Sentinel lymph node (SLN) biopsy is a minimally invasive means of accurately staging the axilla in breastcancer patients. While finding negative SLNs avoids axillary lymph node dissection (ALND), the finding ofmicrometastasis in the SLN mandates a completion ALND. Up to 80% of all SLN-positive patients will have nofurther disease in the axilla. There is a significant gap in our current knowledge in predicting which SLN-positive patients have a low likelihood of non-SLN metastasis and can therefore avoid ALND. A novel intra-operative RT-PCR based assay (GeneSearch ) for detecting SLN micrometastases has been shown tocorrelate with SLN tumor burden in breast cancer patients. The potential utility of this new technology inpredicting which patients will not have further disease in their non-SLNs has not been investigated.Developing a robust clinical prediction rule for non-SLN status using these data will fill this gap in ourknowledge and provide timely conclusions which will have a direct impact on patient care. In order to achievethis over-arching objective, we propose the following specific aims: (1) To determine the impact of quantitativecycle time values of the GeneSearch assay on non-SLN status using both bivariate and multivariable logisticregression analyses, (2) To create and validate (using bootstrap techniques) a clinical prediction rule to predictnon-SLN status in SLN-positive patients using preoperatively- and intraoperatively-available clinicopathologicfactors including data obtained from the GeneSearch assay and (3) To prospectively validate this clinicalprediction rule for non-SLN metastasis in a cohort of SLN-positive patients, and to compare it to currentlyavailable clinical prediction rules and nomograms. We hypothesize that the quantitative RT-PCR cycle time forboth mammoglobin (MMG) and cytokeratin 19 (CK19), as evaluated as continuous values using theGeneSearch assay, will be significantly associated with non-SLN metastasis on bivariate analyses. Inaddition, the cycle time for these markers will predict non-SLN metastasis independent of other factors. Wehypothesize that a valid clinical prediction rule can be created using preoperatively- and intraoperatively-available clinicopathologic factors including data obtained from the GeneSearch assay that will identify asubset of patients in whom the likelihood of non-SLN metastasis is ? 5%. It is anticipated that the addition ofdata from the GeneSearch assay will significantly improve the ability to predict this group of patients over theuse of clinicopathologic factors alone. Finally, we hypothesize that this clinical prediction rule will predict thenon-SLN status of a prospective cohort of SLN-positive patients with an accuracy of 95%, outperformingcurrently available clinical prediction rules and nomograms. The creation and validation of a robust clinicalprediction rule which incorporates novel molecular data to identify a subgroup of patients at low risk of havingnon-SLN metastasis will fill a significant gap in our current knowledge and will reduce unnecessary morbidity ofALND, helping to meet the NCI's Challenge of eliminating suffering due to cancer by 2015. PROJECT NARRATIVE:Up to 80% of breast cancer patients who have minimal disease in their first draining(sentinel) lymph nodes will have no further disease in their axilla. However, currentlythere is no accurate means of predicting which patients will not have residual diseaseand therefore all patients that have a tumor deposit > 0.2 mm in their sentinel lymphnodes will have the remaining lymph nodes removed a procedure that is associatedwith considerable morbidity. We seek to create and validate a clinical prediction rule,incorporating novel molecular data, to identify a subgroup of patients at low risk ofhaving non-SLN metastasis, thereby filling a significant gap in our current knowledgeand reducing unnecessary morbidity for breast cancer patients.
| Chagpar, Anees B (2010) Clinical significance of minimal sentinel node involvement and management options. Surg Oncol Clin N Am 19:493-505 |
