Treating Advanced Unresectable or Metastatic HER2-Positive Breast Cancer: A Spotlight on Tucatinib.

The management of HER2 positive breast cancer has been transformed by the development of targeted therapies. Dual blockade with the monoclonal antibodies, trastuzumab and pertuzumab, added to first-line taxane chemotherapy and second-line therapy with the antibody-drug conjugate, T-DM1, are internationally agreed standards of care for advanced HER2 positive breast cancer, where available. However, until recently, options for patients for third-line therapy and beyond were of modest efficacy or limited by toxicity. In 2019, the results of trials of two exciting new agents for this space were presented. A third-generation HER2 tyrosine kinase inhibitor, tucatinib, combines the efficacy of the second-generation drug, neratinib, with a more manageable toxicity profile and has become a new standard of care after T-DM1, in combination with capecitabine and trastuzumab. The antibody-drug conjugate, trastuzumab deruxtecan, demonstrated remarkable efficacy in heavily pre-treated patients and received accelerated approval in the United States, whilst confirmatory Phase 3 trials are completed. This review will discuss the available data for the post-T-DM1 setting, focusing on tyrosine kinase inhibitors including tucatinib.

Spontaneous cervical haemorrhage of a parathyroid adenoma.

UNLABELLED: Haemorrhage of a parathyroid adenoma is a rare clinical presentation. This report describes a previously fit and well 54-year-old woman who presented with acute neck swelling and pain with an overlying ecchymosis. Admission laboratory tests revealed a raised parathyroid hormone and hypercalcaemia. A computed tomography (CT) scan showed widespread anterior cervical haemorrhage and a lesion at the inferior pole of the left thyroid gland. A working diagnosis of spontaneous haemorrhage from a parathyroid adenoma was made. As she was haemodynamically stable, she was treated conservatively with a period of observation in hospital to monitor for signs of neck organ compression. Follow-up imaging with CT, ultrasound and sestamibi confirmed the likely source of haemorrhage as a parathyroid nodule with significant vascularity. The diagnosis was confirmed on histopathological analysis after elective surgical exploration of the neck 6 months after her presentation. This revealed a benign parathyroid adenoma with evidence of acute and chronic bleeding. The patient made a full recovery with immediate normalisation of her biochemistry post-operatively. Despite developing a hoarse voice in the immediate post-operative period, this resolved completely within 1 month. This case report provides further evidence to support a minimal delay for elective surgery after conservative management to reduce the risks associated with recurrent bleeding. LEARNING POINTS: Haemorrhage of a parathyroid adenoma should be a differential for all cases of acute cervical swelling or ecchymosis with no precipitating factor.The clerking should identify any risk factors for endocrine disease.Blood tests to screen for abnormal parathyroid biochemistry should be performed on admission.Detailed imaging of the neck is essential to identify the source of haemorrhage and risk of compression to vital neck organs.Conservative management is a suitable option for patients who remain haemodynamically stable but all should undergo a period of observation in hospital.Conservatively managed patients should be considered for definitive surgical exploration within a month of presentation to avoid the risks of recurrent bleeding.

An atypical presentation of a typical pulmonary pathogen in an immunosuppressed patient.

We describe a case of a 38-year-old, HIV-positive asthmatic man with a history of intravenous methamphetamine substance misuse who presented with worsening dyspnoea, wheeze, productive cough without haemoptysis and deteriorating exercise tolerance. His chest X-ray was clear and subsequent CT scanning demonstrated multilobar, patchy consolidation and ground glass change in the lung parenchyma. His CD4 count was 864 cells/mm(3) (n=500-1500 cells/mm(3)) and viral load 863 IU/mL. Our primary diagnosis was an atypical pneumonia with associated bronchospasm. The differential diagnosis also included a methamphetamine-induced pulmonary haemorrhage, given the multiple small foci of ground glass change. The patient's sputum cultured Haemophilus influenzae, which was somewhat surprising, given his unusual CT findings. He recovered with antibiotic therapy and a follow-up CT scan at 6 weeks revealed complete resolution of the radiological findings.