At the 2011 San Antonio Breast Cancer Symposium, Joyce O’Shaughnessy, MD, described how the genetic profiles of 12 patients with metastatic triple-negative breast were used to guide treatment for metastatic disease
Patient #10 was a 59-year-old African-American woman with primary chemotherapy-refractory recurrent disease over the chest wall. She had not responded to doxorubicin/cyclophosphamide/docetaxel or to cisplatin. Sequencing revealed a KRAS amplicon with KRAS overexpression. Her diffuse disease responded well to pegylated SN-38, the active moiety of irinotecan, raising the hypothesis that irinotecan and SN-38 may be effective in the treatment of chemotherapy-refractory metastatic triple-negative breast cancer that demonstrates RAS pathway activation.
Patient #2 was a 58-year-old Caucasian woman who had transient responses to preoperative doxorubicin/cyclophosphamide/docetaxel, platinum, and bevacizumab. Whole genome sequencing revealed a high-level BRAF amplicon, and she was enrolled on a phase I study of a novel MEK inhibitor plus a novel AKT inhibitor, to which she had a rapid response.
Patient #9 was a 40-year-old Caucasian patient with cancer recurrence in the brain and cervical lymph nodes 18 months after a preoperative regimen of doxorubicin, cyclophosphamide, and paclitaxel, followed by adjuvant cisplatin. She had a strong family history but tested negative for a BRCA germline mutation. In this highly genomically unstable cancer, sequencing revealed multiple mutations and deletions in genes involved in homologous recombination. She underwent brain radiotherapy and had a complete response to iniparib/gemcitabine/carboplatin, “in keeping with numerous DNA repair mutations present in her cancer,” Dr. O’Shaughnessy noted.
Patient #1 was a 53-year-old African-American woman with metastatic ipsilateral internal mammary and mediastinal nodal recurrence after a pathologic complete response to preoperative chemotherapy 18 months earlier. Sequencing revealed homologous deletion in NF1, plus PTEN deletion. She was treated with a combined PI3K /mTOR inhibitor on a phase I study, and achieved stable disease for 2 months in her very rapidly progressing disease. Progression on the PI3K pathway inhibitor may have been due to activation of the Ras/MAPK pathway in the settings of the NF1 deletion. ■
The startling molecular heterogeneity of metastatic triple-negative breast cancer is now obvious and helps to explain the poor outcomes observed in this patient subset. Comprehensive genomic and transcriptomic interrogation of metastatic triple-negative breast cancer is elucidating the molecular...
Hope Rugo, MD, of the University of California, San Francisco, commented on Dr. O’Shaughnessy’s presentation on molecular pathways in triple-negative breast cancer at the 2011 San Antonio Breast Cancer Symposium. “The really exciting thing is that we have moved from intrinsic subtyping of breast...