Y. Kwon

Trastuzumab treatment beyond brain progression in HER2-positive metastatic breast cancer

BACKGROUND Although trastuzumab therapy improves survival in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, 40% of patients develop brain metastasis (BM) even when extracranial disease is under control. We studied whether trastuzumab therapy beyond or after BM was beneficial to patients with BM. PATIENTS AND METHODS The effect of trastuzumab on survival after BM was analyzed in 78 HER2-positive breast cancer patients. Patients were grouped according to trastuzumab therapy; no treatment and treatment before and after BM were diagnosed. RESULTS Overall survival after the diagnosis of BM as well as time to progression (TTP) of intracranial tumors was prolonged in patients who received trastuzumab after BM was diagnosed. Conversely, BM occurred much later in patients who received trastuzumab before BM. In the multivariate Cox regression model, age at BM <50 years, disease-free interval >or=24 months, TTP of intracranial tumor >or=4.8 months, and trastuzumab treatment after BM were significantly associated with longer survival after the onset of BM. CONCLUSIONS Trastuzumab therapy after the onset of BM in HER2-positive breast cancer patients is associated with a significant survival benefit after BM diagnosis compared with patients who never received or completed trastuzumab before the BM diagnosis.

Potential antitumor effects of nitrogen-containing bisphosphonate in hormone receptor negative breast cancer patients with bone metastases

BackgroundThis retrospective study evaluated, according to hormone receptor status, the antitumor effects of bisphosphonate especially on survival and disease progression in breast cancer patients with metastatic bone disease.MethodsOf 317 patients with initial bone metastasis and known breast cancer subtypes, 230 patients (72.6%) had hormone receptor (HR) positive tumors, and 87 patients (27.4%) had HR negative tumors. We assessed the primary outcome of overall survival (OS), after adjusting for other factors, comparing a group that received bisphosphonates (BPs) with a group that did not receive it.Results87.8% of HR positive and 69.0% of HR negative patients received BPs with a median number of 17.7 cycles. Although BPs treatment made no survival benefit in HR positive group, HR negative patients showed a significant prolonged survival when they received BPs treatment (hazard ratio = 0.56 [95% CI 0.34 to 0.91], P = 0.019). In multivariate analysis, disease free interval > 2 years (P = 0.036), a sum of metastatic sites < 3 (P = 0.034), and BP treatments (P = 0.007) were significant factors for survival in HR negative patients.ConclusionBisphosphonate treatment can result in a survival benefit in metastatic breast cancer patients with HR negative tumors.

CKAP2 (cytoskeleton-associated protein2) is a new prognostic marker in HER2-negative luminal type breast cancer

Background Recently, we reported cytoskeleton-associated protein2 (CKAP2) as a possible new prognostic breast cancer marker. However, it has not yet been applied in clinic. Therefore, clinical significance of CKAP2 was evaluated in comparison with that of Ki-67 in a cohort of breast cancer patients, and the expression difference was analyzed in cell cycle-arrested cancer and fibroblast cells. Methods A total of 579 early breast cancer patients who underwent surgery at the National Cancer Center Hospital in Korea between 2001 and 2005 were accrued. CKAP2-positive cell count (CPCC) and Ki-67 labeling index (Ki-67LI) were evaluated by immunohistochemcal staining. The immunocytochemical staining patterns of CKAP2 and Ki-67 were analyzed in HeLa and human fibroblast cells after synchronization by double thymidine block. Results Although there was a significant correlation (R = 0.754, P < 0.001) between CPCC and Ki-67LI, only CPCC was correlated with DFS in overall population (HR, 2.029; 95% CI, 1.012–4.068; P = 0.046) and HER2-negative luminal subgroup (HR, 3.984; 95% CI, 1.350–11.762; P = 0.012) by multivariate analysis. In immunocytochemical staining, more than 50% of serum-starved or non-mitotic cell phase HeLa cells were positive for Ki-67, in comparison to the low CKAP2-positivity, which might explain the prognostic difference between CPCC and Ki-67LI. Conclusions The current study showed that CPCC but not Ki-67LI is an independent prognostic indicator in early breast cancer, more specifically in HER2-negative luminal breast cancer. The difference between two markers may be related to the lower background expression of CKAP2 in cancer cells.

Magnetic Resonance Imaging (MRI) Assessment of Residual Breast Cancer After Neoadjuvant Chemotherapy: Relevance to Tumor Subtypes and MRI Interpretation Threshold

Purpose: To investigate the diagnostic performance of magnetic resonance imaging (MRI) for predicting pathologic complete response after neoadjuvant chemotherapy (NAC) depending on subtypes of breast cancer using different interpretation thresholds of MRI negativity. Patients and Methods: A total of 353 women with breast cancer who had undergone NAC were included. Pathologic examination after complete surgical excision was the reference standard. Tumors were divided into 4 subtypes on the basis of expression of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2). Tumor enhancement was assessed on early and late phases of MRI. MRI negativity was divided into radiologic complete response (rCR, complete absence of enhancement on both early and late phases) and near‐rCR (no discernible early enhancement but observed late enhancement). Results: Ninety (25.5%) of 353 patients experienced pathologic complete response. When analyzing the data of all patients, sensitivity of MRI was higher for rCR versus near‐rCR (97.72% vs. 90.49%, P < .0001), whereas specificity was lower for rCR versus near‐rCR (44.44% vs. 72.22%, P < .0001). Accuracy was equivalent (84.14% vs. 85.84%). In HR−HER2+ tumors, 100% sensitivity and negative predictive value were achieved by assessing early enhancement only. In HR+HER2− tumors, sensitivity of MRI was higher for rCR versus near‐rCR (96.12% vs. 86.82%, P = .0005). Conclusion: Diagnostic performance of MRI after NAC differs in accordance with the subtypes and threshold of MRI negativity. MRI assessment with consideration of tumor subtypes is required, along with standardization of MRI interpretation criteria in the NAC setting.