The present invention describes methods for determining the risk that a breast precursor lesion will progress to invasive breast cancer and/or the risk of recurrent non-invasive disease in a patient, comprising detecting the presence and/or level of PAPPA and/or PAPPA functional activity in a breast tissue sample obtained from the patient, wherein if PAPPA is not present, or is present at a reduced amount compared to a control, there is the risk of progression to invasive cancer and/or the risk or recurrent disease. In an alternative embodiment, the diagnosis can be carried out by identifying the proportion of mitotic cells in a patient sample that are in prophase or pro- metaphase, wherein if the proportion of cells in prophase or pro-metaphase is 30% or more,this indicates a risk of progression to invasive breast cancer and/or risk of recurrent disease. The present invention also enables the chemosensitisation of mitotically delayed breast cancer cells to anti-proliferative agents, preferably anti-mitotic agents, by restoring normal progression through mitosis. In this embodiment a first drug is applied to release breast cancer cells from the mitotic block and, sequentially,a second drug affecting proliferating cells is administered for cancer cell killing.