Kupstas AR, et al. - Despite postulation of inflammatory breast cancer (IBC) as a distinct biological entity, practice guidelines and previous data infer the influence of standard approximated biological subtype on treatment and outcomes. Researchers here sought to validate these findings in a large recent National Cancer Database (NCDB) patient cohort. They queried NCDB for patients with non-metastatic IBC treated in 2010–2015 with neoadjuvant systemic therapy and surgery. They identified 4,068 patients with IBC (median age 56 years); among these, the approximated biological subtype was oestrogen receptor (ER)+/human epidermal growth factor receptor (HER) 2− in 1,575 (38·7%), HER2+ in 1,323 (32·5%) and ER−/HER2− in 1,170 (28·8%). A total of 3,351 patients (84·0%) were cN+ at presentation, with no differences across subtypes. Observations revealed variation in both treatment response and survival in patients with IBC in association with approximated biological subtype, as among other invasive breast cancers. Multivariable analysis revealed a correlation of ER−/HER2− subtype (hazard ratio 2·89 vs HER2+ as reference) and absence of total pCR (hazard ratio 3·23) with worse survival. Data thereby supported continued tailoring of systemic treatment to approximated biological subtype and revealed the recently improved outcomes in patients with HER2+ disease.