The breast cancer sentinel node dilemma: what to do with isolated tumor cells and micrometastases?

This issue of Breast Disease is dedicated to the sentinel node (SN) procedure in breast cancer, and more specifically on how to treat patients in whom isolated tumor cells or micrometastases are detected. Introduction of population-based breast cancer screening and an increased awareness in the general population regarding breast lumps has resulted in a shift towards clinically node-negative breast cancer stages. As a result, nowadays, around 60% of breast cancer patients have pathologically node-negative disease [1]. The SN procedure is based on the premise that if the first node the breast tissue drains into is clean, the remaining axillary lymph nodes are likely not involved, with no need for removal. Therefore, the introduction of the SN procedure during the nineties of the previous decade was a way to reduce axillary over treatment in many patients, thereby reducing morbidity such as lymph edema and shoulder dysfunction. However, concerns regarding misinterpretation of SN status and axillary recurrences led to an intensified SN pathology protocol, which partly counterbalanced the impact of the SN procedure: of patients who are eligible for the SN procedure, on average 10% have SN isolated tumor cells, and 10% have SN micrometastases [2], which would largely have remained undetected if only examined by routine H&E lymph node histology. If such patients would all undergo axillary surgery the impact of the SN procedure in sparing axillary over treatment would be substantially lower as was presumed before. Indeed, we have shown that in the initial years of the SN procedure, where all patients with isolated tumor cells underwent axillary lymph node dissection, a triple intensive SN pathology protocol led to more than twice as many surgical procedures compared to hospitals using a ‘standard’ SN pathology protocol [3]. It is noticed that till the year 2002, metastases with a diameter of 2 mm or less were classified as pN1a, without distinction between isolated tumor cells and micrometastases. At that time, most of the patients with minimal nodal involvement were treated as if they were node-positive, including the use of adjuvant systemic therapy. Since 2002, however, due to the implementation of the SN procedure with increasing detection frequency of small nodal metastases and because of doubt about the prognostic relevance of isolated tumor cells, the Cancer Staging Manual of the American Joint Committee on Cancer (6th edition) distinguished between isolated tumor cells (pN0(i+), 6 0.2 mm) and micrometastases (pN1mi, 0.2–2.0 mm). In the recently updated 7th edition, the definition of micrometastases has been somewhat widened to include nodal involvement “larger than 0.2 mm and/or more than 200 cells,