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Original Article |
Department of Surgery, Breast Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, MRI 1026, New York, New York 10021
Correspondence: Address correspondence and reprint requests to: Lisa M. Sclafani, MD; E-mail: sclafanl{at}mskcc.org
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
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Methods: We conducted a retrospective review of a prospective database of SLNBs performed at Memorial Sloan-Kettering Cancer Center from 1996 to 2003 to determine the incidence of lymph node metastases by histological subtype. For the favorable subtypes, the patients age, tumor size, estrogen receptor status, lymphovascular invasion, nuclear grade, and histological grade were compared by nodal status to determine their predictive value.
Results: A total of 196 cases with favorable breast cancer subtypes were identified with a 4.1% (8 of 196) sentinel lymph node (SLN) positivity rate. Each of the histological subtypes included patients with positive SLNs, with the exception of adenoid cystic (n = 4) and secretory (n = 1) breast carcinoma, which were quite rare in our series. When compared by nodal status, the patients age, tumor size, estrogen receptor status, lymphovascular invasion, nuclear grade, and histological grade failed to predict those with positive SLNs.
Conclusions: Patients with favorable breast cancer histology have a small risk of axillary SLN metastases. The use of SLNB in these patients should be individualized, taking into consideration the small incidence of axillary metastases and the risks and benefits associated with the SLN procedure.
Key Words: Sentinel lymph node biopsy • Axillary node dissection • Favorable breast cancer subtypes • Breast cancer • Favorable histology
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
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As more experience is gained with SLNB and as longer follow-up is obtained, it is apparent that SLNB is associated with a 1% incidence of allergic dye reactions if isosulfan blue dye is used,2 a 1% to 3% incidence of lymphedema,3 and a 5% to 15% incidence of severe sensory sensations such as pain and numbness,4,5 which can persist for more than 6 months after surgery. Although these are much lower than those associated with axillary dissection, this has to be weighed against the potential for finding lymph node metastases that would be treated with axillary dissection or adjuvant systemic treatment.
The favorable breast cancer histological subtypes include tubular, mucinous (colloid), papillary, medullary, adenoid cystic, and secretory cancers. These have a lower frequency of lymph node metastases compared with infiltrating ductal (IDC) and lobular cancers.6,7 Before the use of sentinel node biopsy, it was suggested that level I/II dissection could be omitted for these favorable subtypes. In a recent study, Wong et al.8 demonstrated the incidence of axillary metastases found on SLNB with serial sectioning of the lymph nodes to be higher than expected for these special subtypes: 17% for tubular cancers, 6% for mucinous cancers, and 21% for pure medullary cancers. The authors believed that these high risks of lymph node metastases justified the use of SLNB in these patients. However, the number of patients in this study of these rare tumors was relatively small, and the incidence of lymph node metastases was higher than previously reported with axillary dissection. We undertook our study to determine the risk of lymph node metastases in favorable-subtype breast cancers and to determine whether SLNB could be omitted in any group of patients with favorable histological subtypes.
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
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The breast cancer subtypes were defined by histopathologic analysis as IDC or pure tubular, pure mucinous (colloid), pure papillary, pure medullary, pure adenoid cystic, or pure secretory breast carcinoma. The cases with mixed ductal/lobular features were classified as IDC. For the purposes of our data analysis, the pure tubular, mucinous, papillary, medullary, adenoid cystic, and secretory carcinomas were classified as favorable subtypes.
Study Sample
For the favorable subtypes, the patients age, tumor size, estrogen receptor (ER) status, presence of lymphovascular invasion (LVI), nuclear grade, and histological grade were compared by nodal status. Exclusion criteria for our study included male breast cancer, previous axillary lymph node dissection or SLNB, neoadjuvant chemotherapy, failed SLNB, recurrent ipsilateral breast cancer, prophylactic mastectomy, and other breast histological diagnoses, including infiltrating lobular carcinoma, ductal carcinoma-in-situ, ductal carcinoma-in-situ with micro-invasion, Pagets disease, phyllodes tumor, sarcoma, anaplastic carcinoma, metaplastic carcinoma, lymphoma, adenosquamous carcinoma, adenoma, and metastatic carcinoma.
A total of 3980 cases fulfilled the criteria for this study. The cases were divided into the specific subtypes as previously described.
Statistical Analysis
Continuous variables were compared by using Wilcoxon’s rank-sum and Student’s t-tests. Categorical variables were compared by using Fishers exact test. Statistical analyses were performed with SPSS 11.5 (SPSS Inc., Chicago, IL) and StatXact 5 (Cytel Software Corp., Cambridge, MA). All P values <.05 were considered statistically significant.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
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). With the exception of adenoid cystic carcinoma (n = 4) and invasive secretory carcinoma (n = 1), which were quite rare in our series, each of the other histological subtypes included patients with positive SLNs.
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Most of the favorable subtypes were ER positive, with low to intermediate nuclear and histological grades and had no evidence of LVI compared with the IDC cases (Table 2). As a subgroup, the medullary cancers were mostly ER negative (5 of 5), with high nuclear and histological grade, and 2 of 6 cases had LVI.
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. Of these eight patients, six had a completion axillary lymph node dissection, and two were found to have additional positive lymph nodes. Seven of the eight patients were treated with adjuvant chemotherapy.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
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Favorable subtypes are defined as "pure" when they have the characteristic histological features in at least 90% of the tumor. Wide variations have been reported in the pathologic diagnosis of these tumors. Differences in lymph node metastases have been described, depending on whether the tumor is "pure" or has features of only the special type. In a report by Paramo et al.11 of mucinous cancers, none of the 19 cases of pure mucinous tumors had lymph node metastases, whereas 12 of 41 cases classified as mixed mucinous tumors had lymph node metastases. The authors of this article actually advocated sentinel node biopsy to differentiate mixed tumors from pure, citing the low incidence of nodal metastases in the pure type. Classification as atypical or variants may be made if the characteristic features are present in <90% of the tumor. This seems to be a particular problem of the medullary type, for which high-grade histological features characterize the tumor, yet the prognosis seems better. Therefore, there may be a reluctance to diagnose this tumor, and categories of "atypical" medullary cancers seem to have a prognosis in between that for a true medullary and a poorly differentiated ductal carcinoma with medullary features.12
These variations in the percentage of histological criteria present may explain variations reported in the incidence of lymph node metastases in other series. Some series based on large multi-institutional breast cancer databases for which the pathology has been read by a variety of pathologists may not be as stringent in including only cases of pure tubular or mucinous cancers. However, they may be more representative of what the community surgeon encounters. Diab and associates’13 large study from the San Antonio breast cancer database showed a 16% incidence of lymph node metastases in their 398 patients with tubular cancer and 14% in their 1048 mucinous cancers. This is much higher than our rates of 4% and 2%, respectively, for those histological types. In a review of Surveillance, Epidemiology, and End Results data, in 1998 Maibenco et al.14 reported a 4.4% incidence of metastases in 408 cases of tubular cancers and 2.9% in 314 mucinous cancers. In both cases, they saw a higher incidence of medullary cancers. In our series, medullary cancers were quite rare and represented only 6 of 196 cases, possibly reflecting a reluctance to diagnose this cancer at our institution because pure medullary cancers are less likely to be treated with adjuvant therapy. Papillary cancers were also rarely diagnosed at our institution, and the reason for this is unclear.
Although the good prognosis for these favorable types is well known, the prognosis of favorable histological subtypes with positive nodes is not well documented. These tumors are rare, and, with the possible exception of tubular and mucinous cancers, most studies are too small to draw conclusions about their natural history and the benefits of treatment.
In one of the few studies to look at prognosis in the favorable subtypes, Diab et al.13 reported that 62 patients with node-positive tubular cancer had a 10-year disease-free survival of 94%, compared with 65% (n = 147) for node-positive mucinous cancer and 57% (n = 16,551) for node-positive IDC. The excellent survival rate of patients with node-positive tubular cancers leads some to question the necessity of axillary staging in these patients, but few would alter management on the basis of a single retrospective study. Nodal status in patients with mucinous cancers seems to be important to prognosis. Although adjuvant treatment was not seen to contribute to improved mortality, the small numbers in this retrospective study make it difficult to make management decisions on the basis of these data alone.
Our results differed from other studies in several ways. We found the incidence of positive lymph nodes in the favorable subtypes to be lower than previously reported, although median tumor size remained the same.8,15–17 Our pathologists may have been more stringent in their diagnosis of the favorable histological subtypes. We saw no effect of size on nodal metastases. Six of our eight patients with positive nodes had tumors <1 cm, none showed LVI, and all but one (medullary) were ER positive and had a low to intermediate nuclear and histological grade. Some groups claim that tumor size and patient age may predict lymph node metastases, but we were unable to show that these factors were significant to define a group that had a lower rate of lymph node metastasis. This could certainly be because of our small number of node-positive patients. Also, most of our patients had tubular or mucinous cancers, and our conclusions may not apply to the rarer subgroups, such as papillary medullary, adenoid cystic, and secretory cancers.
In our series of patients, the finding of a positive node led to a change in treatment in most patients. Six of eight underwent axillary dissection, and of the six, two (one tubular and one papillary carcinoma) had additional positive lymph nodes removed. Seven of the eight node-positive patients were treated with systemic chemotherapy, indicating that in the absence of data to show otherwise, our medical oncology colleagues believe that these node-positive patients may benefit from adjuvant chemotherapy just as other node-positive patients benefit. In this setting, it seems that SLNB did contribute to the decision making, although we cannot prove that it influenced survival.
In conclusion, we believe that SLNB identifies a subgroup of patients who may have a worse prognosis and who might benefit from adjuvant treatment. In deciding whether to perform an SLNB, the treating physician must decide whether the results of the sentinel node biopsy will alter treatment. If so, we believe that our data support the individualized use of SLNB in patients with favorable-histology breast cancer, taking into account the 4% incidence of lymph node metastases and the risks and benefits associated with SLNB in the individual patient.
Received for publication March 19, 2004. Accepted for publication September 20, 2004.
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  B. Cady Regional Lymph Node Metastases; a Singular Manifestation of the Process of Clinical Metastases in Cancer: Contemporary Animal Research and Clinical Reports Suggest Unifying Concepts Ann. Surg. Oncol., June 1, 2007; 14(6): 1790 - 1800. [Abstract] [Full Text] [PDF]
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S. D. Nathanson, R. Slater, D. DeBruyn, A. Kapke, and M. Linden HER-2/neu Expression in Primary Breast Cancer With Sentinel Lymph Node Metastasis Ann. Surg. Oncol., February 1, 2006; 13(2): 205 - 213. [Abstract] [Full Text] [PDF]
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