Seho 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.

The impact of caveolin protein expression in tumor stroma on prognosis of breast cancer

We aimed to investigate the expression of caveolin-1, -2, -3, and platelet-derived growth factor (PDGF) β receptor in breast cancer cells and stroma by immunohistochemistry and to analyze their implications. The expression rates of stromal caveolin-2 and PDGF β receptor increased as the tumor progressed from ductal carcinoma in situ to microinvasive ductal carcinoma, intraductal component of invasive ductal carcinoma (IDC), and IDC (p < 0.001). The expression loss of caveolin-1 in tumor stroma of IDC correlated with high tumor stage (p < 0.001), high nodal stage (p = 0.011), high cancer stage (p = 0.005), estrogen receptor negativity (p = 0.003), and tumor recurrence (p = 0.003). In addition, the expression loss of caveolin-1 in tumor stroma was correlated with a shorter disease-free survival and an overall survival (p < 0.001). In conclusion, the loss of stromal caveolin-1 is related to poor prognosis in IDC.

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.

Clinicopathological Characteristics of Male Breast Cancer

Purpose To investigate clinicopathological characteristics and outcomes of male breast cancer (MBC). Patients and Methods We retrospectively analyzed the data of 20 MBC patients in comparison with female ductal carcinoma treated at Yonsei University Severance Hospital from July 1985 to May 2007. Clinicopathological features, treatment patterns, and survival were investigated. Results MBC consists of 0.38% of all breast cancers. The median age was 56 years. The median symptom duration was 10 months. The median tumor size was 1.7 cm, 27.8% showed node metastasis, and 71.4% were estrogen receptor positive. All 20 cancers were arisen from ductal cells. No lobular carcinoma was found. The incidence of stages 0, I, II, and III in patients were 2, 10, 4, and 3, respectively. All patients underwent mastectomy. One with invasive cancer did not receive axillary node dissection and stage was not exactly evaluated. Adjuvant treatments were determined by pathologic parameters and stage. Clinicopathological parameters and survival rates of MBC were comparable to those of female ductal carcinoma. Conclusion The onset age of MBC was 10 years older and symptom duration was longer than in female patients. No difference in outcomes between MBC and female ductal carcinoma suggests that the biology of MBC is not different from that of females. Therefore, education, an appropriate system for early detection, and adequate treatment are necessary for improving outcomes.

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.

Human Leukocyte Antigen-G (HLA-G) Polymorphism and Expression in Breast Cancer Patients

Human leukocyte antigen-G (HLA-G) is known to be implicated in a tumor-driven immune escape mechanism in malignancies. The purpose of this study was to investigate HLA-G polymorphism and expression in breast cancer. HLA-G alleles were determined by direct DNA sequencing procedures from blood samples of 80 breast cancer patients and 80 healthy controls. Soluble HLA-G (sHLA-G) was measured by enzyme-linked immunosorbent assay (ELISA) from serum specimens. HLA-G expression in breast cancer lesions was also analyzed by immunohistochemistry staining. The presence of HLA-G 3′ untranslated region (UTR) 14-bp sequence was analyzed and found to be associated with reduced risk of breast cancer susceptibility based on HLA-G expression in tissues (P = 0.0407). Levels of sHLA-G were higher in the breast cancer group (median 117.2 U/mL) compared to the control group (median 10.1 U/mL, P<0.001). The area under the receiver operating characteristic curve (AU-ROC) values of sHLA-G for differentiating breast cancer from normal controls and for detecting metastasis from other stages of breast cancer were 0.89 and 0.79, respectively. HLA-G polymorphism and expression may be involved in breast carcinogenesis and sHLA-G concentrations could be used as a diagnostic marker for detecting breast cancer.

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.

How Many Sentinel Lymph Nodes Are Enough for Accurate Axillary Staging in T1-2 Breast Cancer?

Purpose During a sentinel lymph node biopsy (SLNB) for breast cancer, the appropriate number of sentinel lymph nodes (SLNs) to be removed for accurate axillary staging is still controversial. We hypothesized that there might be an optimal threshold number of SLNs. We investigated how many SLNs should be removed to achieve an acceptable accuracy and ensure minimal morbidity. Methods We reviewed data of 328 patients with invasive breast cancer who underwent SLNB followed by complete level I and II axillary dissection between January 2004 and December 2005. The false negative rate (FNR) and accuracy of SLNB according to the number of removed SLNs were evaluated. Results The mean number of SLNs removed was 3.0 (range, 1-14), and that of total retrieved axillary lymph nodes was 17.5 (range, 10-40). In total, 111 (33.8%) patients had positive nodes on the permanent pathological report. Among them, 12 patients had negative SLNs; thus, the overall FNR of SLNB was 10.8% (12/111) and the accuracy was 96.3% (316/328). The FNR was 26.6% for a single SLN, 8.0% for two, and 11.1% for three. In cases where four or more SLNs were removed, the FNR decreased to 0% and accuracy reached 100%. Conclusion Our data suggest that a SLNB should not only remove one or two of the hottest node(s) when other hot nodes exist. We also suggest that four might be an optimal threshold number of SLNs to be removed and that removal of more than four SLNs does not improve axillary staging accuracy.

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).