Molecular Biomarkers for Contemporary Therapies in Hormone Receptor-Positive Breast Cancer
Open Access
- 16 February 2021
- Vol. 12 (2), 285
- https://doi.org/10.3390/genes12020285
Abstract
Systemic treatment of hormone receptor-positive (HR+) breast cancer is undergoing a renaissance, with a number of targeted therapies including CDK4/6, mTOR, and PI3K inhibitors now approved for use in combination with endocrine therapies. The increased use of targeted therapies has changed the natural history of HR+ breast cancers, with the emergence of new escape mechanisms leading to the inevitable progression of disease in patients with advanced cancers. The identification of new predictive and pharmacodynamic biomarkers to current standard-of-care therapies and discovery of new therapies is an evolving and urgent clinical challenge in this setting. While traditional, routinely measured biomarkers such as estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2) still represent the best prognostic and predictive biomarkers for HR+ breast cancer, a significant proportion of patients either do not respond to endocrine therapy or develop endocrine resistant disease. Genomic tests have emerged as a useful adjunct prognostication tool and guide the addition of chemotherapy to endocrine therapy. In the treatment-resistant setting, mutational profiling has been used to identify ESR1, PIK3CA, and AKT mutations as predictive molecular biomarkers to newer therapies. Additionally, pharmacodynamic biomarkers are being increasingly used and considered in the metastatic setting. In this review, we summarise the current state-of-the-art therapies; prognostic, predictive, and pharmacodynamic molecular biomarkers; and how these are impacted by emerging therapies for HR+ breast cancer.Keywords
Funding Information
- Australian Government (Research Training Program)
- Balnaves Foundation (N/A, N/A)
- National Breast Cancer Foundation (-)
This publication has 179 references indexed in Scilit:
- Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trialThe Lancet, 2012
- Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100 000 women in 123 randomised trialsThe Lancet, 2011
- Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical reviewBreast Cancer Research and Treatment, 2011
- Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-upThe Lancet Oncology, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Ki67 in breast cancer: prognostic and predictive potentialThe Lancet Oncology, 2010
- New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)European Journal Of Cancer, 2009
- Expression of Yes-associated protein in common solid tumorsHuman Pathology, 2008
- p21 and p27: roles in carcinogenesis and drug resistanceExpert Reviews in Molecular Medicine, 2008
- Immunohistochemical demonstration of androgen receptor in breast cancer and its relationship to other prognostic factorsThe Journal of Pathology, 1993