Cha Kyong Yom

Clinical Significance of Annexin A1 Expression in Breast Cancer

Purpose The expression of Annexin A1 (ANXA1) is known to be reduced in human breast cancer; however, the role of ANXA1 expression in the development of breast cancer remains unclear. In this study, we determined the relationship between the expression features of ANXA1 and the prognostic factors of breast cancer. Methods Human breast tissues were obtained from patients specimens who had undergone breast surgery or core needle biopsies. The patterns of ANXA1 expression were analyzed by immunohistochemical staining in relation to histopathological diagnosis, clinical characteristics and outcomes. Results One hundred eighty-two cases were included and the mean age of the patients was 46.34 ± 11.5 years. A significant loss of ANXA1 expression was noted in both ductal carcinoma in situ (DCIS) and invasive carcinomas compared to normal breast tissues (p<0.001) and benign breast diseases (p<0.001). There was a significant alteration in ANXA1 expression according to hormone receptor status (p<0.001), cancer intrinsic type (p<0.001), and nuclear grade (p=0.004) in invasive cancer. In a univariate analysis, ANXA1 positivity tended to be related with poor breast cancer-related survival (p=0.062); however, the same results was not realized in multivariate results (p=0.406). HER2 overexpression and TNM staging were significantly associated with relapse-free survivals (RFS) in the multivariate analysis (p=0.037, p=0.048, respectively). In particular, in node-positive patients (p=0.048), HER2 overexpressed patients (p=0.013), and non-triple negative breast cancer patients (p=0.002), ANXA1 overexpression was correlated with poor RFS. Conclusion Although significant loss of ANXA1 expression was noted in breast cancer including DCIS and invasive carcinoma, in cases of invasive cancer, overexpression of ANXA1 was related to unfavorable prognostic factors. And these results imply that ANXA1 plays dualistic roles and is involved in variable mechanisms related to cancer development and progression.

Factors Associated with Re-excision after Breast-Conserving Surgery for Early-Stage Breast Cancer

Purpose Re-excisions after breast-conserving surgery (BCS) for breast cancer cause delays in the adjuvant treatment, increased morbidity, and leads to poor aesthetic results. Thus, efforts to reduce the re-excision rate are essential. This study aimed to conclusively determine the re-excision rate and the factors associated with re-excision after BCS. Methods We retrospectively reviewed the medical records and pathological reports of 711 cases that underwent BCS for early-stage breast cancer. Univariate and multivariate analyses were performed. Results Of the 711 cases of BCS, 71 (10.0%) required re-excision. Patients in the re-excision group were younger than those in the no re-excision group. Non-palpable lesions, the presence of non-mass-like enhancement at magnetic resonance imaging, multifocality, the presence of a ductal carcinoma in situ (DCIS) component, and an infiltrative tumor border were also significantly associated with re-excision. Multivariate analysis indicated that younger age, non-palpable lesions, multifocal lesions, and the presence of a DCIS component were factors which were independently associated with re-excision. Tumors located in the lower inner quadrant had a relatively high involved resection margin rate as well as a narrow resection margin width, especially at the superior and medial margins. Lateral margins showed a tendency toward a wider resection margin width. Conclusion At our institution, the rate of re-excision was low despite the lack of an intraoperative frozen section. Patients with non-palpable or multifocal tumors, a DCIS component, or those who were younger than 50 years were more likely to require re-excision after BCS. These factors should be considered when planning surgical management of early-stage breast cancer. Positive resection margin rates and margin widths differed on a directional basis based on tumor location, and these differences were considerable.

Thyroid “Atypia of undetermined significance” with nuclear atypia has high rates of malignancy and BRAF mutation

“Atypia of undetermined significance” (AUS) in the Bethesda System for Reporting Thyroid Cytopathology is a heterogeneous category for cases that cannot be easily classified into benign, suspicious, or malignant. This study evaluated whether cytomorphology‐based subcategorization could better predict the malignancy risk in cases designated as AUS, and how the subcategories correlated with BRAF mutation status in thyroid fine‐needle aspirates (FNA).

Comparison of Quality of Life Based on Surgical Technique in Patients with Breast Cancer

OBJECTIVE More than 80% of women with breast cancer survive for more than 5 years; quality of life is an important issue in these patients. The aim of this study was to assess differences in quality of life among patients who have undergone breast-conserving surgery, total mastectomy and immediate reconstruction after total mastectomy. METHODS A cross-sectional study was conducted during follow-up visits. Women who underwent surgical treatment at least 2 years prior were eligible if they were aged 20-70 years and had a diagnosis of breast cancer (Stages 0-III). Quality of life was evaluated based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire breast cancer-specific module, Rosenberg Self-esteem Scale, Beck Depression Index, Body Image Scale and sexual scale of the Cancer Rehabilitation Evaluation System. RESULTS A total of 407 patients completed the questionnaires; 254 were treated with breast-conserving surgery, 122 with total mastectomy and 31 with reconstruction after total mastectomy. The mean period between surgery and the survey was 49 months. Women in the breast-conserving surgery group showed better outcomes than women in the total mastectomy and reconstruction after total mastectomy groups with respect to emotional-social function, nausea/vomiting, financial difficulty, body image, arm symptoms and self-esteem. Patients in the reconstruction after total mastectomy group had significantly better outcomes on the sexual scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire breast cancer-specific module and arm symptoms than the total mastectomy group. CONCLUSIONS Quality of life was better in the breast-conserving surgery group than in the total mastectomy or reconstruction after total mastectomy groups, and the total mastectomy and reconstruction after total mastectomy groups had similar quality of life. Efforts to evaluate and improve the quality of life of patients with breast cancer should be continued.

A multi-institutional study of the prevalence of BRCA1 and BRCA2 large genomic rearrangements in familial breast cancer patients

BackgroundLarge genomic rearrangements (LGRs) in the BRCA1/2 genes are frequently observed in breast cancer patients who are negative for BRCA1/2 small mutations. Here, we examined 221 familial breast cancer patients from 37 hospitals to estimate the contribution of LGRs, in a nationwide context, to the development of breast cancer.MethodsDirect sequencing or mutation scanning followed by direct sequencing was performed to screen small mutations. BRCA1/2 small mutation-negative patients were screened for the presence of LGRs using a multiple ligation-dependent probe amplification (MLPA) assay.ResultsUsing a combined strategy to detect the presence of small mutations and LGRs, we identified BRCA1/2 small mutations in 78 (35.3%) out of 221 familial breast cancer patients and BRCA1 LGRs in 3 (2.1%) out of 143 BRCA1/2 small mutation-negative patients: the deletion of exons 11–13, the deletion of exons 13–15, and whole gene deletion of exons 1-24. The novel deletion of exons 11–13 is thought to result from a non-homologous recombination event mediated by a microhomology sequence comprised of 3 or 4 base pairs: c.3416_4357 + 1863delins187 (NG_005905.2: g.33369_44944delins187).ConclusionsIn this study, we showed that LGRs were found in 3.7% (3/81) of the patients who had mutations in BRCA1 or BRCA2, and 7.5% (3/40) of patients with mutations in BRCA1. This suggests that the contribution of LGRs to familial breast cancer in this population might be comparable to that in other ethnic populations. Given these findings, an MLPA to screen for mutations in the BRCA1 gene is recommended as an initial screening test in highly selective settings.

Leptin as a potential target for estrogen receptor-positive breast cancer.

Purpose Leptin is a potent adipokine that plays a significant role in tumor development and the progression of breast cancer. The aim of this study was to evaluate whether leptin affects the response to tamoxifen treatment in estrogen receptor (ER)-positive breast cancer cells. Methods Leptin, leptin receptor (Ob-R), and activation of signaling pathways were studied by Western immunoblotting. The effects of leptin on tamoxifen-dependent growth inhibition were studied in MCF-7 and T-47D cells. Results Leptin was expressed in MCF-7 and T-47D and had a proliferative effect on MCF-7 cells. Leptin significantly inhibited the antiestrogenic effect of tamoxifen in both cells only under β-estradiol (E2) (20 nM) conditions. In MCF-7, the inhibitory effect against tamoxifen was a result from the activation of the ERK1/2 and STAT3 signal transduction pathway. Conclusion Leptin interferes with the effects of tamoxifen under E2 stimulated conditions in ER-positive breast cancer cells. These results imply that inhibition of leptin is expected to enhance the response to tamoxifen in ER-positive breast cancer cells, and, therefore, could be a promising way to overcome endocrine resistance.

Effect of short message service as a reminder on breast self-examination in breast cancer patients: a randomized controlled trial.

Summary This study was a single-blind randomized controlled trial to assess the effectiveness of SMS as a reminder for breast self-examination (BSE). Participants who underwent surgery for breast cancer were recruited and randomized to the intervention group or the control group. Subjects in the intervention group received one text message on the first day of every month that reminded them to complete monthly BSE and the other text message on the fifteenth day of every month that contained information about breast cancer. Primary and secondary outcomes were self-reported BSE adherence and the frequency of BSE over 6 months. Between August 2010 and December 2011, 216 patients were randomly assigned to the SMS group (n = 110) or the control group (n = 106). A total of 202 patients were included in the final analysis. Self-reported BSE adherence and the frequency of BSE over the past six months were significantly higher in the intervention group than in the control group. Multivariate analysis showed that the SMS was the only significant factor for BSE adherence (p < 0.001). The short-term results of our study suggest that SMS is an effective and low-cost method to enhance adherence to BSE with existing information technology infrastructure.

Expression of indoleamine 2,3-dioxygenase and infiltration of FOXP3+ regulatory T cells are associated with aggressive features of papillary thyroid microcarcinoma.

BACKGROUND Indoleamine 2,3-dioxygenase (IDO) is overexpressed in many different types of tumor and is associated with activation of FOXP3+ regulatory T cells (Treg cells) and downregulation of cytotoxic cellular immunity in the tumor microenvironment. It has been suggested that IDO inhibitors can be utilized as an effective therapeutic agent against human cancers. However, the expression of IDO and its association with tumor-infiltrating lymphocytes (TILs) remain unclear in papillary thyroid microcarcinoma (PTMC). METHODS Immunohistochemical staining for IDO expression was performed on 124 PTMC samples. TIL subsets (CD3+, CD8+, and FOXP3+ T cells) were counted in serial sections. The relationships between the expression of IDO and infiltration of TIL subsets, as well as the relationships between these immunomodulating factors and clinicopathologic parameters of PTMCs, were analyzed. RESULTS There was a significant correlation between IDO expression and reduced CD3+ TIL and increased FOXP3+ TIL. IDO expression was found in 31% of PTMC and was associated with aggressive clinicopathologic features of the tumor such as extrathyroidal extension (ETE) and multifocality. High infiltration of FOXP3+ Treg cells in the tumor was associated with lymph node metastasis, ETE, and multifocality. Furthermore, high FOXP3/CD8+ ratio was associated with multifocality and lymph node metastasis, and high FOXP3+/CD3+ ratio was related to ETE and multifocality. In multivariate analyses, IDO expression was found to be an independent predictive factor for ETE and tumor multifocality. CONCLUSIONS IDO expression and infiltration of FOXP3+ Treg cells were closely related to each other and were associated with aggressive features of PTMC, suggesting that disruption of antitumor immunity by IDO expression, and thus, infiltration of FOXP3+ Treg cells may contribute to tumor progression in PTMC.

Abstract P4-11-25: Reappraisal of conventional risk stratification for local recurrence based on clinical outcomes in 285 resected phyllodes tumors of the breast

Background A second resection has been recommended, to ensure a surgical margin of ≥ 1cm for the effective treatment of PTB, but the outcomes of an extensive series of cases casts this clinical approach in doubt. Objective To identify the local recurrence risk factors of phyllodes tumor of the breast (PTB) and determine future optimal surgical treatment according to verified risks. Methods All cases given a diagnosis of PTB and resected between 1989 and 2008 were retrospectively evaluated. Clinicopathologic data and clinical outcomes were analyzed and stratified according to the risks for local recurrence (LR). Results All 285 cases occurred and 200 (70.2%) categorized as benign, 51 (17.9%) as borderline, and 34 (11.9) as malignant. Median follow-up was 6.7 years and during follow-up, there were 20 LRs. All benign PTBs recurred as benign PTB lesions. Mitosis (p = 0.007) and tumor size (p = 0.029) were independent prognostic factors for LR in multivariate analysis. Neither margin status (p = 0.773) nor type of surgery (p = 0.922) had any significance for LR. In the risk stratification for LR, PTBs sized 2 - 5cm with ≥ 10 mitoses / 10 HPF had the highest LR rate (60%) compared with all other groups (p Conclusions Only PTB with 2 - 5 cm and frequent mitoses, is it recommended to follow to ascertain a wide excision and clear margin of 1 cm, it necessary by means of a 2nd surgery could be considered to avoid the risk of LR in this distinct group. Citation Format: Cha Kyong Yom, Wonshik Han, Sung-Won Kim, So Yeon Park, In-Ae Park, Dong-Young Noh. Reappraisal of conventional risk stratification for local recurrence based on clinical outcomes in 285 resected phyllodes tumors of the breast [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-11-25.

Utility of breast MRI for patients with breast-cancer scheduled for breast-conserving surgery.

1086 Background: Purposes of this study is to compare the operation results between MRI group and none MRI group in breast cancer patients underwent BCS and to evaluate the accuracy of breast MRI for assessing tumor size. METHODS Between January 2003 and October 2005, 1610 consecutive patients who underwent breast cancer surgery were studied retrospectively. 750 patients received BCS and 486 patients (64.8%) of MRI group and 264 patients (35.2%) of non-MRI group were studied. To evaluate the accuracy of breast MRI, we compared pathologic tumor size with tumor size with breast MRI and sonography. RESULTS There was no significant difference of pT and N stage between MRI group and non-MRI group in patients received BCS (p=0.065). In MRI group vs. non-MRI group, margin was positive at frozen section in 36 patients (13.6%) vs. 97 (20.0%) with statistical significance (p=0.006). In non-MRI group, 12 patients (4.5%) underwent additional breast resection and none was converted to mastectomy. In MRI group, 70 patients (14.4%) had to resect breast additionally for margin positivity and 2 patients (0.4%) were converted to total mastectomy. Additional resection was performed in MRI group more than non-MRI group (p<0.0001). Local recurrence rate after BCS was not different between MRI group (5.8%) and non-MRI group (5.3%)(p=0.766). 5-year LRFSR was not different between MRI group (94.4%) and non-MRI group (94.6%) (p=0.837). However, 5-year OSR of MRI group was 94.1%, rate of non-MRI group was 90.1% (p=0.044). Tumor size of invasive component and size on MRI was significantly different (p<0.0001), but there was no significant difference between tumor size of invasive component and size on breast sonography (p=0.717). However, tumor size including DCIS component and size on MRI was not different (p=0.548), but tumor size including DCIS component and size on sonography was significantly different (p<0.0001). CONCLUSIONS Margin positivity and additional resection rate was higher in MRI group. OSR was slightly higher in MRI group than in non-MRI group. Breast sonography was more accurate for measuring invasive component than breast MRI, but MRI exhibited more accurate for measuring tumor size including DCIS component.