BackgroundThe development of acquired resistance to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represents a major clinical challenge in the management of hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. Overcoming this resistance requires novel therapeutic strategies that target the underlying molecular escape pathways.Case presentationWe report the case of a patient initially diagnosed in 2011 with pT2N0M0, ER+/HER2- invasive ductal carcinoma. Following multimodality treatment, she experienced disease progression with bone metastases after five years, followed by lymph node metastases at the ten-year mark. Subsequent treatment with the CDK4/6i ribociclib in combination with fulvestrant resulted in disease progression approximately one year later, indicating acquired resistance. Due to progressive bone loss, denosumab was initiated for skeletal support, and bempedoic acid was later added for dyslipidemia.DiscussionThis case provides a clinical basis for exploring two innovative therapeutic concepts to overcome resistance. First, we discuss the complex role of receptor activator of nuclear factor kappa-B ligand (RANKL) inhibition. Given that leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) functions as a decoy receptor for RANKL, we hypothesize that a patient’s LGR4 expression status may dictate the efficacy and safety of denosumab, potentially serving as a predictive biomarker to personalize its use. Second, we propose that bempedoic acid, a supportive care medication, may exert a direct anti-neoplastic effect. Its dual mechanism, inhibiting ATP-citrate lyase (ACLY) to disrupt lipid synthesis and activating AMP-activated protein kinase (AMPK) to suppress mammalian target of rapamycin complex 1 (mTORC1) signaling, positions it as a potential agent to counteract the metabolic reprogramming associated with therapeutic resistance.ConclusionThis case report illustrates the sequential development of acquired therapeutic resistance in the long-term management of metastatic breast cancer. Although a single clinical observation cannot establish definitive efficacy, this scenario generates compelling hypotheses for future studies. It highlights the potential need to explore biomarker-driven approaches—such as evaluating LGR4 expression to guide RANKL inhibition—to personalize treatment. Additionally, it raises the possibility that repurposed supportive care medications, such as bempedoic acid, might offer hypothetical anti-neoplastic benefits, warranting broader clinical validation to overcome complex resistance mechanisms.
Serous endometrial carcinoma is an aggressive histologic subtype of endometrial cancer associated with early dissemination and poor prognosis. Typical metastatic pathways involve pelvic and para-aortic lymph nodes as well as peritoneal surfaces, whereas metastasis to inguinal lymph nodes is extremely uncommon. We report the case of a 42-year-old woman diagnosed with serous endometrial carcinoma confirmed by histopathological and immunohistochemical evaluation of endometrial aspiration biopsy. Imaging revealed metastatic right inguinal lymph nodes measuring up to 21 mm without evidence of additional distant metastases. The patient received four cycles of neoadjuvant chemotherapy consisting of carboplatin and paclitaxel, followed by extensive cytoreductive surgery including radical hysterectomy (type C1), bilateral inguinal lymph node dissection, para-aortic lymphadenectomy up to the level of the left renal vein, and omentectomy. Final histopathological evaluation demonstrated no residual viable tumor, indicating a complete pathological response. At the 12-month follow-up, the patient remains disease-free with no evidence of recurrence. This case highlights the importance of individualized multimodal treatment strategies combining systemic chemotherapy and radical surgery in patients with aggressive histologic subtypes of endometrial carcinoma presenting with atypical metastatic patterns.
We describe an extremely rare clinical case of primary ovarian osteosarcoma (OS) in a 70-year-old woman, along with the diagnostic criteria for this condition. The patient underwent chemotherapy and has been under observation for 27 months. Currently, tumor progression with metastatic lesions of the peritoneum is observed. This case highlights the importance of further studies of primary ovarian OS. Ovarian OS is not included in the 2022 WhO classification of genital tumors, but such cases occur; their diagnosis is difficult, and there is no consensus on the treatment. Accumulat- ing data on the structural features of these tumors and their response to treatment will help improve the understanding of their treatment.
