Stereologic estimation of breast tumor size.

OBJECTIVE: The largest tumor diameter, D(T), is a variable of great clinical value in breast cancer but a biased and imprecise estimator of real tumor size. Three-dimensional, shape-independent estimates would more realistically reflect the tumor bulk and provide more accurate clinical staging. For experimental oncology, the measurements may be useful for precise assessment of tumor burden. STUDY DESIGN: In 64 prospectively collected breast cancers, unbiased stereology was used for estimating the gross tumor volume, V(T), cutting specimens into parallel, equally thick sections with subsequent determination of total tumor sectional area. For comparison, the volume of invasive tumor epithelium, "V"(epi), was obtained by microscopic examination of systematically sampled tissue fractions of the same tumors, embedded in both methacrylate and paraffin. RESULTS: The median D(T) was 2.2 cm, and the median V(T) was 6.72 cm3. The correlation between these variables was not very close (r = .77), and the slope of the regression line was steeper than expected, presumably reflecting a change in tumor shape with growing size. The sampling scheme used for estimation of V(T) proved highly efficient, yielding a mean error coefficient of 9%. The median "V"(epi) in methacrylate was 1.19 cm3, 21% larger than in paraffin. Estimates of "V" (epi) were highly reproducible (r = .97) and correlated highly with point counting-based estimates of the feature (r = .96). "V"(epi) correlated with V(T) (r > or = .75), but the slopes of the regression lines were steeper than expected, corresponding with the correlation found between epithelial volume fraction and tumor size (r = .26). On average, about 25% of the gross tumor was composed of invasive epithelium, but with a wide range. CONCLUSION: In breast cancer, realistic estimates of tumor volume, volume of invasive epithelium and epithelial volume fraction can be obtained by efficient stereologic techniques, which seem useful for clinical and experimental oncology. In the present methodologic study, baseline data were generated. Further studies are needed to assess the clinical value of stereologic tumor size estimates as compared with traditional staging parameters.