Emile Daraï

Background: Despite early diagnosis, approximately 20% of patients with ER-positive and HER2-negative breast cancer (BC) will experience disease recurrence. Improved survival has been reported with adjuvant treatment combining cyclin-dependent kinase 4/6 inhibitors with endocrine therapy, in high-risk patients with ER-positive and HER2-negative BC, regardless of age. Older patients have higher rates of ER-positive/HER2-negative BC than younger patients. Methods: In this real-world data analysis, MonarchE and NataLEE high-risk patients accounted for 9.5% and 33% of patients undergoing upfront surgery, respectively. Significantly higher eligibility rates were observed in patients who underwent a mastectomy, >70 years and ≤40 years for adjuvant abemaciclib and ribociclib, and in patients >80 years for ribociclib. Results: Eligibility rates in patients ≤40 years and >80 years who underwent mastectomy were 27.8% and 24.7% for abemaciclib, respectively, and 56.6% and 65.2% for ribociclib, respectively. A higher discontinuation rate for abemaciclib was reported in patients aged ≥65 years and it can be assumed that discontinuation rates may increase in even older patients. Conclusions: If the results of the NataLEE trial translate into clinical practice, the number of patients potentially eligible for adjuvant CDK4/6 inhibitors may increase, especially in the elderly population.

The mainstay of treatment of advanced ovarian cancer (AOC) involves chemotherapy, and debulking surgery. However, despite optimal surgical procedure and adjuvant chemotherapy, 60% of patients with AOC will relapse within 5 years. Most recurrences occur in the peritoneal cavity, suggesting the existence of occult sanctuaries where ovarian cancer cells (OCC) are protected. In murine models, surgical stress favors tumor growth; however, it has never been established that surgery may affect OCC sensitivity to subsequent chemotherapy. In this study, we investigated how the surgical stress could affect the chemosensitivity of OCC. To avoid bias due to tumor burden in peritoneal cavity and duration of surgery, we used peritoneal biopsies from patients without a malignancy at precise time points. During laparotomies, peritoneal biopsies at the incision site were performed at the time of incision (H0 sample) and 1 h after initiation of surgery (H1 sample). We evaluated the chemoresistance to Taxol (0–20 µM) induced by H0 or H1 incubation (24 h) in two ovarian cancer cell lines OVCAR3 and SKOV3 and a primary cancer cell lines derived in our laboratory. Our results indicate that stressed peritoneum overexpressed cytokines, resulting in OCC increased resistance to therapy. Among these cytokines, IL8 was responsible for the resistance to apoptosis through the AKT pathway activation. Chemoresistance in OCC persists through the establishment of an autocrine IL8 loop. Finally, in a cohort of 32 patients, we showed an impact of IL8 tumoral overexpression on chemosensitivity and survival outcomes with a significant association to earlier recurrence. Our study demonstrated that precision surgery where targeted treatment would be used in combination with surgery is essential to obtain better tumor control.

Tumour features associated with isolated invasive breast cancer (BC) ipsilateral local recurrence (ILR) after breast conservative treatment (BCT) and consequences on overall survival (OS) are still debated. Our objective was to investigate these points.

Sentinel lymph node biopsy (SLNB) remains under discussion for large size tumors. The aim of this work has been to study the false negative rate (FNR) of SLNB for large tumors and predictive factors of false negative (FN).A study of a multicentric cohort, involved patients presenting N0 breast cancer with a SLNB eventually completed by complementary axillary lymph node dissection (cALND). The main criteria were the FNR and the predictive factors of FN.12.415 patients were included: 748 with tumors ≥30 mm, 1101 with tumors >20 and < 30 mm and 10.566 with tumors ≤20 mm, with a cALND respectively for 501 patients (67%), 523 (62.1%) and 2775 (26.3%). The FNR were respectively: 3.05% (IC95%: 1.3-4.8) for tumors ≥30 mm*, 3.5% (1.8-5.2) for tumors >20 and < 30 mm*, 1.8% (1-2.4) for tumors ≤20 mm (p < 0.05) (*Not significant). At multivariate analysis, SN number harvested ≤2 (OR:2.0, p = 0.023) and tumor size >20 and < 30 mm (OR:2.07, p = 0.017) were significant predictive factors of FN, without significant value for tumor size ≥30 mm (OR:1.83, p = 0.073).The FNR of SLNB was not higher amongst large size tumors compared to tumors of a smaller size. These results support the validation of SNLB for tumors up to 50 mm.

This was the first study to investigate the relative expression of microRNA in type 1 EC according to LVSI status. This microRNA expression profile may provide a basis for further study of the microRNA function in EC, and be used as a diagnostic tool for LVSI status.

Objective: To evaluate delivery and neonatal outcomes in women with resected or in situ bowel endometriosis.Design: Retrospective cohort study.Setting: France.Population and sample: Analysis of 72 pregnancies from 67 women followed for colorectal endometriosis from 2001 to 2014 in six centres including two university expert centres for endometriosis.Methods: Univariate analysis of maternal and neonatal outcomes.Main outcome measures: Routes for delivery and rate of complications.Results: The colorectal surgery group comprised 41 women and the in situ colorectal group, 26 women. Overall, half of the women underwent caesarean section. A high incidence of postoperative complications (39%) was observed after caesarean section with no difference between the groups. Surgical difficulties at newborn extraction (22%) and postoperative complications (39%) occurred more often in women with anterior deep infiltrating endometriosis (respectively 63 versus 11%, P = 0.007 and 67% versus 26%, P = 0.046) independently of prior surgery for endometriosis. In the remaining half, vaginal delivery required an operative procedure in 28% of the women with a significant increase in postpartum complications compared with those who did not require a procedure (P = 0.001). Overall, the incidence of postpartum complications was lower after vaginal delivery (14%) than after caesarean section (39%) (P = 0.03).Conclusion: Pregnant women with colorectal endometriosis, irrespective of prior surgery, should be informed of the high risk of delivery by caesarean section. Vaginal delivery is preferrable in this setting because of the lower incidence of postpartum complications.Tweetable Due to the incidence of postpartum complications whatever the route of delivery, women should receive level III maternal care.

Deep infiltrating endometriosis (DIE) affects several anatomical locations including the bladder, torus uterinum, uterosacral ligament, rectovaginal septum and bowel. It is the most debilitating form of endometriosis and causes severe pain, digestive and urinary symptoms as well as infertility. Faced with an infertile woman suffering from DIE, the dilemma is whether to opt for first-line IVF treatment or for surgery. In the absence of high-level of evidence from randomized studies, several factors should be taken into account in the decision-making process. The main criterion is whether the patient wants in-vitro fertilization (IVF) treatment or not. Secondly, while previous reports have demonstrated the positive impact of surgery on pregnancy, they also underline the risk of severe complications requiring management in expert centers. Despite the availability of predictive models or scoring systems, the decision mainly boils down to the couple's characteristics. It seems logical to propose first-line IVF when spontaneous fertility is not possible due to associated male infertility or tubal obstruction; for women aged ≥35 years; or in women with diminished ovarian reserve. Conversely, first-line surgery could be the best option for women without these characteristics. However, this strategy is mainly based on low-level of evidence underlining the requiring of randomized trials.