Simple SummaryHER2-positive breast cancers are usually diagnosed from clinical findings, and often in a large size, with extensive microcalcifications, and/or with axillary involvement, which may compromise conservative surgery, both in the breast and in the axilla. Nevertheless, HER2-positive breast cancers are usually good responders to neoadjuvant treatment and most of them disappear, although breast microcalcifications do not always do so, nor is an omission of axilla clearance accepted when the initial involvement was extensive. Therefore, it is of great interest to have accessible clinical tools that allow us to determine, with precision, when complete pathological response occurs. In a population of 132 patients with HER2 breast cancers, we have found that the Ki67 value, hormonal receptors condition, and Magnetic Resonance Imaging findings, performed after primary systemic therapy, permit the selection of those patients in whom the benefits of neoadjuvant can safely be transferred to surgical extension.AbstractHuman epidermal growth factor receptor 2 (HER2)-enriched breast cancers (BC) present the highest rates of pathological response to primary systemic therapy (PST), but they are also the ones that tend to be larger at diagnosis, with microcalcifications and, often, with axillary involvement. If we do not have a reliable method to predict the degree of response, we may not be able to transfer the benefits of PST to surgery. The post-PST surgery planning is guided by the findings in the magnetic resonance imaging (MRI), whose predictive capacity, although high, is far from optimal. Thus, it seems interesting to find other variables to improve it. A retrospective observational study including women with HER2 BC treated with PST and further surgery was conducted. Information regarding clinical, radiological, and histopathological variables was gathered from a total of 132 patients included. Radiological complete response (rCR) was achieved in 65.9% of the sample, and pathological complete response (pCR), according to Miller and Payne criteria, in 58.3% of cases. A higher Ki67 value, the absence of Hormonal Receptors expression, and an rCR was significantly related to a pCR finding. This information impacts directly in surgery planning, as it permits adjustment of the breast resection volume.