be considered only after a multidisciplinary collective formal decision and after the woman gave her informed consent.

[Menopausal hormonal therapies: impact on mammographic breast density]. / Thérapeutiques hormonales de la menopause: impact sur la densité mammographique.

Whether qualitative-classified or quantitative-measured, mammographic density, which changes according to physiological variations, is nowadays commonly recognized as a factor increasing the relative risk of breast cancer. The present review aims at clarifying the impact of menopausal hormonal therapies on mammographic density. Neither Tibolone nor Raloxifene seem to have any negative impact on mammographic density. In some instances, oestrogens-progestin hormonal replacement therapies may increase mammographic density and thus reduce sensitivity and specificity of screening mammograms. Shorter intervals between mammographies combined with additional physical examination and breast ultrasonography appear to be the best way to reduce interval cancers.

[Cowden's disease in a young girl: mammographic problems]. / Maladie de Cowden chez une jeune fille: les problèmes sénologiques.

A 14-year-old girl consulted for multiple breast nodules which were found to result from Cowden's disease, also called multiple hamartomatosis. Mammography and sonography examinations were completed with nuclear magnetic resonance imaging after injection of paramagnetic contrast product. Cowden's disease is a rare condition resulting in the development of tumors in genodermatous tissue; The cause remains unknown. In cases involving the breast, cutaneous lesions are markers of precancerous development since cancer occurs in 28 to 30% of these cases.

[Gonadoblastoma. Review of the literature. Apropos of a case]. / Le gonadoblastome. Revue de la littérature. A propos d'une observation.

Gonadoblastoma, which was described for the first time by Scully in 1953, is a rare tumour of the gonads. Only about 150 cases have been reported. Anatomo-pathologically it shows itself by a combination of large primitive germinal cells, small cells which resemble the immature cells found in the granulosa and in the Sertoli and sometimes Leydig-theco interstitial cells. Calcification is suggestive. Gonadoblastomas usually develop in a dysgenetic gonad. Pure gonadic dysgenesis is more commonly found. The subjects usually are of feminine phenotype and can demonstrate somatic or sexual abnormalities. The caryotypes most frequently found are 46 XY or 45 XO/46 XY. It is rare for the Y chromosome to be absent. All patients with gonadoblastomas should be HY antigen positive. The tumour is benign but the germinal epithelium can change towards a seminoma type. Because of this it is wise to carry out laparotomy with removal of both adnexae if there is a gonadoblastoma present. The case we have studied illustrates the typical profile of a gonadoblastoma. It occurred in a young woman who had pure gonadic dysgenesis with a caryotype 46 XY (Swyer's syndrome). It was bilateral associated on the left side with a seminoma, and for this reason we carried out bilateral extirpation of the adnexae followed up by therapy with cobalt.

[Prescription of hormone replacement therapy. Review on the management with abnormal mammography]. / Prescription d'un traitement hormonal substitutif. Mise au point sur la conduite à tenir devant une anomalie mammographique.

Mammography must be performed before restauring RHT. We discuss the radiological contrindications before RHT, and the predictive positive value of malignancy for stellate lesions, round opacities, diffuse microcalcifications, cluster of microcalcifications. Ultrasonography is essential for differentiating benign from malignant lesions. Diagnosis strategy (clinical follow-up, fine needle aspiration, biopsy, surgery) depends also on personal and familial history.

Breast inflammation: clinical examination, aetiological pointers.

Red, hot, and painful breast inflammation can have a large number of causes. The history of the condition and clinical observations usually give a pointer to the aetiological diagnosis, which is based on the classic triad of clinical, radiological and histopathological examinations, and guide the choice of additional investigations for rapid therapeutic management of this breast emergency. In breastfeeding women, the cause is often mastitis or, more rarely, an abscess; in non-breastfeeding women, the problem may be mastitis or a periareolar abscess, inflammatory lesions sometimes with secondary infection, or more rarely a real abscess, regardless of a catalogue of various causes. In all cases, the possibility must be considered of inflammatory breast cancer.

[Management of hot flushes for breast cancer survivors]. / Traitement des bouffées de chaleur après cancer du sein.

Hot flushes experienced by breast cancer survivors present specific issues due to their frequency, severity and difficulty to treat. After an evaluation of her symptoms and expression of her expectations and requests, each patient will be provided a clear, synthetic, comprehensible, supported and prioritized view of all treatment options. Any prescribed treatment will be a shared medical decision making. An algorithm of treatment propositions, documented by evidence-based medicine, is proposed. As randomized trials show that placebo-induced reduction of hot flushes frequency represents to 25 to 75%, non-pharmacological approaches selected by the patient should be preferred at first, to the exception however of phytoestrogens. The first-line treatment for severe hot flushes should be, depending on each specific context, venlafaxine, paroxetine or gabapentine. In case of inefficiency, treatments of second- and third-line will be proposed. Prescription of progestin or of a menopausal hormone therapy should remain exceptional and limited to cases where all other treatments failed, after obtaining the patient's informed consent following exhaustive information. Indications of stellate ganglion block remain to be defined.