Predicting the Benefit of Adjuvant Aromatase Inhibitor Therapy in Postmenopausal Breast Cancer Patients with Phosphorylated S6K1 Expression Status / 한국유방암학회지

PURPOSE: Phosphorylated ribosomal S6 kinase 1 (pS6K1) is a major downstream regulator of the mammalian target of rapamycin (mTOR) pathway. Recent studies have addressed the role of S6K1 in adipogenesis. pS6K1 may affect the outcome of estrogen depletion therapy in patients with hormone-sensitive breast cancer due to its association with adipogenesis and increased local estrogen levels. This study aimed to investigate the potential of pS6K1 as a predictive marker of adjuvant aromatase inhibitor (AI) therapy outcome in postmenopausal or ovarian function-suppressed patients with hormone-sensitive breast cancer.METHODS: Medical records were retrospectively reviewed in postmenopausal or ovarian function-suppressed patients with estrogen receptor-positive and node-positive primary breast cancer. pS6K1 expression status was scored on a scale from 0 (negative) to 3+ (positive) based on immunohistochemical analysis.RESULTS: A total of 428 patients were eligible. The median follow-up duration was 44 months (range, 1–90). In patients with positive pS6K1 expression, AIs significantly improved disease-free survival (DFS) compared to selective estrogen receptor modulators (SERMs) (5 year-DFS: 83.5% vs. 50.7%, p = 0.016). However, there was no benefit of AIs on DFS in the pS6K1 negative group (5 year-DFS 87.6% vs. 91.4%, p = 0.630). On multivariate analysis, AI therapy remained a significant predictor for DFS in the pS6K1 positive group (hazard ratio, 0.39; 95% confidence interval, 0.16–0.96; p = 0.041). pS6K1 was more effective in predicting the benefit of AI therapy in patients with ages < 50 (p = 0.021) compared to those with ages ≥ 50 (p = 0.188).CONCLUSION: pS6K1 expression may predict AI therapy outcomes and serve as a potential predictive marker for adjuvant endocrine therapy in postmenopausal and ovarian function-suppressed patients with hormone-sensitive breast cancer. AIs may be more effective in patients with pS6K1 positive tumors, while SERM could be considered an alternative option for patients with pS6K1 negative tumors.

Phosphorylated S6 Kinase-1 as Predictive Marker of Lapatinib Efficacy in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer Patients

PURPOSE: The 40S ribosomal protein S6 kinase-1 (S6K1) is a crucial downstream effector of the PI3K/AKT/mTOR pathway. S6K1 overexpression is found in 10% to 30% of breast cancers and is associated with aggressive disease and poor prognosis. Herein, we investigated the relationship between the expression of phosphorylated S6K1 (p-S6K1) and efficacy of lapatinib in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. METHODS: We retrospectively analyzed the data of 36 patients with HER2-positive metastatic breast cancer treated with lapatinib between January 2010 and September 2014. The p-S6K1 expression status of the primary tumor was assessed via immunohistochemistry using a mouse monoclonal antibody. RESULTS: Fourteen of the 36 patients (38.9%) had p-S6K1-positive tumors. The median progression-free survival (PFS) of patients with p-S6K1-positive tumors was significantly longer than that of patients with p-S6K1-negative tumors (13.4 months vs. 7.1 months, p=0.025). In multivariate analysis, p-S6K1 positivity remained an independent, favorable predictive factor for PFS (hazard ratio, 0.32; 95% confidence interval, 0.11–0.97; p=0.044). CONCLUSION: The high expression of p-S6K1 was significantly associated with prolonged PFS, suggesting that p-S6K1 can be a potential biomarker for predicting the efficacy of lapatinib in patients with HER2-positive metastatic breast cancer.

Serial Serum HER2 Measurements for the Detection of Breast Cancer Recurrence in HER2-Positive Patients / 한국유방암학회지

PURPOSE: The measurement of serum human epidermal growth factor receptor 2 (HER2) extracellular domain levels is a well-established method for evaluating whether a metastatic HER2-positive breast cancer patient will respond to HER2-targeted treatment. However, little is known about the value of serum HER2 for detecting disease relapse following curative surgical treatment in breast cancer patients. The purpose of this study was to evaluate the sensitivity of serum HER2, carcinoembryonic antigen (CEA), and carcinoma antigen 15-3 (CA 15-3) for the detection of disease recurrence in postoperative breast cancer patients with a primary HER2-positive tumor. METHODS: Serial measurements were taken of serum HER2, CEA, and CA 15-3 levels in patients with primary invasive HER2-positive breast cancer who underwent curative surgical treatment between January 2008 and December 2010. Following treatment, serum HER2 levels were monitored every 6 months using a chemiluminescence immunoassay. RESULTS: Overall, 264 patients were analyzed in this retrospective study. The median follow-up period was 27.7 months, and 24 patients relapsed during follow-up. The sensitivity of serum HER2, CEA, and CA 15-3 for the detection of disease recurrence was 37.5%, 25.1%, and 12.5%, respectively. Sensitivity increased to 45.8% when all three tumor markers were combined in the analysis. In a subgroup of patients without liver disease, the sensitivity of serum HER2, CEA, and CA 15-3 was 57.1%, 21.4%, and 14.3%, respectively. Of the 264 patients in this study, 80 patients had chronic hepatitis, liver cirrhosis, or abnormal aspartate aminotransferase or alanine aminotransferase levels during the follow-up period. Following the exclusion of these patients, the sensitivity of serum HER2 for the detection of disease recurrence increased to 57.1%. CONCLUSION: Serial serum HER2 measurement may be useful for the detection of disease relapse in patients with HER2-positive breast cancer. Abnormal liver function can result in elevated serum HER2 in the absence of disease recurrence.

Giant juvenile fibroadenoma of the breast: a case report and brief literature review

A girl (age, 12 years 11 months) consulted the pediatric endocrinology clinic because of a rapidly growing right breast mass over 13 cm observed during the preceding 3 months. A surgical excision was performed, and the mass was diagnosed as a giant juvenile fibroadenoma. Giant juvenile fibroadenomas are rare, usually occurring between 10 and 18 years of age, and characterized by massive and rapid enlargement of an encapsulated mass. The etiology is believed to be an end-organ hypersensitivity to normal levels of estrogen. We report a case of giant juvenile fibroadenoma and present a review of the diagnostic workup and management of a large breast tumor during adolescence.

Expression of Immunohistochemical Markers before and after Neoadjuvant Chemotherapy in Breast Carcinoma, and Their Use as Predictors of Response / 한국유방암학회지

PURPOSE: For patients with breast carcinoma, immunohistochemical markers are important factors in determining the breast cancer subtype and for establishing a therapeutic plan, including the use of neoadjuvant chemotherapy (NACT). However, it is not clear whether the expression of certain markers changes after NACT. METHODS: We assessed estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, p53, and Bcl-2 expression in specimens from 345 breast cancer cases before and after NACT. We analyzed the association between response to NACT and the expression of the markers in pre-NACT specimens. We also compared the expression between pre- and post-NACT specimens. RESULTS: ER and PR expression was negatively associated with pathological complete response (pCR). HER2 was associated with pCR in all cases, but the association was lost when the cases were subdivided according to hormone receptor status. The pre-NACT tumor size of cases with pCR after NACT was smaller than that of cases with residual disease. HER2-enriched and triple-negative breast cancers were more likely to achieve pCR than luminal A type cancers. PR expression and the Ki-67 index decreased after NACT. A decrease in the Ki-67 index was also demonstrated in hormone receptor positive and HER2-enriched subtypes, but no similar tendency was observed in the triple-negative subtype. CONCLUSION: A patient with breast cancer scheduled for NACT should be assessed for the breast cancer subtype, as this will influence the treatment plans for the patient. The expression of PR and Ki-67 after NACT should be interpreted carefully because NACT tends to reduce the expression of these molecules.

Rhabdoid Colorectal Carcinomas: Reports of Two Cases

Rhabdoid colorectal carcinomas are very rare and only 10 cases have been previously reported. We report two cases of rhabdoid colorectal carcinoma, one arising in the sigmoid colon of a 62-year-old man and another in the rectum of an 83-year-old woman. In both cases, the patients had advanced tumors with lymph node metastases. The tumors mostly showed a diffuse arrangement with rhabdoid features and small glandular regions were combined. Transitional areas from the adenocarcinomas to the rhabdoid tumors were also noted. Adenocarcinoma cells were positive for mixed cytokeratin (CK), CK20 and epithelial membranous antigen (EMA), but focal positive for vimentin. The rhabdoid tumor cells were positive for mixed CK, but focal positive or negative for CK20 and EMA. In addition, they were diffusely positive for vimentin, but negative for desmin. The histological and immunohistologial findings of these two cases suggest that the rhabodid tumor cells originated from dedifferentiated adenocarcinomas.

Fine Needle Aspiration Cytology of Parathyroid Lesions

BACKGROUND: There has been an increase in the use of fine needle aspiration cytology (FNAC) for the diagnosis of parathyroid lesions (PLs). Differentiation between a thyroid lesion and a PL is not easy because of their similar features. We reviewed parathyroid aspirates in our institution and aimed to uncover trends in diagnostic criteria. METHODS: We selected 25 parathyroid aspirates (from 6 men and 19 women) confirmed surgically or immunohistochemically from 2006 to 2011. RESULTS: Major architectural findings of PLs include scattered naked nuclei, loose clusters, a papillary pattern with a fibrovascular core, tight clusters, and a follicular pattern. These architectures were commonly admixed with one another. Cytological features included anisokaryosis, stippled chromatin, a well-defined cell border, and oxyphilic cytoplasm. Eighteen of the 25 patients were diagnosed with PL using FNAC. Seven patients had been misdiagnosed with atypical cells (n=2), benign follicular cells (n=2), adenomatous goiter (n=2) and metastatic carcinoma (n=1) in FNAC. Using clinicoradiologic data, the sensitivity of the cytological diagnosis was 86.7%. The cytological sensitivity decreased to 50% without this information. CONCLUSIONS: FNAC of PL is easily confused with thyroid lesions. A combination of cytological parameters and clinical data will be required to improve the diagnostic sensitivity of PLs.

Fine-Needle Aspiration Cytology of Pleomorphic Carcinomas of the Lung

BACKGROUND: Pleomorphic carcinoma (PC) is a rare pulmonary malignancy. Because of its rarity and histological heterogeneity, cytopathologists might suspect PC only rarely on the basis of its cytological specimen. In addition, cytological findings from fine needle aspiration (FNA) specimens have rarely been described. Hence, we investigated the cytological features of FNA in the cases of PC. METHODS: We reviewed 7 FNA specimens of PC. The patients had undergone surgical resection at the Korea Cancer Center Hospital between 2007 and 2011. The cytological features of PC were assessed and compared with the histopathological features of the corresponding surgical specimen. Immunocytochemical analysis with cytokeratin and vimentin was performed on the cell blocks. RESULTS: The tumor cells were either dispersed or arranged in loose aggregates, and generally lacked any glandular or squamous differentiation. Pleomorphic or spindle shape tumor cells were observed, and mono-, bi-, or multi-nucleated giant cells were frequently observed. The background showed necrosis and contained numerous lymphocytes and neutrophils. Immunocytochemically, the tumor cells were positive for cytokeratin and vimentin. CONCLUSIONS: PC displays characteristic cytological features. It might therefore be possible to make an accurate diagnosis of PC by assessing the degree of nuclear atypia.

Invasive Cribriform Carcinoma Arising in Malignant Phyllodes Tumor of Breast: A Case Report

Phyllodes tumor is an uncommon fibroepithelial neoplasm of the breast. And it is characterized by expanded stroma with increased cellularity and elongated epithelium-lined clefts. Mammary carcinomas within phyllodes tumors have been rarely reported. To date, however, no reports have described the invasive cribriform carcinoma arising in malignant phyllodes tumor. Here, we report a 62-year-old woman who presented with a large breast mass. Microscopically, the mass was a typical malignant phyllodes tumor showing well developed leaf-like architecture and stromal overgrowth with high cellularity and nuclear pleomorphism. In a portion of the tumor, however, the epithelial component showed a cribriform pattern of proliferation in the absence of myoepithelial cells, suggestive of the invasive cribriform carcinoma. To our knowledge, this is rare and it is difficult to make a differential diagnosis of it. Here, we report our case with a review of literatures.

Cancer Subtypes of Breast Carcinoma with Micropapillary and Mucinous Component Based on Immunohistochemical Profile

BACKGROUND: Micropapillary carcinoma (MPC) is known to have a worse prognosis than the other subtypes of breast cancer. Occasionally, MPC is observed in association with invasive ductal carcinoma not otherwise specified (IDC NOS), as well as mucinous carcinoma. METHODS: We examined the immunohistochemical expression of an estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) in 127 cases of surgically resected MPC or IDC NOS with MPC. Further, we classified these cases based on their immunohistochemical profile. RESULTS: Among the IDC NOS with MPC cases, 47 were luminal A (62.7%), 10 were luminal B (13.3%), and 9 were HER2 (12.0%). The MPC cases included 4 luminal A (50.0%), 2 luminal B (25.0%) and 1 HER2 (12.5%) subtypes. Of the mucinous carcinomas with MPC, 4 were grouped as luminal A (57.1%), 1 as luminal B (14.3%), and 2 as HER2 (28.6%) subtypes. However, among the mucinous carcinomas, 33 were categorized as luminal A (89.2%), 3 as luminal B (8.1%), and 1 as HER2 (2.7%) subtype, indicating a low incidence of HER2 subtype as compared to the other subtypes. CONCLUSIONS: The luminal B and HER2 subtypes were prevalent in carcinomas with MPC. This result explains the poor prognosis of breast carcinomas with an MPC pattern.

Histological and Immunohistochemical Evaluation of Ductal Carcinoma In Situ Co-Existing with Triple-Negative Carcinoma of the Breast

BACKGROUND: Triple-negative breast carcinomas (TNBCs) are associated with high-grade histological tumor and a poor clinical outcome. In this study, we evaluated the histology and immunohistochemical features of DCIS co-existing with TNBC to determine the characteristics of the precursor lesions of TNBC. METHODS: Among the 1,610 cases of breast carcinoma, we selected the TNBCs with DCIS (n=196), and compared the pathological and immunohistochemical findings of the DCIS with those of the invasive carcinoma areas. RESULTS: Among the 1,610 breast carcinomas, the TNBCs accounted for 330 cases (20.5%) and there were 196 cases with DCIS. The TN-DCIS cases exhibited high nuclear (94.5%) and histological (94.5%) grades, comedo-necrosis (68.9%) and a small extent of the DCIS-involved area. Immunohistochemically, a p53 expression was present in 48.4% of the TN-DCIS cases and a high Ki-67 index was present in 31.5%. The same TN immunohistochemical profiles as the carcinoma were detected in 109 of the 124 (87.9%) cases, but different profiles were observed in 15 of the 124 (12.1%) cases. The 15 discordant cases were associated with a low histological grade (p=0.037), low p53-positivity (p=0.006) and a low Ki-67 index (p=0.026), as compared to the invasive carcinomas. CONCLUSIONS: The results of this study suggest that TN DCIS is a highly probable, but not obligate, precursor lesion of TNBC.