Cancer Topics - Contrasting Cases: Systemic Therapy for Metastatic Triple-negative Breast Cancer

In this month's ASCO eLearning Podcast, Dr. Helen Chew, Professor of Medicine and leader of the Clinical Breast Cancer Program at University of California Davis Comprehensive Cancer Center, brings us two patient cases on systemic therapy for metastatic triple negative breast cancer.  This podcast episode appears as a resource in ASCO eLearning's recently updated Genetics & Genomics course collection in the course Hereditary Breast and Ovarian Cancer Syndrome. Click the links to learn more about these courses, including CME and MOC credit details. If you are interested in purchasing a course or the entire collection, go to shop.asco.org Transcript Hello, my name is Helen Chew. I am Professor of Medicine and leader of the Clinical Breast Cancer Program at the University of California Davis Comprehensive Cancer Center. Today, we compare two patient cases on systemic therapy for metastatic triple negative breast cancer. Systemic therapy for metastatic triple negative breast cancer remains a challenge. The mainstay of therapy is cytotoxic chemotherapy. In March 2019, based on the Impassion130 trial, the anti-PD-L1 antibody, atezolizumab, was approved in combination with nab-paclitaxel for metastatic triple negative breast cancer that expresses PD-L1.  However, for triple negative breast cancer without PD-L1 expression, immunotherapy is not an option. In addition, there are many indications for genetic counseling and testing, including patients diagnosed with breast cancer at age 45 years or younger and patients with triple negative breast cancer diagnosed at age 60 years or younger. Results of genetic testing may influence treatment options in metastatic breast cancer. Before we explore treatment options, let’s look at two similar cases where treatment choices may differ. Can you identify the key differences? Let’s begin with Case 1, a 45-year-old woman with metastatic triple negative breast cancer to the liver and lungs. Two years earlier, she had received preoperative anthracycline and paclitaxel for a stage II, triple negative breast cancer. She had a limited family history of cancer and underwent genetic counseling and testing. No pathogenic mutations were found in a panel of genes associated with hereditary cancers.  At the time of her metastatic recurrence, biopsy of a liver lesion confirmed metastatic carcinoma, consistent with triple negative breast cancer. There was no PD-L1 staining. The patient received carboplatin and gemcitabine for 6 cycles. She now has disease progression. Case 2 is a 57-year-old woman who also has metastatic triple negative breast cancer involving the chest wall, liver and bones. Three years earlier, she had received adjuvant anthracycline and paclitaxel for a stage II, triple negative breast cancer. She had no family history of breast or ovarian cancer, but underwent genetic counseling and testing revealing a pathogenic germline BRCA1 mutation. At the time of metastatic recurrence, chest wall biopsy confirmed metastatic triple negative breast cancer with no PD-L1 staining. The patient received carboplatin for 6 cycles with an initial response.  Nine months later, she has disease progression. In each of these cases, what option would you recommend for subsequent therapy? The choices include additional chemotherapy, such as capecitabine, eribulin or vinorelbine, or a PARP inhibitor. In Case 1, the correct answer is chemotherapy, including any of the named options. This patient does not harbor a germline BRCA mutation so would not benefit from a PARP inhibitor. In Case 2, the correct answer is a PARP inhibitor. In both the OlympiAD and EMBRACA phase III trials, patients with germline BRCA mutations and previously treated HER2-negative metastatic breast cancer were randomized to either chemotherapy of physicians’ choice or to olaparib or talozoparib, respectively. Approximately 40-50% had triple negative metastatic breast cancer in these two trials.  Patients who received the PARP inhibitors had significantly improved progression-free survival compared to chemotherapy in both trials. Both PARP inhibitors, olaparib and talozoparib, are approved for patients with HER2-negative metastatic breast cancer who have germline BRCA mutations.  These two cases of metastatic triple negative breast cancer share similarities. Both cases met criteria for genetic counseling and testing, including the young age at diagnosis for Case 1 and the diagnosis of triple negative breast cancer at age 60 or younger in Case 2. Both cases were treated similarly at initial presentation and on metastatic recurrence.  However, the key difference is that no pathogenic mutation was detected in Case 1. In contrast, a germline BRCA1 mutation was found in Case 2.  PARP inhibitors are associated with improved progression-free survival compared to the chemotherapy given in the OlympiAD and EMBRACA trials in patients with germline BRCA mutations and HER2 negative, previously treated metastatic breast cancer.   In addition, although both cases received a platinum-based regimen at metastatic recurrence, the TNT trial revealed that only patients with germline BRCA mutations and triple negative metastatic breast cancer had improved progression-free survival with carboplatin compared to docetaxel. No difference in progression-free survival was seen in the trial population of triple negative metastatic breast cancer without a germline mutation. Thank you for listening to this week’s episode of the ASCO eLearning Weekly Podcast. For more information on the treatment of metastatic breast cancer, including additional patient cases and opportunities for self-evaluation, visit the comprehensive eLearning center at elearning.asco.org