Grade, stage and receptor status: three different things on one breast report

Grade is how abnormal the cells look: three features scored and added into grade 1, 2 or 3 (see `nottingham-grade`). Stage is how much cancer there is and how far it has travelled: the size of the tumour, whether it has reached the lymph nodes, whether it has gone further, written as a TNM category and a stage from 0 to IV. Receptor status is what the cancer will respond to: whether its cells carry oestrogen and progesterone receptors and whether they carry too much HER2. Only the third chooses which treatment page you read. The first two decide how much treatment is needed and how likely it is to work.

The clearest demonstration that they are separate comes from the UK dataset itself. Setting out why the Nottingham Prognostic Index and PREDICT exist alongside TNM, it says the UICC staging system is required for the national dataset and applies to all breast cancers, but that 'its stratification power is limited in early stage disease, which comprises a large proportion of cases typically presenting in UK practice (i.e. small and/or node-negative tumours) and, crucially, does not incorporate histological grade or receptors status' (RCPath G148). A stage 1 breast cancer can be grade 1 and hormone receptor-positive, or grade 3 and triple-negative, and those two people have the same stage and very different diseases. The American prognostic stage exists to patch exactly this hole by folding grade and the receptors into the stage number, which is why a triple-negative grade 3 tumour generally carries a higher prognostic stage than its anatomical stage.

The practical consequence is the order in which the three arrive and the order in which they matter. The receptors arrive with the biopsy and choose the treatment route within days. The grade arrives with the biopsy and is confirmed, and sometimes changed, on the surgical specimen. The full stage is not known until the nodes have been examined, and sometimes not until scans are done, which is why an early conversation gives a plan rather than a stage. A fourth number, Ki-67, is sometimes quoted as well; it measures how many cells are dividing, it overlaps with the mitotic count already inside the grade, and the international working group that reviewed it accepted it as prognostic but found clinical utility only in a narrow group (see `ki-67-in-tnbc`).