Paired tumor sequencing and germline testing in breast cancer management: An experience of a single academic center.

BACKGROUND: Genetic testing for cancer predisposition is recommended to women with breast cancer who meet the criteria for such testing. After the FDA approvals of the poly ADP ribose polymerase (PARP) inhibitors, olaparib and talazoparib, for treatment of metastatic breast cancer, carrying germline mutations in BRCA1 and BRCA2 genes, the genetic testing result has become critical in their care. With the recent FDA approval of alpelisib for the treatment of PIK3CA-mutated hormone-receptor positive metastatic breast cancer, tumor molecular profiling to identify somatic mutations and potential molecularly targeted agents is increasingly utilized in the treatment of advanced breast cancer. AIM: Combining germline and somatic sequencing (paired testing) offers an advantage over a single technique approach. Our study evaluates the role of paired testing on the management of breast cancer patients. METHODS AND RESULTS: Forty-three breast cancer patients treated at Rush University Medical Center underwent paired germline and somatic variant testing in 2015 to 2017. A retrospective chart review was conducted with the analysis of demographic, clinical, and genomic data. Three actionable germline variants were found in the CHEK2 (2) and ATM (1) genes. 95% of tumors had somatic mutations. Seventy-seven percent of tumors had genomic alterations targetable with agents approved for breast cancer and 88% had molecular targets for agents approved for other cancers. Clinical examples of such use are described and potential future directions of tumor and paired testing are discussed. CONCLUSIONS: Germline variants were present in a relatively small patient group not routinely tested for inherited alterations. Potentially targetable somatic alterations were identified in the majority of breast cancers. Paired testing is a feasible and efficient approach that delivers valuable information for the care of breast cancer patients and eliminates serial testing.

Atypical challenging and first case report of babesiosis in Ecuador.

UNLABELLED: Babesia is known to be prevalent in the Eastern United States and other temperate countries but the prevalence of babesia is not well known in the tropical malaria-endemic countries because of the higher prevalence of malaria. A 72-year-old Hispanic male from Ecuador presenting with increasing left lower quadrant abdominal pain and distention for one year. He experienced nausea, vomiting, diarrhea, fever, chill, and myalgias. He reported 9 kg weight loss over the last two months. Patient moved to Chicago recently from Ecuador where he worked at a banana plantation and had frequent exposure to many insects and animals. Vital signs were normal but patient appeared chronically ill. Mild tenderness to palpation over the left side of the abdomen with marked splenomegaly, measuring 16 cm below the costal margin. Laboratory results with no leukocytosis hemoglobin 7.8 × 10(9)/L; and platelet count, 55 × 10(9)/L. Sodium was 128 mmol/L. Labs showed elevated LDH, ESR and ferritin values. The haptoglobin was low with a positive Combs test. CT abdomen showed moderate splenomegaly with large patchy, wedge-shaped hypodense area in posterior mid and upper spleen suggesting splenic infarction. Rapid malaria screening was negative, but a peripheral smear identified plasmodium species in more than 0.5% of red blood cells. Treatment with atovaquone and proguanil started. Two weeks later, molecular testing revealed Babesia DNA. This report details a case of babesiosis in a patient coming from a malaria-endemic region. The initial workup and blood work highly suggested a plasmodium infection. However the polymerase chain reaction confirmed the diagnosis of a Babesia microti. LEARNING OBJECTIVES: We report the first case of human Babesiosis in previously healthy individual from Ecuador.