Cisplatin Monotherapy as a Treatment Option for Patients with HER-2 Negative Breast Cancer Experiencing Hepatic Visceral Crisis or Impending Visceral Crisis.

INTRODUCTION: Hepatic visceral crisis (VC), characterized by a rapid total bilirubin increase with disease progression, poses a life-threatening risk in advanced breast cancer (ABC). International consensus guidelines define VC and touch on impending VC (IVC). Limited data exist on systemic treatments for hepatic VC/IVC. This study explores the safety and efficacy of cisplatin monotherapy in patients with Human Epidermal Growth Factor Receptor 2- negative breast cancer (BC) and hepatic IVC/VC. METHODS: In this retrospective single-center cohort study data of patients treated with cisplatin monotherapy (60-80 mg/m2, every 3-4 weeks) between 2016 and 2023 at a reference Cancer Centre in Southern Poland were analyzed. RESULTS: 33 female patients (24/33 hormonal-positive) with the mean age 53.84 years were included. Participants progressed on median 2 prior palliative systemic treatment lines. In 10/23 patients hepatic VC and in 23/33 IVC (rapid, symptomatic liver progression; extensive liver involvement; alanine or aspartate aminotransferase > 2 × normal limit; significant increases in lactate dehydrogenase, alkaline phosphatase, or gamma-glutamyl transferase) were identified. Median progression-free survival was 1.87 months and median overall survival 2.67 months. 33% of the patients presented stable disease or partial response. Eight patients experienced adverse events grade ≥ 3: in five the dose of cisplatin was reduced; two stopped the treatment. CONCLUSION: Due to the hepatotoxicity of BC-active drugs, specific recommendations for systemic treatment are scarce. Our study explored cisplatin's potential use, finding it to be a viable option in patients with performance status 0 or 1 experiencing hepatic IVC/VC, irrespective of liver function parameters and other factors.

Non-metastatic primary neuroendocrine neoplasms of the breast: a reference cancer center's experience of a heterogenous entity.

Background: Primary neuroendocrine neoplasms of the breast (Br-NENs) are rare. The classification has been updated in recent years making interpretation of the data published challenging. It is unclear whether neuroendocrine differentiation is associated with poorer prognosis and what treatment approaches should be applied. Methods: The database for breast cancer patients treated between 2009 and 2022 at the Maria Sklodowska-Curie National Research Institute of Oncology Branch Krakow was explored to search for Br-NENs. Patients' medical and pathological data were collected and analyzed. Results: We included 22 females with Br-NEN without metastases at the time of diagnosis. The median age was 64 years (range: 28-88), Of the cases, 18 were hormone receptor positive, all were HER-2 negative, the median Ki67 was 27% (10-100%). The median tumor size at the time of diagnosis was 29.5mm (7-75mm), 9 patients were N-positive. DCIS was present in 5 cases. Only one case was negative for chromogranin and synaptophysin staining, but data were missing for 4 cases. Nine patients received adjuvant chemotherapy, mainly based on anthracyclines and taxanes, while 16 received adjuvant hormonal therapy and 15 received postoperative radiotherapy. Radical surgery was performed in all patients, but two underwent suboptimal tumorectomy. One patient had local recurrence, three experienced metastatic disease, all involving the lungs, but these patients are still alive. The median follow-up was 96 months (8-153). Two patients died, with a follow up time of no recurrence >4 years. Our results were compared to twelve case series collecting clinical data on Br-NENs, with median patient number of 10.5 (range: 3-142). Conclusion: Br-NENs represent a heterogenous group of diseases, lacking data from prospective studies or clinical trials. There are no established treatment standards tailored for Br-NENs. Our patients' cohort exhibited a favorable prognosis, potentially attributed to lower tumor stage and Ki67 index compared to other reported case series. We suggest that radical surgery and postoperative radiotherapy be administered akin to standard treatment for breast cancer of no special type. ESMO also advocates for this approach in systemic treatment, although we recommend considering platinum-based chemotherapy for patients with poorly differentiated Br-NENs exhibiting high Ki67.

Clinical analysis of metaplastic breast carcinoma with distant metastases: A multi­centre experience.

Metaplastic breast cancer (BC-Mp), which includes a range of epithelial and mixed epithelial-mesenchymal tumours, are rare malignancies with an unfavourable prognosis. The limited literature on BC-Mp focuses mainly on retrospective data for radically treated patients. Notably absent are studies dedicated to the palliative treatment of BC-Mp with distant metastases. The present retrospective study investigated treatment modalities and prognosis in a multi-centre cohort of 31 female participants diagnosed with distant metastatic BC-Mp, including 7 patients with de novo metastatic disease. The median age of the patients was 61 years (range, 33-87 years), with 38.7% presenting local lymph node involvement. Lungs were the most common site for the metastatic disease (61.3%). Median Ki-67 index was 50% (range, 35-70%), and 80.7% of cases were classified as grade 3. Human epidermal growth factor receptor 2 (HER2)+ and estrogen receptor+ were detected in 12.9 and 6.5% of cases, respectively. A total of 62.4% of patients received first-line palliative systemic treatment. The 1- and 2-year overall survival (OS) were 38.5 and 19.2%, respectively. Receiving ≥1 line of palliative treatment was significantly associated with improved OS (P<0.001). Factors such as age, Ki-67 index, HER2 or hormonal status, presence of specific epithelial or mesenchymal components, location of metastases or chemotherapy regimen type did not influence OS. The present study provided insights into the clinicopathological profile, systemic treatment experience, prognostic factors and OS data of BC-Mp with distant metastases, emphasizing the imperative for clinical trials in this population.

Antibody-drug conjugates in HER-2 negative breast cancers with poor prognosis.

Antibody drug conjugates (ADCs) comprise a rapidly growing class of targeted drugs that selectively deliver a cytotoxic agent to cancer cells, reducing the side effects associated with conventional chemotherapy. Breast cancer (BC) is a heterogeneous entity. The need for effective therapies for HER-2 negative BCs with poor prognosis, such as triple-negative or endocrine-resistant BC, remains unmet due to the lack of potential targets for treatments. These BC subtypes are not candidates for hormonal or anti-HER-2 agents. However, ongoing clinical trials exploring the use of ADCs with a wide range of targets have shown potential for this treatment modality. In this review, we present the current state of knowledge regarding the role of ADC and speculate on novel approaches including ADC combination therapies, new molecular targets, and the role of other subclasses of ADCs (bicycle drug conjugates, bispecific ADCs, immune modulating ADCs) in this clinical scenario.