Biological significance of occult micrometastases in histologically negative axillary lymph nodes in breast cancer patients using the recent American Joint Committee on Cancer breast cancer staging system.

The biological significance of occult metastases in axillary lymph nodes of breast cancer patients is controversial. The purpose of the study was to determine the prognostic significance of occult micrometastases using the current American Joint Committee on Cancer (AJCC) staging system in a cohort of women with node-negative breast cancer, of whom 5% received adjuvant systemic therapy and who all had long-term follow-up. We studied a cohort of 214 consecutive histologically node-negative breast cancer patients with a median follow-up of 8 years. Blocks of the axillary lymph nodes were assessed for occult micrometastases by examination of an additional hematoxylin-eosin-stained slide and by immunohistochemical staining using an antibody to low molecular weight keratin. Occult metastases were classified according to the sixth edition of the AJCC cancer staging manual. We examined the prognostic effects of occult micrometastases and other clinicopathologic features on recurrence outside the breast with disease-free interval (DFI) and survival from breast cancer with disease-specific survival (DSS). Cytokeratin-positive tumor cells were identified in the lymph nodes in 29 of 214 cases (14%). Two cases had isolated tumor cells and no cluster larger than 0.2 mm [pN0(i+)], whereas 27 of 214 (13%) had micrometastases (larger than 0.2 mm and

Ascertaining prognosis for breast cancer in node-negative patients with innovative survival analysis.

Clinical decisions to administer adjuvant systemic therapy to women with early breast cancer require knowledge about baseline prognosis, which is only assessable in the absence of such adjuvant treatment, which most patients currently do receive. The Cox model is the standard tool for assessing the effect of prognostic factors; however, there may be substantive differences in the estimated prognosis obtained by the Cox model rather than a log-normal model. For more than 50 years, clinical breast cancer data for cohorts of patients have supported the choice of a log-normal model. The prognostic impact of model type is examined here for a cohort of breast cancer patients, only 7% of whom received adjuvant systemic therapy. We quantitated prognosis utilizing Kaplan-Meier, Cox, and log-normal survival analyses for 415 consecutive T1-T3, M0, histologically node-negative patients who were operated on for primary breast cancer at Women's College Hospital between 1977 and 1986. Recurrence outside the breast for disease-free interval (DFI) and breast cancer death for disease-specific survival (DSS) were the events of interest. The patient follow-up for these investigations was 96% complete: a median 8 years for those surviving. Factors used in these investigations were age, weight, tumor size, histology, tumor grade, nuclear grade, lymphovascular invasion, estrogen receptor (ER), progesterone receptor (PR), combined ER/PR receptor, overexpression of neu oncoprotein, DNA ploidy, S-phase, and adjuvant therapy. In our study we found evidence against the Cox assumption of proportional hazards, which is not an assumption for the log-normal approach. We identified patients with greater than 96% and others with less than 40% DSS at 10 years. The difference in prognosis determined by using the Cox versus the log-normal model ranged for DFI from 1.2% to 8.1%, and for DSS from 0.4% to 6.2%; interestingly, the difference was more substantial for patients with a high risk of recurrence or death from breast cancer. Estimated prognoses may differ substantially by survival analysis model type, by amounts that might affect patient management, and we think that the log-normal model has a major advantage over the Cox model for survival analysis.

Prognostic factors affecting the natural history of node-negative breast cancer.

PURPOSE: We undertook a natural history investigation of a broad selection of prognostic factors in a cohort of women with node-negative breast cancer. PATIENTS AND METHODS: The cohort consisted of 415 consecutive histologic node-negative (T1-3, M0) patients, operated on for primary breast cancer at Women's College Hospital, Toronto, Canada, between 1977 and 1986. Only 7% of these patients were given adjuvant systemic therapy; further, for the 48% of women who underwent lumpectomy, only 29% received adjuvant radiotherapy to the breast. Paraffin-embedded tumour tissue was available for the majority of patients. The following factors were examined for their univariate and multivariate effects on time to recurrence outside the breast (DFI) and survival from breast cancer (DSS): age, weight, tumour size, estrogen receptor, progesterone receptor, histologic type, tumour grade, nuclear grade, lymphovascular invasion, overexpression of neu oncoprotein, DNA ploidy, % cells in S-phase, and adjuvant therapy. Multivariate analyses utilized a Cox model with a step-wise factor selection for the 260 patients with complete information. RESULTS: A worse prognosis was indicated when there was lymphovascular invasion (for DFI, p < 0.001; for DSS, p = 0.0046), high %S-phase (for DFI, p = 0.08; for DSS, p = 0.02), high tumour grade (for DFI, p = 0.02; for DSS, p = 0.03), and overexpression of neu oncoprotein (for DSS, p = 0.07). CONCLUSIONS: In our natural history investigation, two factors, lymphovascular invasion and tumour grade, are of particular interest since they may be readily incorporated into clinical practice. Overexpression of neu oncoprotein may also play a role in determining prognosis for women administered adjuvant systemic therapy.