Integrative Expression,Survival Analysis and Cellular miR-2909 Molecular Interplay in MRN Complex Check Point Sensor Genes (MRN-CSG) Involved in Breast Cancer

BackgroundBreast cancer, an emerging global challenge, is evidenced by recent studies of miRNAs involvement in DNA repair gene variants (MRE11, RAD50, and NBN as checkpoint sensor genes (CSG) – MRN-CSG). The identification of various mutations in MRN-CSG and their interactions with miRNAs is still not understood. The emerging studies of miR-2909 involvement in other cancers led us to explore its role as molecular mechanistic marker in breast cancer.Materials and MethodsThe genomic and proteomic data of MRN-CSG of breast cancer patients (8426 samples) was evaluated to identify the mutation types linked with the patient's survival rate. Additionally, molecular, 3D-structural and functional analysis was performed to identify miR-2909 as regulator of MRN-CSG.ResultsThe genomic and proteomic data analysis shows genetic alterations with majority of missense mutations [RAD50 (0.7%), MRE11 (1.5%), and NBN (11%)], though with highest MRE11 mRNA expression in invasive ductal breast carcinoma as compared to other breast cancer types. The Kaplan–Meier survival curves suggest higher survival rate for unaltered groups as compared to the altered group. Network analysis and disease association of miR-2909 and MRN-CSG shows strong interactions with other partners. The molecular hybridization between miR-2909-RAD50 and miR-2909-MRE11 complexes showed thermodynamically stable structures. Further, argonaute protein, involved in RNA silencing, docking studies with miR-MRE11-mRNA and miR-RAD50-mRNA hybridized complexes showed strong binding affinity.ConclusionThe results suggest that miR-2909 forms strong thermodynamically stable molecular hybridized complexes with MRE11 and RAD50 mRNAs which further strongly interacts with argonaute protein to show potential molecular mechanistic role in breast cancer.     

Comparison of retroperitoneal and transperitoneal surgical routes in laparoscopic nodal staging for locally advanced cervical cancers (FIGO IB3-IVA)

BackgroundThis study compares morbidity and mortality associated with retroperitoneal and transperitoneal para-aortic lymphadenectomy (PAAL) for pretherapeutic nodal staging of locally advanced cervical cancers (FIGO IB3–IVA).MethodsPre-, per- and postoperative data of patients treated for locally advanced stage cervical cancer between 1999 and 2018 in 12 French referral centers (FRANCOGYN Study Group) were retrospectively collected.ResultsThe study was conducted using a sample of 448 patients, of whom 223 (49,8%) underwent retroperitoneal (group 1) and 225 (50,2%) had transperitoneal PAAL (group 2). No differences were noted concerning clinical and histological characteristics between the two groups. Among these 448 patients, 23 (5,1%) had an intraoperative complication (9 (2,0%) in group 1 and 14 (3,1%) in group 2, p = 0.28) and 47 (10,5%) had a postoperative complication (22 (4,9%) in group 1 and 25 (5,6%) in group 2, p = 0.44), only one of which required revision surgery but the patient died. The length of hospital stay was significantly shorter in group 1 than in group 2 (3.97 versus 4.88 days, p < 0.001). There was no significant difference in mortality between the two groups; 34 of 223 patients in group 1 (15.3%) and 40 of 225 patients in group 2 (15.6%) died (HR = 0.968, 95% CI [0.591–1.585]). There was no significant difference in recurrence-free or overall survival between the two groups.ConclusionRetroperitoneal PAAL appears as a valuable and safety surgical route for nodal staging in locally advanced cervical cancer compared with standard transperitoneal PAAL.     

Systemic treatment for triple negative breast cancer in older patients: A Young International Society of Geriatric Oncology Review Paper

Breast cancer is the most common type of cancer affecting women worldwide and its risk increases with age. Compared with other breast cancer subtypes, triple negative breast cancer (TNBC) behaves more aggressively, with earlier relapses and poorer survival outcomes. Although the incidence of TNBC decreases with age, it still affects about 10% of older women with breast cancer. The management of TNBC in older patients is particularly challenging as chemotherapy is the main treatment choice in both early and advanced diseases and older patients are often prone to increased treatment-related toxicities. This review highlights the specific considerations in this vulnerable group of patients and summarizes the current evidence for TNBC management in older adults from early to late stage of disease.     

Prepectoral implant-based breast reconstruction with TiLOOP® Bra Pocket – a single-centre retrospective study

BackgroundPrepectoral implant-based reconstruction using synthetic meshes is feasible with good outcomes. We present our data using TiLOOP® Bra Pocket, a novel ready-to-use mesh pocket which acts as an internal bra and prevents the implant from dislocating or twisting.Materials and MethodsA single-centre retrospective cohort study was performed to assess short-term complication rates and cosmetic outcomes in patients with prepectoral implant-based reconstruction using the TiLOOP® Bra Pocket. The primary endpoint was complication rates during the first 6 months. The secondary endpoint was the cosmetic outcome after 6 to 12 months, which was judged by two breast surgeons using the Harvard score.ResultsA total of 63 breasts (43 patients) were reconstructed using the TiLOOP® Bra Pocket between 2018 and 2020, 57 were immediate reconstructions. The overall complication rate was 30,2% (n = 19/63). Major complications occurred in seven breasts (n = 7/63; 11,1%) and minor complications occurred in 12 breasts (12/63; 19,0%). The unplanned revision rate was 12,7%. The cosmetic outcome was good (Harvard score: mean 3, range 1–4; SD 0,75). Seventeen cosmetic complications were observed (17/63; 27,0%) and six cosmetic revision surgeries were performed (6/63; 9,5%).ConclusionThe use of the TiLOOP® Bra Pocket is convenient and standardized because the pocket is preformed and does not require to be sewn first. Cosmetic outcome is good; however, the surgical morbidity needs to be addressed in future reconstructions. Careful patient selection and preparation techniques are vital in order to achieve acceptable complication rates and satisfying cosmetic results.     

Review of Variables Associated With Positive Surgical Margins Using Scout Reflector Localizations for Breast Conservation Therapy

ObjectiveTo evaluate factors contributing to positive surgical margins associated with reflector guidance for patients undergoing breast conserving therapy for malignancy.Materials and MethodsA retrospective IRB-approved review of our institutional database was performed for malignant breast lesions preoperatively localized from January 1, 2018 to December 31, 2020. The following data was recorded using electronic medical records: lesion type and grade, lesion location, reflector and wire placement modality, use of intraoperative ultrasound, margin status, patient age, family history, BMI, and final pathology. Statistical analysis was performed with univariate summary statistics and logistic regression. P < .05 was significant.ResultsA total of 606 image-guided pre-surgical localizations were performed for lumpectomies of breast malignancies. A total of 352 of 606 (58%) wire localizations and 254 of 606 (42%) SCOUT reflector localizations were performed. Sixty out of 352 (17%) of wire-localized patients had positive surgical margins, whereas forty-eight out of 254 (19%) of reflector-localized patients had positive surgical margins. (OR = 1.12, P value: .59). For reflector guided cases, the use of intraoperative ultrasound (IOUS) was associated with decreased positive margin status (OR = 0 .28, 95% CI = [0.14, 0.58]) while in situ disease was associated with increased positive margin status (OR = 1.99, 95% CI = [1.05, 3.75]). No association between modality used for localization (mammography vs. ultrasound) and positive margin status was observed (OR = 0.63, 95% CI = [0.33, 1.19]). No association between positive margins and age, family history, tumor location and BMI was observed.ConclusionFor reflector guided surgeries, the use of IOUS was associated with decreased positive margins, by contrast the presence of ductal carcinoma in situ was associated with increased positive margins. There was no statistically significant difference in surgical outcomes for reflector-guided localization compared to wire localizations of the breast.