Gene-expression assays to tailor adjuvant endocrine therapy for HR+/HER2- breast cancer.

Adjuvant endocrine therapy represents the standard of care for almost all HR+/HER2- breast cancers and different agents and durations are currently available. In this context, the tailoring and optimization of adjuvant endocrine treatment by reducing unnecessary toxic treatment while taking into account the biological heterogeneity of HR+/HER2- breast cancer represents a clinical priority. There is therefore a significant need for the integration of biological biomarkers in the choice of adjuvant endocrine therapy beyond currently used clinicopathological characteristics. Several gene-expression assays have been developed to identify patients with HR+/HER2- breast cancer who will not derive benefit from the addition of adjuvant chemotherapy. By enhancing risk stratification and predicting therapeutic response, genomic assays have also shown to be a promising tool for optimizing endocrine treatment decision. We here review evidence supporting the use of most common commercially available gene-expression assays (Oncotype DX, MammaPrint, Breast Cancer Index, Prosigna and EndoPredict) in tailoring adjuvant endocrine therapy. Available data on the use of genomic tests to inform extended adjuvant treatment choice based on the risk of late relapse and on the estimated benefit of a prolonged endocrine therapy are discussed. Moreover, preliminary evidence regarding the use of genomic assays to inform de-escalation of endocrine treatment, such as shorter durations or omission, for low risk patients are reviewed. Overall, gene expression assays are emerging as potential tools to further personalize adjuvant treatment for patients with HR+/HER2- breast cancers.

Oligometastatic breast cancer: Dissecting the clinical and biological uniqueness of this emerging entity. Can we pursue curability?

Metastatic breast cancer represents an incurable condition, however, the increasing interest towards the oligometastatic entity is now challenging this assumption. Up to 20% of patients with metastatic breast cancer present with oligometastatic disease, which refers to metastatic breast cancer presenting or recurring with limited metastatic burden. In the last years, progressive advancements in imaging techniques, the growing availability of minimally invasive locoregional treatments, alongside the increasing expectations from a patient perspective, have contributed to rising the awareness towards this emerging entity. In the present work we comprehensively reviewed available evidence regarding oligometastatic breast cancer, focusing on clinical and biological notions virtually supporting the adoption of a curative approach when treating this condition. We also discussed main areas of uncertainties, providing a research agenda that may guide and fine-tune the future investigation in this field.

Neoadjuvant Chemotherapy and Immunotherapy in Luminal B-like Breast Cancer: Results of the Phase II GIADA Trial.

PURPOSE: The role of immunotherapy in hormone receptor (HR)-positive, HER2-negative breast cancer is underexplored. PATIENTS AND METHODS: The neoadjuvant phase II GIADA trial (NCT04659551, EUDRACT 2016-004665-10) enrolled stage II-IIIA premenopausal patients with Luminal B (LumB)-like breast cancer (HR-positive/HER2-negative, Ki67 ≥ 20%, and/or histologic grade 3). Patients received: three 21-day cycles of epirubicin/cyclophosphamide followed by eight 14-day cycles of nivolumab, triptorelin started concomitantly to chemotherapy, and exemestane started concomitantly to nivolumab. Primary endpoint was pathologic complete response (pCR; ypT0/is, ypN0). RESULTS: A pCR was achieved by 7/43 patients [16.3%; 95% confidence interval (CI), 7.4-34.9]; the rate of residual cancer burden class 0-I was 25.6%. pCR rate was significantly higher for patients with PAM50 Basal breast cancer (4/8, 50%) as compared with other subtypes (LumA 9.1%; LumB 8.3%; P = 0.017). Tumor-infiltrating lymphocytes (TIL), immune-related gene-expression signatures, and specific immune cell subpopulations by multiplex immunofluorescence were significantly associated with pCR. A combined score of Basal subtype and TILs had an AUC of 0.95 (95% CI, 0.89-1.00) for pCR prediction. According to multiplex immunofluorescence, a switch to a more immune-activated tumor microenvironment occurred following exposure to anthracyclines. Most common grade ≥3 treatment-related adverse events (AE) during nivolumab were γ-glutamyltransferase (16.7%), alanine aminotransferase (16.7%), and aspartate aminotransferase (9.5%) increase. Most common immune-related AEs were endocrinopathies (all grades 1-2; including adrenal insufficiency, n = 1). CONCLUSIONS: Luminal B-like breast cancers with a Basal molecular subtype and/or a state of immune activation may respond to sequential anthracyclines and anti-PD-1. Our data generate hypotheses that, if validated, could guide immunotherapy development in this context.

Postsurgical Pyoderma Gangrenosum in a Breast Cancer Patient: A Case Report and Literature Review.

Pyoderma gangrenosum is a rare skin necrotizing disease that can arise on a site of surgical trauma. Its pathogenesis has recently been related to dysregulation of the immune system, with inflammatory bowel disease representing the most commonly underlying systemic conditions. Several authors have also reported an association with solid malignancies (especially gastrointestinal and breast cancer). We describe the case of a 39-year-old patient diagnosed with a locally advanced, triple-negative breast cancer who developed a pyoderma gangrenosum on the surgical wound after a CVC implant with systemic complications. As the diagnosis and management of postsurgical pyoderma gangrenosum can be challenging for clinicians, underlying conditions as autoimmune disease and solid tumors have to be considered in order to guide treatment.