Contralateral parenchymal enhancement on MRI: A potential breast cancer survival biomarker

Parenchymal enhancement in the healthy breast seen on pre-treatment dynamic contrast-enhanced magnetic resonance imaging (MRI) of women with estrogen receptor (ER)-positive/HER2-negative breast cancer is an independent marker of survival, researchers from the University Medical Centre Utrecht in the Netherlands in collaboration with Memorial Sloan Kettering Cancer Center in New York City report in the November issue of European Radiology. This latest research confirms their discovery in 2015 that contralateral parenchymal enhancement (CPE) is significantly associated with long-term outcome of breast cancer patients and may be a risk stratification biomarker.

Breast parenchyma is believed to be important for breast cancer risk prediction, treatment response, and outcomes assessment. The authors had hypothesized that if there is symmetry in both breasts of a woman, a disease-free breast could be comparable to a cancerous breast before tumorigenesis. In a retrospective study of 531 women with unilateral invasive breast cancer treated at UMC Utrecht, they had determined that “the 10% most enhancing part of the parenchyma was found to be associated with long-term patient outcome, particularly in patients with ER-positive/HER2-negative breast cancer.”¹

The new study analyzed the CPE of 302 patients with ER-positive/HER2-negative invasive ductal carcinoma who had been treated at the Memorial Sloan Kettering Cancer Center in New York City. Led by Bas H.M. van der Velden, PhD, of the university’s Image Sciences Institute and Kenneth G.A. Gilhuijs, PhD, principal investigator for both studies, the research team validated their earlier findings. They also determined that CPE did not show a correlation with menstrual cycle or was significantly higher in premenopausal women compared to perimenopausal or postmenopausal women.

The 302 patients had an interquartile range in age from 42 to 57 years (median 48 years) and were followed for a median of 88 months. Thirty-seven women (13%) experienced disease recurrence: local for 16%, regional for 19%, and distant for 65%.

Dr. van der Velden and colleagues determined that patients in the high CPE group had significantly better survival than patients in the low CPE group, with a cumulative invasive disease-free survival at 10 years at 93% compared to 72% in the low CPE group. Cumulative overall survival at 10 years was also better, 98% compared to 82%. The subgroup of patients who received endocrine therapy with high CPE had a fourfold to fivefold better invasive disease-free survival and overall survival than patients with low CPE.

The authors also compared their findings with established biomarkers, specifically the Nottingham Prognostic Index (NPI) and PREDICT, prognostic models to predict breast cancer survival.^2,3 “In patients considered to be at high risk according to NPI or PREDICT, a subgroup with relatively good survival was identified using CPE. Patients with high CPE had a significantly better invasive disease-free survival and overall survival compared to patients with low CPE,” they wrote.

They recommend additional research to validate CPE as a biomarker in a multi-cohort prospective study. This multi-cohort study is currently ongoing in the Netherlands, funded by the Dutch Cancer Society. The authors hope that their findings can lead to “a practical, widely accessible and inexpensive test for risk stratification of ER-positive/HER2-negative breast cancer that can have a practice changing impact.”

REFERENCES

1. van der Velden BHM, Dmitriev I, Loo CE, et al. Association between parenchymal enhancement of the contralateral breast in dynamic contrast-enhanced MR imaging and outcome of patients with unilateral invasive breast cancer. Radiology. 2015;276(3):675-685.
2. Galea MH, Blamey RW, Elston CE, et al. The Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat. 1992;22(3):207-19.
3. Wishart GC, Azzato EM, Greenberg DC, et al. PREDICT: a new UK prognostic model that predicts survival following surgery for invasive breast cancer. Breast Cancer Res. 2010;12(1):R1 doi:10.1186/bcr2464.
4. van der Velden BHM, Sutton EJ, Carbonaro LA, et al. Contralateral parenchymal enhancement on dynamic contrast-enhanced MRI reproduces as a biomarker of survival in ER-positive/HER2-negative breast cancer patients. Eur Radiol. 2018;28(11):4705-4716.