Human 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.