Lymph Node Staging in Localized Breast Cancer

Laura Dominici, MD

In patients with localized breast cancer, staging the regional lymph nodes is an important part of the diagnostic process, informs treatment and management strategies, and can also provide prognostic insight. The American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) published guidelines for lymph node staging, with the last guideline updated in 2010. Staging now generally involves dissection of the sentinel nodes, not the axillary nodes. Still, the best management for patients that have detectable axillary disease remains a major issue.

Today we are speaking with Laura Dominici, MD, assistant professor of surgery at Harvard Medical School and a surgical oncologist at Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, who has recently penned an editorial in the Journal of Clinical Oncology discussing these issues.

 -Interviewed by Anna Azvolinsky 

Cancer Network: Dr. Dominici, could you describe what the current guidelines recommend for lymph node dissection in breast cancer patients?

Dr. Dominici: Certainly. For women with clinically node-negative breast cancers, the evaluation of the axillary nodes with a sentinel lymph node biopsy has really become the standard of care. Sentinel node evaluation continues to provide the necessary staging information and informs the clinical decision-making while sparing many women the morbidities of an axillary lymph node dissection. For women with clinically node-positive breast cancers, however, the axillary lymph node dissection remains the standard of care.

Cancer Network: Is this the standard for most surgeons or is there still debate about the sentinel node biopsy approach?

Dr. Dominici: It is really generally accepted that women with clinically node-negative disease should be offered a sentinel lymph node biopsy. Where there is more debate is regarding the technique of how those nodes are evaluated from a pathologic standpoint. The recommendation for the pathologic evaluation of nodes is careful sectioning and hematoxylin and eosin staining. There is really no recommendation for routine use of immunohistochemistry to evaluate the sentinel nodes, although this has become common practice. This is where we may identify nodes with occult metastases, which are typically very small volume. The debate really results from a lack of standardization as to whether or not pathologists should be using immunohistochemistry and what the clinical implications of nodal disease using that technique should be.

Cancer Network: There was a recent study published in the Journal of Clinical Oncology analyzing outcomes after sentinel node biopsy for which you wrote the accompanying editorial. Can you briefly describe the study and the results?

Dr. Dominici: This study looked at more than 8,000 patients from two prospective cohorts with stage I breast cancer diagnoses. There was a long median follow-up of 6.5 to 9 years, and the cohorts were a series of patients, one from MD Anderson Cancer Center and one from the American College of Surgeons Oncology Group (ACOSOG) Z10 trial. What the study was looking at was outcomes in patients with designated stage IA vs IB disease, which was one of the new designations in 2010, and this found no significant differences in survival endpoints, either recurrence-free or overall survival. The authors are really noting the lack of prognostic utility of the stage IA and IB designations and questioning whether or not it benefits patients to make these distinctions. They are also questioning whether patients in the IB group may end up receiving more and potentially unnecessary treatment.

Cancer Network: What are the implications of this study? Have other studies demonstrated similar results previously?

Dr. Dominici: This study raises important questions about the clinical implications of small-volume nodal disease. It does also suggest that the AJCC staging system really continues to place emphasis on defining the anatomic features of breast cancer rather than the biologic features that have increasing recognition of their clinical importance. It also questions the relevance of this kind of fine-tuning of the nomenclature about the degree of nodal disease, if it is really not prognostic or useful for clinical decision-making. The ACOSOG Z10 trial was a prognostic study of sentinel lymph nodal and bone marrow metastases in women with stage I and IIA breast cancer. There was also the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 trial, which was titled “Surgery to Remove Sentinel Lymph Nodes With or Without Removing Lymph Nodes in the Armpit in Women Treated for Breast Cancer.” This study also demonstrated that the identification of occult small tumor volume deposits in the sentinel lymph nodes did not have a significant impact on either overall or recurrence-free survival.

Cancer Network: What can still be improved and what are the main questions for staging and guidelines?

Dr. Dominici: The TNM, or tumor-node-metastasis staging, is the traditional system used and is an anatomic staging system developed by the AJCC. They have been refining over time, with the last revision in 2010. And again, many of the revisions that have been done are focusing on classifying or clarifying anatomic findings that may influence staging. But, particularly in breast cancer, there really has not been any attempt to incorporate the widely used genomic testing, which relies heavily upon biologic features of tumors that we know are prognostic. The next revision is planned for 2016. In order for the staging system to really still be clinically relevant, the significance of these biologic features will need to be incorporated into the upcoming revision.

Cancer Network: Are there any studies you can highlight that may help to update this guideline?

Dr. Dominici: Absolutely, there have been a number of studies looking at the prognostic features of the biologic aspects of the tumors, and the biggest ones are the ones looking at the use of oncotype. That is one area where biologic features have been identified to have significant clinical and prognostic impact on cancer treatment. There have also been a number of studies looking at very small HER2-positive cancers, which would be quite early-stage in the current staging guideline, that show the significant benefit of the use of adjuvant therapy in those patients with HER2-positive disease or even triple-negative disease.

Cancer Network: Thank you so much for joining us today, Dr. Dominici.

Dr. Dominici: Thank you so much for having me.