Early Results of Omitting Completion Axillary Lymph Node Dissection in Sentinel Lymph Node Metastasis-Positive Breast Cancer Patients ()
1. Introduction
Sentinel lymph node biopsy (SNB) has been used as a standard procedure for the management of early breast cancer patients who have no clinical axillary lymph node metastasis (N0) [1,2]. If the SN is negative, axillary dissection (ALND) can be omitted, but if the SN is positive for metastasis, completion ALND is generally warranted [3]. However, after release of the results of the American College of Surgeon’s Oncology Group (ACOSOG) Z0011 randomized clinical trial [4], the National Comprehensive Cancer Network’s (NCCN) Practice Guidelines issued in 2012 recommended avoidance of completion ALND as an option in selected SNB-positive cases [5].
Since March 2003, which predates that NCCN recommendation, we have been omitting the completion ALND in N0 patients even if they are SNB-positive. The scientific basis for that policy is as follows: 1) First, in the case of axillary node micrometastasis, it was reported that the incidence of axillary recurrence is low even when completion ALND is not performed, and the survival results do not differ between the dissected and non-dissected patient groups [6-8], and 2) then, even in the case of overt axillary metastasis, it was shown that rescue surgery was feasible and there was no effect on survival [6-8]. Therefore, since 2003 we obtain written informed consent and then skip ALND in selected SNB-positive cases. To date, the median follow-up period for our patients has been over 3.7 years, and we think that our data are of value for assessing lymph node recurrence. Accordingly, we report here the results of our comparative analysis of SNB-positive patients who did not undergo completion ALND and SNB-negative patients. We compared the two patient groups in regard to the clinicopathological findings and recurrence, tested for associations between recurrence and the clinicopathological findings, and also analyzed the recurrence-free survival.
2. Patients and Methods
We identified the SN using CT-lymphography (CTLG) combined with dye-staining [9,10] because our institution is not equipped with RI facilities. Clinicopathological studies to determine the metastatic status of SNs were performed on 2-mm sections of hematoxylin-eosin (HE)- stained surgical permanent specimens. SNB-positive cases were treated by one of two methods chosen in accordance with each patient’s expressed desire after written informed consent had been obtained. That is, when the SNB was positive for metastasis following the surgery, the patient was allowed to choose one of two treatment options: 1) performance of completion ALND, followed by performance of adjuvant therapy, or 2) performance of appropriate adjuvant therapy, including axillary radiation therapy, with repeat performance of dissection at the time of any overt recurrence. For patients whose SNB was negative for metastasis, adjuvant therapy was decided on the basis of the subtype classification of the primary lesion. This study was carried out after its design had been approved by the Ethics Committee of National Hospital Organization Higashi-Tokushima Medical Center.
From March 2003 through September 2012, our hospital treated 663 primary breast cancer patients by performing axillary surgery that was limited to SNB. This study enrolled 489 of those patients who had invasive ductal carcinoma, while 46 patients who had undergone preoperative chemotherapy, 102 patients with ductal carcinoma in situ and 26 patients with a special pathological subtype of disease were excluded.
Recurrent breast cancer can have various presentations: axillary lymph node recurrence, recurrence in other lymph nodes (i.e., the ipsilateral supraclavicular, subclavicular and internal mammary nodes), distant recurrence, recurrence in the ipsilateral breast and recurrence in the contralateral breast. For this study, contralateral breast cancer recurrence was considered to be development of a new lesion and thus excluded from the category of “recurrence”.
The clinicopathological findings were analyzed for associations with the SNB status, i.e., positive or negative for metastasis. Recurrence was also analyzed for association with the status of SN metastasis. Moreover, for all recurrent events (excluding contralateral breast cancer recurrence), the status of recurrence and the clinicopathological findings were analyzed for associations and recurrence-free survival was also analyzed.
For statistical analyses of the data, Fisher’s exact test was used to analyze for associations between the status of SN metastasis (positive vs. negative) and the clinicopathological findings, including recurrence. Clinicopathological characteristics that showed possible association with recurrence in univariate analysis, were analyzed by multivariate analysis using logistic regression analysis. Recurrence-free survival was analyzed using the Cox proportional hazards model, taking into account several covariates. Statistical tests provided two-sided p values, and a significance level of p < 0.05 was used. Statistical analyses were carried out using the R statistical environment version 2.13.0 (http://www.r-project.org/).
3. Results
3.1. Demographic Data for the 489 Enrolled Patients and Comparison of Pathological Findings in SNB-Negative Patients and SNB-Positive Patients
The age range was 29 - 85 years (median: 55 y), with 33% being ≤49 yo and 67% being ≥50 yo. The number of biopsied lymph nodes per patient was 1 - 3, with a mean of 1.7. Receptor analyses indicated that the rates of ERpositive, PgR-positive, HER2-positive and triple-negative (TNBC) patients were 80%, 70%, 6% and 11%, respectively. The tumor size was ≤2 cm in 86% of the patients, while 62% were nuclear grade 1. The surgical procedure was breast-conserving therapy in 91% of the patients. SNB-negative patients numbered 430 (87.9%), while 59 patients (12.1%) were SNB-positive. Table 1 shows that comparative analysis of the clinicopathological characteristics as a function of the SNB-negative/-positive status found no statistically significant differences.
3.2. Comparison of Adjuvant Therapy in SNB-Negative and SNB-Positive Patients
Table 2 shows the results of comparison of the types of adjuvant therapy administered to the SNB-negative and SNB-positive patients. Axillary radiation was administered to 18 of the 59 SNB-positive patients, but to none of the 430 SNB-negative patients. Chemotherapy was administered to 34 of the 59 SNB-positive patients and to 38 of the 430 SNB-negative patients. Finally, hormonal therapy was administered to a majority of the patients, regardless of the status of SN metastasis. It is thus clear that the SNB-positive patients received more potent adjuvant therapies, i.e., axillary radiation and chemotherapy, compared with the SNB-negative patients.
3.3. Events of Recurrence
Table 3 compiles the data on the events of recurrence (some overlapping exists). The median follow-up period was 3.7 years, and recurrence was documented in 21 patients. The types of recurrence were distant metastatic events in 10 patients (2.0%), axillary node recurrence in 6 patients (1.2%), recurrence in other nodes in 3 patients (0.6%) and recurrence in the ipsilateral breast in 7 patients (1.4%). No recurrence was seen in 468 patients.