Background: Breast cancer is traditionally classified into three clinical subtypes based on hormone receptor and HER2 status (i.e., luminal-like, HER2-positive, and triple negative). Each subtype has distinct clinical-pathological and molecular characteristics and requires tailored treatments. Recent research efforts have been focusing on a new classification, identifying the so-called “HER2-low” category, including tumors characterized by a low level of HER2 expression (immunohistochemistry score 1+ or 2+ without in situ hybridization amplification). Emerging evidence shows that patients with HER2-low tumors can derive benefit from selected anti-HER2 therapies. This represents a major advancement in the field of breast oncology, where a broader proportion of patients with breast cancer can ultimately benefit from new effective targeted treatment strategies. Summary: The antibody-drug conjugate trastuzumab deruxtecan has proven impressive efficacy in patients with HER2-low breast cancer, and several other drugs are currently under investigation in this subset of patients. Additional investigation is needed to address open issues that exist in this field, including appropriate pathological assessment of HER2-low status, clarification of its prognostic implications, and global access to newly approved drugs. Key Message: Our review aims to summarize the available evidence regarding HER2-low breast cancer, illustrating the current challenges that are being addressed and the future perspectives in this exciting new field.

Locally advanced breast cancer (LABC) may rarely present with acute severe bleeding. A case report dealing with transcatheter arterial embolization to control acute bleeding in a patient with a voluminous ulcerated breast mass is described. Our findings confirm that the endovascular approach is effective in such patients in order to stabilize the patient whenever conventional treatments have failed or bleeding may be life-threatening.

Dose-dense (DD) adjuvant chemotherapy represents a standard treatment for patients with high-risk node-positive early-stage HER2-negative breast cancer (BC). In this exploratory analysis of the GIM2 trial, we investigated the efficacy of DD chemotherapy among patients with HER2-negative BC according to HER2 immunohistochemistry (IHC) score. Patients with node-positive early BC were randomized to receive either DD or standard schedule anthracycline- and taxane-based chemotherapy. HER2 status was assessed locally. Tumours with HER2 score 0 were classified as HER2-zero, those with a HER2 score 1+ or 2+ without ISH amplification as HER2-low. Tumours classified as HER2-negative with unknown IHC score were considered as a separate subgroup. Overall, 1243 subjects were eligible for this analysis, with 475 (38.2%) tumours classified as HER2-zero, 446 (35.9%) as HER2-low and 322 (25.9%) as HER2-negative with unknown IHC score. At a median follow-up of 14.9 years (IQR 8.4-16.2), no interaction was observed between treatment effect and HER2 status in invasive disease-free survival (iDFS) (p for interaction = 0.42) nor in overall survival (OS) (p for interaction = 0.34). Efficacy of DD chemotherapy was observed regardless of HER2 status: among patients with HER2-zero tumours, adjusted hazard ratio (aHR) for iDFS was 0.62 (95% confidence interval [CI] 0.45-0.85) and for OS was 0.55 (95% CI 0.36-0.84). Among patients with HER2-low tumours, aHR was 0.82 (95% CI 0.61-1.11) for iDFS and 0.84 (95% CI 0.57-1.23) for OS. In patients with HER2-negative high-risk early BC, the benefit of DD chemotherapy was observed irrespective of HER2 status. (NCT00433420).

Background/Objectives: Zuska disease is a rare inflammatory condition of the mammary gland, characterized by recurrent non-puerperal abscesses in the periareolar region, often complicated by fistula formation. It predominantly affects women who smoke, particularly perimenopausal women. This study aims to investigate the clinical features, treatment outcomes, and recurrence rates of Zuska disease in a cohort of patients. Methods: We conducted a retrospective analysis of 19 patients diagnosed with Zuska disease and treated at the Breast Surgery Clinic of San Martino Policlinic Hospital between January 2021 and June 2024. Data were collected on demographics, clinical presentation, imaging findings, surgical interventions, intraoperative cultures, and postoperative outcomes. The types of surgeries performed, antibiotic therapy regimens, and histological findings were recorded. Results: The mean age of the patients was 43.8 years. The most common presentation was a painful breast mass without fistula formation (12 patients), signs of a past abscess with negative preoperative ultrasound findings (five patients), and abscesses with fistulas (two patients). Intraoperative cultures revealed a range of bacterial species. Recurrence occurred in five patients (26%), and reoperation was required in three cases. All patients were free of symptoms at follow-up, with an average recurrence time of 13.6 months. Conclusions: Zuska disease presents significant treatment challenges due to its recurrent nature. While surgical interventions, such as abscess drainage and ductal excision, are effective, recurrence remains common, particularly in patients with risk factors like smoking. A personalized therapeutic approach, tailored to each patient’s clinical profile, is essential to improving long-term outcomes. Early diagnosis, timely surgical management, and lifestyle modifications play a crucial role in reducing recurrence. Future studies should focus on optimizing treatment protocols and developing individualized strategies for managing comorbidities.