Multifocal and Multicentric Breast Cancer: Does Each Focus Matter?

Nathan J. Coombs, John Boyages

From the New South Wales Breast Cancer Institute, University of Sydney, Journal of Clinical Oncology, Vol 23, No 30 (October 20), 2005: pp. 7497-7502

Tumor size is an important predictor of axillary lymph node metastases with size demonstrating a direct correlation with the probability of node involvement. For unifocal disease, tumor staging is dependent on the maximum dimension of the tumor and is used as an approximation of tumor volume.

Multifocality or multicentricity in breast cancer may be defined as the presence of two or more tumor foci within a single quadrant of the breast or within different quadrants of the same breast, respectively.  Detailed serial-sectioning of mastectomy specimens identifies additional separate tumor deposits in approximately 30% of women with breast cancer. This is associated with adverse patient outcome, a propensity for axillary nodal involvement when compared with unifocal tumors, and a possible increased risk of local recurrence following breast conserving surgery. Whether multifocality confers any significant effect on overall survival when controlling for known prognostic factors remains controversial.

Most authors use The American Joint Committee on Cancer (AJCC) and the International Union Against Cancer recommendations to assess multifocal tumors. This uses the diameter of the largest tumor focus and lymph node status to stage the disease. This assumes that the prognosis is dependent solely on the largest (and possibly more aggressive) foci and extent of axillary lymph node involvement. This is the convention used for studies of screen detected breast cancer and it takes no account of the total tumor load. The probability of node involvement increases with tumors of more advanced stage when classified by the AJCC criteria,  but some authors have demonstrated that aggregate tumor size or estimates of tumor volume  may be a more accurate predictor of tumor behavior in the presence of more than one focus.

The aims of this study were to assess whether, in multifocal and multicentric disease, the largest foci dimension or the aggregate tumor size is a more accurate predictor of node status and, by inference, tumor behavior in the relationship between tumor size and axillary node involvement.

PURPOSE: The identification of multiple tumors in the breast is associated with increased nodal involvement when compared with similar staged unifocal disease. This study compares two methods of tumor size assessment to predict tumor behavior in the relationship between size and axillary node involvement for patients with multifocal and multicentric breast cancer.

METHODS: The histologic reports of every patient with multifocal breast cancer treated in New South Wales between April 1995 and September 1995 were examined. Tumors were assessed using two size estimates: (1) largest tumor focus diameter and (2) the aggregate diameters of all tumor foci. The dimensions were compared with unifocal tumors and against node positivity.

RESULTS: Ninety-four (11.1%) of 848 women had multifocal breast cancer and of these 49 women (52.1%) had axillary node involvement compared with 37.5% with unifocal breast cancer (P =.007). The use of aggregate dimension reclassified significant numbers of multifocal tumors at a more advanced stage. Use of this method to stage cancers, rather than the largest tumor size, removed the excess node positivity when compared with unifocal, stage-matched breast carcinomas.

CONCLUSION: The tendency of breast tumors to metastasize is a reflection of the total tumor load. Failure to measure the additional tumor burden provided by multiple small foci may understage a woman's disease. This may deny patients the opportunity of adjuvant therapies if the contribution of the smaller foci to the incidence of node positivity and survival is ignored.