Accuracy of the extent of axillary nodal positivity related to primary tumor size, number of involved nodes, and number of nodes examined

Abstract

Purpose: While a number of studies have evaluated the minimum number of axillary nodes that need to be examined to accurately determine nodal positivity or negativity, there is little information on the number of nodes which must be examined to determine the extent of nodal positivity. This study attempts to determine for patients with 1–3 positive nodes the probability that the number of positive nodes reported is the true number of positive nodes as well as the probability that 4 or more nodes could be positive based on primary tumor size and number of nodes examined.

Materials and Methods: From 1979 to 1998, 1652 women with Stages I–II invasive breast cancer underwent an axillary dissection as part of their breast conservation therapy and had more than 10 lymph nodes examined. The mean and median number of nodes identified in the dissection was 19 and 17 (range, 11–75). The median age was 55 years. A total of 1155 women had T1 tumors and 497 had T2 tumors. Of the 459 node-positive women, 72% had 1–3 positive nodes, 18% had 4–9 positive nodes, and 10% had 10 or more positive nodes. A mathematical model based on tumor size and number of nodes examined was created using the hypergeometric distribution and Bayes Theorem. The resulting model was used to estimate the accuracy of the reported number of positive nodes and the probability of 4 or more positive nodes based on various observed sampling combinations.

Results: For patients with T1 tumors and 1, 2, or 3 positive nodes, the minimum number of nodes examined needed for a 90% probability of accuracy is 19, 20, and 20. For T2 tumors and 1, 2, or 3 positive nodes, a minimum of 20 nodes is required. The probability of 4 or more positive nodes increases as tumor size and the number of reported positive nodes increase and as the number of examined nodes decreases. For a 10% or less probability of 4 or more positive nodes, a patient with a T1 tumor and 1, 2, or 3 observed positive nodes would require a minimum of 8, 15, and 20 nodes removed. For a T2 tumor and 1, 2, or 3 observed positive nodes, the corresponding numbers are 10, 16, and 20.

Conclusion: The accuracy of the extent of axillary nodal positivity is influenced by the number of observed positive nodes, tumor size, and the number of nodes examined. Underestimation of the number of positive nodes will result in errors in the assessment of an individual’s risk for locoregional recurrence, distant disease, and breast cancer death and will adversely impact on treatment recommendations. This model provides the clinician with a means for assessing the accuracy of the number of positive nodes reported in patients with 1–3 positive nodes.

Introduction

Breast cancer recurrence rates and survival are significantly influenced by the pathologic status of the axillary nodes. Knowledge of the presence or absence of nodal positivity provides important prognostic information and not infrequently impacts on recommendations for local-regional treatment and/or systemic therapy. A number of studies have focused attention on the minimum number of axillary nodes which need to be examined to accurately determine nodal positivity or negativity 1, 2, 3, 4, 5. The majority of these studies suggest that at least 10 nodes should be examined to avoid a false-negative axilla.

However, there is little information on the number of nodes which need to be examined in node positive patients to accurately determine if a specific number are involved. The total number of positive nodes influences the risk of a locoregional recurrence, distant disease, and breast cancer death 6, 7. Commonly accepted subdivisions of node positive patients with prognostic significance include the categories of 1–3 positive nodes vs. 4 or more 8, 9, 10, 11. The finding of 4 or more positive nodes is generally considered an indication for postmastectomy radiation or treatment to the supraclavicular region in patients with an intact breast receiving radiation 12, 13. These patients are also candidates for an Intergroup prospective randomized trial evaluating dose-intense chemotherapy with peripheral stem cell rescue. Therefore, the accurate determination of the number of positive nodes is important for treatment decisions as well as prognosis.

Much of our knowledge on the prognostic and therapeutic significance of the number of positive axillary nodes has been derived from patients who have had a complete dissection in which the mean or median number of nodes removed ranges from 15 to 20 or higher 7, 14, 15. However, there appears to be a trend in surgical practice to remove fewer axillary nodes in order to decrease subsequent morbidity. A Level I–II dissection in patients undergoing breast conservation therapy appears to accurately assess the status of the axillary nodes in the majority of patients 14, 16, 17, 18. The sentinel node biopsy procedure may ultimately replace the axillary dissection as the primary staging procedure especially in axillary node negative women (19). However, in axillary node positive women, an underestimation of the number of positive nodes has the potential for adversely affecting treatment recommendations and therefore outcome.

The purpose of this study was to develop a mathematical model based on tumor size and number of nodes examined in patients with 1–3 positive nodes that would assess the probability that the number of positive nodes found is the true number of positive nodes as well as the probability that 4 or more nodes would be positive if more nodes had been examined.