Patterns of care and the survival of elderly patients with high-risk endometrial cancer: A case-control study from the FRANCOGYN group.

BACKGROUND: The standard of care of endometrial cancer involves complex procedures such as pelvic and para-aortic lymphadenectomy and omentectomy, particularly for high-risk endometrial cancer. Few data are available about these complex surgical procedures and adjuvant therapy in elderly women. We aim to examine treatment and survival of elderly women diagnosed with high-risk endometrial cancer. STUDY DESIGN: We performed a case-control study of women diagnosed between 2001 and 2013 with high-risk endometrial cancers. Women older than 70 years (n = 198) were compared with patients <70 years (n = 198) after matching on high-risk for recurrence and LVSI status. RESULTS: Elderly patients had lymphadenectomies less frequently compared with younger patients (76% vs 96%, p < 0.001) and no adjuvant treatment more frequently (17% vs 8%, p = 0.005) due to less chemotherapy being administered (23% vs 46%, p < 0.001). The 3-year DFS, CSS and OS of patients ≥70 years was 52% (43-61), 81% (74-88) and 61% (53-70), respectively. These were significantly lower than the 3-year DFS, CSS, and OS of younger patients, which was 75% (68-82) (p < 0.001), 92% (87-96) (p < 0.008) and 75% (69-82) (p = 0.018), respectively. Cox proportional hazard models found that elderly women had 57% increased risk of recurrence (hazard ratio 1.57, 95% CI 1.04-2.39) compared with younger patients. CONCLUSION: Although we found an independently significant lower DFS in elderly patients with high-risk endometrial cancer when compared with young patients, elderly women are less likely to be treated with lymphadenectomy and chemotherapy. Specific guidelines for management of elderly patients with high-risk endometrial cancer are required to improve their prognosis.

[Pap smear before 25 years old]. / La pratique du frottis cervico-vaginal avant 25 ans.

OBJECTIVES: Current French recommendations advocate cervical-vaginal screening for cervical cancer from age 25 whereas earlier screening is mostly found in current clinical practice although its consequences are not well understood. METHODS: A literature review using the MedLine database on the natural history of HPV infections, cytological screening, management of cytological and histological anomalies in adolescents and young women. RESULTS: The adolescent and young woman have some characteristics that distinguish them from adult women: a high prevalence of HPV infections (making the use of the HPV test unprofitable), accompanied by a higher clearance; frequency of minor cytological abnormalities (for which a cytological surveillance without colposcopy is sufficient) and low-grade histological lesions of low grade the usual prognosis of which is complete recovery; and rarity of CIN3 lesions and absence of invasive lesions, allowing no treatment in patients with CIN2 lesions and compliant to cytological and colposcopic surveillance. CONCLUSION: Cervical screening in the adolescent and young woman is not a logical attitude and the discovery of cytological or histological lesions requires specific behavior in this particular population.

[Can new molecular profiles in epithelial ovarian cancer modify therapeutics?] / Les nouveaux profils moléculaires dans le cancer de l'ovaire peuvent-ils modifier les stratégies thérapeutiques ?

Epithelial ovarian cancer (EOC) affects 4500 women a year in France, with a survival of 30% at 5 years. Treatment is based on extensive surgery and chemotherapy. Around 15% of EOCs are due to genetic mutation predisposition essentially with mutated BRCA1 and BRCA2 genes. Four histological subtypes are described (serous, endometrioid, and mucinous cells to clear), corresponding to different carcinogenesis and distinct molecular mutations. High-grade serous EOCs have a mutation of the BRCA genes in 20-30% of cases. This mutation causes a deficit of repair by homologous recombination of DNA in case of double strand break, allowing greater sensitivity to platinum salts and the use of PARP inhibitors, a protein involved in the repair of single-strand breaks of DNA. PARP inhibitors have shown efficacy in patients mutated BRCA but this effectiveness remains to be demonstrated in patients without congenital mutation, but with acquired BRCAness profile EOC. The BRCAness profile is defined by a tumor having a defect in DNA repair counterpart (not limited to BRCA mutation). Molecular definition of BRCAness is still not consensual but is necessary for the use of PARP inhibitors. Gene expression analyses have identified four subgroups of high-grade serous CEO: mesenchymal, proliferative, differentiated and immunoreactive. These four subtypes, not mutually exclusive, although correlated with prognosis, are not yet used in clinical routine.

Screening BRCA1 and BRCA2 unclassified variants for splicing mutations using reverse transcription PCR on patient RNA and an ex vivo assay based on a splicing reporter minigene.

BACKGROUND: Many unclassified variants (UV) of BRCA1 or BRCA2 may have an effect on pre-mRNA splicing. Patient blood samples suitable for RNA extraction are not always available for testing UVs at the RNA level. METHODS: Analyses of RNA from patient peripheral blood were performed, using a one-step reverse transcriptase-PCR (RT-PCR) protocol, and were compared with an ex vivo splicing assay based on PCR-amplified patient DNA inserted into a splicing reporter minigene. Using both methods 20 variants found in 17 patients were examined. RESULTS: Data from patient RNA and from the minigene assay were fully concordant, but the ex vivo splicing assay, which is monoallelic, clarified several ambiguities in the patient RNA data. Two intronic variants induced strong splicing defects: BRCA1 c.4987-5T-->A (IVS16-5T-->A) induced exon 17 skipping and BRCA2 c.316+5G-->C (IVS3+5G-->C) induced complete skipping of exon 3. Of the exonic variants, BRCA2 c.7805G-->C (p.Arg2602Thr), at the last base of exon 16, induced both exon skipping and activation of a cryptic exonic donor site, and BRCA2 c.8023A-->G (p.Ile2675Val) generated a strong donor site within exon 18. These four variants were thus classified as pathogenic, because of the total absence of a normal transcript from the corresponding allele. Variant BRCA2 c.9501+3A-->T (IVS25+3A-->T) induced incomplete skipping of exon 25, suggesting a mutation with incomplete penetrance, and BRCA2 c.8257_8259del (p.Leu2753del) modified the alternative splicing of exons 17 and 18. CONCLUSIONS: We show that functional analysis using a splicing reporter minigene is sensitive and specific, and should be used for initial screening of potential splicing defects, especially when patient RNA is not readily available.