Sentinel lymph node biopsy for risk-reducing mastectomy.

Risk-reducing mastectomy (RRM) confers 90-95% decreased risk of breast cancer, and may reduce mortality, especially in high-risk groups such as BRCA carriers. Risk of occult disease in RRM specimen is ~5%. This demands axillary staging: sentinel lymph node (SLN) biopsy is no longer possible, axillary clearance confers significant risks and may prove negative. Contemporaneous SLN biopsy allows axillary staging with minimal further dissection. Women undergoing RRM and SLN biopsy between June 2005 and July 2010 were reviewed retrospectively from our prospectively maintained database of 1,522 SLN procedures in 1,498 patients. SLN(s) localized using routine tracer methods. SLNs and mastectomy specimens underwent routine histologic examination. Eighty-three RRMs with SLN biopsy were performed in 71 patients (12 bilateral). Indications for RRM: contralateral invasive (55), in situ (5) disease, BRCA 1/2 mutation (12), and strong family history (10). Mean number of SLNs: 1.35. Occult disease was detected in four cases (4.8%), with one case of occult invasive lobular carcinoma (1.2%). Remaining occult disease was lobular in situ neoplasia (LISN). SLNs were negative in all cases. Our findings are comparable to those in the literature: 4.8% rate of occult disease overall, 1.2% invasive. The significant risk with SLN biopsy is lymphoedema, quoted around 7%. We have had no reports of symptomatic lymphoedema in patients undergoing RRM and SLN biopsy. We propose that SLN at the time of mastectomy requires only limited further dissection, and confers minimal risk compared with secondary axillary surgery.

Matrix metalloproteinase-8 functions as a metastasis suppressor through modulation of tumor cell adhesion and invasion.

Collagenase-2 (matrix metalloproteinase-8, MMP-8) is an MMP mainly produced by neutrophils and associated with many inflammatory conditions. We have previously described that MMP-8 plays a protective role in cancer through its ability to regulate the inflammatory response induced by carcinogens. Moreover, it has been reported that experimental manipulation of the expression levels of this enzyme alters the metastatic behavior of human breast cancer cells. In this work, we have used mutant mice deficient in MMP-8 and syngenic melanoma and lung carcinoma tumor cells lines overexpressing this enzyme to further explore the putative antimetastatic potential of MMP-8. We report herein that MMP-8 prevents metastasis formation through the modulation of tumor cell adhesion and invasion. Thus, tumor cells overexpressing MMP-8 have an increased adhesion to extracellular matrix proteins, whereas their invasive ability through Matrigel is substantially reduced when compared with control cells. Analysis of MMP-8 in breast cancer patients revealed that the expression of this metalloproteinase by breast tumors correlates with a lower incidence of lymph node metastasis and confers good prognosis to these patients. On this basis, we propose that MMP-8 is a tumor protective factor, which also has the ability to reduce the metastatic potential of malignant cells in both mice and human.