The oncologist
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Triple-negative breast cancer, characterized by tumors that do not express estrogen receptor (ER), progesterone receptor (PR), or HER-2 genes, represents an important clinical challenge because these cancers do not respond to endocrine therapy or other available targeted agents. The metastatic potential in triple-negative breast cancer is similar to that of other breast cancer subtypes, but these tumors are associated with a shorter median time to relapse and death. One important goal is therefore the identification of prognostic factors and markers to reliably select high and low risk subsets of patients with triple-negative disease for different treatment approaches of subtypes with differential responsiveness to specific agents. ⋯ Triple-negative breast cancer is clearly a distinct clinical subtype, from the perspective of both ER and HER-2 expression, but further subclassification is needed. At present, there is not a clear, proven effective single agent that targets a defining vulnerability in triple-negative breast cancer. This article will review the clinical problem of triple-negative disease, potential prognostic factors, demonstrated efficacy of currently available therapeutic options, and new potential therapies.
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Clinicians have limited accuracy in the prediction of patient survival. We assessed the accuracy of probabilistic clinician prediction of survival (CPS) and temporal CPS for advanced cancer patients admitted to our acute palliative care unit, and identified factors associated with CPS accuracy. Eight physicians and 20 nurses provided their estimation of survival on admission by (a) the temporal approach, "What is the approximate survival for this patient (in days)?" and (b) the probabilistic approach, "What is the approximate probability that this patient will be alive (0%-100%)?" for ≥24 hours, 48 hours, 1 week, 2 weeks, 1 month, 3 months, and 6 months. ⋯ Probabilistic CPS was significantly more accurate than temporal CPS for both physicians and nurses, although this analysis was limited by the different criteria for determining accuracy. With the probabilistic approach, nurses were significantly more accurate at predicting survival at 24 hours and 48 hours, whereas physicians were significantly more accurate at predicting survival at 6 months. The probabilistic approach was associated with high accuracy and has practical implications.
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An existing and validated palliative prognostic (PaP) score predicts survival in terminally ill cancer patients based on dyspnea, anorexia, Karnofsky performance status score, clinical prediction of survival, total WBC, and lymphocyte percentage. The PaP score assigns patients to three different risk groups according to a 30-day survival probability--group A, >70%; group B, 30%-70%; group C, <30%. The impact of delirium is known but was not incorporated into the PaP score. ⋯ The revision of the PaP score was carried out by modifying the cutoff values used for prognostic grouping without, however, affecting the partial scores of the original tool. The performance of the D-PaP score was better than that of the PaP score and its key feature of simplicity was maintained.
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In developed countries, there has been a remarkable improvement in mortality from breast cancer, but almost all of that benefit has occurred in the estrogen receptor (ER)(+) and human epidermal growth factor receptor (HER)-2(+) subsets. Triple-negative breast cancer, defined as tumors that are negative for ER, progesterone receptor, and HER-2, represent a minority of breast cancers. However, because of the poor prognosis in this particular subtype, triple-negative disease accounts for a disproportionate number of metastatic cases and breast cancer deaths. ⋯ More recently, poly(ADP-ribose) polymerase inhibitors appear to take advantage of the concept of synthetic lethality, or dual pathway inhibition, in attacking triple-negative and BRCA-associated tumors. These and other studies in triple-negative disease will help us to better identify effective treatment options and improve outcomes in these patients. This article addresses the nature of, and therapeutic strategies for, triple-negative breast cancer.
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To describe the clinical studies that led to the FDA approval of rituximab in combination with fludarabine and cyclophosphamide (FC) for the treatment of patients with chronic lymphocytic leukemia (CLL). ⋯ On the basis of the demonstration of clinically meaningful prolongation of PFS, the FDA granted regular approval to rituximab in combination with FC for the treatment of patients with CLL. The magnitude of the treatment effect in patients 70 years and older is uncertain.