Breast Cancer and Early Detection of Risk for Recurrences
A dynamic risk profile with CETC/CTCs
Presentation at Early Detection Conference 2021
Pachmann Katharina, Fluhrer Joachim, Pachmann Peter, Schott Dorothea
Abstract
As of the end of 2020, there were 7.8 million women alive who were diagnosed with breast cancer in the past 5 years, making it the world’s most prevalent cancer.
Survival rates differ considerably. In high income countries, the 5 year survival rate can be 90 %. In low income countries it is 40% to 60 % Screening and early treatment has contributed significantly to the reduction in mortality and hormone treatment such as ER blockers and Aromatase Inhibitors contribute substantially to reduce the risk of recurrence in ER positive BCs.
Distant recurrences occur steadily during the 20 years after diagnosis with 22% for women with zero positive lymph nodes, 31% for women with one to three positive lymph nodes and 52% for women with four to nine positive lymph nodes but up to now, there is no reliable biomarker to assess risk or early detection of recurrence of breast cancer.
We here present a biomarker to assess the risk of recurrence that may aid in appropriate treatment / treatment change = Early Detection: the identification and enumeration of the changes of intravasal tumour cells in correlation with the risk of breast cancer recurrence = treatment failure in ER + ve Breast Cancer on enocrine therapy. All patients had been treated with primary surgery plus/minus adjuvant chemotherapy. according to the guidelines.
During an observation time of up to 15 years changes in the number of intravasal tumour cells were determined in 65 patients on SERM using the maintrac® approach for immunflluorescent staining of tumor cells
A dynamic risk profile (DRiP test) was instituted from the sequential analysis of blood for the presence of live CETC/CTCs.
An increase in CETC/CTC numbers more than twofold or repeatedly was seen in 38 % of patients. This was associated with a median survival time of 1.58 years
A decrease in CTC/CETC numbers was seen in 62 % of patients. This was associated with no recurrence during the time of monitoring.
The results were statistically highly significant (p<0.001).
Comparable results were obtained for 50 patients who were treated with aromatase inhibitors (AI). An increase in CETC/CTC numbers more than twofold or repeatedly was seen in 34 % of patients. This was associated with a median survival time of 4.9 years.
A decrease in CTC/CETC numbers was seen in 66 % of patients. This was associated with a median recurrence time of 7.9 years
The results were statistically highly significant (p<0.001). Note that under AI the median recurrence time was higher in patients with increasing cell numbers but also more patients suffered relapse possibly due to a higherfraction of patients with poorer prognosis.
Conclusion
DRiP testing by regular enumeration of CTC/CETCs of ER+ve BC over a 15 year period may identify treatment effectiveness and/or Early Detection of the increased risk for recurrence in breast cancer under SERM and AI.
Results
Fig. 1
Live CETC/CTCs were defined as EpCAM-positive cells, lacking PI-staining and with intact morphology, and only these cells were counted (Fig.1).
Circulating epithelial-antigen positive cells were found repeatedly during the time of observation (Fig 2). This resulted in a trajectory of cell numbers during the observation.
An increase in CTC/CETC number was seen in 38 % of patients. This was associated with a median survival time of 1.58 years
A decrease in CTC/CETC numbers was seen in 62 % of patients. This was associated with no recurrence during the time of monitoring (up to 15 years)
The results were statistically highly significant (p<0.001)
Fig. 2
Comparable results were obtained for 50 patients who were treated with aromatase inhibitors (AI). An increase in CETC/CTC numbers more than twofold or repeatedly was seen in 34 % of patients. This was associated with a median survival time of 4.9 years.
A decrease in CTC/CETC numbers was seen in 66 % of patients. This was associated with a median recurrence time of 7.9 years.
The results were statistically highly significant (p<0.009). Fig3. Note that under AI the median recurrence time was higher in patients with increasing cell numbers but also more patients suffered relapse possibly due to a higher fraction of patients with poorer prognosis.
Discussion
Using an approach of epithelial cell enumeration with minimal cell loss, circulating cells are already detectable before detection of an asymptomatic breast cancer. Often the number of these cells already present at an elevated level in early breast cancer including DCIS.
fig.3
Conclusion
DRiP testing by serial enumeration of CETC/CTCs in ER+ve BC may identify effectiveness of treatment and/or Early Detection of the increased risk for recurrence in breast cancer under SERM.
References
Available upon request
Acknowledgement and Contact
The authors like to thank the participating patient and clinics for supplying for supplying the data and information for this pilot study.
The authors also thank the Laboratory Pachmann for anlaysing the sample and Simfo for data collection and statistical evaluation.
For further details and queries, contact Dr. Joachim Fluhrer here.