Nodal Ratio Predicts Breast Cancer Recurrence, Survival

PHILADELPHIA—At the 48th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), researchers presented two analyses showing that in node-positive breast cancer, the nodal ratio—the number of positive nodes divided by the number of nodes resected—is superior to the absolute nodal count as a clinical predictor of treatment outcomes. Further, using nodal ratios, M.D. Anderson researchers were able to partially reconcile differences in locoregional recurrence rates in trials of postoperative radiation therapy in mastectomy patients. [See also article on page 45 concerning the benefit of radiotherapy after mastectomy.]

Wendy A. Woodward, MD, PhD, of The University of Texas M.D. Anderson Cancer Center (abstract 10), reexamined data from the British Columbia Randomized Radiation Trial, conducted in patients with node-positive breast cancer treated with mastectomy and adjuvant chemotherapy. This study demonstrated improved overall survival in patients with positive nodes who also received postoperative radiation therapy. Similar results were seen when patients were stratified by the number of involved nodes.

Somewhat surprisingly, these results did not lead to universal adoption of radiotherapy, "partially because locoregional recurrence rates in patients with 1 to 3 positive nodes were higher than the rates seen in some North American series," Dr. Woodward said. The apparently higher rate of locoregional failure in women classified as low risk in the British Columbia study may have been an artifact of the relatively small number of nodes resected.

The researchers compared patients from the no-radiation arm of the British Columbia trial (123 women, all premenopausal) with similar patients (505 women 50 years of age or younger) who received mastectomy and chemotherapy but no radiation as part of M.D. Anderson Cancer Center clinical trials.

The median number of nodes dissected was 11 in the British Columbia patients and 17 in the M.D. Anderson patients (P < .0001). Other clinical factors such as T stage, nodal status, estrogen-receptor status, and nodal ratio did not differ between the two datasets.

At 15 years, locoregional recurrence rates were significantly different between the two datasets in risk groups classified by the number of positive nodes: 26% (British Columbia) vs 11% (M.D. Anderson) in women with 1 to 3 positive nodes, and 61% vs 30%, respectively, in women with 4 to 9 positive nodes.

However, when patients were reclassified according to nodal ratio, there were no significant differences between the two datasets in the lowest risk cohorts. Nodal ratios of 0% to 10% were associated with locoregional recurrence rates of 15% (British Columbia) and 9% (M.D. Anderson), and nodal ratios of 10% to 20% with locoregional recurrence rates of 25% and 18%, respectively.

The predictive use of nodal ratios is most relevant for patients with 1 to 3 positive nodes because the higher the nodal ratio, the greater the likelihood that the patient had additional positive nodes that were not detected, Dr. Woodward said. For example, if 3 nodes were resected and all were positive, the nodal ratio would be 100% and the chance of there being more positive nodes would be high.

In a multivariate analysis in the overall cohort, the nodal ratio was the most accurate predictor of local recurrence, with "far and away" the highest hazard ratio, compared with other factors, Dr. Woodward said. "We conclude that the nodal ratio is superior to the absolute number of nodes for grouping patients with similar local failure risks," she said. "Nodal ratios of 20% or higher are associated with a local failure risk that most would agree warrants postmastectomy irradiation."

Patient Survival and Nodal Ratio

Patricia Tai, MD, of the Allan Blair Cancer Center, Regina, Saskatchewan, Canada (abstract 12), and her colleagues looked at nodal ratio in a population database of all breast cancer cases in Saskatchewan with onset between 1981 and 1995, with follow-up information updated in 2005.

The series included 1,255 node-positive patients who had dissection of 10 or more axillary nodes. Nodal ratio was classified as low (25% or less) in 53% of patients, medium (more than 25% up to 75%) in 31% of patients, and high (more than 75%) in 16% of patients.

The nodal ratio was highly predictive of overall survival in a multivariate analysis that also included other known prognostic factors, Dr. Tai said.

Furthermore, the nodal ratio identified subsets of women who benefited from radiation therapy. Regional radiation therapy reduced the rate of locoregional recurrences in women with a medium nodal ratio, but not a low or a high ratio.

Radiotherapy was associated with improved overall survival in women with medium and high but not low nodal ratios, Dr. Tai said. For women with 25% to 75% positive nodes, 10-year overall survival was 48% with radiotherapy and 32% without (P =.006). In women with a high nodal ratio, 10-year overall survival was 19% with radiotherapy and 10% without (P = .008).

Dr. Tai concluded that the nodal ratio is a highly significant prognostic factor in patients who have had adequate axillary dissection. Regional radiotherapy does not benefit those with a low nodal ratio, but does result in significant improvements in survival in those with more than 25% positive nodes.

Take Home Point

In node-positive breast cancer, nodal ratio (number of positive nodes/number of nodes dissected) better predicts treatment outcome than does the absolute number of positive nodes, and may help identify patients who would benefit from postoperative radiotherapy.