Thank you for giving us a chance to respond to the comments of Drs. Cody and Van Zee. They raise two questions regarding our work showing that the number of tumor free axillary lymph nodes is correlated to outcome in breast carcinoma. First, they point out that our study is relatively small, and that only 23% of the cohort falls into the at-risk population (≥ 20 lymph nodes). We agree that larger studies are necessary to validate our results, and hope that our study will stimulate larger cohort analysis. Unfortunately, most investigators have not recorded the total number of lymph nodes from their medical record databases. For example, in the Nurses Health Study at the Channing Laboratory and Harvard Medical School, investigators have abstracted from medical records the number of “positive” lymph nodes from > 4000 incident breast carcinoma cases, but did not enter the denominator in the database. Second, Drs. Cody and Van Zee point out that although statistical significance is not achieved, many of the criteria of aggressive disease (tumor size, age, nuclear and histologic grade, and lymphovascular invasion) tend to be overrepresented in the ≥ 20 lymph node group. They suggest that surgeons may selectively perform more aggressive axillary lymph node dissections based on a knowledge of these unfavorable tumor characteristics and that this may explain the poor outcome of patients with ≥ 20 lymph nodes. We have considered this hypothesis and provide three points that suggest it is not a valid explanation. First, surgeons may be biased on the basis of physical findings (e.g., peau d'orange, retracted nipple). However, “lymph node negative” patients generally have less aggressive tumors that do not exhibit significant physical findings. Second, tumor size also might compel surgeons to perform more aggressive axillary lymph node dissections. Size determination prior to pathologic analysis of a tumor generally is regarded as inaccurate, and thus not likely to significantly impact the surgical approach. Furthermore, our study shows that the size (volume) of the axillary lymph node dissection does not predict the number of lymph nodes found within it (see table 1 in the original article), indicating that aggressive (high volume) axillary lymph node dissections do not necessarily yield high lymph node numbers. Finally, pathologic information from a prior excisional biopsy also may bias the surgical approach. To assess this factor, we have performed a new analysis limited to those patients without a prior excisional biopsy. These patients' tumors were assessed by either a core needle biopsy or frozen section, which only determine the presence of invasive carcinoma but do not assign nuclear/histologic grade, receptor status, or ploidy. Thus the surgeon was blinded to potential aggressive characteristics in the 124 cases without prior excisional biopsy. The outcomes for patients with and without prior biopsy were virtually identical, indicating that by limiting our analysis to nonbiopsied patients we do not define a population of patients with more (or less) aggressive disease (Cox proportional hazards model: relative risk = 1.05; P = 0.897), (Mantel-Cox log rank test: P = 0.8966). When we then analyze lymph node number in the patients with no prior biopsy by multivariate analysis, it retains strong independent statistical significance (Table 1). As seen in the full 290 patient analysis, only 2 variables (≥ 20 negative lymph nodes and tumor necrosis) are statistically significant (with even higher relative risks). This suggests that even when surgeons have no information regarding the predictive characteristics of tumors, lymph node number is a strong independent predictor of survival. Robert L. Camp M.D., Ph.D.*, Eric B. Rimm D.Sc. , David L. Rimm M.D., Ph.D. , * Department of Pathology, Yale University, School of Medicine, New Haven, Connecticut, Departments of Nutrition, and Epidemiology, Harvard School of Public Health, and the Channing Laboratory;, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, Department of Pathology, Yale University, School of Medicine, New Haven, Connecticut