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Continuous low-dose 5-FU was popularized as a therapy for pretreated metastatic breast cancer for the past few decades, spurred by the advent of the electronic infusion pump. Capecitabine, otherwise known by its trade name Xeloda, is a prodrug of 5-fluorouracil (5-FU), which is administered orally in many chemotherapy regimens, and plays a role in metastatic breast cancer treatment refractory to traditional anthracyclines and taxane therapy. In this case presentation, we describe a unique case of refractory de-novo stage IV triplenegative breast cancer presented with right breast primary invasive ductal carcinoma, extensive lymphadenopathy, with biopsy proven bone marrow infiltration, diffuse hepatomegaly, splenomegaly, significant hyperbilirubinemia, and bone marrow failure treated with continuous 5-FU infusion and subsequently oral capecitabine after initial treatment failure with nab-paclitaxel and sacituzimab govitecan. With this case presentation, the authors aim to showcase the versatility of 5-FU and its prodrug in treatment of metastatic triple-negative breast cancer with severe bone marrow and liver involvement while highlighting key physiologic and pharmacologic mechanisms. [ABSTRACT FROM AUTHOR]

Abstract Background Overexpression of HER2 plays an important role in cancer progression and is the target of multiple therapies in HER2‐positive breast cancer. Recent studies have also highlighted the presence of activating mutations in HER2, and HER3 that are predicted to enhance HER2 downstream pathway activation in a HER2‐dependent manner. Methods In this report, we present two exceptional responses in hormone receptor‐positive, HER2‐nonamplified, HER2/HER3 co‐mutated metastatic breast cancer patients who were treated with the anti‐HER2‐directed monoclonal antibodies, trastuzumab and pertuzumab. Results Both patients acheived exceptional responses to treatment, suggesting that combined trastuzumab, pertuzumab, and endocrine therapy could be a highly effective therapy for these patients and our observations could help prioritize trastuzumab deruxtecan as an early therapeutic choice for patients whose cancers have activating mutations in HER2.

Continuous low-dose 5-FU was popularized as a therapy for pretreated metastatic breast cancer for the past few decades, spurred by the advent of the electronic infusion pump. Capecitabine, otherwise known by its trade name Xeloda, is a prodrug of 5-fluorouracil (5-FU), which is administered orally in many chemotherapy regimens, and plays a role in metastatic breast cancer treatment refractory to traditional anthracyclines and taxane therapy. In this case presentation, we describe a unique case of refractory de-novo stage IV triple-negative breast cancer presented with right breast primary invasive ductal carcinoma, extensive lymphadenopathy, with biopsy proven bone marrow infiltration, diffuse hepatomegaly, splenomegaly, significant hyperbilirubinemia, and bone marrow failure treated with continuous 5-FU infusion and subsequently oral capecitabine after initial treatment failure with nab-paclitaxel and sacituzimab govitecan. With this case presentation, the authors aim to showcase the versatility of 5-FU and its prodrug in treatment of metastatic triple-negative breast cancer with severe bone marrow and liver involvement while highlighting key physiologic and pharmacologic mechanisms.

Purpose of Review: The treatment of breast cancer is evolving at accelerated rates. As systemic therapy continues to improve, the roles of surgery and radiation are being re-considered. The intent of this review is to discuss recent studies and potential future directions for the locoregional management of breast cancer following neoadjuvant chemotherapy. Recent Findings: For patients treated with neoadjuvant chemotherapy, treatment decisions hinge on the tumor's biomarkers and patient's response to systemic therapy. For patients who sustain a pCR, clinical trials are investigating the role of de-escalated surgery and radiation. For patients with residual disease, escalated systemic therapies have been found to be of benefit. Surgery and radiation remain a mainstay of treatment. Summary: As the indications for neoadjuvant chemotherapy expand, locoregional management continues to develop and therapy is being increasingly tailored to an individual's particular response. Practitioners must know when therapy can be safely de-escalated and indications for escalation. [ABSTRACT FROM AUTHOR]