Effect of large tumor size on cancer-specific mortality in node-negative breast cancer

To examine the relationship between large tumor size and breast cancer-specific mortality (BCSM), especially in a subset of patients with negative lymph nodes (LNs).

We used the Surveillance, Epidemiology and End Results registry to identify 107,705 female patients diagnosed from January 1, 1990, through December 31, 2003, as having invasive breast cancer and treated with surgery and LN dissection. Relevant issues unclear in the database were studied in an additional 335 patients with locally advanced disease treated with neoadjuvant chemotherapy.

In the multivariable analysis, a significant interaction was found between tumor size and LN involvement (P<.001). In LN-negative diseases, the relationship between tumor size and BCSM was piecewise. Using 21- to 30-mm tumors as the reference, the hazard ratio (HR) of BCSM increased with increasing tumor size until a peak at 41 to 50 mm (HR, 1.49; P<.001), after which increasing tumor size was unexpectedly related to decreasing hazard, with a nadir at 61 to 80 mm (HR, 1.06; P=.70). The 61- to 80-mm tumors exhibited a significantly lower BCSM compared with the 41- to 50-mm (P=.02) and greater than 80-mm (P=.03) subgroups. This pattern remained after stratification by estrogen receptor status but was not observed in patients with LN-positive disease. Further analysis indicated that the survival advantage of 61- to 80-mm tumors in LN-negative disease might result from its low risk of distant metastasis.

A relatively larger tumor size without LN involvement may be a surrogate for biologically indolent disease of distant metastasis. Our findings, if validated in other large databases, may provide better understanding of breast cancer biology.