Ki67 is a significant predictive and prognostic marker over a wide range of cut points suggesting that data-derived cut point optimization might not be possible. Ki67 could be used as a continuous marker; in addition, the scientific community could define standardized cut points for Ki67. Our analysis explains the variability observed for Ki67 cut points in previous studies; however, this should not be seen as weakness, but as strength of this marker. MSRDs are an easy new approach for visualization of biomarker effects on outcome across molecular subtypes in breast cancer. The experience with Ki67 could provide important information regarding the development and implementation of other quantitative biomarkers.
Gastrointestinal (GI) adverse events (AEs) are frequently observed in patients receiving EGF receptor (EGFR; also known as HER1 or ErbB1) tyrosine kinase inhibitor therapy. GI AEs are among the most common and most impactful on a patient's quality of life. Severe diarrhea can result in fluid and electrolyte losses, leading to dehydration, electrolyte imbalances and renal insufficiency. Afatinib is an irreversible, oral, ErbB family blocker, inhibiting EGFR (ErbB1), HER2 (ErbB2) and ErbB4 receptor kinases. It also inhibits transphosphorylation of ErbB3. Similar to reversible tyrosine kinase inhibitors of EGFR, GI AEs - in particular, diarrhea - have frequently been observed in afatinib-treated patients. This article summarizes current data on afatinib-associated diarrhea and provides strategies for its management. Patient education, early identification, timely management and ongoing assessment will help to prevent aggravation, afatinib dose reductions or therapy discontinuation, encouraging patient compliance and allowing patients to obtain the maximum therapeutic benefit from this agent.
In the context of neoadjuvant therapy (NT) for breast cancer patients, different targeted therapy approaches are currently evaluated in clinical trials. Serum markers could help to monitor and optimize such treatment strategies. We investigated human epidermal growth factor receptor 2 serum (sHER2) levels in 175 breast cancer patients participating in the GeparQuattro trial. This study incorporated NT approaches and additional trastuzumab treatment for all patients with HER2-positive tumors. Human epidermal growth factor receptor 2 serum levels were measured by enzyme-linked immunosorbent assay (ELISA) before initiation of NT and after NT (pre-surgery) in a HER2-positive (n = 90) and a HER2-negative patient cohort (n = 85). Median pre-chemotherapy sHER2 levels were higher in patients with positive HER2 status of the primary tumor than in patients with negative HER2 status (14.9 ng/ml vs. 7.7 ng/ml, P < 0.001). A pre-chemotherapy sHER2 cut-off level of 10 ng/ml had the best sensitivity and specificity in discriminating between HER2-positive and HER2-negative primary tumors. In HER2-positive patients, we found a significant positive association between pathological complete remission (pCR) and elevated sHER2 levels (above 15 ng/ml, P = 0.045) and a decrease of sHER2 levels during NT (P = 0.02), which was also significant in multivariate analysis (OR = 3.29, 95% CI 1.001-10.89, P = 0.049). In HER2-negative patients, we observed no association between sHER2 levels and pCR (P > 0.05). Monitoring sHER2 levels in the presence of anti-HER2 treatment might be an adjunct to the clinical evaluation during NT.
A positive margin in breast conserving surgery is associated with an increased risk of local recurrence. Failure to achieve clear margins results in re-excision procedures. Methods for intraoperative assessment of margins have been developed, such as frozen section analysis, touch preparation cytology, near-infrared fluorescence optical imaging, x-ray diffraction technology, high-frequency ultrasound, micro-CT, and radiofrequency spectroscopy. In this article, options that might become the method of choice in the future are discussed.
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