Durable Clinical Benefit of Pertuzumab in a Young Patient with BRCA2 Mutation and HER2-Overexpressing Breast Cancer Involving the Brain

Hindawi Publishing Corporation Case Reports in Oncological Medicine Volume 2016, Article ID 5718104, 5 pages http://dx.doi.org/10.1155/2016/5718104 Case Report Durable Clinical Benefit of Pertuzumab in a Young Patient with BRCA2 Mutation and HER2-Overexpressing Breast Cancer Involving the Brain Anna Koumarianou,1 Christina Kontopoulou,2 Vassilis Kouloulias,3 and Christina Tsionou4 1 Hematology-Oncology Unit, Fourth Department of Internal Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Rimini 1, Haidari, 12462 Athens, Greece 2 Second Radiology Department, Attikon University Hospital, National and Kapodistrian University of Athens, Rimini 1, Haidari, 12462 Athens, Greece 3 Radiotherapy Unit, Second Radiology Department, Attikon University Hospital, National and Kapodistrian University of Athens, Rimini 1, Haidari, 12462 Athens, Greece 4 Maternity-Health, 30 Papanikoli Street, Halandri, 15232 Athens, Greece Correspondence should be addressed to Anna Koumarianou; Received 8 September 2015; Revised 23 February 2016; Accepted 22 March 2016 Academic Editor: Guido Fadda Copyright © 2016 Anna Koumarianou et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Patients with HER2-positive breast cancer and brain metastases have limited treatment options, and, as a result of their poor performance status and worse prognosis, they are underrepresented in clinical trials. Not surprisingly, these patients may not be fit enough to receive any active treatment and are offered supportive therapy. BRCA2 mutations are reported to be rarely associated with HER2-overexpressing advanced breast cancer and even more rarely with brain metastases at diagnosis. We report on a BRCA2positive breast cancer patient with metastatic disease in multiple sites, including the brain, and poor performance status who exhibited an extraordinary clinical and imaging response to the novel anti-HER2 therapy pertuzumab after multiple lines of therapy including anti-HER2 targeting. To our knowledge, the clinicopathologic and therapeutic characteristics of this patient point to a unique case and an urgent need for further investigation of pertuzumab in patients with brain metastases. 1. Introduction Brain involvement of metastatic breast cancer is largely dependent on the molecular subtype of the disease, and in the case of HER2-overexpressing tumors, it affects 30% of patients and is associated with devastating symptoms and quality of life [1, 2]. Several studies confirm that the median survival from diagnosis of brain metastases is from 6 months for patients who do not receive trastuzumab to 13 months for those who receive trastuzumab [1, 3, 4]. With few exceptions, there are hardly any prospective phases II-III clinical studies interrogating the role of anti-HER2 drugs in brain involvement [5, 6]. A plausible explanation for such a serious underrepresentation of patients in clinical trials is the poor performance status of this patient subgroup due to the tumoral involvement of the central nervous system. A recent study combining trastuzumab and pertuzumab for patients with metastatic disease resulted in survival improvement of 15.7 months [7]. Because this study did not include patients with brain metastases, there is no established experience about such anti-HER2 therapy’s potential administration and benefit in patients relapsing after trastuzumab and lapatinib. With regard to patients with HER2-overexpressing metastatic breast cancer who are BRCA2 carriers, there is a scarcity of information in the published literature [8], so there is not much data on their survival and responses to the available treatments. However, a recent meta-analysis including breast 2 Case Reports in Oncological Medicine 6 cycles of 6 cycles of Breast pegylated doxorubicin, trastuzumab, lapatinib, cancer diagnosis, trastuzumab, and zoledronic acid 34 years and zoledronic acid old Whole brain radiotherapy Nov 2009 Feb 2010 Oct 2010 7 cycles of lapatinib, tamoxifen, and LHRH agonist Death: July 2015, 40 years old BRCA2 + test April 2011 Sept 2011 Feb 2012 Nov 2012 Jan 2013 April 2013 June 2013 July 2013 Feb 2014 Mar 2014 Spine radiotherapy and intrathecal methotrexate Stereotactic brain radiotherapy 4 cycles of paclitaxel, trastuzumab, and zoledronic acid 4 cycles of carboplatin, docetaxel, trastuzumab, and zoledronic acid 6 cycles of lapatinib, capecitabine, zoledronic acid 8 cycles of carboplatin, paclitaxel, trastuzumab, and zoledronic acid 3 cycles of carboplatin, gemcitabine, trastuzumab, and zoledronic acid 8 cycles of pertuzumab, trastuzumab, docetaxel, and denosumab and 6 cycles of pertuzumab, trastuzumab, and denosumab Figure 1: Timeline of patient’s diagnosis and treatments. cancer patients who are BRCA2 mutation carriers indicated no survival differences compared to patients without BRCA2 mutations [9]. 2. Case Presentation A 34-year-old female with abdominal pain and headache presented at the emergency department in November 2009. Upon clinical examination, she had a red, hard, fixed right breast with a fixed lymph nodal mass in the right axilla. She was living in the outskirts of Sparta with her husband and two children. She was never a smoker or an alcohol drinker. Her past medical history included a pituitary adenoma; she had no brothers or sisters, but she had a remarkable family history, as her father and uncle died of metastatic breast cancer. Her imaging with computed tomography (CT) and laboratory investigations revealed a single brain and multiple lung, liver, and bone metastases. A full blood count and biochemistry were normal except for the following: hemoglobin: 9.8 g/dL (normal value; nv 12–16); aspartate aminotransferase: 78 U/L (nv 5–40); alanine aminotransferase: 96 U/L (nv 5– 35); gamma-glutamyl transferase: 216 U/L (nv 7–49); alkaline phosphatase: 261 U/L (nv 25–125); lactic acid dehydrogenase: 778 U/L (<250); and tumor markers: Ca 15-3 >1000 U/mL (nv < 31) and CEA > 50 ng/mL (nv < 5). Histologic and immunohistochemical examination of a true-cut biopsy revealed an invasive ductal adenocarcinoma, grade III differentiation, estrogen receptor (ER) strong nuclear positivity in 70% of cells, progesterone receptor (PR) nuclear positivity in less than 3%, HER2 strongly positive (+3), Ki-67 nuclear positivity in 40% of cells, and p53 nuclear positivity in 60% of cells according to the histopathology. Following stereotactic brain radiotherapy to the single lesion, the patient was treated according to the 2009 NCCN first-line strategy recommendations, which included paclitaxel, trastuzumab, and zoledronic acid [10]. Reevaluation after four cycles revealed disease progression (PD) in the lung and liver according to the RECIST criteria of response. A second line of therapy was init (...truncated)