HR+, HER2- Metastatic Breast Cancer
Disease Heterogeneity and 1L Treatment
Hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) is the most common subtype of metastatic breast cancer (MBC), representing approximately 73% of all cases.1 HR+, HER2- breast cancer can be further categorized based on gene expression patterns, histological features, clinical and biological properties, and response to treatment.2,3
Approximately 60% of patients with advanced HR+, HER2- breast cancer have ≥1 disease-related factor more likely to confer a poor prognosis.4 These include negative progesterone receptor (PgR) status, visceral metastases, liver metastases (a subset of visceral metastases), and high tumor grade.4
HR+, HER2- MBC: Factors Likely to Confer a Poor Prognosis
Negative PgR status
Visceral metastases
Liver metastases (a subset of visceral metastases)
High tumor grade
Patients with HR+, HER2- MBC harboring ≥1 prognostic factor displayed a significantly shorter real-world progression-free survival and overall survival compared to those with no prognostic factors.5 In addition, outcomes for patients with HR+, HER2- MBC vary depending on the presence of certain prognostic factors.6-8
Patients who lack PgR expression displayed a lower disease-free survival than patients with PgR expression.6
Disease-free survival as a function of time since mastectomy or breast-conserving surgery based on PgR status. X-axis displays years since mastectomy or breast-conserving surgery, from 0 to 12 years, and Y-axis displays rate of disease-free survival, from 0.0 to 1.0. Both PgR status groups begin at a disease-free survival rate of 1.0 at 0 years with a gradual decline to approximately 0.75 at around 12 years. Over 0 to 12 years, patients with PgR-positive status display a higher rate of disease-free survival when compared to those with PgR-negative status.6
Patients with visceral metastases had a worse overall survival than patients with bone-only metastases.7
Probability of survival as a function of time since first distant metastases based on site of metastases. X-axis displays months after first distant metastases, from 0 to 120 months, and Y-axis displays probability of survival, from 0.0 to 1.0. All groups begin with a probability of survival rate of 1.0 at 0 months with a decline to approximately 0.0 at 120 months. Patients with bone-only metastases show a higher probability of survival when compared to those with bone and visceral metastases or visceral-only metastases.7
Patients with high-grade tumors or intermediate-grade tumors showed worse overall survival than patients with low-grade tumors.8
Probability of survival as a function of time since breast cancer diagnosis based on tumor grade. X-axis displays years since breast cancer diagnosis, from 0 to 15 years, and Y-axis displays probability of survival, from 0.0 to 1.0. All groups begin with a probability of survival rate of 1.0 at 0 years with a gradual decline to approximately 0.9 to 0.5 at around 15 years. In general, patients with low grade tumors show a higher probability of survival, followed by those with intermediate grade tumors; those harboring high grade tumors display a lower probability of survival.8
Endocrine therapy (ET) remains the backbone of therapy for estrogen receptor–positive (ER+), HER2- advanced breast cancer (ABC) following 30 years of therapeutic advancement.9,10 Three classes of ETs are approved to target the estrogen pathway in patients with ER+, HER2- MBC, including aromatase inhibitors (AIs), selective estrogen receptor modulators (SERMs), and selective estrogen receptor degraders (SERDs).9,11,12
- AIs prevent estrogen conversion from precursor molecules9,10
- SERMs interact with ER to modify ER activity9,10
- SERDs lead to intranuclear immobilization and cytosolic degradation of ER9,10
Standard treatment for patients with HR+, HER2- MBC includes ET + cyclin-dependent kinase 4/6 inhibitors (CDK4/6i).13,14 Treatment with ET + CDK4/6i improves outcomes when compared to treatment with ET alone.15,16
- In a pooled analysis of randomized trials of ET ± CDK4/6i in patients with HR+, HER2- MBC approved by the United States Food and Drug Administration, the addition of CDK4/6i resulted in 41% reduction in the risk of disease progression or death (CDK4/6i in the pooled analysis included palbociclib, ribociclib, and abemaciclib; ET in the pooled analysis included AI or fulvestrant)15
- Patients treated with ET + CDK4/6i in first-line (1L) or greater settings derived similar progression-free survival benefits, regardless of de novo metastatic status, site of metastasis, and histological classification, when compared to those treated with ET alone15
As healthcare providers, it is important to identify patients with HR+, HER2- MBC who may be at risk for less optimal outcomes based on clinical and pathological factors, and to understand the benefits of ET + CDK4/6i for 1L treatment. Additional information on MBC trials with ET + CKD4/6i can be found in linked resources below.
References
- Howlader N, et al. J Natl Cancer Inst. 2014;106(5):dju055.
- Eliyatkin N, et al. J Breast Health. 2015;11(2):59-66.
- Prat A, et al. Breast. 2015;24(suppl 2):S26-S35.
- Davie A, et al. ESMO Open. 2021;6(4):100226.
- Vidal GA, et al. Clin Breast Cancer. 2021;21(4):317-328.e7.
- Sun J-Y, et al. Onco Targets Ther. 2016;9:1707-1713.
- Solomayer E-F, et al. Breast Cancer Res Treat. 2000;59(3):271-278.
- Dalton LW, et al. Mod Pathol. 2000;13(7):730-735.
- Chen YC, et al. Expert Opin Investig Drugs. 2022;31(6):515-529.
- Patel R, et al. NPJ Breast Cancer. 2023;9(20). doi: 10.1038/s41523-023-00523-4
- Le Romancer M, et al. Endocr Rev. 2011;32(5):597-622
- Patel HK, Bihani T. Pharmacol Ther. 2018;186:1-24.
- Gennari A, et al. Ann Oncol. 2021;32(12):1475-1495.
- Burstein HJ, et al. J Clin Oncol. 2021;39(35):3959-3977.
- Gao JJ, et al. Lancet Oncol. 2020;21(2):250-260.
- Gao JJ, et al. Lancet Oncol. 2021;22(11):1573-1581.
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