Cole Relaxation Frequency as a Prognostic Parameter for Breast Cancer

Abstract

We previously reported successful classification of breast cancer versus benign tissue using the Cole relaxation frequency measured on tissue excised during breast surgery as part of a study at two urban hospitals in the U.S. Midwest. Using that health system's cancer registry, we have discovered retrospectively that outcomes for patients who participated in the initial study can be classified correctly in 3 well-differentiated categories: nonrecurrent (NR); recurrent with no metastasis (RNM); and recurrent with metastasis (RM). As Cole relaxation frequency increases, the classification moves from NR to RNM and finally to RM. Multivariate analysis showed a significant association of "time-cancer-free" for all patients in these recurrent categories, with P-values ranging between 0.0001 to 0.0047. Thus, this follow-up report shows the potential feasibility of using Cole relaxation frequency as a prognostic parameter in a larger prospective study.

Keywords: Cole relaxation frequency; bioelectrical impedance; breast cancer; prognosis; recurrence.

Figure 1

Likelihood regions obtained from a quadratic fit of likelihood (L) data vs normalized Cole relaxation frequency (nCRF). Three regions are identified: no recurrence (L-NR) with nCRF of <3; recurrence with no metastasis (L-RNM) with nCRF of 3–6; recurrence with metastasis (L-RM) with nCRF of >6. The standard error bars for the L-RNM region (plotted in blue) are very small compared to the L-RM region (plotted in red) due to a smaller number of data points in the L-RM region.

Figure 2

This plot compares exceedance averaged time-cancer-free for normalized Cole relaxation frequency (nCRF, in green) and Nottingham Prognostic Index (NPI, in red). The prognosis for time-cancer-free (years) is plotted on the vertical axis. The slope of the nCRF plot changes abruptly at two region boundaries — where L-NR changes to L-RNM and where L-RNM changes to L-RM. NPI plots do not have similar demarcations at the boundary of regions NPI-1 to NPI-2, but there is a change of slope at NPI-2 to NPI-3. The t-test for independence for these regions is displayed below the figure and shows that NPI is only a prognostic parameter for recurrence with metastasis, while nCRF distinguishes all regions, one from the other, allowing statistically significant discrimination of no recurrence (NR), recurrence with no metastasis (RNM), and recurrence with metastasis (RM).