The Significance of Serum HER2 Levels at Diagnosis on Intrinsic Subtype-Specific Outcome of Operable Breast Cancer Patients.

PURPOSE: This study evaluated the association of serum HER2 (sHER2) levels at diagnosis with clinicopathologic parameters and disease free survival (DFS) in operable breast cancer patients according to intrinsic subtype. METHODS: The sHER2 levels were measured using a chemiluminescence immunoassay. The HER2 status in all tumor tissues was determined by immunohistochemistry, and confirmed in equivocal cases by fluorescence in situ. RESULTS: There were 436 consecutive stage I-III breast cancer patients with sHER2 result at diagnosis between Nov 2004 and Dec 2011. High sHER2 levels (≥ 15 ng/ml) were reported in 52 patients (11.9%) and HER2 overexpression in tumor tissue was observed in 111 patients (25.5%). High sHER2 levels were associated significantly with advanced stage (P < 0.001), mastectomy (P = 0.012), neoadjuvant chemotherapy (P < 0.001), anti-HER2 therapy (P < 0.001) and hormone therapy (P = 0.022). The patients with high sHER2 levels had a worse DFS (P < 0.001). In multivariate analysis, high sHER2 levels were associated significantly with worse DFS (HR = 2.25, 95% CI 1.27-3.99, P = 0.005). High sHER2 levels were associated with worse DFS in the HR+/HER2-, HR+/HER2+ and HR-/HER2+ subtypes (P = 0.043, 0.003 and 0.041, respectively). CONCLUSIONS: These results show that the sHER2 level at diagnosis is a useful prognostic factor in patients with operable breast cancer, especially in the HR+/HER2-, HR+/HER2+ and HR-/HER2+ subtypes.

Impact of Molecular Subtype Conversion of Breast Cancers after Neoadjuvant Chemotherapy on Clinical Outcome.

PURPOSE: The aim of this study was to examine molecular subtype conversions in patients who underwent neoadjuvant chemotherapy (NAC) and analyze their clinical implications. MATERIALS AND METHODS: We included consecutive breast cancer patients who received NAC at the National Cancer Center, Korea, between August 2002 and June 2011, and had available data on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) receptor status prior to NAC. Molecular subtypes, hormone receptor (HR) status, and ER and PR Allred scores before and after NAC were compared, and the long-term outcomes were analyzed. RESULTS: Of 322 patients, 32 (9.9%) achieved a pathologic complete response after NAC. HR+/HER2- tumors tended to convert into triple negative (TN) tumors (10.3%), whereas 34.6% of TN tumors gained HR positivity to become HR+/HER2- tumors. Clinical outcomes of molecular subtype conversion groups were compared against patients who remained as HR+/HER2- throughout. The HR+/HER2- to TN group had significantly poorer recurrence-free survival (RFS) (hazard ratio, 3.54; 95% confidence interval [CI], 1.60 to 7.85) and overall survival (OS) (hazard ratio, 3.73; 95% CI, 1.34 to 10.38). Patients who remained TN throughout had the worst outcomes (for RFS: hazard ratio, 3.70; 95% CI, 1.86 to 7.36; for OS: hazard ratio, 5.85; 95% CI, 2.53 to 13.51), while those who converted from TN to HR+/HER2-showed improved comparable survival outcomes. CONCLUSION: Molecular subtypes of breast cancers changed frequently after NAC, resulting in different tumor prognostication. Tumor subtyping should be repeated after NAC in patients with breast cancer.

A case of Hodgkin's lymphoma associated with sensory neuropathy.

Peripheral neuropathies occur in lymphoma patients. Causes of neuropathy include chemotherapy, opportunistic infections, and the lymphoma itself. We report a patient with lymphoma whose chief complaint was a sensory loss in the hands and feet. Electrophysiologic studies and sural nerve biopsy showed sensory polyneuropathies. We hypothesize that this neuropathy is associated with lymphoma-related ganglionopathy, and among the possible causes, we suspect that a systemic cause such as a paraneoplastic syndrome is the most likely pathogenic etiology. However, further follow-up will be necessary to see whether sensory symptoms change with lymphoma treatment.