Hope S. Rugo

Patients whose breast cancer was previously called HER2-negative may now be eligible for an effective HER2-directed drug if their tumour has even low-level HER2 staining, so pathology reports must now distinguish HER2-low (1+ or 2+/ISH-negative) from HER2-zero. This applies to metastatic disease after at least one line of chemotherapy; it does not mean these patients benefit from trastuzumab or other older HER2 drugs.

The third trial to show carboplatin's benefit persists beyond pathological complete response and the trial that closed the neoadjuvant PARP inhibitor route in unselected triple-negative disease; PARP inhibition survives only in germline BRCA carriers.

Sacituzumab govitecan is a standard second-line or later treatment for metastatic triple-negative breast cancer, roughly doubling survival compared with the chemotherapies it was tested against. Patients should expect neutropenia and diarrhoea, which are manageable with growth factor support and loperamide. Trials are now testing it earlier, in first-line combinations with pembrolizumab and after surgery for residual disease.

The clearest demonstration that PD-L1 positive in triple-negative breast cancer means different things depending on the kit; with atezolizumab withdrawn, pembrolizumab's 22C3 combined positive score of 10 is the surviving standard, and roughly a quarter of patients get a different answer depending on which assay their laboratory runs.

It fixes the AR-positive share of ER-negative disease at about one in eight and shows anti-androgens give modest, non-toxic benefit, the rationale for enzalutamide and later CDK4/6 and PI3K combinations in LAR tumours.