Genome and transcriptome sequencing in prospective metastatic triple-negative breast cancer uncovers therapeutic vulnerabilities.

Triple-negative breast cancer (TNBC) is characterized by the absence of expression of estrogen receptor, progesterone receptor, and HER-2. Thirty percent of patients recur after first-line treatment, and metastatic TNBC (mTNBC) has a poor prognosis with median survival of one year. Here, we present initial analyses of whole genome and transcriptome sequencing data from 14 prospective mTNBC. We have cataloged the collection of somatic genomic alterations in these advanced tumors, particularly those that may inform targeted therapies. Genes mutated in multiple tumors included TP53, LRP1B, HERC1, CDH5, RB1, and NF1. Notable genes involved in focal structural events were CTNNA1, PTEN, FBXW7, BRCA2, WT1, FGFR1, KRAS, HRAS, ARAF, BRAF, and PGCP. Homozygous deletion of CTNNA1 was detected in 2 of 6 African Americans. RNA sequencing revealed consistent overexpression of the FOXM1 gene when tumor gene expression was compared with nonmalignant breast samples. Using an outlier analysis of gene expression comparing one cancer with all the others, we detected expression patterns unique to each patient's tumor. Integrative DNA/RNA analysis provided evidence for deregulation of mutated genes, including the monoallelic expression of TP53 mutations. Finally, molecular alterations in several cancers supported targeted therapeutic intervention on clinical trials with known inhibitors, particularly for alterations in the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways. In conclusion, whole genome and transcriptome profiling of mTNBC have provided insights into somatic events occurring in this difficult to treat cancer. These genomic data have guided patients to investigational treatment trials and provide hypotheses for future trials in this irremediable cancer.

Referral patterns and adjuvant chemotherapy use in patients with stage II colon cancer.

BACKGROUND: Little is known about the actual rate of use of adjuvant chemotherapy in stage II colon cancer and about referral patterns that give patients access to this treatment. PATIENTS AND METHODS: We searched the tumor registry at Baylor University Medical Center at Dallas to identify patients with stage II colon cancer who underwent resection between 1995 and 2003. The rates of referral to medical oncology and adjuvant chemotherapy use were calculated and potential predictive variables were analyzed using univariate and multivariate techniques. RESULTS: We identified 287 patients with stage II colon cancer. A total of 160 patients (56%) were referred to a medical oncologist. Eighty patients (28%) received adjuvant chemotherapy. Age < 50 years, private insurance status, lower comorbidity score, higher T stage, and poor tumor differentiation were significant predictors of adjuvant chemotherapy use (P