Metastatic breast cancer is a leading cause of death worldwide, with almost 40,000 women in the United States succumbing to the disease in 2013. Although advances in the treatment of breast cancer have been made, metastatic disease is still largely considered incurable. In a prospective, multicenter, molecular-screening study, researchers investigated whether the identification of individual genomic alterations could lead to personalized targeted therapy in women with advanced breast cancer (André F, et al. Lancet Oncol. 2014;15:267-274).
From June 16, 2001, to July 30, 2002, researchers recruited 423 patients with breast cancer with metastasis accessible for biopsy from 18 centers in France. The researchers utilized comparative genomic hybridization (CGH) array and Sanger sequencing on PIK3CA and AKT1 to assess metastatic biopsy samples from 5 of the centers. The primary end point was the proportion of patients to whom a targeted therapy could be offered.
Biopsy samples were obtained from 407 of the 423 enrolled patients. The study’s results showed that CGH array and Sanger sequencing was feasible in 67% and 70% of patients, respectively. In 195 (46%) patients, a targetable genomic alteration was identified, most frequently in PIK3CA, CCND1, and FGFR1 (25%, 19%, and 13% of identified genomic alterations, respectively). Of the 195 patients, 107 (55%) had multiple targetable genomic alterations. Rare genomic alterations (defined as occurring in <5% of the general population) were noted in 117 (39%) patients, including AKT1 mutations, and EGFR, MDM2, FGFR2, AKT2, IGF1R, and MET high-level amplifications. Genomic analyses led to personalized therapy in 13% of the 423 patients (N = 55).
Of the 423 patients who received personalized therapy, 9% had an objective response, 21% had stable disease for more than 16 weeks, and 9% achieved clinical benefit, defined as an objective response, stable disease for at least 24 weeks, or both.
Biopsy-related serious (ie, grade 2 and grade 3) adverse events were reported in 9 patients, including grade 2/3 pneumothorax (N = 4), grade 2/3 pain (N = 2), grade 3 hematoma (N = 1), grade 2 thrombosis (N = 1), and grade 3 hemorrhagic shock (N = 1). Biopsy confirmed an alternative diagnosis in 4 patients, including evidence of lung cancer, skin cancer, and benign lung disease.
The investigators suggested that new strategies to guide individual treatment options are necessary for patients who have metastatic breast cancer that is refractory to standard treatments. Furthermore, multigene screening allowed for the identification of patients with genomic alterations that could be matched to drugs under evaluation in phase 1 and 2 trials.
