Management of BRCA mutation carriers

Pathogenic mutations in two autosomal dominant genes, BRCA1 and BRCA2 , with high penetrance are supposed to be the cause for an approximated 5–7% risk of all breast cancer (BC) and ovarian cancer (OC). Compared to sporadic BC, BRCA mutated ( BRCAmut ) BC differs for lifetime risk of onset and sensitivity to systemic therapies. A hereditary BC syndrome should be taken into account when there are numerous relatives with BC early-onset (typically before menopause). Moreover, BRCAmut carriers showed a lifetime possibility of manifesting OC. When a BC diagnosis is made in young patients or in suspicious personal relatives' anamnesis, be aware of being carriers of a BRCA mutation may influence the decision making-process about surgical procedure and prevention strategies. In this review, we examined surgical treatment choice for BRCAmut BC, risk of ipsilateral breast recurrence (IBR) and contralateral breast cancer (CBC). We examined the role of breast-conserving therapy (BCT), risk-reducing mastectomy (RRM) and preventive risk-reducing salpingo-oophorectomy (RRSO) with a special consideration about advantage in terms of mortality reduction for both conservative and prophylactic measures. We also reviewed the sensitivity of mutated BC to platinum-based antineoplastic drugs and poly (ADP-ribose) polymerase inhibitors (PARPi) by emphasizing the results of clinical trials recently published

Level II Oncoplastic Surgery as an Alternative Option to Mastectomy with Immediate Breast Reconstruction in the Neoadjuvant Setting: A Multidisciplinary Single Center Experience

: Oncoplastic surgery level II techniques (OPSII) are used in patients with operable breast cancer. There is no evidence regarding their safety and efficacy after neoadjuvant chemotherapy (NAC). The aim of this study was to compare the oncological and aesthetic outcomes of this technique compared with those observed in mastectomy with immediate breast reconstruction (MIBR), in post-NAC patients undergoing surgery between January 2016 and March 2021. Local disease-free survival (L-DFS), regional disease-free survival (R-DFS), distant disease-free survival (D-DFS), and overall survival (OS) were compared; the aesthetic results and quality of life (QoL) were evaluated using BREAST-Q. A total of 297 patients were included, 87 of whom underwent OPSII and 210 of whom underwent MIBR. After a median follow-up of 39.5 months, local recurrence had occurred in 3 patients in the OPSII group (3.4%), and in 13 patients in the MIBR group (6.1%) (p = 0.408). The three-year L-DFS rates were 95.1% for OPSII and 96.2% for MIBR (p = 0.286). The three-year R-DFS rates were 100% and 96.4%, respectively (p = 0.559). The three-year D-DFS rate were 90.7% and 89.7% (p = 0.849). The three-year OS rates were 95.7% and 95% (p = 0.394). BREAST-Q highlighted significant advantages in physical well-being for OPSII. No difference was shown for satisfaction with breasts (p = 0.656) or psychosocial well-being (p = 0.444). OPSII is safe and effective after NAC. It allows oncological and aesthetic outcomes with a high QoL, and is a safe alternative for locally advanced tumors which are partial responders to NAC

Post-Operative Functional Outcomes in Early Age Onset Rectal Cancer

Background: Impairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (<50 years) is rising, there is little data on functional outcomes in this group. Methods: The REACCT international collaborative database was reviewed and data on eligible patients analysed. Inclusion criteria comprised patients with a histologically confirmed rectal cancer, <50 years of age at time of diagnosis and with documented follow-up including functional outcomes. Results: A total of 1428 (n=1428) patients met the eligibility criteria and were included in the final analysis. Metastatic disease was present at diagnosis in 13%. Of these, 40% received neoadjuvant therapy and 50% adjuvant chemotherapy. The incidence of post-operative major morbidity was 10%. A defunctioning stoma was placed for 621 patients (43%); 534 of these proceeded to elective restoration of bowel continuity. The median follow-up time was 42 months. Of this cohort, a total of 415 (29%) reported persistent impairment of functional outcomes, the most frequent of which was bowel dysfunction (16%), followed by bladder dysfunction (7%), sexual dysfunction (4.5%) and infertility (1%). Conclusion: A substantial proportion of patients with early-onset rectal cancer who undergo surgery report persistent impairment of functional status. Patients should be involved in the discussion regarding their treatment options and potential impact on quality of life. Functional outcomes should be routinely recorded as part of follow up alongside oncological parameters

Multidisciplinary approach to fetal adenocarcinoma of the lung: A case report

This paper reports a case of high-grade fetal lung adenocarcinoma with particularly aggressive clinical and biological features in a 57-year-old man. Our patient first underwent neoadjuvant chemotherapy followed by surgery, and was then treated with adjuvant chemotherapy. Next, he had radiotherapy on the mediastinal region and prophylactic whole brain radiation therapy (WBRT). Following radiotherapy treatment, the patient started maintenance therapy with a somatostatin analogue. After 58 months of follow-up he is asymptomatic and disease free

The effect of Mg concentration in silicate glasses on CO 2 solubility and solution mechanism: Implication for natural magmatic systems

International audienceFollowing an experimental approach conducted between 0.5 and 1.5 GPa, we investigated the change in CO2 solubility as a function of the XMg (MgO/(MgO+CaO)) for a range of silicate glasses. The synthesised CO2-bearing glasses have XMg up to 0.72, stoichiometric NBO/T (degree of polymerization) up to 2.6 corresponding to highly depolymerized compositions analogues to kimberlites. Several samples were synthesised with 17O enrichment to investigate the CO2 dissolution mechanism via the change in O species environments by NMR spectroscopy.The experimental results show that CO2 solubility increases with NBO/T in agreement with previous works. In addition, increasing XMg strongly decreases CO2 solubility: from 18 to 7 wt.% CO2 as XMg ranges from 0 to 0.6 (1.5 GPa and NBO/T ~ 2).17O NMR results demonstrate that CO2 molecules dissolve as CO3^2- groups showing a signal at +146 ppm for which the intensity is linearly correlated to the wt.% CO2 determined by Raman. The analysis of the oxygen environments as a function of CO2 content for MgO^NBO (+62 ppm) and CaO^NBO (+103 ppm) show that CO2 dissolves preferentially in the vicinity of Ca2+ atoms. The difference in CO2 solubility is explained by the ability for Mg2+ cations to act as a weak network former and to be present in four-fold coordination or by the stronger affinity of CO2 molecules for Ca2+ rather than for Mg2+. We show that the CO2 solubility is negatively correlated to the melt ionic field strength which reflects the variation in the affinity of CO2 molecules for one cation or another.Strongly depolymerized mantle melts, such as kimberlites, melilitites, nephelinites and basanites will exhibit lower CO2 solubility than currently assumed due to their high MgO content which must imply degassing at greater depth, potentially in the sub-lithospheric mantle