Ralph Moss

This week, the online life sciences magazine The Scientist published an article whose implications for breast cancer research are profound.

Tumor cell lines - living cells taken from tumors and cultured in the laboratory - are the mainstay of cancer research at the most fundamental level, and are used as the model for studying tumor behavior and response to treatment. For the past 25 years, most of the laboratory research into metastatic breast cancer has been based on a single breast tumor cell line known as MDA-MB-435. At least 650 papers have been published on studies involving this cell line. Yet it has been revealed that this supposed breast cancer cell line may in fact not be composed of breast cancer cells at all. Instead, it appears that the cells are derived from melanoma. For 25 years, therefore, breast cancer research using this cell line - and it is one of the most widely used - has been based on an incorrect model. Melanoma-derived tumor cells are not biologically equivalent to breast cancer cells; they have different molecular and genetic characteristics.

Cell lines - even when correctly sourced and identified - are an intrinsically flawed model, and in the past I have often cautioned against the tendency to read too much into the results of cancer research done on tumor cell lines. The inferential leap from Petri dish to living human cancer patient is simply too large: an enormous number of drugs and experimental techniques show significant activity in cultured cancer cell lines, only to exhibit no benefit whatever when given to human subjects in a clinical setting. Furthermore, cell lines can degenerate over time, becoming genetically unstable. But these are relatively small concerns compared to the discovery that MDA-MB-435, the cornerstone of breast cancer research, is not breast cancer at all.

We are constantly being reminded that this is the era of evidence-based medicine. But if the very cell lines which have provided the foundation for breast cancer research for the past quarter century have now been conclusively shown to be melanoma cells, not breast cancer, how solid or trustworthy is the evidence on which current breast cancer treatment is based? Evidence built on such flawed foundations more closely resembles hearsay than science.

A Case of Mistaken Identity by Megan Scudellari. The Scientist, September 16th 2008 (registration required)