False-negative tests in breast cancer management

We review the sensitivity of different diagnostic tests for breast cancer management based on recent experience in a 34-year-old patient. False-negative tests at diagnosis of early disease and of relapse resulted in diagnostic and therapeutic delays. Initial mammography and breast ultrasonography were falsely negative despite a palpable breast lump. Clinical examination and axillary ultrasound missed macroscopically involved lymph nodes. At relapse, metastatic lesions were missed despite symptoms, three years after primary treatment. CA 15-3 was normal; bone and liver metastases were missed by standard and more advanced imaging techniques including liver ultrasonography, nuclear bone scan and PET-CT scan. Worsening of clinical symptoms, lab results and abnormal tissue biopsies finally led to the diagnosis of extensive metastatic disease. Genetic screening showed an abnormality within the BRCA-1 region of unknown clinical importance. This review highlights 1) that diagnostic tests managing symptomatic breast cancer patients may have a low sensitivity, 2) the importance of clinical findings and other markers for disease, such as lactate dehydrogenase and 3) the need for diagnostic biopsies for clinically suspect symptoms despite normal imaging and biochemistry.