Pregnancy in a Young Patient with Metastatic HER2-Positive Breast Cancer-Between Fear of Recurrence and Desire to Procreate.

Breast cancer is the most frequent neoplasm among women and the second leading cause of death by cancer. It is the most frequent cancer diagnosed during pregnancy. Pregnancy-associated breast cancer is defined as breast cancer that is diagnosed during pregnancy and/or in the postpartum period. Data about young women with metastatic HER2-positive cancer who desire a pregnancy are scarce. The medical attitude in these clinical situations is difficult and nonstandardized. We present the case of a 31-year-old premenopausal woman diagnosed in December 2016 with a stage IV Luminal HER2-positive metastatic breast cancer (pT2 N0 M1 hep). The patient was initially treated by surgery in a conservative manner. Postoperatively, the presence of liver metastases was found by CT investigation. Consequently, line I treatment (docetaxel l75 mg/m² iv; trastuzumab 600 mg/5 mL sq) and ovarian drug suppression (Goserelin 3.6 mg sq at 28 days) was administered. After nine cycles of treatment, the patient's liver metastases had a partial response to the therapy. Despite having a favorable disease evolution and a strong desire to procreate, the patient vehemently refused to continue any oncological treatment. The psychiatric consult highlighted an anxious and depressive reaction for which individual and couple psychotherapy sessions were recommended. After 10 months from the interruption of the oncological treatment, the patient appeared with an evolving pregnancy of 15 weeks. An abdominal ultrasound revealed the presence of multiple liver metastases. Knowing all the possible effects, the patient consciously decided to postpone the proposed second-line treatment. In August 2018, the patient was admitted in the emergency department with malaise, diffuse abdominal pain and hepatic failure. Abdominal ultrasound found a 21-week-old pregnancy which had stopped in evolution, multiple liver metastases and ascites in large quantity. She was transferred to the ICU department where she perished just a few hours later. Conclusions/Discussion: From a psychological standpoint, the patient had an emotional hardship to make the transition from the status of a healthy person to the status of a sick person. Consequently, she entered a process of emotional protection of the positive cognitive distortion type, which favored the decision to abandon treatment and try to complete the pregnancy to the detriment of her own survival. The patient delayed the initiation of oncological treatment in pregnancy until it was too late. The consequence of this delay in treatment led to the death of the mother and fetus. A multidisciplinary team worked to provide this patient with the best medical care and psychological assistance throughout the course of the disease.

Fully Automated Generation of Prebiotically Relevant Reaction Networks from Optimized Nanoreactor Simulations.

The nanoreactor approach first introduced by the group of Martínez [Wang et al. Nat. Chem. 2014, 6, 1044-1048] has recently attracted much attention because of its ability to accelerate the discovery of reaction pathways. Here, we provide a comprehensive study of various simulation parameters and present an alternative implementation for the reactivity-enhancing spherical constraint function, as well as for the detection of reaction events. In this context, a fully automated postsimulation evaluation procedure based on RDKit and NetworkX analysis is introduced. The chemical and physical robustness of the procedure is examined by investigating the reactivity of selected homogeneous systems. The optimized procedure is applied at the GFN2-xTB level of theory to a system composed of HCN molecules and argon atoms, acting as a buffer, yielding prebiotically plausible primary and secondary precursors for the synthesis of RNA. Furthermore, the formose reaction network is explored leading to numerous sugar precursors. The discovered compounds reflect experimental findings; however, new synthetic routes and a large collection of exotic, highly reactive molecules are observed, highlighting the predictive power of the nanoreactor approach for unraveling the reactive manifold.

Inherent Reactivity of Spiro-Activated Electrophilic Cyclopropanes.

The kinetics of the ring-opening reactions of thiophenolates with geminal bis(acceptor)-substituted cyclopropanes in DMSO at 20 °C was monitored by photometric methods. The determined second-order rate constants of the SN 2 reactions followed linear relationships with Mayr nucleophilicity parameters (N/sN ) and Brønsted basicities (pKaH ) of the thiophenolates as well as with Hammett substituent parameters (σ) for groups attached to the thiophenolates. Phenyl-substituted cyclopropanes reacted by up to a factor of 15 faster than their unsubstituted analogues, in accord with the known activating effect of adjacent π-systems in SN 2 reactions. Variation of the electronic properties of substituents at the phenyl groups of the cyclopropanes gave rise to parabolic Hammett relationships. Thus, the inherent SN 2 reactivity of electrophilic cyclopropanes is activated by electron-rich π-systems because of the more advanced C1-C2 bond polarization in the transition state. On the other hand, electron-poor π-systems also lower the energetic barriers for the attack of anionic nucleophiles owing to attractive electrostatic interactions.

Carcinomatous-like mastitis due to axillary lymphadenopathy in a case of nasopharyngeal carcinoma: A case report.

Nasopharyngeal carcinoma (NPC) is a rare form of malignancy, accounting for 2% of all cancers of the head and neck in Europe. Axillary lymph node metastases are very rare in these cases. This is a case report of a 40-year-old premenopausal woman diagnosed in May 2015 with T1N2M0 stage III NPC, treated with induction chemotherapy, followed by chemo-radiotherapy. Post-therapeutic computed tomography (CT) scan showed partial response (PR) on the primary tumor and complete response (CR) on the latero-cervical lymph nodes. In 2017, our patient developed left carcinomatous-like mastitis with axillary lymphadenopathy. This raised suspicions of a carcinomatous mastitis. The pathology report with immunohistochemistry (IHC) of the third biopsy highlighted axillary metastasis of a non-keratinizing squamous cell carcinoma (NSCC). There are very few references in the literature regarding axillary metastases from squamous cell carcinoma of the head and neck (HNSCC). As far as we know, this is the first case report of mastitis due to NPC. To conclude, treatment consisted of two surgical excisions of axillary lymphadenopathy associated with local radiotherapy and chemotherapy (neo-adjuvant, adjuvant). The second surgery, performed after radiotherapy, required plastic surgery. A psychiatric evaluation was necessary, revealing a reactive anxiety disorder. This case required multidisciplinary management, where oncology, plastic surgery, pathology and psychiatric specialists collaborated in deciding the therapeutic approach.