Neu Perspectives, Therapies, and Challenges for Metastatic HER2-Positive Breast Cancer.

Even though gene amplification or protein overexpression occurs in approximately one-fifth of all breast cancers, the discovery of HER2 has, nevertheless, had profound implications for the disease. Indeed, the characterization of the receptor resulted in a number of significant advances. Structurally, unique features provided avenues for the development of numerous compounds with target-specificity; molecularly, biological constructs revealed a highly complex, internal signal transduction pathway with regulatory effects on tumor proliferation, survival, and perhaps, even resistance; and clinically, disease outcomes manifested its predictive and prognostic value. Yet despite the receptor's utility, the beneficial effects are diminished by tumor recurrence after neo- or adjuvant therapy as well as losses resulting from the inability to cure patients with metastatic disease. What these observations suggest is that while tumor response may be partially linked to uncoupling cell surface message reception and nuclear gene expression, as well as recruitment of the innate immune system, disease progression and/or resistance may involve a reprogrammable signaling mainframe that elicits alternative growth and survival signals. This review attempts to meld current perceptions related to HER2-positive metastatic breast cancer with particular attention to current biological insights and therapeutic challenges.

Unusual Relapse of Chronic Lymphocytic Leukemia After Remission.

Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia with over 20,000 estimated cases in 2017. Leukemic involvement of the nervous system from CLL causing neurologic symptoms is reported in only about one percent of patients. Unfortunately, there is no current standard therapy for the treatment of CLL leptomeningeal disease. In this case, we discuss an unusual presentation of CLL leptomeningeal disease misdiagnosed as chronic rebound headache. A 61-year-old female was diagnosed with Rai stage I CLL in 2002. She presented at that time with peripheral blood lymphocytosis and subsequent flow cytometry revealed a mature B cell population consistent with CLL. She was monitored clinically as there were no indications for therapy. In 2006, she developed B symptoms along with hemolytic anemia refractory to steroids and was initiated on chemotherapy with fludarabine, cyclophosphamide, and rituximab (FCR). She had a complete response after six cycles. The patient was in her usual state of health until 2016, when she complained of chronic headaches. She took acetaminophen and ibuprofen regularly and was diagnosed with rebound headaches by neurology. These symptoms progressed and the patient developed encephalopathy requiring inpatient admission. Magnetic resonance imaging (MRI) revealed abnormal enhancement in the cerebellar peduncles and dentate nuclei symmetrically; a lumbar puncture performed revealed evidence of CLL consistent with leptomeningeal disease. Therapy was started with oral ibrutinib at 560 mg daily for better central nervous system (CNS) penetration. After three months of therapy, she had complete resolution of symptoms and MRI abnormalities. Leptomeningeal disease is a rare complication of CLL that clinicians should be aware of and ibrutinib can be an effective, tolerable therapy for this debilitating disease.

Metastatic Breast Cancer with BRCA Mutation Discovered By Next-Generation Sequencing Responding to Olaparib.

Breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2) mutations are associated with hereditary breast and ovarian cancer syndromes (HBOC). However, certain individuals with breast cancer do not meet high-risk factors for hereditary breast cancer screening based on age, family history, and biology of malignancy. We present a patient with relapsed breast cancer who developed progressive disease with significant tumor burden causing a recurrent pleural effusion. Next-generation sequencing (NGS) done on a tumor biopsy was positive for the BRCA2 mutation. Olaparib was initiated with a resolution of the pleural effusion and a significant decrease in the size of the malignant lymphadenopathy and pulmonary lesions.  There are numerous reports of comprehensive molecular profiling improving access to therapy, most notably for lung cancer, as well as melanoma. However, this has not been widely utilized for breast cancer. However, in our case, NGS provided our patient with an effective therapy and should be considered for the future management of metastatic breast cancer.

Reducing Over-Utilization of Cardiac Telemetry with Pop-Ups in an Electronic Medical Record System.

Non-invasive cardiac monitoring has well-established indications and protocols. Telemetry is often overused leading to a shortage of tele-beds and an increment of hospital expenses. In some cases, patients are kept on telemetry longer than the indicated length because providers are unaware of its ongoing use. We investigated the effect of reminder pop-ups, incorporated into an electronic medical record (EMR), on minimizing the use of telemetry. Three regional hospitals implemented an electronic pop-up reminder for discontinuing the use of telemetry when no longer indicated. A retrospective analysis of data for patients on telemetry, outside of the intensive care unit (ICU), was conducted and comparisons were drawn from pre- and post-implementation periods. A composite analysis of the number of days on telemetry was calculated using the Kruskal-Wallis test. With the implementation of the pop-up reminder, the median number of days on telemetry was significantly lower in 2016 than in 2015 (2.25 vs 3.61 days, p < 0.0001). Overutilization of telemetry is widely recognized, despite not being warranted in non-ICU hospitalizations. The implementation of a pop-up reminder built into the electronic medical record system reduced the overuse of telemetry by 37% between the two time periods studied.