Human epidermal growth factor 2 (HER-2)-positive breast cancer represents 15–20% of all breast cancer subtypes and has an aggressive biological behavior with worse prognosis. The development of HER-2-targeted therapies has changed the disease’s course, having a direct impact on survival rates and quality of life. Drug development of HER-2-targeting therapies is a prolific field, with numerous new therapeutic strategies showing survival benefits and gaining regulatory approval in recent years. Furthermore, the acknowledgement of the survival impact of HER-2-directed therapies on HER-2-low breast cancer has contributed even more to advances in the field. The present review aims to summarize the newly approved therapeutic strategies for HER-2-positive breast cancer and review the new and exploratory HER-2-targeted therapies currently under development.

Background: Tumor budding (TB) is a dynamic process associated with the epithelial–mesenchymal transition and a well-established prognostic biomarker for colorectal cancer. As part of the tumor microenvironment, tumor buds demonstrate increased cell motility and invasiveness. Current evidence demonstrates that high levels of TB correlate with disease progression and worst outcomes across different solid tumors. Our work aims to demonstrate the clinical applicability of TB analysis and its utility as a prognostic factor for patients with early breast cancer (EBC). Methods: Retrospective, single-center, observational study, enrolling patients with EBC diagnosed in a Portuguese hospital between 2014 and 2015. TB classification was performed according to the International Tumor Budding Conference 2016 guidelines. Results: A statistically significant relation was found between higher TB score and aggressive clinicopathological features (angiolymphatic/perineural invasion-p < 0.001; tumor size-p = 0.012; nuclear grading-p < 0.001; and Ki-67 index-p = 0.011), higher number of relapses (p < 0.001), and short disease-free survival (DFS) (p < 0.001). Conclusion: We demonstrate that high TB correlates with shorter DFS and aggressive clinicopathological features used in daily practice to decide on the benefit of chemotherapy for EBC. TB represents a needed prognostic biomarker for EBC, comprising a new factor to be considered in the adjuvant decision-making process by identifying patients at a high risk of relapse and with higher benefit on treatment intensification. Clinical trials incorporating TB are needed to validate its prognostic impact.

Introduction: Bladder cancer is the tenth most common cancer worldwide, with Europe having the highest incidence rates. Regarding the treatment of metastatic disease, first-line treatment for fit patients is cisplatin-containing combination chemotherapy. However, a significant percentage of patients are ineligible for platinum-based chemotherapy, or progress under these regimens. Recently, immune checkpoint blockade has become a treatment option for this group of patients. In this report, we present the case of a male patient diagnosed with metastatic bladder cancer who did not tolerate cisplatin-containing chemotherapy and achieved complete response after treatment with pembrolizumab. Patient concerns: A 58 years-old Caucasian man with a medical history of high-grade urothelial carcinoma pT3bN0R0 under a watchful waiting strategy for 6 months presented to the Medical Oncology appointment with two axillary and cervical adenopathies. Diagnosis: Cervicothoracoabdominal computed tomography confirmed the presence of two large necrotic lymphadenopathies in the cervical and axillary lymphatic chains, and bone scintigraphy revealed dorsal (D11) and lumbar (L5) metastatic lesions. Ultrasonography-guided biopsy of the axillary nodule revealed the presence of metastatic tissue of primary urothelial origin. Interventions: The patient was initiated on a palliative chemotherapy regimen of carboplatin area under the curve 5 plus gemcitabine (1000 mg/m²). During the first cycle of chemotherapy, acute kidney failure akin 2 developed due to nonobstructive toxic acute tubular necrosis with progressive deterioration of kidney function. Therefore, palliative chemotherapy with carboplatin plus gemcitabine was changed to 200 mg of pembrolizumab every 21 days. Outcomes: Overal survival of 57 months with an immune complete response according to the immune Response Evaluation Criteria in Solid Tumours criteria and an excellent quality of life. Conclusion: This case illustrates that second-line therapy with ICIs (pembrolizumab or atezolizumab) has favourable results in achieving an immune complete response after intolerance to cisplatin-based regimens. ICIs provide durable responses that improve overall survival and quality of life.

Introduction: Breast cancer comprises several different pathological entities defined by the presence or absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2). During the disease course, the increase in tumor heterogeneity contributes to the discordant expression of estrogen/progesterone receptors and HER2 status between primary and metastatic lesions. We describe a case that demonstrates the clinical relevance of molecular reassessment during metastatic breast cancer progression. Patient concerns: A 40-year-old Caucasian woman with germline breast cancer gene mutation was referred to a general surgery appointment after breast ultrasound revealed a suspicious nodular lesion in 2012. Diagnosis: Ultrasound-guided microbiopsy revealed an invasive ductal carcinoma of no special type, hormone receptor-positive, and HER2-negative. Interventions: The patient underwent modified radical left mastectomy, adjuvant radiotherapy, chemotherapy, and endocrine therapy. Four years after the diagnosis, HER2 positive lung progression was documented, and the patient received anti-HER2 targeted systemic therapy for 15 months. New disease progression with a triple-negative profile was found, and palliative systemic treatment was changed to carboplatin for 3 months until new progression. Based on the results of the OlympiAD trial, monotherapy with Olaparib 300 mg twice daily for 28 days was initiated. Outcomes: After seven cycles of treatment, patient showed progressive improvement in quality of life and maintained stable disease without significant adverse events. Conclusion: The clinical relevance of hormone receptor and HER2 status discordance between primary tumors and metastatic lesions has been studied in recent years. This case report illustrates the clinical impact of molecular changes during disease progression and the adaptation of treatment options. This allows for an increase in both survival and quality of life in patients with metastatic breast cancer.