Metastatic breast cancer subtypes and central nervous system metastases

e11581 Background: The relapse pattern, survival and response to therapy are known to be different between breast cancer (BC) subtypes defined by combining hormone-receptor (HR) and HER2 status. Our aim was to study incidence and predictors of central nervous system metastases (CNS-M) and the outcome after CNS-M according to tumor subtype. Methods: 488 patients (pts) treated with at least one line of chemotherapy for metastatic BC were retrospectively evaluated. According to the combination of HR and HER2 status, tumors were grouped in: Luminal (Lum): HR+/HER2-, Luminal/HER2+ (Lum/HER2+): HR+/HER2+, pure HER2 positive (pHER2+): HR-/HER2+, and triple negative (TN): HR-/HER2-. All HER2+ patients received treatment with Lapatinib or Trastuzumab in addition to chemotherapy for metastatic disease. Median follow up was 34 months. Results: 133 pts (27%) developed CNS-M, with a median time to CNS progression of 43 months. The rate of CNS-M by subtype was: Lum 18%, Lum/HER2+ 37%, pHER2+ 49%, TN 25% (p <0.001). Multivariate analysis confirmed that, compared with Lum tumors, Lum/HER2+ ( HR 2.556, p<0.001), pHER2+ (HR 4.444, p<0.001) and TN (2.249, p=0.011) subtypes were at higher risk of CNS-M. Median overall survival (OS) CNS-M was 8.8 months in the whole series (IC 95% 6.6-11.0). Median OS in months by subtype was: Lum 9, Lum/HER2+ 18, pHER2+ 7, TN 7 (p<0.001). Multivariate analysis revealed that belonging to the Lum/HER2+ subtype (HR 0.528 compared with the Lum subtype, p<0.001) and having isolated CNS (HR 0.398, compared with CNS-M plus systemic progression, p<0.001) predicted significantly reduced risk of death. Conclusions: Among pts with a known increased risk of brain metastases, the Lum/HER2+ subtype appears associated with the longest OS after CNS-M, probably due to different biology and better extracranial disease control by chemotherapy, hormonal therapy and target agents. These results suggest that these patients may benefit from a more aggressive treatment of CNS-M and, possibly, from the screening for asymptomatic CNS lesions

Underuse of Anthracyclines in Women with HER-2+ Advanced Breast Cancer

This article examines how discouraging the use of anthracyclines in combination with trastuzumab in patients with human epidermal growth factor receptor 2 positive metastatic breast cancer because of fears of cardiotoxicity has influenced the use of these agents in this patient setting

Common and rare variants in TMEM175 gene concur to the pathogenesis of Parkinson’s Disease in Italian patients

Parkinson’s disease (PD) represents the most common neurodegenerative movement disorder. We recently identified 16 novel genes associated with PD. In this study, we focused the attention on the common and rare variants identified in the lysosomal K+ channel TMEM175. The study includes a detailed clinical and genetic analysis of 400 cases and 300 controls. Molecular studies were performed on patient-derived fibroblasts. The functional properties of the mutant channels were assessed by patch-clamp technique and co-immunoprecipitation. We have found that TMEM175 was highly expressed in dopaminergic neurons of the substantia nigra pars compacta and in microglia of the cerebral cortex of the human brain. Four common variants were associated with PD, including two novel variants rs2290402 (c.-10C > T) and rs80114247 (c.T1022C, p.M341T), located in the Kozak consensus sequence and TM3II domain, respectively. We also disclosed 13 novel highly penetrant detrimental mutations in the TMEM175 gene associated with PD. At least nine of these mutations (p.R35C, p. R183X, p.A270T, p.P308L, p.S348L, p. L405V, p.R414W, p.P427fs, p.R481W) may be sufficient to cause the disease, and the presence of mutations of other genes correlated with an earlier disease onset. In vitro functional analysis of the ion channel encoded by the mutated TMEM175 gene revealed a loss of the K+ conductance and a reduced channel affinity for Akt. Moreover, we observed an impaired autophagic/lysosomal proteolytic flux and an increase expression of unfolded protein response markers in patient-derived fibroblasts. These data suggest that mutations in TMEM175 gene may contribute to the pathophysiology of PD

Characteristics and patterns of care of endometrial cancer before and during COVID-19 pandemic

Objective: Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. Methods: This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. Results: Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p&lt;0.001). While, the prevalence of patients undergoing sentinel node mapping (with or without backup lymphadenectomy) has increased during the COVID-19 pandemic (46.7% in period 1 vs. 52.8% in period 2; p&lt;0.001). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p&lt;0.001). Adjuvant therapy use has increased during COVID-19 pandemic (p&lt;0.001). Conclusion: Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic

Prolasso degli organi pelvici e sessualità: studio sulla qualità della vita dopo intervento chirurgico di correzione del prolasso

: Introduzione La sfera della sessualità è spesso gravemente inficiata nelle pazienti portatrici di prolasso degli organi pelvici. Scopo dell’articolo è indagare la qualità della vita sessuale delle pazienti prima e dopo l’intervento chirurgico. Materiali e metodi È stato condotto uno studio osservazionale di coorte su pazienti sottoposte a intervento chirurgico di sospensione laterale laparoscopica (LLS) e isterectomia per via vaginale con colpopessi uterosacrale (USLs). È stata indagata l’attività sessuale, la comparsa di dispareunia e il grado di soddisfazione nel rapporto col partner al tempo 0 e a 6-12-24 mesi postoperatori nei 2 gruppi. Risultati Sono state sottoposte a intervento chirurgico 195 pazienti portatrici di prolasso: 145 nel gruppo USLs e 41 nel gruppo LLS. Al tempo 0 erano sessualmente attive il 59% del gruppo LLS e il 32,5% del gruppo USLs. La dispareunia era sperimentata dal 60,9% delle pazienti LLS (I grado: 30,4%, II grado: 21,7%, III grado: 8,7%) e dall’80% delle pazienti USLs (I grado: 44%, II grado: 20%, III grado: 16%). 6 mesi dopo l’intervento chirurgico tra le pazienti sessualmente attive, nel gruppo LLS il 15,8% sperimentava dispareunia (tutte di I grado), che nel 10,5% era persistente mentre nel 5,3% de novo; nel gruppo USLs il 37,5% presentava dispareunia, nel 29% dei casi di I grado, nel l’8,3% dei casi di II grado; la dispareunia era persistente nel 16,7%, de novo nel 20,8%. 12 mesi post-intervento nel gruppo LLS la dispareunia era riscontrata nell’ 11% delle pazienti attive (tutte di I grado e di tipo persistente); nel gruppo USLs la prevalenza di dispareunia era del 18,2% (I grado: 9,1%, II grado: 9,1%), di tipo persistente. Infine a 24 mesi post intervento, nel gruppo LLS nessuna lamentava dispareunia; nel gruppo USLs andate a controllo, 2 ( il 40%) presentavano dispareunia (I grado: 20%, II grado: 20%), in 1 paziente de novo, nell’altra di tipo persistente. In risposta al questionario pre operatorio per l’item Relazione col partner, la mediana dei punteggi era di 25 nel gruppo LLS (35 pazienti) e di 33 nel gruppo USLs (70 pazienti). Ai successivi controlli a 6, 12 e 24 mesi la mediana dei punteggi è stata di 0 in entrambi i gruppi in tutti e tre i controlli temporali. Conclusioni Gli interventi chirurgici di sospensione laterale uterina per via laparoscopica e di isterectomia per via vaginale con colpopessi uterosacrale si sono dimostrati efficaci nel migliorare la sessualità riducendo la dispareunia e aumentando il grado di soddisfazione soggettivo della paziente nel rapporto col partner