Complete Durable Response From Carboplatin and Olaparib in a Heavily Pretreated Triple-Negative Metastatic Breast Cancer With Germline BRCA2 and “BRCAness” Mutations

Case Presentation, Management, and Outcome The patient is a 62-year-old female with stage IV triple-negative invasive ductal carcinomaof the left breast, cT3N1M1, nuclear grade3,diagnosed in July2013(Fig 1A). She was treated with dose-dense doxorubicin 60 mg/mandcyclophosphamide600mg/m for four cycles followed by paclitaxel once per week starting in November 2013. She had a good response in the left breast and pulmonary nodules per scans. After discussion, she had a simple mastectomy in January 2014. Pathology revealed two foci of residual invasive ductal carcinomawith treatment effect (0.11 cm and 0.1 cm) and ductal carcinoma in situ with comedo necrosis. Three sentinel lymph nodes were negative. In July 2014, progression was found in the lung, and the largest pulmonary nodule was 6.4 mm. While undergoing restaging work-up in August, magnetic resonance imaging scans of the brain showed a 3-cm mass in the left frontal lobe. The resected lesion showed metastatic adenocarcinoma positive for PTEN loss, BRCA2 9435_9436delGT,MYC amplification, TP53 R196*, FAS loss, and RB1 loss according to a next-generation sequencing-based assay from FoundationOne. The left frontal area was treated with Gamma Knife surgery in September. Gemcitabine 800 mg/m on days 1 and 8 every 3 weeks was started in October. Because of progression in January 2015, the patient was considered for the Study of Glembatumumab Vedotin (CDX-011) in Patients With Metastatic, gpNMB Over-Expressing, Triple Negative Breast Cancer (METRIC) trial. She was tested for BRCA at the same time, and Integrated BRCAnalysis confirmed germline BRCA2 mutation of 9663delGT. Her breast tumor had glycoprotein NMB overexpression, but she was randomly assigned to the control arm with capecitabine 1,250 mg/m. On the basis of scans, she had stable disease by mid-March. In May, capecitabine was stopped because of progression (Fig 1B). With rapid