BACKGROUND Multicentric breast carcinomas have a higher frequency of axillary lymph node metastasis than unifocal tumors of similar stage. It remains unclear whether this merely reflects larger tumor volumes or a different biologic behavior. The authors have shown previously that when aggregate tumor diameter are used for staging, unifocal and multifocal tumors have a similar frequency of axillary lymph node metastasis. However, summing diameter overestimates actual tumor volume because volume is proportional to the third power of the diameter. Therefore, the aim of the current study was to reanalyze the relation between size and axillary lymph node status by correcting for tumor volumes and surface areas. METHODS Volumes and surface areas of 122 breast tumor specimens with multiple macroscopic nodules (two foci: n = 95; three foci: n = 22; three foci: n = 5) were calculated by approximating the shape of each tumor nodule to an ellipsoid (for volume) or to a prolate spheroid (for area). For comparison, the authors used an internal control series, comprised of 469 macroscopic unifocal tumors. For all patients, multiple assessments of largest tumor size and combined size of all foci were correlated with the status of axillary lymph nodes. The associations between lymph node status, tumor volume or area, and multifocality were modeled using univariate and multivariate logistic regression. RESULTS When either the largest or the aggregate tumor volume was used as a size estimate, tumor specimens with multiple nodules had a higher frequency of lymph node involvement compared with unifocal tumors of a similar volume or area. The odds ratio (OR) for having positive lymph nodes was 2.34 for aggregate volume measurement (P < 0.001). Surface area estimates yielded similar results (OR = 2.2, P < 0.001). CONCLUSIONS Breast tumors with multiple macroscopic nodules had a different biology, with a propensity to dissemination at smaller tumor volumes (i.e., there was another factor besides volume alone that accounted for the differences in behavior). Cancer 2004;100:20–7. © 2003 American Cancer Society.

BACKGROUND For unifocal invasive breast carcinoma, increasing tumor diameter predictably correlates with a greater frequency of lymph node involvement, thereby facilitating treatment decisions. In invasive breast tumors presenting with multiple nodules, however, it is unclear whether tumor size correlates with lymph node dissemination in a similar manner. METHODS The authors analyzed a series of 101 invasive breast carcinomas presenting with multiple macroscopically apparent lesions (2 foci: n = 77; 3: n = 20; 4: n = 4). Two different assessments of the tumor size (diameter of largest focus and combined diameter of all the foci) were then correlated with the status of axillary lymph nodes. For comparison with unifocal tumors, the authors used both external and internal control series (the latter consisting of 469 patients from their institution). The associations between lymph node status, tumor size, and multifocality were modeled using univariate and multivariate logistic regression, for each modality of tumor size assessment. RESULTS The logistic curves for multifocal and unifocal tumors were significantly different when the largest diameter was used as a tumor size estimate. Multifocal cases had higher frequencies of lymph node involvement than unifocal lesions of similar size category. In a multivariate logistic regression, the odds ratio of positive lymph node status in multifocal versus unifocal cases was 2.8 using largest diameter as a tumor size estimate (P < 0.0001). When the combined diameter assessment was used, however, the regression curve of multifocal cases was similar to that of unifocal cases, and the frequency of lymph node positivity was not significantly different in multifocal versus unifocal cases of the same size (odds ratio, 1.4; P = 0.13). CONCLUSIONS The authors' results show that, if aggregate diameters are used, unifocal and multifocal breast carcinomas are similar with respect to frequency of regional lymph node metastasis. Currently used algorithms, which use the diameter of the largest nodule, result in understaging of multifocal breast carcinomas due to underestimation of actual tumor size. Cancer 2002;94:1383–90. © 2002 American Cancer Society. DOI 10.1002/cncr.10331