RESUMO
There is a clinical need to predict sensitivity of metastatic hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer to endocrine therapy, and targeted RNA sequencing (RNAseq) offers diagnostic potential to measure both transcriptional activity and functional mutation. We developed the SETER/PR index to measure gene expression microarray probe sets that were correlated with hormone receptors (ESR1 and PGR) and robust to preanalytical and analytical influences. We tested SETER/PR index in biopsies of metastastic HR+/HER2- breast cancer against the treatment outcomes in 140 patients. Then we customized the SETER/PR assay to measure 18 informative, 10 reference transcripts, and sequence the ligand-binding domain (LBD) of ESR1 using droplet-based targeted RNAseq, and tested that in residual RNA from 53 patients. Higher SETER/PR index in metastatic samples predicted longer PFS and OS when patients received endocrine therapy as next treatment, even after adjustment for clinical-pathologic risk factors (PFS: HR 0.534, 95% CI 0.299 to 0.955, p = 0.035; OS: HR 0.315, 95% CI 0.157 to 0.631, p = 0.001). Mutated ESR1 LBD was detected in 8/53 (15%) of metastases, involving 1-98% of ESR1 transcripts (all had high SETER/PR index). A signature based on probe sets with good preanalytical and analytical performance facilitated our customization of an accurate targeted RNAseq assay to measure both phenotype and genotype of ER-related transcription. Elevated SETER/PR was associated with prolonged sensitivity to endocrine therapy in patients with metastatic HR+/HER2- breast cancer, especially in the absence of mutated ESR1 transcript.
RESUMO
BACKGROUND: Given their early age at diagnosis, young breast cancer survivors (YBCSs) face issues that differ widely from their older counterparts. PATIENTS AND METHODS: We mailed a survey to 2209 patients who were ≤ 45 years at the time of breast cancer (BC) diagnosis. Each survey was composed of the Quality of Life in Adult Cancer Survivors instrument, Menopause Symptom Scale, and questions aimed at obtaining pertinent background information. RESULTS: One thousand ninety patients completed the survey. Mean age at time of diagnosis was 39.5 years; median years from diagnosis was 6.6 years. Distress related to vaginal dryness (P = .0002) and pain from intercourse (P = .0014) was significantly higher in patients who were < 5 years from diagnosis compared with those > 10 years from diagnosis. In the area of financial problems, black women had greater distress than did white women (P = .0010). Compared with white women, Hispanic women had worse family distress scores (P = .0028) and summary cancer-specific scores (P = .0076). Patients > 10 years from diagnosis had less sexual interest (P = .003) than did women who were closer to diagnosis. Women ≥ 40 years at diagnosis had significantly lower sexual interest (P = .0016) than did women < 40 years. Stage and neoadjuvant chemotherapy did not have a significant effect on quality of life (QOL). CONCLUSION: Even in comparison to stage and neoadjuvant chemotherapy, race, age at diagnosis, and time from diagnosis have significant long-term effects on QOL after treatment for BC.