Comparison of sentinel lymph node biopsy guided by the multimodal method of indocyanine green fluorescence, radioisotope, and blue dye versus the radioisotope method in breast cancer: a randomized controlled trial.

PURPOSE: This study aimed to evaluate the identification rate and surgery time of sentinel lymph node biopsy (SLNB) by a multimodal method (MMM) using a mixture of indocyanine green (ICG), radioisotope (RI), and blue dye (BD) compared with the RI alone. METHODS: In this phase II randomized study, 86 patients with clinically node-negative breast cancer were enrolled and received SLNB with either MMM or RI. We compared the identification rate, number of sentinel lymph nodes (SLNs), and detection time of SLNB and evaluated the safety. RESULTS: The mean age of the MMM group and RI group was 48.2 and 51.0 years (p = 0.12), respectively. There were no differences in histopathologic factors, including tumor size, node positivity, and hormone receptor positivity between groups. SLNs were identified in all patients of both groups (100 % in the MMM group and 100 % in the RI group). The average number of SLNs in the MMM group was more than that in the RI group (3.4 ± 1.37 vs. 2.3 ± 1.04, respectively; p < 0.001). The time to detect the first sentinel lymph node was similar in each group (6.5 ± 5.16 vs. 8.0 ± 4.35 min; p = 0.13). In the MMM group, percutaneous lymphatic drainage was visualized by fluorescent imaging in 90.7 % (39 of 43 patients). During and after the operation, there were no complications, including allergic reactions, skin staining, or necrosis. CONCLUSIONS: This study is the first randomized trial that compared MMM using ICG, RI, and BD and the conventional RI method for SLNB. MMM is a feasible and safe method for SLNB.

Accumulation of p53 determined by immunohistochemistry as a prognostic marker in node negative breast cancer; analysis according to St Gallen consensus and intrinsic subtypes.

BACKGROUND: This study evaluated the prognostic impact of p53 accumulation by immunohistochemistry (IHC) in lymph node-negative breast cancer (LNN-BC), and in subgroups of St Gallen consensus and intrinsic subtypes. METHODS: A total 845 with a pathologic diagnosis of LNN-BC patients that underwent surgery at the National Cancer Center, Korea between 2001 and 2005 were retrospectively reviewed. RESULTS: The median age was 48 years (range: 25-85) and median follow-up period was 66.0 months (range: 9-101). Univariate analysis determined that tumor size, estrogen receptor (ER), progesterone receptor (PgR), p53, and Ki-67 were significant for disease free survival (DFS). Of these factors, PgR negativity (HR 3.57; 95% CI 1.26-10.09; P = 0.01) and p53 positivity (HR 3.17; 95% CI 1.51-6.65; P = 0.002) were independent prognostic factors in multivariate analysis. In the subanalysis for 4 intrinsic subtypes (luminal A, luminal B, HER2-overexpression, and triple-negative subtypes) and risk groups by St Gallen consensus, there were significant differences of DFS rates by p53 (5-year DFS rate, luminal A; 97.2% for p53 (-) vs 93.8% for p53 (+); P = 0.03, triple-negative subgroups; 94.1% vs 78.7%; P = 0.002, intermediate-risk group; 96.5% vs 90.7%; P = 0.003). CONCLUSIONS: P53 has prognostic power in LNN-BC, and gives the additional prognostic information for intrinsic subtypes and St Gallen consensus.

Worse prognosis of metaplastic breast cancer patients than other patients with triple-negative breast cancer.

The present study was designed to assess the clinical characteristics and outcomes of metaplastic breast cancer (MBC) compared to general invasive ductal carcinoma (IDC) and the triple-negative subtype (TN-IDC). The study population included 35 MBC and 2,839 IDC patients, including 473 TN-IDC diagnoses, from the National Cancer Center, Korea between 2001 and 2008. The clinicopathological characteristics and clinical outcomes were retrospectively reviewed. Mean age of patients was 47.4 years for the MBC group and 48.3 years for the IDC group. The MBC patients presented with a larger tumor size (>/=T2, 74.3% vs. 38.8%, P < 0.001), more distant metastasis at the first diagnosis (8.6% vs. 2.0%, P = 0.04), higher histologic grade (grade 3, 65.7% vs. 41.4%, P < 0.001), fewer estrogen receptor (ER), and progesterone receptor (PgR) positivity (ER+, 5.7% vs. 65.4%, P < 0.001; PgR+, 8.6% vs. 55.8%, P < 0.001), higher Ki-67 expression (35.5 +/- 26.2% vs. 20.6 +/- 19.8%, P = 0.024), and more TN subtypes (80.0% vs. 16.7%, P < 0.001) compared to the IDC group. Fifteen (46.8%) MBC patients and 260 (9.3%) IDC patients experienced disease recurrence with a median follow-up of 47.2 months (range 4.9-100.6 months). MBC was a poor prognostic factor for disease recurrence and overall survival in univariate and multivariate analysis (HR 3.89 in recurrence, 95% CI: 1.36-11.14, P = 0.01; HR 5.29 in death, 95% CI: 2.15-13.01, P < 0.001). MBC patients also experienced more disease recurrence (HR 3.99, 95% CI: 1.31-12.19, P = 0.01) and poorer overall survival (HR 3.14, 95% CI: 1.19-8.29, P = 0.02) compared to the 473 TN-IDC patients, as reflected by aggressive pathological features. Patients with MBC appeared to have inherently aggressive tumor biology with poorer clinical outcomes than those with general IDC or TN-IDC.

Prognostic Impact of [18F] FDG-PET in operable breast cancer treated with neoadjuvant chemotherapy.

BACKGROUND: This study aimed to evaluate the usefulness of serial [(18)F] 2-fluoro-2-deoxy-D: -glucose-positron emission tomography ([(18)F] FDG-PET) in potentially operable breast cancer with neoadjuvant chemotherapy. METHODS: Serial positron emission tomography was undertaken in 66 breast cancer patients who comprised a subset of the population in a phase III randomized neoadjuvant trial at National Cancer Center, Korea. We assessed the peak standardized uptake value (SUVp) in the primary tumor and axillary nodes before and after neoadjuvant chemotherapy and calculated the reduction rate (RR) of the SUVp. By means of a receiver operating characteristic curve, we identified an optimal cutoff value for the RR for predicting the pathologic response and evaluated the prognostic power of this cutoff value. RESULTS: Ten patients (15.2%) experienced a pathologic complete response (pCR) in the primary tumor, and 19 patients (28.8%) experienced a pCR in the axillary nodes. The mean RR of the SUVp in primary tumors was 70.3% +/- 28.7%, and this value was significantly different by the pathological response (89.2% +/- 11.1% in pCR vs. 66.9% +/- 29.6% in non-pCR, P < .001). When 84.8% of the RR was used as a cutoff value for the pCR, sensitivity and specificity was 70.0% and 69.6%, respectively. Ten patients (15.2%) developed recurrent disease at a median follow-up period of 61.5 (range, 13.5-71.8) months. In a univariate analysis, the 5-year disease-free survival (DFS) was correlated with the clinical T stage (91.1% in T1/2 vs. 71.4% in T3/4, P = .02), HER-2 status (77.8% in positive vs. 96.9% in negative, P = .03), and the 84.8% RR of the SUVp in the primary tumor (95.8% vs. 78.5%, P = .04). HER-2 positivity was a significant independent prognosticator in the multivariate analysis (hazard ratio 8.73, 95% confidence interval 1.03-73.84, P = .04). The presence of a pCR in the primary tumor or nodes was not a prognostic factor in this subset of patients. The RR of the SUVp in the axillary nodes was not correlated with the nodal pCR and DFS. CONCLUSIONS: The RR of the SUVp in the primary tumor was correlated with the pathologic response and DFS. This study suggests the possible prognostic value of the RR in positron emission tomography by neoadjuvant chemotherapy.

The invasive lobular carcinoma as a prototype luminal A breast cancer: a retrospective cohort study.

BACKGROUND: Although the invasive lobular carcinoma (ILC) is the second most frequent histologic subtype in Western countries, its incidence is much lower in Asia, and its characteristics are less well known. METHODS: We assessed the clinical characteristics and outcomes of 83 Korean patients (2.8%) with ILC for comparison with 2,833 (97.2%) with the invasive ductal carcinoma (IDC), including 1,088 (37.3%) with the luminal A subtype (LA-IDC). RESULTS: The mean age of all patients was 48.2 years, with no significant differences among the groups. Compared to IDC, ILC showed a larger tumor size (≥ T2, 59.8% vs. 38.8%, P = 0.001), a lower histologic grade (HG 1/2, 90.4% vs. 64.4%, P < 0.001), more frequent estrogen receptor positive (90.4% vs. 64.4%, P < 0.001), progesterone receptor positive (71.1% vs. 50.1%, P < 0.001) and HER2 negative (97.5% vs. 74.6%, P < 0.001) status, and lower Ki-67 expression (10.3% ± 10.6% vs. 20.6% ± 19.8%, P < 0.001), as well as being more likely to be of the luminal A subtype (91.4% vs. 51.2%, P < 0.001). Six (7.2%) ILC and 359 (12.7%) IDC patients developed disease recurrence, with a median follow-up of 56.4 (range 4.9-136.6) months. The outcome of ILC was close to LA-IDC (HR 0.77 for recurrence, 95% CI 0.31-1.90, P = 0.57; HR 0.75 for death, 95% CI 0.18-3.09, P = 0.70) and significantly better than for the non-LA-IDC (HR 1.69 for recurrence, 95% CI 1.23-2.33, P = 0.001; HR 1.50 for death, 95% CI 0.97-2.33, P = 0.07). CONCLUSIONS: ILC, a rare histologic type of breast cancer in Korea, has distinctive clinicopathological characteristics similar to those of LA-IDC.

Risk factors for malignancy in benign papillomas of the breast on core needle biopsy.

BACKGROUND: This study was designed to evaluate the clinical and pathologic parameters of benign papillomas diagnosed on core needle biopsy (CNB) and predict malignancy risk after surgical excision. METHODS: We retrospectively reviewed clinicopathologic findings for 160 CNB-diagnosed benign papillomas followed by surgical excision from 154 patients. RESULTS: Ten (6.3%) of the excised lesions were diagnosed as malignant. Univariate analysis showed that those that were palpable on physical examination, detected as a mass on mammography, or >1 cm on sonography were significantly associated with malignancy. In multivariate analysis, lesions that were palpable (odds ratio (OR), 29.2; 95% confidence interval (CI), 4.06-209.58; P = 0.001) or detected as a mass (OR, 5.68; 95% CI 1.08-29.87; P = 0.04) remained significantly associated with malignancy. In a CART analysis, including all variables, lesions that were palpable and associated with a mass on mammogram were confirmed as malignant. CONCLUSIONS: Breast lesions diagnosed as benign papillomas on CNB had a 6.3% risk of being malignant. The risk was highest for lesions that were palpable and detectable as a mass on a mammogram. In addition, the low-risk patients avoid immediate surgical excision, although they should be followed carefully.

Metaplastic breast cancer: clinicopathological features and its prognosis.

AIMS: The prognosis of metaplastic breast cancer (MBC) is reportedly worse than that of triple-negative invasive ductal carcinoma (TN-IDC), but the determinants of poor prognosis are not yet known. METHODS: Patients from two Korean cancer centres were included in this study (67 MBC and 520 TN-IDC). Characteristics of the two disease groups, including clinical parameters, histological features, chemoresponsiveness, disease recurrence and survival estimates, were evaluated. RESULTS: MBC presented with larger tumours, more frequent distant metastasis and higher histological grade compared with TN-IDC (p<0.001). All but nine patients with MBC had triple-negative disease. Disease-free survival and overall survival (OS) of MBC were worse than TN-IDC (p<0.001). Multivariable analysis of disease-free survival revealed MBC type as an independent prognostic factor (HR 2.53; 95% CI 1.32 to 4.84) along with lymph node metastasis and implementation of breast conserving surgery. For OS, MBC type remained a significant prognostic factor (HR 2.56; 95% CI 1.18 to 5.54). Chemoresponsiveness of MBC and TN-IDC were similar in both neoadjuvant (p=1.000) and advanced disease settings (p=0.508). For a given MBC type, risk factors for disease recurrence included the presence of a squamous component (HR 4.0; 95% CI 1.46 to 10.99) and lymph node metastasis (HR 4.76; 95% CI 1.67 to 13.60); the risk factor for OS was initial distant metastasis (HR 10.77; 95% CI 2.59 to 44.76). CONCLUSIONS: MBC had worse survival outcomes compared with TN-IDC. Poor prognosis for MBC was likely caused by frequent recurrence with high initial stage and the unique biology of MBC itself.