Trials and papersHER2-positive breast cancer

NCCN is the source of the category grades on the triple-negative breast cancer page and the first major guideline to place an antibody-drug conjugate first line for the disease.

Platinum and immunotherapy are now consensus for early triple-negative disease; the open votes have moved to who can safely receive less.

This is the European standard the UK page for triple-negative breast cancer is compared against; NICE guidance covers the same ground with a narrower set of funded drugs.

One person, one tumour, one report, and it is not evidence that anyone should treat themselves. What it does contribute is unusually well documented: serial imaging through the course, a baseline biopsy and an excised specimen scored by the same pathology department, antibody titres, and a named protocol with doses. The design choices are the interesting part. Two different viruses in sequence to stay ahead of the antiviral antibody response, frequent dosing to keep infectious virus concentrated in the tumour, and the neoadjuvant setting rather than the late metastatic setting in which oncolytic viruses are normally tested. The result also cannot be attributed to the viruses alone: the tumour was surgically removed and a year of trastuzumab followed, and the phenotype change to HER2 3+ is itself a plausible reason the disease behaved differently this time.

AI can take over one reader's work in double-reading screening programmes while finding more cancers. Whether the extra cancers found are ones that would have harmed women, and whether interval cancers fall, is the question the trial's primary endpoint will answer.

St Gallen is where de-escalation questions in triple-negative disease (who needs the full KEYNOTE-522 regimen, who can skip adjuvant pembrolizumab) are first put to a vote; the 2023 panel framed intensity and duration as the central problem.

For HER2-positive metastatic breast cancer that has progressed after trastuzumab and a taxane, trastuzumab deruxtecan is now the standard second-line treatment and T-DM1 has moved later in the sequence. The benefit is large enough that ADC design, not just the target, is understood to be what matters. Patients need lung monitoring because of the risk of pneumonitis.

The external validation the 2017 paper asked for; it is why residual cancer burden is reported in UK and European pathology and used as a trial entry criterion rather than an MD Anderson curiosity.