Hope for Patients With Metastatic Breast Cancer
December 7th, 2021
For 74% of patients who have metastatic breast cancer, the disease is fatal within five years.1 Comprehensive genomic profiling (CGP) quickly identifies actionable alterations that can inform breast cancer treatment options. Therapies that target specific alterations often extend overall survival time and improve quality of life. By identifying the underpinnings of malignant disease, liquid biopsies continue to pave the way for precision medicine, dramatically changing the landscape of care for advanced cancer patients.2,3
Studies Demonstrate that All Breast Cancer Patients Should be Tested
PlasmaMATCH was the first prospective, multicenter study assessing the feasibility and clinical utility of ctDNA analysis to guide therapy in patients with advanced breast cancer. Conducted at the Institute of Cancer Research London, the study found that Guardant360® detected significantly more targetable alterations than hotspot testing, including over 35 percent more PIK3CA mutations4 that can now be targeted by recently FDA-approved therapies.5 Guardant360 also detected many more ESR1 mutations and found previously-undetected microsatellite instability (MSI) and ERBB2 amplifications and mutations, all of which are clinically actionable.
Aberrant mutations in breast cancer, such as human epidermal growth factor receptor 2 (ERBB2/HER2) are common. Recommended guidelines also include testing for PIK3CA and BRCA1/2, and liquid biopsies such as Guardant360 CDx go beyond the recommendations to test for NTRK1 and MSI as well. Fortunately, a number of approved therapeutics exist that directly target these mutations6-11, including monoclonal antibodies;14-16 PARP inhibitors16,17 that target BRCA1/2-mutated advanced breast cancers; and PI3K inhibitors18 for PIK3CA-mutated late-stage breast cancers. Other targeted therapies being researched include AKT inhibitors,19,20 STAT3 inhibitors,11,22 and anti-androgen therapies.23-26
The use of genomic data to guide cancer treatment has become indispensable. Liquid biopsies such as Guardant360 CDx are increasingly being used to identify treatment-relevant genomic mutations in metastatic breast cancer.
- Institute. NC SEER Stat Fact Sheets: Breast Cancer. 2018. Available from: https://seer.cancer.gov/statfacts/html/breast.html.
- El Sayed R, El Jamal L, El Iskandarani S, Kort J, Abdel Salam M, Assi H. Endocrine and targeted therapy for hormone-receptor-positive, HER2-negative advanced breast cancer: insights to sequencing treatment and overcoming resistance based on clinical trials. Front Oncol. 2019;9:510.
- Goldhirsch, A. et al. Strategies for subtypes–dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann. Oncol. 22, 1736–1747 (2011).
- Kingston B, Bye H, Hubank M, et al. The genomic landscape of breast cancer based on ctDNA analysis: data from the plasmaMATCH trial. Presented at: 2019 San Antonio Breast Cancer Symposium; December 10-14; San Antonio, TX. Abstract GS3-07Marker for Patient Selection? Clinical Lung Cancer. 2016;S1525-7304:30057–30052.
- Ibrahim MF, Hilton J, Addison C, et al. Strategies for obtaining bone biopsy specimens from breast cancer patients – Past experience and future directions. J Bone Oncol. July 2016
- Roychowdhury, S. & Chinnaiyan, A. M. Translating cancer genomes and transcriptomes for precision oncology. CA Cancer J. Clin. 66, 75–88 (2016).
- Andre, F. et al. Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicentre, prospective trial (SAFIR01/UNICANCER). Lancet Oncol. 15, 267–274 (2014).
- Balko, J. M. et al. Molecular profiling of the residual disease of triple-negative breast cancers after neoadjuvant chemotherapy identifies actionable therapeutic targets. Cancer Discov. 4, 232–245 (2014).
- Paratala, B. S. et al. RET rearrangements are actionable alterations in breast cancer. Nat. Commun. 9, 4821 (2018).
- Jiang, Y. Z. et al. Genomic and transcriptomic landscape of triple-negative breast cancers: subtypes and treatment strategies. Cancer Cell 35, 428–440.e425 (2019).
- Yates, L. R. et al. Genomic evolution of breast cancer metastasis and relapse. Cancer Cell 32, 169–184.e167 (2017).
- Loibl, S. & Gianni, L. HER2-positive breast cancer. Lancet 389, 2415–2429 (2017).
- Swain, S. M. et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N. Engl. J. Med. 372, 724–734 (2015).
- Verma, S. et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N. Engl. J. Med. 367, 1783–1791 (2012).
- Geyer, C. E. et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N. Engl. J. Med. 355, 2733–2743 (2006).
- Park, J. W. et al. Adaptive randomization of neratinib in early breast cancer. N. Engl. J. Med. 375, 11–22 (2016).
- Robson, M. et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N. Engl. J. Med. 377, 523–533 (2017).
- Hurvitz, S. A. et al. Talazoparib in patients with a germline BRCA-mutated advanced breast cancer: detailed safety analyses from the phase III EMBRACA trial. Oncologist https://doi.org/10.1634/theoncologist.2019-0493 (2019).
- André, F. et al. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N. Engl. J. Med. 380, 1929–1940 (2019).
- Kim, S. B. et al. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 18, 1360–1372 (2017).
- Jones, R. H. et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 21, 345–357 (2020).
- Yu, H., Lee, H., Herrmann, A., Buettner, R. & Jove, R. Revisiting STAT3 signalling in cancer: new and unexpected biological functions. Nat. Rev. Cancer 14, 736–746 (2014).
- Bonnefoi, H. et al. A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1). Ann. Oncol. 27, 812–818 (2016)
- Gucalp, A. et al. Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic breast cancer. Clin. Cancer Res. 19, 5505–5512 (2013).
- Carneiro BA, Elvin JA, Kamath SD, Ali SM, Paintal AS, Restrepo A, Berry E, Giles FJ, Johnson ML. FGFR3-TACC3: A novel gene fusion in cervical cancer. Gynecologic Oncology Reports. 2015;13:53–56.
- Chae YK, Pan A, Davis AA, Raparia K, Mohindra NA, Matsangou M, Giles FJ. Biomarkers for PD-1/PD-L1 Blockade Therapy in Non-Small-cell Lung Cancer: Is PD-L1 Expression a Gooz.