Steroidhormon som prediktor

Søknadssammendrag

Populærvitenskapelig prosjektsammendrag

Hvert år diagnostiseres mer enn 3000 kvinner med brystkreft i Norge og brystkreft er dermed den vanligste krefttypen blant kvinner. Omtrent 70% av brystkrefttumorer er hormonsensitive og de fleste pasienter i denne subgruppen mottar endokrin behandling. Til tross for nylige terapeutiske fremskritt vil En andel av disse kvinnene kun ha delvis eller ingen respons til den endokrine behandlingen, og mange opplever . bivirkninger som fatigue (tretthet), fordøyelsesproblemer, menopausale symptomer, muskel- og beinendringer, vektøkning og økt risiko for hjerte-og karsykdommer. Fordeler og ulemper ved endokrin behandling bør nøye vurderes innenfor denne undergruppen av pasienter. Derfor er biomarkører for å kunne predikere respons til behandling og behandlingsrelaterte bivirkninger. Selv om fremskritt innen genomforskning har gitt oss et innblikk i heterogeniteten i undergrupper av brystkreft, er det fortsatt ikke mulig å forutsi svulstens respons til behandling. Fedme er en risikofaktor for postmenopausal hormonsensitiv brystkreft og er assosiert med dårligere prognose. Det er vist at produksjonen av østrogen i fettvev hos overvektige personer spiller en rolle i brystkreftrisikoen. Imidlertid er mekanismen for hvordan fedme korrelerer med endokrin behandlingsresistens uklart. I dette prosjektet vil vi undersøke steroidhormonmetabolisme i brystkreftvev og serum fra en regional brystkreftbiobank. Det overordnede målet er å identifisere nye biomarkører for å predikere endokrin behandlingsresistens og behandlingsrelaterte bivirkninger, både hos normalvektige og overvektige brystkreftpasienter. Prosjektet vil gi nye strategier for personrettet behandling av brystkreft, og kartlegge mekanismer for å motvirke negative effekter av behandlingen.

Sluttrapport

Bakgrunn, målsetting og metode

Metabolic reprogramming in breast cancer involves changes in steroid hormone synthesis and metabolism. Alterations in estrogen levels in both breast tissue and blood may influence carcinogenesis, breast cancer growth, and response to therapy. Our aim was to examine whether serum and tissue steroid hormone concentrations could predict the risk of recurrence and treatment-related fatigue in patients with estrogen receptor (ER)-positive breast cancer. We have used an in-house liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify steroid hormones in serum and breast cancer tissue in patients with ER-positive breast cancer. Several multivariate statistical methods [such as partial least squares discriminant analysis (PLS-DA) and linear mixed models (LIMM)] have been used to examine the association of serum steroid hormone levels and breast cancer recurrence and treatment-related fatigue in 66 postmenopausal patients from the Radiation study. These methods have been applied to examine the association of breast cancer tissue steroid hormone levels and recurrence in 40 breast cancer patients obtained from the Regional Breast Cancer Biobank.

Gjennomføring

The project has been carried out in line with the plan. Due to coronavirus restrictions, however, we had a little delay in validating the LC-MS/MS method in the lab and collecting the clinical data. We applied to prolong the project for 6 months and obtained permission from the Breast Cancer Society and Stiftelsen Dam. We have used the extension to publish one journal article and to write one manuscript. The user panel has followed the whole process.

Resultater og virkninger

We have developed a reliable and fast LC-MS/MS method to simultaneously quantify nine steroid hormones in serum and six in breast cancer tissue in patients with breast cancer. We found that breast cancer patients with low baseline levels of serum cortisol were more likely to experience recurrence. Both serum cortisol and cortisone levels decreased in relapse-free patients but increased in patients with recurrence during 7-15 years follow-up. Our results demonstrate that cortisol and cortisone may act as potential biomarkers indicating individual risk of recurrence. In addition, we confirmed that serum and tissue estrone levels were highly correlated in patients with an ER-positive disease. In the future, we plan to examine the spatial distribution and quantification of steroid hormones in breast cancer tissue in patients, and then examine the association of steroid hormone metabolism/biology and prognosis/treatment response in patients with ER-positive breast cancer. If succees, our findings will enable a rational assignment of endocrine therapy based on the molecular portrait and analysis of an individual’s tumor.