Hyung Seok Park

Characteristics and outcomes according to molecular subtypes of breast cancer as classified by a panel of four biomarkers using immunohistochemistry

To investigate the significance of immunohistochemical molecular subtyping, we evaluated outcomes of subtypes based on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67. Using tissue microarrays, 1006 breast cancer patients between November 1999 and August 2005 were categorized into four subtypes: luminal A (ER+ and/or PR+, HER2-, Ki-67 < 14%), luminal B (ER+ and/or PR+, HER2-, Ki-67 ≥ 14% or ER+ and/or PR+, HER2+), HER2-enriched (ER-, PR-, HER2+), and triple-negative breast cancer (TNBC) (ER-, PR-, HER2-). Demographics, recurrence patterns, and survival were retrospectively analyzed using uni-/multivariate analyses. Luminal A, luminal B, HER2-enriched, and TNBC accounted for 53.1%, 21.7%, 9.0%, and 16.2% of cases, respectively. Luminal A presented well-differentiation and more co-expression of hormone receptors comparing to luminal B. HER2-enriched showed larger size and higher nodal metastasis. TNBC demonstrated younger age at diagnosis, larger size, undifferentiation, higher proliferation, and frequent visceral metastases. The peak of recurrence for luminal A was at 36 months postoperatively, while that for HER2-enriched and TNBC peaked at 12 months. The relapse risk of luminal B was mixed. Luminal A showed the best survival, but no difference was observed between the other three subtypes. When matched by nodal status, however, TNBC showed the worst outcomes in node-positive patients. In multivariate analyses, luminal A remained a positive prognostic significance. Immunohistochemically-defined subtypes showed different features, recurrence patterns, and survival. Therefore, molecular subtypes using four biomarkers could provide clinically useful information of tumor biology and clinical behaviors, and could be used for determining treatment and surveillance strategies.

Molecular Subtypes and Tumor Response to Neoadjuvant Chemotherapy in Patients with Locally Advanced Breast Cancer

Objective: Pathologic complete response (pCR) is the most predictive factor for patients with neoadjuvant chemotherapy and we investigated the rate of pCR according to molecular subtypes defined by immunohistochemical staining. Methods: Our subjects comprised 257 breast cancer patients who received 3 cycles of anthracycline/taxane-based neoadjuvant chemotherapy. The patients were classified into 4 subtypes: luminal A, luminal B, HER2 and triple negative. We analyzed the pCR rate and treatment outcome according to these subtypes. Results: Of a total of 257 patients, the pCR rate of luminal A, luminal B, HER2 and triple negative was 3.9, 5.0, 10.5 and 21.1%, respectively (p = 0.001). The 5-year disease-free survival of the pCR group (88.4%) was higher than that of the non-pCR group (65.6%), but it was not significant (p = 0.228). Among patients who have residual disease, the 5-year disease-free survival of luminal A, luminal B, HER2 and triple negative was 64.0, 65.7, 75.2 and 66.5%, respectively (p = 0.243). Triple negative and HER2 subtypes are more sensitive to neoadjuvant chemotherapy. Conclusion: To increase the pCR rate, type-specific approaches according to subtypes, such as an addition of trastuzumab, increasing the number of cycles or a novel regimen, should be considered.

Risk predictors of underestimation and the need for sentinel node biopsy in patients diagnosed with ductal carcinoma in situ by preoperative needle biopsy

Diagnosis of ductal carcinoma in situ (DCIS) by core needle biopsy showed a high rate of underestimation of invasiveness, and performing sentinel lymph node biopsy (SLNB) in DCIS patients was controversial.

Clinicopathologic Features and Outcomes of Metaplastic Breast Carcinoma: Comparison with Invasive Ductal Carcinoma of the Breast

Purpose Metaplastic breast carcinoma (MBC) is rare. Its clinicopathologic features and prognosis are uncertain. The aim of this study was to evaluate the clinicopathologic characteristics and outcomes in comparison with invasive ductal carcinoma (IDC). Materials and Methods We reviewed the data of 29 patients with MBC and 4,851 patients with IDC, who received surgery at Yonsei University Severance Hospital between 1980 and 2008. Various clinicopathologic features, recurrence free, and overall survival were investigated and compared to each other. Results Stage IV cases at diagnosis were more common in MBC (10.3%) than in IDC (0.9%). The incidence rates of triple negative breast cancer (TNBC) were significantly higher in MBC (84.0%) than in IDC (20.1%). Larger tumors (>2 cm) and lower tendency of axillary metastasis were frequently observed in MBC. Only one of 24 preoperative core needle biopsies (CNB) correctly diagnosed MBC. There was no significant difference in survival between the two groups. Conclusion MBC was characterized by a higher incidence of TNBC, larger tumor size, and lower tendency of axillary metastasis, and was difficult to diagnose with CNB. Although the incidence of stage IV disease at diagnosis was higher in MBC, the survival rates of stage I-III were comparable to those of IDC.

Clinicopathological features of infiltrating lobular carcinomas comparing with infiltrating ductal carcinomas: a case control study

BackgroundInfiltrating lobular carcinoma (ILC) is the second most common type of invasive breast cancers and it has been reported to have some unique biologic and epidemiologic characteristics.MethodsClinicopathological features of 95 patients with ILC, their relapse free survival (RFS) and overall survival (OS) were retrospectively investigated and compared with those of 3,621 patients with infiltrating ductal carcinoma-not otherwise specified (IDC-NOS) between January 1984 and December 2005.ResultsILC constitutes 2.3% of all invasive breast cancers. There were no difference between the ILC and the IDC-NOS groups regarding age at diagnosis, tumor size, nodal status, and treatment modalities except hormone therapy. The ILC group showed more estrogen receptor expression, less HER-2 expression and higher bilaterality. RFS and OS of the ILC patients were similar to those of the IDC. IDC-NOS metastasized more frequently to the lung and bone, whereas, ILC to the bone and ovary.ConclusionsThe incidence of ILC was relatively low in Korean breast cancer patients. Comparing to IDC-NOS ILC showed some different features such as higher estrogen receptor expression, less HER-2 expression, higher bilaterality and preferred metastatic sites of bone and ovary. Contralateral cancers and bone and ovary evaluation should be considered when monitoring ILC patients.

A nomogram for predicting underestimation of invasiveness in ductal carcinoma in situ diagnosed by preoperative needle biopsy

It is unnecessary to perform axillary staging in patients with ductal carcinoma in situ (DCIS) of the breast because of the low incidence of axillary metastasis. However, diagnosis of DCIS by core needle biopsy showed a high rate of underestimation of invasive cancer. Thus, it is necessary to predict invasiveness in DCIS patients on core before surgery. We analyzed 340 patients with DCIS diagnosed by needle biopsy. The cases were divided into training and validation sets. Logistic regression was performed to predict the presence of invasive cancer in the final pathology, and a nomogram was constructed from the training set using the presence of palpability, the presence of ultrasonographic calcification and mass, the biopsy tools, and the presence of microinvasion. The model was subsequently applied to the validation set. The nomogram for the training set was both accurate and discriminating, with an area under the receiver operating characteristic curve (AUC) of 0.75. When applied to the validation group, the model accurately predicted the likelihood of invasive cancer (AUC: 0.71). Our nomogram will allow surgeons to easily and accurately estimate the likelihood of invasive cancer in patients with DCIS as diagnosed by preoperative needle biopsy.

Oncologic safety of breast‐conserving surgery compared to mastectomy in patients receiving neoadjuvant chemotherapy for locally advanced breast cancer

Breast‐conserving surgery (BCS) in patients with large tumors shrunk by neoadjuvant chemotherapy (NCT) remains controversial. We investigated oncologic outcomes of BCS in patients receiving NCT to treat locally advanced breast cancer (LABC).

The Impact of a Focally Positive Resection Margin on the Local Control in Patients Treated with Breast-conserving Therapy

OBJECTIVE The aim of the study was to investigate the parameters affecting positive margin and the impact of positive margin on outcomes after breast-conserving therapy in patients with breast cancer. METHODS Characteristics and survival of 705 patients attempted breast-conserving therapy between January 1994 and December 2004 were retrospectively analyzed using χ(2) tests, the Kaplan-Meier methods and multivariate analyses. RESULTS Ninety-five (13.5%) showed positive margins at initial resection. Among them, 28 (4.0%) had negative margin on the initial frozen section; however, they finally turned out a focally positive margin with intraductal carcinoma on the permanent pathology. Positive margin at initial resection was significantly associated with lobular histology (P = 0.001), four or more involved lymph nodes (P = 0.015) and the presence of extensive intraductal component (P < 0.001). A focally positive margin did not influence local (P = 0.250; 95% confidence interval, 0.612-6.592) or regional failure (P = 0.756; 95% confidence interval, 0.297-5.311). Patients with a focally positive margin showed an advanced nodal stage and received a higher dose of irradiation and more systemic therapy. Nodal involvements were the most significant factor for locoregional failure. CONCLUSIONS Although the achievement of negative margins is the best way to reduce local failure, patients with a focally positive margin and favorable risk factors such as node negativity and older age could have an option of close follow-up with adequate boost irradiation and adjuvant therapy instead of conversion to total mastectomy.

Cyclooxygenase-2 expression in proliferative Ki-67-positive breast cancers is associated with poor outcomes.

In order to investigate the implications of cyclooxygenase-2 (COX-2) expression in combination with Ki-67 on breast cancer outcomes, the COX-2 and Ki-67 expression levels and other clinicopathologic parameters were investigated in 861 breast cancers. Clinicopathological parameters and survival were investigated in association with the expression levels of both COX-2 and Ki-67 using univariate and multivariate analyses. COX-2 expression was positive in 493 (57.3%) of invasive tumors. COX-2 was associated with favorable markers, but was not related to survival outcome by itself. However, COX-2 in proliferative tumors [COX-2(+)/Ki-67(+)] were significantly associated with unfavorable factors and the worst survival, but COX-2 in non-proliferative tumors [COX-2(+)/Ki-67(−)] showed significantly favorable parameters and better outcomes. COX-2(−)/Ki-67(any) showed intermediate prognosis. The statistical significance was maintained in stage-matched and multivariate analyses. The results of present study suggest that COX-2 expression is a common event in breast cancers and may play in a different ways by the proliferation status of the tumor cells. Further studies should be carried out to verify the role of COX-2 by proliferative conditions of breast tumor cells.

Association between Genetic Polymorphisms of CYP2D6 and Outcomes in Breast Cancer Patients with Tamoxifen Treatment

The aim of the study was to evaluate the association between genetic polymorphisms of CYP2D6 and outcomes in breast cancer patients with tamoxifen treatment. We evaluated the CYP2D6 genetic polymorphisms in 766 breast cancer patients. Among them, 110 patients whose samples were prospectively collected before surgery and treated with tamoxifen were included to evaluate the association between CYP2D6 and outcomes. The genotypes of CYP2D6 were categorized as extensive metabolizer (EM), intermediate metabolizer (IM), and poor metabolizer (PM) according to the activity score. The clinicopathologic features of 110 patients were not significantly different among the three groups except for the T-stage and nodal status. The high T-stage and axillary metastasis were more frequent in the PM group. While recurrence-free and overall survival in the PM group was poorer than the other groups, there was no significant difference between the EM and the IM group. The difference between the PM and the other groups on univariate analysis disappeared on multivariate analysis. These conflicting results suggest that the clinical value of CYP2D6 polymorphisms is still unclear and more large-sized and comprehensively designed trials are necessary.