Pomen PIK3CA in AKT1 aktivirajočih mutacij za izhod bolezni in sistemsko zdravljenje operabilnega invazivnega lobularnega karcinoma dojke

Ribnikar, Domen (author), Šeruga, Boštjan (mentor), Eitan, Amir (comentor)

Uvod in namen: Vpliv PIK3CA aktivirajočih mutacij na prognozo in učinkovitost dopolnilne endokrine terapije (ET) pri bolnicah z zgodnjim invazivnim lobularnim karcinomom (ILC) dojke ni jasen. Metode: V našo raziskavo smo vključili bolnice z zgodnjim invazivnim lobularnim karcinomom dojke, ki so bile na Onkološkem inštitutu Ljubljana zdravljene med leti 2003 in 2008. S pomočjo metode Kaplan-Meier smo izračunali čas do prvega oddaljenega razsoja bolezni in celokupno preživetje v celotni skupini bolnic z ozirom na PIK3CA mutacijski status v primarnem tumorju dojke. Povezanost med PIK3CA aktivirajočo mutacijo in učinkovitostjo dopolnilne ET pa smo analizirali s pomočjo Coxovih modelov v skupini bolnic z ER+ in/ali PR+ tumorji. Rezultati: Mediana starost vseh bolnic ob diagnozi je bila 62.8 let in mediani čas opazovanja je bil 10.8 let. Med 365 bolnicami, ki so bile vključene v raziskavo, smo identificirali PIK3CA aktivirajočo mutacijo pri 45%. Ugotovili smo, da prisotnost PIK3CA mutacije v primarnem ILC dojke ne vpliva na čas do prvega oddaljenega razsoja bolezni (p=0.36) in ne na celokupno preživetje (p=0.42). Pri bolnicah s prisotno aktivirajočo PIK3CA mutacijo je vsako leto zdravljenja s tamoksifenom zmanjšalo tveganje za smrt za 27%, pri bolnicah zdravljenih z zaviralci aromataze pa za 21% v primerjavi z bolnicami, ki niso prejele HT. Vrsta in trajanje ET nista imela vpliva na čas do prvega oddaljenega razsoja bolezni, je pa podaljšana ET imela ugoden vpliv na celokupno preživetje. Zaključki: Prisotnost aktivirajoče mutacije PIK3CA v primarnem operabilnem ILC dojke ne vpliva na čas do prvega oddaljenega razsoja bolezni in tudi ne na celokupno preživetje. Bolnice s prisotno PIK3CA aktivirajočo mutacijo so imele statistično pomembno zmanjšanje tveganja smrti ne glede na to, ali so v dopolnilnem hormonskem zdravljenju prejele tamoksifen ali zaviralce aromataze.

• Language: Slovenian
• Keywords: invazivni lobularni karcinom, PIK3CA aktivirajoča mutacija, endokrina terapija, genomika invazivnega lobularnega karcinoma dojke
• Work type: Doctoral dissertation
• Organization: MF - Faculty of Medicine
• Year: 2023
• PID: 20.500.12556/RUL-145713
• Publication date in RUL: 11.05.2023

Secondary language

• Language: English
• Title: The role of PIK3CA and AKT1 activating mutations for the disease outcome and systemic therapy of operable invasive lobular breast carcinoma

Abstract

Background and purpose: The role of PIK3CA activating mutations on outcomes and efficacy of adjuvant endocrine therapy (ET) in patients with early-stage invasive lobular carcinoma (ILC) is unclear. Methods: A single institution study of patients with early-stage ILC treated between 2003 and 2008 was performed. Distant metastasis-free survival (DMFS) and overall survival (OS) were collected based on PIK3CA activating mutation status in the primary tumor. An association between PIK3CA mutation status and prognosis in all patient cohort was analyzed by Kaplan-Meier survival curve, whereas an association between PIK3CA mutation and ET was analyzed in ER and/or PR- positive group of our patients by the Cox proportional hazards model. Results: Median age at diagnosis of all patients was 62.8 years and median follow-up time was 10.8 years. Among 365 patients, PIK3CA activating mutations were identified in 45%. PIK3CA activating mutations were not associated with differential DMFS and OS (p=0.36 and p=0.42, respectively). In patients with PIK3CA mutation, each year of tamoxifen or AI decreased the risk of death by 27% and 21% compared to no ET. The type and duration of ET did not have significant impact on DMFS, however longer duration of ET had a favourable impact on OS. Conclusions: PIK3CA activating mutations are not associated with an impact on DMFS and OS in early-stage ILC. Patients with PIK3CA mutation had a statistically significantly decreased risk of death irrespective of whether they received TAM or an AI.

• Keywords: Invasive lobular carcinoma, PIK3CA mutation, endocrine therapy, genomics of invasive lobular carcinoma