Is invasion a necessary step for metastases in breast cancer?

To review the empirical evidence to support the conventional (sequential) model of breast cancer progression, which is based on the paradigm that cancer passes through several stages, including an in situ stage prior to an invasive stage, and thereafter (in some cases) disseminates to the lymph nodes and distant organs. We review the cancer literature of the last 50 years which relates to the prevention of invasive breast cancer (through radiotherapy or surgery) and reductions in the mortality for breast cancer. For both invasive cancers and DCIS, the literature indicates that prevention of in-breast invasive recurrences does not prevent death from breast cancer. Moreover, the presence of residual cancer cells in the breast after breast-conserving surgery does not compromise the cure rate. We propose an alternate (parallel) model of breast cancer wherein there is a small pool of cancer stem cells which have metastatic potential from their inception and which disseminate synchronously through several routes-to the breast stroma, to the lymph nodes and to distant organs. Cancer cells which disseminate to the breast give rise to cells which make up the bulk of the tumour mass but these are not the source of the distant metastases.