Extent Of Axillary Node Involvement Research Articles

Validation of the Louisville Breast Sentinel Node Prediction Models and a Proposed Modification to Guide Management of the Node Positive Axilla

The ACOSOG Z11 trial is rapidly changing use of axillary dissection, but it is not known how generalizable the Z11 results are. This study compares characteristics of the Z11 patients with the larger group of sentinel node-positive patients and evaluates two previously described Louisville algorithms to determine whether they might still be useful to predict extent of axillary node involvement and guide management of the axilla. The Yale Breast Center database was queried to calculate the Louisville prediction points for patients with a positive sentinel node and to compare the predicted with actual results. Of 1215 sentinel node biopsies performed between 2004 and 2010, 282 (23%) had at least one positive node. Thirty-one per cent of these patients would have been eligible for Z11. This group had much less axillary node involvement than the 69 per cent who were ineligible. The Yale data confirmed the accuracy of the two Louisville models and showed that tumor size, number of positive sentinel nodes, and proportion of positive sentinel nodes were all significant predictors. However, these results were much more robust if at least three sentinel nodes had been removed. The Z11 patients were clearly a good risk group. The data validate the two Louisville models and suggest that the models may be useful to select patients to avoid axillary dissection, both among the currently Z11-eligible and -ineligible populations. A modified algorithm is proposed in which all patients with a positive sentinel node have at least three total nodes removed.

Lessons From the Initial Adjuvant Cyclophosphamide, Methotrexate, and Fluorouracil Studies in Operable Breast Cancer

In 1975, we presented our first report on the efficacy of cyclophosphamide, methotrexate, and fluorouracil (CMF) delivered in 1-month cycles for 12 months as adjuvant treatment for nodepositive breast cancer. These results, along with those reported in a similar patient population by the National Surgical Adjuvant Breast and Bowel Project, raised hopes that chemotherapy could have a more central role in the primary management of this common cancer, and were of seminal importance for all the studies on adjuvant systemic therapy conducted throughout the world. Among the numerous questions to be answered after the first CMF study was the optimal duration of treatment. In fact, a relatively short-term effective adjuvant chemotherapy would spare the patients a considerable amount of toxicity. For this reason, in September 1975, we started a new randomized study with the intent of evaluating the possibility of reducing the duration of CMF without compromising its therapeutic effects. The 5-year results of the study showed that 1-month cycles for 6 months of CMF yielded results that were identical to those obtained with 12 cycles. The long-term analysis after a median follow-up of 25 years confirmed that a longer duration of the same drug regimen was unable to improve treatment outcome. The pattern of relapse-free survival was superimposable in the two treatment groups, the estimated relapse-free survival rates were 39% after 12 cycles and 38% after six cycles of CMF, and the overall survival rates were 40% in both treatment arms. In the multivariate analysis, the only variable able to influence treatment outcome was the extent of axillary node involvement; patients with more than three involved nodes were at a significantly higher risk of disease relapse and death (hazard rate, 2.3; P .0001). Neither estrogen-receptor status nor size of the primary tumor was able to affect therapeutic outcome significantly. In response to the early results observed in the abovementioned study, in the early 1980s our own research group tested in a random fashion whether the inclusion of a non– crossresistant agent such as doxorubicin (DOX) could be of benefit in patients with positive nodes. The choice of DOX was based on its great efficacy in metastatic and locally advanced breast cancer and on the low reported incidence of congestive heart failure when the total dose was less than 400 mg/m of the body-surface area. In women at high risk of disease relapse because of extended axillary involvement ( three positive nodes), we reasoned that DOX, either given first and followed sequentially by CMF or interspersed with CMF, had the potential to improve treatment outcome. A 20-year analysis confirmed the superiority of the sequential delivery of DOX as first treatment for four cycles followed by intravenous CMF (DOXCMF) compared with the alternating delivery of the same regimens (CMF/DOX). In fact, after DOXCMF, the risk of developing disease relapse was reduced by approximately 32% (P .0017) and the risk of dying as a result of all causes was reduced by approximately 26% (P .018). The improved outcome in the sequential arm was not impaired by the occurrence of congestive heart failure. It is important to note that the 5-year joint efficacy analysis of the National Epirubicin Adjuvant Trial and of the Scottish Cancer Trials Breast Group reported a highly significant benefit in favor of the sequential administration of epirubicin for four cycles followed by CMF compared with CMF alone, supporting the hypothesis that single-agent anthracyclines given first, before CMF, can indeed improve treatment outcome. In patients with one to three involved axillary nodes, we randomly assessed whether the addition of single-agent DOX for four cycles administered after intravenous CMF given for approximately 6 months could overcome resistance putatively induced by the alkylating regimen alone. The 20-year analysis showed that approximately half of the patients in this study were alive and disease free regardless of whether they received CMF alone or CMF sequentially followed by DOX. Although available long-term results failed to detect any statistically significant difference from the addition of DOX in the overall population of patients enrolled onto the study, a retrospective analysis on the predictive relevance of the status of human epidermal growth factor receptor (HER2) showed a trend for an increased benefit of the DOX combination in patients with HER2-positive tumors. This observation further emphasizes the need for a priori characterization of markers predicting for response, and for eventually tailoring adjuvant treatment to individual patients—a goal that is currently being pursued, but was inconceivable at the time when the study protocol was designed. JOURNAL OF CLINICAL ONCOLOGY C E L E B R A T I N G 2 5 Y E A R S O F J C O VOLUME 26 NUMBER 3 JANUARY 2

Prediction in breast cancer of the extent of axillary node involvement from the size and lymphovascular invasion status of the primary tumour: Medico-legal considerations

Aim To ascertain for medico-legal purposes in the United Kingdom, the extent to which in breast cancer primary tumour size and lympho-vascular invasion (LVI) status determine axillary node staging. Methods Four hundred and fifty symptomatic patients had their tumour sizes stratified into 1 cm ranges and the percentage incidence/probability of the axillary stage being 1, 2 or 3 was calculated separately for those tumours that showed no evidence of LVI and those that did. Results The presence of LVI has a marked effect on the likelihood and extent of axillary node involvement for all primary tumour sizes. Conclusions This needs to be recognized and quantified when prediction of this extent is made for medico-legal purposes. Within the constraints of the ‘balance of probabilities’ argument in UK law, it is rarely possible to differentiate between the likelihood of the axillary stage being 2 or 3.

Basic principles and value of lymphadenectomy in breast carcinoma

Axillary lymph node dissection combined with resection of the primary tumor remains the standard surgical treatment for invasive breast cancer. Tumor size and the extent of axillary node involvement have the greatest influence on the prognosis and are therefore the most important indicators when planning adjuvant therapy. The extent of axillary lymph node dissection in small primary tumors and the value of resecting the internal mammary nodes are still being debated. Furthermore, the importance of axillary dissection could be influenced by other recently established factors.

Assessment of axillary lymph node status.

Three methods of assessing axillary lymph node status were compared: In 149 patients assessed clinically, positive nodes were not detected in 31 (45%) of 69 patients with pathologic Stage II disease. Histologic examination of selected axillary nodes biopsied from 54 patients immediately prior to mastectomy, failed to detect metastatic disease in 11 (42%) of 26 patients with pathologic Stage II disease. Examination of lymph nodes in the axillary tail of 95 mastectomy specimens failed to diagnose axillary involvement in six (14%) of 43 patients with pathologic Stage II disease. Thus, none of the techniques determined the extent of axillary node involvement.