Effect of Very Small Tumor Size on Cancer-Specific Mortality in Node-Positive BC

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J Clin Oncol. 2011 Jul 1;29(19):2619-2627, JY Wo, K Chen, BA Neville, NU Lin, RS Punglia

Results of this his retrospective study, based on data from the SEER database, of patients with breast cancer suggest that having ≥ 4 positive lymph nodes in association with smaller tumors may indicate more aggressive disease.

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Results of this his retrospective study, based on data from the SEER database, of patients with breast cancer suggest that having ≥ 4 positive lymph nodes in association with smaller tumors may indicate more aggressive disease.

SUMMARY

OncologySTAT Editorial Team

In breast cancer, tumor size and lymph node (LN) involvement are important prognostic factors. Greater tumor size in node-negative patients is predictive of higher risk of LN involvement and increased risk of breast– cancer specific mortality (BCSM). However, LN involvement with small tumors may indicate that the small tumors may be aggressive. This retrospective study evaluated the relationship between tumor size and BCSM in patients with axillary LN involvement. Data were obtained from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Cancer database. Included were patients diagnosed with unilateral breast cancer (American Joint Committee on Cancer stages I, II, or III) between 1990 and 2002 who were treated with breast-conserving surgery or mastectomy. Minimum follow-up was 4 years. Tumor sizes were classified as T1a (≤ 0.5 cm), T1b (> 0.5 and ≤ 1.0 cm), T1c (> 1.0 and ≤ 2 cm), and T2 (> 2.0 and ≤ 5.0 cm). LN involvement was classified as N0 (0 positive LNs), N1 (1–3 positive LNs), and N2 (≥ 4 positive LNs). A total of 50,949 patients were eligible, of whom 6997 (13.7%) died of breast cancer. LN involvement differed significantly based on tumor size, histologic grade, estrogen receptor (ER) status, progesterone receptor (PR) status, and number of LNs dissected. Older age, non–African American race, smaller tumor size, lower histologic grade, ER positivity, PR positivity, and limited LN dissection were associated with absence of LN involvement.

Breast–cancer specific survival was associated, on univariate analysis, with year of diagnosis, age, race, tumor size, LN involvement, tumor grade, ER status, PR status, and number of LNs dissected. On multivariate analysis, tumor size and LN involvement significantly interacted (P < .001) with respect to BCSM. Independent factors significantly associated with increased BCSM were earlier year of diagnosis, older age, African American race, higher tumor grade, absence of ER status, absence of PR status, more extensive LN dissection, larger tumor size, and greater LN involvement.

In patients with ≥ 4 positive LNs, tumors sized > 0.5 and ≤ 1.0 cm (ie, T1b) were associated with significantly lower BCSM compared with smaller tumors (ie, T1a; hazard ratio [HR], 0.60; 95% CI, 0.39–0.91; P = .02). Unadjusted 8-year breast–cancer specific survival (BCSS) was 62%, 74%, 69%, and 57%, respectively, in patients with T1aN2+, T1bN2+, T1cN2+, and T2N2+ disease. BCSM did not differ significantly among patients with T1aN2+ vs T1cN2+ or T2N2+ tumors. In patients with 1 to 3 positive LNs, BCSM did not differ significantly between patients with T1a tumors vs T1b or T1c tumors. BCSM was significantly greater in patients with T2N1 tumors compared with those with T1aN1 tumors (HR, 2.01; 95% CI, 1.38–2.93; P < .001). In general, in patients with small tumors and LN involvement, BCSM decreased with increasing tumor size to a threshold value, after which BCSM increased with tumor size. This effect increased with the extent of nodal involvement (N0 vs N1 vs N2+; P < .001).

In ER-negative patients with ≥ 4 positive LNs, BCSM was significantly lower in patients with T1b tumors compared with those with T1a tumors (HR, 0.52; 95% CI, 0.29–0.94; P = .03), although T1a tumors did not differ significantly from T1c or T2 tumors. In addition, T2N1 tumors were associated with increased BCSM compared with T1aN1 tumors (HR, 1.66; 95% CI, 0.99–2.78; P = .05).

In ER-positive patients with ≥ 4 positive LNs, BCSM did not differ significantly among patients with T1a, T1b, T1c, or T2 tumors. In ER-positive patients with 1 to 3 positive LNs, BCSM was significantly higher in patients with T2N1 tumors compared with those withT1aN1 tumors (P = .002).

Very small tumors with extensive nodal involvement were associated with increased risk of BCSM, suggesting that these represent more aggressive tumor types.

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