Sentinel lymph node biopsy (SLNB) has been adopted as an applicable alternative to the standard axillary lymph node dissection (ALND) level I and II. It makes possible a less extensive axillary surgery in patients with early breast cancer with negative lymph node, who would not benefit from further dissection, in order to prevent unnecessary morbidity. On the other hand, SLNB is not appropriate in every clinical circumstance. In some clinical situations like tumor size T1 and T2, SLNB is, meanwhile, regarded as a standard procedure. In other settings like increased age and body mass index, pregnancy, ductal carcinoma in situ (DCIS), neoadjuvant chemotherapy, advanced disease (T3 and T4), prior surgery and multifocal/multicentric disease, there is a controversial debate about the importance of SLNB. This article reviews the absolute and relative contraindications of this procedure in respect to the latter three clinical situations.

For the advanced breast cancers T3 and T4, there seems to be an increasing evidence of an acceptable accuracy, although it should be further evaluated in randomized clinical trials (RCT). The indication of SLNB in previously operated patients depends on the type of prior surgery. A diagnostic biopsy does not represent a contraindication, whereas the sentinel node biopsy should not be used after an extensive breast surgery neither in the context of oncologic nor non-oncologic purposes. In the context of multicentric disease, there is growing evidence that SLNB is suitable, but actually it should be restricted to RCT. However, the multifocal disease is only a relative contraindication, that is it could be applied in well-selected patients.

The treatment of lymph node metastasis in human cancers has been a source of controversy for many years. Several contemporary randomized trials indicate no survival advantage to performing axillary dissection in contrast to merely observing the axilla after invasive breast cancer. This assumption is confirmed since survival advantages cannot be demonstrated when comparing greater or lesser lymph node dissections or dissection vs. observation of regional lymph nodes in melanoma and breast cancer and all other epithelial cancers.

Many recent studies indicate that axillary metastases, when they do occur in this era of mammographic screening and small invasive cancers, demonstrate metastases in the axillary sentinel nodes only in from 20% to almost 100% depending on primary cancer size. For instance, in T1a and T1b cancers, 50–100% of lymph node metastases, infrequently discovered, are contained entirely within the sentinel nodes. In T2 cancers, this proportion is roughly 25–50%, and in T3 cancers it ranges from 20% to 40%. A number of recent articles have demonstrated no difference in survival and very little nodal recurrence when patients with positive sentinel nodes are not followed by axillary dissection although the axillary disease tends to be less advanced in observed compared to treated patients with axillary dissection. Nevertheless, basic principles have been reconfirmed in these reports.

It has also been shown in animal research that clones of particular metastatic site cells demonstrate organ specificity. Transplanted human breast cancers demonstrate specific homing abilities to selective distant metastatic organ sites such as lymph nodes, bone, lung, or even adrenal gland. Genetic profiles of the different clones of cells with high metastatic specificity are each unique. Thus it is assumed that lymph node specific metastatic cells (and other organ-site-specific cells) have no ability to lodge and grow in other metastatic sites; this has been demonstrated clinically in clinical trials previously mentioned.

Therefore, there is no benefit in performing subsequent axillary dissections even when the sentinel node biopsy is positive, because of: (1) very low risk (≤2%) of recurrent clinical nodal metastases, (2) the lack of impact on disease specific or overall survival, (3) most lymph node metastases are limited to the sentinel nodes, and (4) lymph node metastases are only indicators not governors of the distant metastases. The American College of Surgeons Oncology Group (ACOSOG) Z-11 Trial was designed to specifically address this point, but unfortunately was closed early because of poor accrual; nevertheless, 900 patients were enrolled and will be analyzed over time to address this point.