The promise of personalized therapies for breast cancer can only be fulfilled through tissue-based correlative science studies. Unfortunately, access to a tissue bank has been the major barrier to the development of prognostic or predictive tests. This chapter describes issues related to tissue acquisition and banking for breast cancer in the multicenter clinical trial setting.
Although survival outcome of patients has improved greatly over the past 2 decades due to incremental benefits achieved from systemic therapies, it has become quite clear that molecular heterogeneity of breast cancer dictates treatment response and not every patient derives significant benefit from a given therapy.1,2 Development of assays that enable assessment of baseline risk and expected degree of benefit from systemic therapy in specific clinical contexts has become a top priority in the research agenda for breast cancer.
These kinds of correlative science studies need tumor tissue with good clinical annotation. Best source of such materials is from randomized phase 3 clinical trials. Unfortunately, tissue procurement is most difficult in such a setting. Ideally every single tumor operated should be snap frozen according to a uniform standard operating procedure and archived in a proper environmental condition. However, reality is that in a typical practice setting in North America, procurement of snap frozen biopsy tissue in expectation of future correlative science studies is often difficult, if not impossible. Because patients usually are presented with the option of enrolling into a clinical trial only after cancer diagnosis is made, the window of opportunity to procure snap frozen tumor tissue often gets lost. National infrastructure to procure snap frozen tissue samples from all tumors operated and store in an ideal environment before shipping to a central bank does not exist, and liquid nitrogen or dry ice may not be readily available in a community oncology setting. For this reason, frozen tissue procurement in large phase 3 multicenter adjuvant clinical trials has not been successful.
Surprisingly, even procurement of formalin-fixed paraffin-embedded tumor blocks has been lacking in phase 3 adjuvant clinical trials until only recently, which is now mandated by many clinical trial groups. Although the utility of archived formalin-fixed paraffin-embedded tumor tissue has been limited by technological barriers, recent development of gene expression analysis methods enabled National Surgical Adjuvant Breast and Bowel Project (NASBP) investigators to use these nonideal materials from already completed trials for the development of the OncotypeDx assay (Genomic Health Inc., Redwood City, California), which is now widely used in the prognostication of outcome in patients with estrogen receptor positive, node-negative breast cancer.1,3 Therefore there is now a clear scientific rationale to mandate tumor block collection in all clinical trials.
Most molecular profiling methods dictate the importance of using snap frozen tissue as the starting material. This has especially been the norm for gene expression profiling studies using microarrays. Ideally in an academic setting with active clinical investigation, dedicated personnel such as pathology ...