Impact of hormone receptor status and tumor subtypes of breast cancer in young BRCA carriers.

BACKGROUND: Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its prognostic impact on prognosis of young patients harboring a pathogenic variant (PV) in the BRCA1 and/or BRCA2 genes. PATIENTS AND METHODS: This international, multicenter, retrospective cohort study included young patients (aged ≤40 years) diagnosed with invasive breast cancer and harboring germline PVs in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest [disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS)] were first investigated according to hormone receptor expression (positive versus negative), and then according to breast cancer subtype [luminal A-like versus luminal B-like versus triple-negative versus human epidermal growth factor receptor 2 (HER2)-positive breast cancer]. RESULTS: From 78 centers worldwide, 4709 BRCA carriers were included, of whom 2143 (45.5%) had hormone receptor-positive and 2566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% versus 9.6%, P < 0.001), while the rate of second primary breast cancer was lower (9.1% versus 14.7%, P < 0.001) compared to patients with hormone receptor-negative disease. The 8-year DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive versus negative disease changed over time for DFS, BCSS, and OS (P < 0.05 for interaction of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-year DFS: 60.8% in luminal A-like versus 63.5% in triple-negative versus 65.5% in HER2-positive and 69.7% in luminal B-like subtype). CONCLUSIONS: In young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor-positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.

Menopausal symptoms in epithelial ovarian cancer survivors: a GINECO VIVROVAIRE2 study.

OBJECTIVE: We have previously shown that epithelial ovarian cancer (EOC) and its treatments have negative effects on long-term quality of life (QoL) and fatigue. The present multicenter study investigated the main menopausal symptoms and gynecological management of EOC survivors (EOCS). METHODS: 166 patients with relapse-free ≥3 years after the end of treatment attended a consultation with a gynecologist, including a questionnaire related to vasomotor symptoms (VMS) and sexuality, a clinical examination, a blood sample and an osteodensitometry. QoL, fatigue, insomnia and mood disorders were measured with validated questionnaires and correlated to VMS. VMS and QoL were assessed according to natural menopause (NM) or surgical menopause (SM). RESULTS: Mean age at the survey was 62 [21-83] years and stage III/IV (48%). Mean delay since the end of treatment was 6 years. Fifty-nine patients (36%) had SM. Half of patients reported VMS. Seventy-two percent of EOCS with SM had VMS compared to 41% with NM (P < .001). VMS were not associated with poor global QoL, fatigue, insomnia or mood disorders. Two-thirds of EOCS reported a decrease in libido. Patients with SM showed a greater decrease in libido than NM (P < .02). Fourteen percent of them had osteoporosis and 50% osteopenia. Among the 85 patients with VMS, 80 did not receive HRT after cancer treatment. At the time of the survey, only 7 (4%) patients were receiving hormone replacement therapy (HRT). CONCLUSIONS: VMS and sexual disorders are frequently reported by EOCS, particularly among patients with SM. Most EOCS with menopausal symptoms could benefit from HRT to improve these symptoms.

Contraceptive practices and cervical screening in women with cystic fibrosis.

STUDY QUESTION: Is gynaecological management of women with cystic fibrosis (CF) adequate? SUMMARY ANSWER: Gynaecological care (frequency of follow-up, cervical screening and contraceptive use among sexually active women) in women with CF fails to reach the recommended level. WHAT IS KNOWN ALREADY: Little is known about gynaecological follow-up and cervical screening in CF. Only few studies have described contraceptive practices in cohorts of CF women. STUDY DESIGN, SIZE, DURATION: We did a cross-sectional study in a cohort of 155 CF women attending the Lyon adult centre. Women attending the CF adult centre in 2014 completed a written questionnaire about their contraceptive choices, frequency of gynaecological follow-up and cervical screening. Other clinical data were collected from the CF adult centre registry. PARTICIPANTS/MATERIALS, SETTING, METHODS: One hundred and twenty women (100%) answered the questionnaire, among whom two were post-menopausal (46 and 59 years of age), and five were pregnant. MAIN RESULTS AND THE ROLE OF CHANCE: Seventy-four per cent of the women declared they had undergone gynaecological follow-up (89% of the women with transplantation), and only 55% reported having at least one previous Pap smear test. Among the transplanted patients, only 58% had had a Pap smear test, despite immunosuppressive treatment. The overall rate of contraception was only 64% and in diabetic women, it was 61%. Among contraception users; 65% used oral contraception, predominantly combined estrogen-progestagen (47%); among diabetic patients, 26% used progestin-only contraception. Intrauterine device accounted for 10% of patients using contraception, and tubal ligation only 4%. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its cross-sectional design. Despite an internal validation of the questionnaire showing an almost perfect agreement, the risk of recall bias has to be taken into account. WIDER IMPLICATIONS OF THE FINDINGS: This study of practices highlights the importance of improved information regarding sexuality, fertility and reproductive health in young women with CF. A regular gynaecological follow-up and cervical screening is mandatory in this population. Better gynaecological care and contraceptive advice would help to avoid unplanned pregnancies, and optimize contraceptive selection in relationship to specific clinical conditions.

Thoracic endometriosis syndrome: CT and MRI features.

Thoracic endometriosis is considered to be rare, but is the most frequent form of extra-abdominopelvic endometriosis. Thoracic endometriosis syndrome affects women of reproductive age. Diagnosis is mainly based on clinical findings, which can include catamenial pneumothorax and haemothorax, non-catamenial endometriosis-related pneumothorax, catamenial haemoptysis, lung nodules, and isolated catamenial chest pain. Symptoms are typically cyclical and recurrent, with a right-sided predominance. Computed tomography (CT) is the first-line imaging method, but is poorly specific; therefore, its main role is to rule out other pulmonary diseases. However, in women with a typical clinical history, some key CT findings may help to confirm this often under-diagnosed syndrome. MRI can also assist with the diagnosis, by showing signal changes typical of haemorrhage within diaphragmatic or pleural lesions.

Characteristics and clinical outcomes of breast cancer in young BRCA carriers according to tumor histology.

BACKGROUND: Young women with breast cancer (BC) have an increased chance of carrying germline BRCA pathogenic variants (PVs). Limited data exist on the prognostic impact of tumor histology (i.e. ductal versus lobular) in hereditary breast cancer. METHODS: This multicenter retrospective cohort study included women aged ≤40 years with early-stage breast cancer diagnosed between January 2000 and December 2020 and known to carry germline PVs in BRCA1/2. Histology was locally assessed in each center. The Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival and overall survival. RESULTS: Of 4628 patients included from 78 centers worldwide, 3969 (86%) had pure ductal, 135 (3%) pure lobular, and 524 (11%) other histologies. Compared with ductal tumors, lobular tumors were more often grade 1/2 (57.7% versus 22.1%), stage III (29.6% versus 18.5%), and luminal A-like (42.2% versus 12.2%). Lobular tumors were more often associated with BRCA2 PVs (71.1% BRCA2), while ductal tumors were more often associated with BRCA1 PVs (65.7% BRCA1). Patients with lobular tumors more often had mastectomy (68.9% versus 58.3%), and less often received chemotherapy (83.7% versus 92.9%). With a median follow-up of 7.8 years, no significant differences were observed in disease-free survival (adjusted hazard ratio 1.01, 95% confidence interval 0.74-1.37) or overall survival (hazard ratio 0.96, 95% confidence interval 0.62-1.50) between patients with ductal versus lobular tumors. No significant survival differences were observed according to specific BRCA gene, breast cancer subtype, or body mass index. CONCLUSIONS: In this large global cohort of young BRCA carriers with breast cancer, the incidence of pure lobular histology was low and associated with higher disease stage at diagnosis, luminal-like disease and BRCA2 PVs. Histology did not appear to impact prognosis.

Human papillomavirus prevalence, persistence and cervical dysplasia in females with cystic fibrosis.

BACKGROUND: A higher risk of human papillomavirus (HPV)-related cervical intra-epithelial neoplasia (CIN) is suspected among females with cystic fibrosis (CF). METHODS: We conducted a single center prospective cohort study among females attending the Lyon adult CF center. We performed a cervical cytology (Hologic Thinprep®) and HPV testing with genotyping (Clinical Arrays Papillomavirus; Genomica, enabling 35 genotype detection, 20 of which are high-risk (HR-HPV)) at inclusion. We followed all females with positive HPV tests at 6, 12 and 24 months to evaluate HPV persistence, and performed a colposcopy in cases of abnormal cytology. RESULTS: We included eighty-five participants, 18 (21%) of whom were lung-transplanted. The mean age at inclusion was 31.9 (range 18-59) years. The prevalence of HPV (all types) was 31.8%. HR-HPV was found in 25.9% of the whole cohort, 44.4% of transplanted patients, and 20.1% of nontransplanted patients. Genotype-specific HR-HPV persistence at 12 months was 43.5% among transplanted and 34.6% among nontransplanted patients. Overall, 17.6% (15/85) of females had an abnormal cytology: 44.4% (8/18) among transplanted and 10.4% (7/67) among nontransplanted patients. CIN was identified in 12 (14.1%) patients (6 low-grade, 6 high-grade). High-grade CIN developed in 4 nontransplanted patients. CONCLUSION: Transplanted females had high HR-HPV, abnormal cervical cytology and CIN prevalence rates compared to large published cohorts in the general non-CF population. Although HR-HPV prevalence and persistence were globally not significantly different in nontransplanted females compared to the general population, we reported high frequencies of abnormal cytology and CIN. Cervical cancer screening and prevention should be promoted among females with CF.

Association between recent pregnancy or hormonal contraceptive exposure and outcome of desmoid-type fibromatosis.

BACKGROUND: The role of both hormonal contraception and pregnancy on the outcomes of desmoid-type fibromatosis (DF) is debatable. MATERIALS AND METHODS: In the present study, we selected female patients of childbearing age from the prospective ALTITUDES cohort. The primary study endpoint was event-free survival (EFS), with an event defined as relapse or progression. We estimated the risk of events according to the use of hormonal contraception [estrogen-progestin (EP) and progestin] and pregnancy status using multivariate time-dependent models, controlling for major confounders. RESULTS: A total of 242 patients (median age, 34.7 years) were included in the present study. The abdominal wall was the most common tumor site (51%). Patients were managed by active surveillance (80%) or surgery (20%). Pregnancy occurred within 24 months before, at the time of, and after DF diagnosis in 33%, 5%, and 10% of the cases, respectively. Exposure to hormonal contraception was documented within 24 months before, at the time of, and after diagnosis in 44%, 34%, and 39% of the cases, respectively. The 2-year EFS was 75%. After adjusting for DF location, tumor size, front-line treatment strategy, and hormonal contraception, we observed an increased risk of events occurring at 24 months after pregnancy [hazard ratio (HR) = 2.09, P = 0.018]. We observed no statistically significant association between the risk of events and current EP exposure (HR = 1.28, P = 0.65), recent EP exposure (within 1-24 months, HR = 1.38, P = 0.39), current progestin exposure (HR = 0.81, P = 0.66), or recent progestin exposure (HR = 1.05, P = 0.91). CONCLUSIONS: In our study, a recent history of pregnancy was associated with an increased risk of progression/relapse in patients with newly diagnosed DF, whereas hormonal contraception did not demonstrate an association with progression/relapse.

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).

[How to diagnose menopause? Postmenopausal women management: CNGOF and GEMVi clinical practice guidelines]. / Comment diagnostiquer la ménopause ? RPC Les femmes ménopausées du CNGOF et du GEMVi.

The diagnosis of menopause is sometimes difficult. The objective of this chapter is to describe the process of diagnosing menopause in a physiological situation, then in different clinical situations: women using hormonal contraception (per os, implant or intrauterine device), women with a history of hysterectomy, women previously treated for cancer. A review of the literature was carried out via Pubmed, Medline and Cochrane Library. The recommendations of international societies were also taken into account: International Menopause Society (IMS) https://www.imsociety.org, European Menopause and Andropause Society (EMAS) https://www.emas-online.org. In a classic situation, the diagnosis of menopause is a clinical diagnosis, made retrospectively, based on a 12-month period of consecutive amenorrhoea in a compatible age group (after 45 years of age). No hormonal dosage or imaging is indicated to make a diagnosis of menopause in a classic situation. In women using oestroprogestogen or progestative-only-pill contraception, implant, or Levonorgestrel-intrauterine device (LNG IUD), hormonal assays or pelvic ultrasound are neither recommended to make a diagnosis of menopause (grade C), nor to decide to stop contraception (grade C). The proposed strategy is the discontinuation of oral contraception, removal of the implant or LNG-IUD, and clinical follow-up (occurrence of amenorrhea) (expert opinion). In women with a history of hysterectomy, in the absence of evaluable clinical symptoms (amenorrhea), a repeat FSH≥40 combined with low estradiol (<20pg/ml) at least 3 months after the procedure could be a diagnostic orientation towards menopausal status. After cancer, in women who have received gonadotoxic treatment, the classic clinical criteria of 12 months of amenorrhea cannot be used to make a diagnosis of menopause with certainty (expert opinion). No further examination can be recommended to make a definite diagnosis of menopause (expert opinion). In breast cancer, the hormonal status to be taken into account when choosing initial hormone therapy is the one found before starting any treatment. If at the time of diagnosis of breast cancer the menopausal status is not known due to hormonal contraception, it is preferable to consider the patient as non-menopausal by default for the choice of hormone therapy for the cancer.

[Human papillomavirus and systemic lupus erythematosus]. / Papillomavirus humain et lupus érythémateux systémique.

Infection with human papillomavirus (HPV) is one of the most widespread sexually transmitted diseases and the main risk factor for cervical cancer. Underlying conditions, like immunosuppression, favour the persistence and the progression of cervical lesions to an aggressive form. Patients with autoimmune diseases, and particularly systemic lupus erythematosus (SLE), may be prone to HPV infection and cervical dysplasia. However, the risk factors for developing persistent HPV-related infection, dysplasia and cancer are not identified for patients with SLE. The existence of an increased risk of cervical cancer compared to the general population remains debated. Thus, HPV vaccine is recommended for SLE patients as well as for the general population. Vaccine coverage of SLE patients is not known in France. Adolescents with chronic health condition seem to be insufficiently vaccinated regarding their vulnerability to infectious diseases. Strategies are required to decrease HPV vaccination barriers.

Borderline ovarian tumors: Guidelines from the French national college of obstetricians and gynecologists (CNGOF).

It is recommended to classify Borderline Ovarian Tumors (BOTs) according to the WHO classification. Transvaginal and suprapubic ultrasonography are recommended for the analysis of an ovarian mass (Grade A). In case of an undetermined ovarian lesion on ultrasonography, it is recommended to perform a pelvic MRI (Grade A) with a score for malignancy (ADNEX MR/O-RADS) (Grade C) included in the report and to formulate a histological hypothesis (Grade C). Pelvic MRI is recommended to characterize a tumor suspected of being BOT (Grade C). It is recommended to evaluate serum levels of HE4 and CA125 and to use the ROMA score for the diagnosis of indeterminate ovarian mass on imaging (grade A). If there is a suspicion of a mucinous BOT on imaging, serum levels of CA 19-9 may be proposed (Grade C). For Early Stages (ES) of BOT, if surgery without risk of tumor rupture is possible, laparoscopy with protected extraction is recommended over laparotomy (Grade C). For treatment of a bilateral serous ES BOT with a strategy to preserve fertility and/or endocrine function, bilateral cystectomy is recommended where possible (Grade B). For mucinous BOTs with a treatment strategy of fertility and/or endocrine function preservation, unilateral salpingo-oophorectomy is recommended (grade C). For mucinous BOTs treated by initial cystectomy, unilateral salpingo-oophorectomy is recommended (grade C). For serous or mucinous ES BOTs, routine hysterectomy is not recommended (Grade C). For ES BOTs, lymphadenectomy is not recommended (Grade C). For ES BOTs, appendectomy is recommended only in case of a macroscopically pathological appendix (Grade C). Restaging surgery is recommended in cases of serous BOTs with micropapillary architecture and an incomplete abdominal cavity inspection during initial surgery (Grade C). Restaging surgery is recommended for mucinous BOTs after initial cystectomy or in cases where the appendix was not examined (Grade C). If restaging surgery is decided for ES BOTs, the following procedures should be performed: peritoneal washing (grade C), omentectomy (grade B), complete exploration of the abdominal cavity with peritoneal biopsies (grade C), visualization of the appendix and appendectomy in case of a pathological macroscopic appearance (grade C) as well as unilateral salpingo-oophorectomy in case of a mucinous BOT initially treated by cystectomy (grade C). In advanced stages (AS) of BOT, it is not recommended to perform a lymphadenectomy as a routine procedure (Grade C). For AS BOT in a patient with a desire to fall pregnant, conservative treatment involving preservation of the uterus and all or part of the ovary may be proposed (Grade C). Restaging surgery aimed at removing all lesions, not performed initially, is recommended for AS BOTs (Grade C). After treatment, follow-up for a duration greater than 5 years is recommended due to the median recurrence time of BOTs (Grade B). It is recommended that a systematic clinical examination be carried out during follow-up of a treated BOT (Grade B). If the determination of tumor markers is normal preoperatively, the routine dosage of tumor markers in BOT follow-up is not recommended (Grade C). In case of an initial elevation in serum CA 125 levels, it is recommended to monitor CA 125 during follow up (Grade B). In case of conservative treatment, it is recommended to use transvaginal and transabdominal ultrasound during follow up of a treated BOT (Grade B). In the event of a BOT recurrence in a woman of childbearing age, a second conservative treatment may be proposed (Grade C). A consultation with a physician specialized in Assisted Reproductive Technique (ART) should be offered in the case of BOTs in women of childbearing age (Grade C). When possible, a conservative surgical strategy is recommended to preserve fertility in women of childbearing age (Grade C). In the case of optimally treated BOT, there is no evidence to contraindicate the use of ART. The use of hormonal contraception after serous or mucinous BOT is not contraindicated (Grade C). After management of mucinous BOT, for women under 45 years, given the benefit of Hormonal Replacement Therapy (HRT) on cardiovascular and bone risks, and the lack of hormone sensitivity of mucinous BOTs, it is recommended to offer HRT (Grade C). Over 45 years of age, HRT can be prescribed in case of a climacteric syndrome after individual benefit to risk assessment (Grade C).

Safety of assisted reproductive techniques in young women harboring germline pathogenic variants in BRCA1/2 with a pregnancy after prior history of breast cancer.

BACKGROUND: Knowledge is growing on the safety of assisted reproductive techniques (ART) in cancer survivors. No data exist, however, for the specific population of breast cancer patients harboring germline BRCA1/2 pathogenic variants. PATIENTS AND METHODS: This is a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤40 years with stage I-III breast cancer, between January 2000 and December 2012, harboring known germline BRCA1/2 pathogenic variants. Patients included in this analysis had a post-treatment pregnancy either achieved through use of ART (ART group) or naturally (non-ART group). ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection, and embryo transfer under hormonal replacement therapy. RESULTS: Among the 1424 patients registered in the study, 168 were eligible for inclusion in the present analysis, of whom 22 were in the ART group and 146 in the non-ART group. Survivors in the ART group conceived at an older age compared with those in the non-ART group (median age: 39.7 versus 35.4 years, respectively). Women in the ART group experienced more delivery complications compared with those in the non-ART group (22.1% versus 4.1%, respectively). No other apparent differences in obstetrical outcomes were observed between cohorts. The median follow-up from pregnancy was 3.4 years (range: 0.8-8.6 years) in the ART group and 5.0 years (range: 0.8-17.6 years) in the non-ART group. Two patients (9.1%) in the ART group experienced a disease-free survival event (specifically, a locoregional recurrence) compared with 40 patients (27.4%) in the non-ART group. In the ART group, no patients deceased compared with 10 patients (6.9%) in the non-ART group. CONCLUSION: This study provides encouraging safety data on the use of ART in breast cancer survivors harboring germline pathogenic variants in BRCA1/2, when natural conception fails or when they opt for ART in order to carry out preimplantation genetic testing.

[Borderline Ovarian Tumours: CNGOFS Guidelines for Clinical Practice - Hormonal Contraception and MHT/HRT after Borderline Ovarian Tumour]. / Tumeurs frontières de l'ovaire. Recommandations pour la pratique clinique du CNGOF ­ Contraception hormonale et THM/THS après tumeur frontière de l'ovaire.

Contraceptive options and menopause management are frequent clinical issues among women previously treated for a borderline ovarian tumour (BOT). OBJECTIVES: To synthesize knowledge on BOT and risk related to hormonal contraception and to menopausal hormone therapy (MHT), and to propose recommendations on contraception and MHT after BOT treatment. METHODS: Systematic review of the literature about hormonal contraception and BOT and on MHT and BOT was conducted on PubMed/Medline and the Cochrane Library. RESULTS: There are no data concerning hormonal contraception after BOT. Current or previous oral contraception is associated with a trend towards decreased risk of serous BOT. Mucinous BOT risk is not or slightly decreased by oral contraception. Hormonal contraception is thus not contraindicated in women previously treated for a BOT (grade C). MHT is associated with a trend towards increased risk of serous BOT. No relation was found between MHT and risk of mucinous BOT. Serous BOTs with high-risk histological criteria (micropapillary pattern, stromal microinvasion or peritoneal implants) are at high-risk of invasive potentially hormone-sensitive recurrence. Hence, caution is needed in the decisions of using MHT after serous BOT with one of these high-risk histological criteria, and MHT should be discussed on a case to case basis. MHT can be prescribed without restriction in women previously treated for mucinous and serous BOT without high-risk histological criteria (grade C). CONCLUSION: Hormonal contraception can be used after BOT. The histological characteristics of the tumour must be taken into account when deciding on the use of HRT/THM.

Improvement in contraceptive coverage and gynecological care of adult women with cystic fibrosis following the implementation of an on-site gynecological consultation.

OBJECTIVE: Our study aimed to evaluate the impact of the introduction of a new gynecologic referral service in our adult Cystic Fibrosis (CF) center on contraceptive coverage, gynecological follow-up regularity, and cervical cancer screening coverage. STUDY DESIGN: We implemented an on-site gynecological consultation in our adult CF center in 2015. We compared the results of two surveys conducted successively in 2014 and in 2017 in a cohort of women with CF attending the Lyon CF center. Women completed the same self-report written questionnaire as in 2014. Main outcome measures were the comparisons of contraceptive coverage, gynecological follow-up regularity, and cervical cancer screening coverage between 2014 and 2017. RESULTS: All the 136 women (100%) who attended the clinic in 2017 participated. Contraceptive prevalence rate increased from 69%(CI95%:60.3-78.1) to 86%(CI95%:79.6-92.9) between 2014 and 2017 (p = 0.005). Among transplanted patients, the contraceptive prevalence rate was 92.3%(CI95%:82.0-100) in 2017. Long acting reversible contraceptive use markedly increased from 10% to 21.6% (p = 0.005). The proportion of women that reported an access to gynecological care increased between 2014 and 2017 (74%(CI95%:66.3-82.0) vs 91%(CI95%:86.9-95.4), p < 0.005) and reached 100% among transplanted patients. Cervical cancer screening improved (55%(CI95%:51.2-68.8) vs 85%(CI95%:78.6-90.6) women ever screened) (p < 0.0005) and reached 100% among transplanted patients. CONCLUSIONS: We observed an improvement in contraceptive coverage and gynecological care of adult women with CF following the implementation of a dedicated gynecological consultation in the CF center. IMPLICATIONS: Service linkages and formal links between CF centers and gynecologists can facilitate access to disease-specific contraceptive counseling, adequate gynecological management and cervical cancer screening.

[Borderline Ovarian Tumours: CNGOF Guidelines for Clinical Practice - Short Text]. / Tumeurs frontières de l'ovaire. Recommandations pour la pratique clinique du CNGOF ­ Texte court.

This work was carried out under the aegis of the CNGOF (Collège national des gynécologues et obstétriciens français) and proposes guidelines based on the evidence available in the literature. The objective was to define the diagnostic and surgical management strategy, the fertility preservation and surveillance strategy in Borderline Ovarian Tumor (BOT). No screening modality can be proposed in the general population. An expert pathological review is recommended in case of doubt concerning the borderline nature, the histological subtype, the invasive nature of the implant, for all micropapillary/cribriform serous BOT or in the presence of peritoneal implants, and for all mucinous or clear cell tumors (grade C). Macroscopic MRI analysis should be performed to differentiate the different subtypes of BOT: serous, seromucinous and mucinous (intestinal type) (grade C). If preoperative biomarkers are normal, follow up of biomarkers is not recommended (grade C). In cases of bilateral early serous BOT with a desire to preserve fertility and/or endocrine function, it is recommended to perform a bilateral cystectomy if possible (grade B). In case of early mucinous BOT, with a desire to preserve fertility and/or endocrine function, it is recommended to perform a unilateral adnexectomy (grade C). Secondary surgical staging is recommended in case of serous BOT with micropapillary appearance and uncomplete inspection of the abdominal cavity during initial surgery (grade C). For early-stage serous or mucinous BOT, it is not recommended to perform a systematic hysterectomy (grade C). Follow up after BOT must be pursued for more than 5 years (grade B). Conservative treatment involving at least the conservation of the uterus and a fragment of the ovary in a patient wishing to conceive may be proposed in advanced stages of BOT (grade C). A new surgical treatment that preserves fertility after a first non-invasive recurrence may be proposed in women of childbearing age (grade C). It is recommended to offer a specialized consultation for Reproductive Medicine when diagnosing BOT in a woman of childbearing age. Hormonal contraceptive use after serous or mucinous BOT is not contraindicated (grade C).

[Follow-up of patients treated for an epithelial ovarian cancer, place of hormone replacement therapy and of contraception: Article drafted from the French Guidelines in oncology entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY under the aegis of CNGOF and endorsed by INCa]. / Surveillance après traitement initial d'une tumeur épithéliale de l'ovaire, place du traitement hormonal de la ménopause et de la contraception. Article rédigé sur la base de la recommandation nationale de bonnes pratiques cliniques en cancérologie intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY sous l'égide du CNGOF et labellisée par l'INCa.

OBJECTIVES: To define follow-up modalities after an epithelial ovarian, tubal or primitive peritoneal cancer. To define possibilities of hormone replacement therapy (HRT) and contraceptive use after treatment. METHODS: Systematic review of the literature in French and English langage conducted on Pubmed/Medline and the Cochrane Library. RESULTS: After the treatment of an epithelial ovarian, tubal or primitive peritoneal cancer, symptoms evaluation for follow-up is recommended at 3 months, 6 months, 12 months, 18 months, 24 months, and then yearly (Grade B). Only patients with an initial complete surgery (CC0, without any macroscopic signs of disease), and with a good general condition (ECOG 0) should be followed with paraclinic tests, with a serum HE4 or CA125 concentration measurement, from 6 months after the end of treatments (GradeC). Systematic follow-up with CT of the chest, abdomen, and pelvis is not recommended (GradeC). Imaging test is recommended in case of an increased serum concentration of HE4 or CA125 (Grade B). An HRT should be proposed to women younger than 45 after a non-conservative treatment for a high grade serous (GradeC) or for a mucinous (GradeC) ovarian, tubal or primitive peritoneal adenocarcinoma. HRT is not contra-indicated in women older than 45 presenting a climacteric syndrome after the treatment of a high grade serous (Grade B) or of a mucinous (GradeC) ovarian, tubal or primitive peritoneal adenocarcinoma.

[Part I drafted from the short text of the French Guidelines entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY and endorsed by INCa. (Diagnosis management, surgery, perioperative care, and pathological analysis)]. / Partie 1 rédigée sur la base de la recommandation nationale de bonnes pratiques cliniques en cancérologie intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY et labélisée par l'INCa. (Explorations diagnostiques et bilan d'extension, chirurgie, soins périopératoires et anatomopathologie).

Faced to an undetermined ovarian mass on ultrasound, an MRI is recommended and the ROMA score (combining CA125 and HE4) can be proposed (grade A). In case of suspected early stage ovarian or fallopian tube cancer, omentectomy (at least infracolonic), appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C) and pelvic and para-aortic lymphadenectomy are recommended (grade B) for all histological types, except for the expansive mucinous subtype where lymphadenectomy may be omitted (grade C). Minimally invasive surgery is recommended for early stage ovarian cancer, if there is no risk of tumor rupture (grade B). Laparoscopic exploration for multiple biopsies (grade A) and to evaluate carcinomatosis score (at least using the Fagotti score) (grade C) are recommended to estimate the possibility of a complete surgery (i.e. no macroscopic residue). Complete medial laparotomy surgery is recommended for advanced cancers (grade B). It is recommended in advanced cancers to perform para-aortic and pelvic lymphadenectomy in case of clinical or radiological suspicion of metastatic lymph node (grade B). In the absence of clinical or radiological lymphadenopathy and in case of complete peritoneal surgery during an initial surgery for advanced cancer, it is possible not to perform a lymphadenectomy because it does not modify the medical treatment and the overall survival (grade B). Primary surgery is recommended when no tumor residue is possible (grade B).

[Part II drafted from the short text of the French guidelines entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY and endorsed by INCa. (Systemic and intraperitoneal treatment, elderly, fertility preservation, follow-up)]. / Partie 2 rédigée à partir de la synthèse de la recommandation nationale de bonnes pratiques cliniques intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY et labélisée par l'INCa. (Traitement systémique et intrapéritonéal, personnes âgées, préservation de la fertilité et suivi).

Adjuvant chemotherapy with carboplatin and paclitaxel is recommended for all high-grade ovarian or Fallopian tube cancers, stage FIGO I-IIA (grade A). After a complete first surgery, it is recommended to deliver 6 cycles of intravenous (grade A) or to propose intraperitoneal (grade B) chemotherapy, to be discussed with patient, according to the benefit/risk ratio. After a complete interval surgery for a FIGO III stage, the hyperthermic intra peritoneal chemotherapy (HIPEC) can be proposed in the same conditions of the OV-HIPEC trial (grade B). In case of tumor residue after surgery or FIGO stage IV, chemotherapy associated with bevacizumab is recommended (grade A). For BRCA mutated patient, Olaparib is recommended (grade B).

Management of epithelial cancer of the ovary, fallopian tube, primary peritoneum. Long text of the joint French clinical practice guidelines issued by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY, endorsed by INCa. (Part 2: systemic, intraperitoneal treatment, elderly patients, fertility preservation, follow-up).

Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).

Management of epithelial cancer of the ovary, fallopian tube, and primary peritoneum. Long text of the Joint French Clinical Practice Guidelines issued by FRANCOGYN, CNGOF, SFOG, and GINECO-ARCAGY, and endorsed by INCa. Part 1: Diagnostic exploration and staging, surgery, perioperative care, and pathology.

An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). For FIGO stages III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancer (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B).