In Hye Song, Young-Ae Kim, Sun-Hee Heo, Won Seon Bang, Hye Seon Park, Yeon ho Choi, Heejae Lee, Jeong-Han Seo, Youngjin Cho, Sung Wook Jung, Hee Jeong Kim, Sei Hyun Ahn, Hee Jin Lee, Gyungyub Gong
Cancer Res Treat. 2022;54(4):1111-1120. Published online December 21, 2021
Purpose
The expression of major histocompatibility complex class I (MHC I) has previously been reported to be negatively associated with estrogen receptor (ER) expression. Furthermore, MHC I expression, level of tumor-infiltrating lymphocytes (TILs), and expression of interferon (IFN) mediator MxA are positively associated with one another in human breast cancers. This study aimed to investigate the mechanisms of association of MHC I with ER and IFN signaling.
Materials and Methods
The human leukocyte antigen (HLA)-ABC protein expression was analyzed in breast cancer cell lines. The expressions of HLA-A and MxA mRNAs were analyzed in MCF-7 cells in Gene Expression Omnibus (GEO) data. ER and HLA-ABC expressions, Ki-67 labeling index and TIL levels in tumor tissue were also analyzed in ER+/ human epidermal growth factor receptor 2 (HER2)- breast cancer patients who randomly received either neoadjuvant chemotherapy or estrogen modulator treatment followed by resection.
Results
HLA-ABC protein expression was decreased after β-estradiol treatment or hESR-GFP transfection and increased after fulvestrant or IFN-γ treatment in cell lines. In GEO data, HLA-A and MxA expression was increased after ESR1 shRNA transfection. In patients, ER Allred score was significantly lower and the HLA-ABC expression, TIL levels, and Ki-67 were significantly higher in the estrogen modulator treated group than the chemotherapy treated group.
Conclusion
MHC I expression and TIL levels might be affected by ER pathway modulation and IFN treatment. Further studies elucidating the mechanism of MHC I regulation could suggest a way to boost TIL influx in cancer in a clinical setting.
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Purpose
Axillary lymph node dissection (ALND) may be avoidable for breast cancer patients with 1-2 positive lymph nodes (LN) after breast-conserving therapy. However, the effects of ALND after mastectomy remain unclear because radiation is not routinely used. Herein, we compared the benefits of post-mastectomy ALND versus sentinel node biopsy (SNB) alone for breast cancer patients with 1-3 metastatic LNs.
Materials and Methods
A total of 1,697 patients with pN1 disease who underwent mastectomy during 2000-2015 were identified from an institutional database. Outcomes were compared using the inverse probability of treatment weighted method.
Results
Patients who underwent SNB tended to have smaller tumors, a lower histology grade, a lower number of positive LNs, and better immunohistochemical findings. After correcting all confounding factors regarding patient, tumor, and adjuvant treatment, the SNB and ALND groups did not differ in terms of overall survival (OS) and disease-free survival (DFS), distant metastasis and locoregional recurrence. The 10-year DFS and OS rates were 83% and 84%, respectively, during a median follow-up period of 93 months.
Conclusion
ALND did not improve post-mastectomy survival outcomes among patients with N1 breast cancer, even after adjusting for all histopathologic and treatment-related factors.
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Cancer Res Treat. 2018;50(1):275-282. Published online April 14, 2017
Purpose
We evaluated the effect of positive superficial and/or deep margin status on local recurrence (LR) in invasive breast cancer treated with breast-conserving surgery (BCS) followed by radiotherapy.
Materials and Methods
In total, 3,403 stage 1 and 2 invasive breast cancer patients treated with BCS followed by radiotherapy from January 2000 to December 2008 were included in this study. These patients were divided into three groups according to margin status: clear resection margin status for all sections (group 1, n=3,195); positive margin status in superficial and/or deep sections (group 2, n=121); and positive peripheral parenchymal margin regardless of superficial and/or deep margin involvement (group 3, n=87). The LR-free survival between these three groups was compared and the prognostic role of margin status was analyzed.
Results
Across all groups, age, tumor size, nodal status, and human epidermal growth factor receptor 2 status did not significantly differ. High grade, positive extensive intraductal component, hormone receptor positivity, hormone therapy received, and chemotherapy not received were more prevalent in groups 2 and 3 than in group 1. Five-year LR rates in groups 1, 2, and 3 were 1.9%, 1.7%, and 7.7%, respectively. Multivariate analysis revealed that group 3 was a significant predictor for LR (hazard ratio [HR], 4.78; p < 0.001), but that positive superficial and/or deep margin was not (HR, 0.66; p=0.57).
Conclusion
Superficial and/or deep margin involvement following BCS is not an important predictor for LR.
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Purpose
The purpose of this study was to compare treatment outcomes between combined gonadotropin-releasing hormone agonist and tamoxifen (GnRHa+T) and sequential adriamycin and cyclophosphamide chemotherapy and tamoxifen (AC->T) in premenopausal patients with hormone-responsive, lymph-node–negative breast cancer.
Materials and Methods
In total, 994 premenopausal women with T1-T2, lymph-node–negative, hormone-receptor-positive, HER2-negative breast cancer between January 2003 and December 2008 were included in this retrospective cohort study. GnRHa+T and AC->T were administered to 608 patients (61.2%) and 386 patients (38.8%), respectively. Propensity score matching and inverse probability weighting were applied to the original cohort, and 260 patients for each treatment arm were included in the final analysis. Recurrence-free, cancer-specific, and overall survival was compared between the two treatment groups.
Results
A total of 994 patients were followed up for a median of 7.4 years (range, 0.5 to 11.4 years). The 5-year follow-up rate was 98.7%, and 13 patients were lost to follow-up. In propensity=matched cohorts (n=520), there was no difference in recurrence-free, cancer-specific, and overall survival rates between the two treatment groups (p=0.306, p=0.212, and p=0.102, respectively), and this was maintained after applying inverse probability weighting.
Conclusion
GnRHa+T is a reasonable alternative to AC-> T in patients with premenopausal, hormoneresponsive, HER2-negative, lymph-node–negative, T1-T2 breast cancer.
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PURPOSE The aims were to evaluate the main risk factors (RFs) of breast cancer and to estimate the individual disease-probability from combinations of RFs in Korean female. MATERIALS AND METHODS: We conducted case-control study of 1, 687 incident cases of invasive carcinoma and 1, 238 controls during 1996~2000. A breast cancer disease-probability model was established by a general modeling process using a multivariate logistic regression model, which included the main Korean RFs and synergistic interaction-terms. RESULTS: The main Korean RFs selected were age, family history of second relatives, BMI, age at first full term pregnancy, breast-feeding, and a special test on the breasts. Two synergisms were observed between age and breast-feeding, and between special test and age at first fullterm pregnancy. The disease-probability and model are shown in Table 4, and Appendix 1. CONCLUSION: The availability of previous Western models was limited for Korean female due to the differences inhazard-rates and the characteristics of breast cancer between Asian and Western females. Due to limited basic data, i.e. incidence, hazard-rate and cancer-cohorts, the developing-probability of breast cancer for Korean females was not calculated.
Therefore, the disease-probability was calculated instead.
This approach might be more beneficial for Koreans, and help in the decision- making for regular screening or hospital visit-interval, counseling in breast-cancer clinics, prescribing high-risk population, and in educating for primary prevention, although it over-estimates the relative probability compared to the developing-probability and the 65% predictive validity.
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The Loss of P16ink4Expression is Strongly Associated with Hypermethylation-Related Inactivation in Breast Carcinoma Gyungyub Gong, Mi-Jung Kim, Yhong-Hee Shim, Gyeong Hoon Kang, Sei Hyun Ahn, Jae Y. Ro Journal of Breast Cancer.2006; 9(2): 84. CrossRef
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PURPOSE To evaluate the results of adriamycin-based adjuvant chemotherapy with or without high dose chemotherapy (HDC) with stem cell transplantation (SCT) in breast cancer with 10 or more positive axillary nodes. MATERIALS AND METHODS Seventy-one breast cancer patients who had undergone surgery and had 10 or more positive axillary nodes were included in this study held between January 1997 and December 1999. The pathologic and clinical records were reviewed retrospectively. RESULTS Twenty-nine patients were treated with adriamycin followed by 8 courses of CMF (group I); 22 patients received 4 courses of adriamycin and 7 patients received 3 courses of adriamycin. Twenty-six patients received median 6 courses of CAF (group II) and 16 patients underwent HDC and autologous SCT (group III). With a median follow-up of 27.1 months, relapses were observed in 24 patients (33.8%) and the 3-year disease-free survival (DFS) rate was 57.1%; group I/II 55.4%, and group III 62.7%. The three-year overall survival (OS) rate was 86.1%; group I/II 83.0%, group III 93.8%.
There were no difference in the 3-year DFSs or in the OSs of group I and group II. However, patients who received only 3 courses of the sequential adriamycin in group I showed a significantly poorer 3-year OS than those that received 4 courses of adriamycin (42.9% vs. 95.5%). CONCLUSION Our study shows that adriamycin-containing combination chemotherapy is as effective as HDC with SCT in patients with 10 or more positive axillary lymph nodes judging by 3-year DFS and OS, and shows that three courses of adriamycin seems to be inadequate.
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Alternative Therapy and Abnormal Liver Function During Adjuvant Chemotherapy in Breast Cancer Patients Jin-Hee Ahn, Sung-Bae Kim, Mi Ra Yun, Jung-Shin Lee, Yoon-Koo Kang, Woo Kun Kim Journal of Korean Medical Science.2004; 19(3): 397. CrossRef
PURPOSE Cancers are highly individual in their response to chemotherapy, however attempts to predict tumor response to drugs using in vitro cell culture have largely failed. A new technology, the histoculture drug response assay (HDRA), appears to have solved many previous problems. The purpose of this study is to evaluate the reliability of HDRA in a chemosensitivity test for breast cancer. MATERIALS AND METHODS Tumor specimens from breast cancer patients were evaluated by HDRA using different chemotherapeutic agents. Each specimen was tested using a blind method in order to determine the reproducibility of HDRA results for the same tissue and with a triplicated assay in order to determine reproducibility by different examiners. The evaluative power of this assay and the chemosensitivity of drugs for each specimen was determined. RESULTS Specimens of 92.9% (65/70) were successfully cultured and evaluated for chemosensitivity. The reproducibility of HDRA for the same tissue was 75% (100% agreement) and 100% (over 70% agreement), respectively. And the reproducibility by different examiners was 78.9% (100% agreement) and 94.7% (over 70% agreement), respectively.
Each specimen demonstrated a response to at least one agent. CONCLUSION The evaluative power and reproducibility of HDRA were high, therefore it might serve as a reliable clinical method for chemosensitivity testing. However, there is a need for clinical trial in which patients are initially randomized for treatment either by HDRA direction or by clinician's choice.
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Patient-Derived Ex Vivo Cultures and Endpoint Assays with Surrogate Biomarkers in Functional Testing for Prediction of Therapeutic Response Yoshiyuki Tsukamoto, Yuka Hirashita, Tomotaka Shibata, Shoichi Fumoto, Shusaku Kurogi, Chisato Nakada, Keisuke Kinoshita, Takafumi Fuchino, Kazunari Murakami, Masafumi Inomata, Masatsugu Moriyama, Naoki Hijiya Cancers.2023; 15(16): 4104. CrossRef
Comparison of Forcep-biopsy and Cryo-biopsy by a Flexible Bronchoscopy Jae Hyun Kim, Jung Min Choi, Sung Eun Song, Eun Mi Lee, Song Ju Lee, Chul Ho Oak, Tae Won Jang, Man Hong Jung, Hee Kyung Jang Tuberculosis and Respiratory Diseases.2009; 66(2): 110. CrossRef
Can the Histoculture Drug Response Assay Predict the Clinical Results of Chemotherapy in Breast Cancer? Yong Sik Jung, Young Up Cho, Young Jin Suh, Jeong Soo Kim, Se-Jeong Oh, Cheol Wan Lim, Moon Bo Kim, Heung Kyu Park Journal of Breast Cancer.2007; 10(3): 193. CrossRef
A Feasibility Study of Adenosine Triphosphate-based Chemotherapy Response Assay (ATP-CRA) as a Chemosensitivity Test for Lung Cancer Shin Myung Kang, Moo Suk Park, Joon Chang, Se Kyu Kim, Haeryoung Kim, Dong-Hwan Shin, Kyung Young Chung, Dae Joon Kim, Joo Hyuk Sohn, Sung Ho Choi, Jeongmi Kim, Eun Jin Yoon, Joo-Hang Kim Cancer Research and Treatment.2005; 37(4): 223. CrossRef
PURPOSE A specialized breast surgeon is important to give comprehensive treatments to breast cancer patients. The purpose of this study was to evaluate the characteristics and treatment results of breast cancer patients in my breast clinic, and to share the experience of clinical management and data base recording and its clinical use. MATERIALS AND METHODS I had performed 1,018 breast cancer surgeries from Mar. 1992 to Mar. 1998 at the Breast Clinic in Asan Medical Center. RESULTS The results were as follows; 1,008 cases were female (99.0%), and 10 cases were male (1.0%). The peak incidence was in 40~49 years of age (36.5%), followed by 30~39 years (24.0%) and 50~59 years (23.3%). 647 cases (63.6%) were under the age of 50. The most common operative method was a modified radical mastectomy in 747 cases (73.4%), and breast conserving surgery was performed in 173 cases (17.0%). Immediate breast reconstruction was performed in 63 cases (tissue expander with implant in 50 cases, direct implant in 4 cases, TRAM flap in 8 cases, and LD flap in one case), and SSM (skin-sparing mastectomy) through circumareolar incision was done in 9 cases. According to TNM classificasion, the most common was stage II in 49.2% (501 cases), and the proportion of early-breast cancer (stage 0 and I) was 33.7%. The axillary lymph node metastasis was present in 43.5%. The 5-year overall survival and disease free survival rate was 81.4% and 70.7%. There was no local recurrence in breast conserving surgery by median follow-up of 32 months. CONCLUSION As a breast surgeon, I have tried to apply the appropriate operation methods according to the patients condition. The survival data was fairly good, and there was no local recurrence after breast conserving surgery yet. Data computerization was very useful for evaluating the characteristics of the patients.
Hyu Kyung Kim, Jae Rak Chung, Chul Hee Lee, Jae Hoo Park, Hong Rae Cho, Byung Kyun Ko, Young Sae Park, Yeong Ju Woo, Jae Hee Suh, Sei Hyun Ahn, Gyung Yub Gong
PURPOSE Axillary lymph node metastases (ALNM) are the most important prognostic indicator in breast carcinoma. Because of relatively low incidence of axillary metastasis in the patients with Tl breast carcinoma, axillary lymph node dissection is now no longer considered to be the standard treatment. A reliable prediction of ALNM.may reduce the need for axillary lymph node dissection and may facilitate to select appropriate treatment modality. We have attempted to identify histopathologic/immunohistochemical factors correlated with ALNM in the patients with Tl breast carcinoma.
MATERIAL AND METHODS: Forty-one patients with Tl breast carcinoma who underwent modified radical mastectomy and axillary dissection between January 1993 and February 1999 were studied. We investigated the relationship between ALNM and the histopathologic/immunohistochemical factors (size, lymphatic-vascular invasion (LVI), histologic grade, age, estrogen receptor (ER) status, progesterone receptor (PR) status, p53 protein, cathepsin D (CD), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor (TGF)- B 2, and microvessel density (MVD)). RESULTS Fourteen (34.2%) out of the 41 patients with Tl breast carcinoma had ALNM. There are five statistically significant factors correlated with ALNM; lymphatic-vascular invasion (P=0.002), histologic grade (P 0.047), immunohistochemical expression of CD (P=0.005) and TGF- B 2 (P=0.004), and microvessel density (P=0.002). CONCLUSION The histopathologic/immunohistochemical features of the primary breast tumor, such as LVI, increase in MVD, TGF- B 2 and CD expression, and histologic grade might be useful predictors of ALNM in patients with Tl breast carcinoma.
Jeong Gyun Kim, Tae Won Kim, Je Hwan Lee, Sung Bae Kim, Cheolwon Suh, Kyoo Hyung Lee, Jung Shin Lee, Sei Hyun Ahn, Hyesook Chang, Sang Hee Kim, Woo Kun Kim
PURPOSE Though the therapy using regimens similar to western countries has been done by medical oncologists in several different centers in Korea, there is no large scale study about the results of those adjuvant chemotherapy as in western country and it is not clear whether the results are same in Korean population as in western countries not only in overall outcome but also depending on various prognostic categories. It is important to review whether Korean patients would have equivalent results as in western countries or not when they were treated with the same standardized regimens. We examined the effect of adjuvant systemic chemotherapy on survival and analyzed prognostic factors. MATERIALS AND METHODS A retrospective analysis of survival and prognostic factors was done in 341 consecutive breast cancer patients who received curative operation followed by systemic conventional adjuvant chemotherapy between 1989 and 1996. The survival rate was compared using Kaplan-Meier method and Log-rank method. To evaluate an independent prognostic factors, Cox proportional hazard model was used. RESULTS After median follow up of 56 months (range 28 118 months), the mean disease-free survival (DFS) and overall survival (OS) was 81.0+/-2.7 and 91.5+/-2.6 months respectively. The 5-year DFS and OS rate was 61% and 77%, respectively. On univariate analysis, prognostic factors significant for DFS were tumor size (<2 cm vs. > 2 cm), hormonal receptor status, and histologic grade. Prognostic factors affecting both DFS and OS are as follows: age ((pound)40 vs 41-50 vs. (3)51), number of axillary node involvement, .and stage. Multivariate analysis showed that the number of axillary node involvement was the strongest adverse predictor. CONCLUSION The effect of adjuvant chemotherapy in Korean patients is not different from western countries and this report emphasizes the prognostic importance of number of axillary node involvement in breast cancer patients and necessity of intensive management of those with four or more positive nodes.
PURPOSE This study was conducted to investigate whether breast cancer with p53 protein overexpression (p53+) and loss of p16 protein expression (p16-) shows different body size indicator (height, weight, body mass index) associations as compared with breast tumors without p53 protein overexpression and the loss of p16 expression (p53-, p16+). MATERIALS AND METHODS A hospital based case-control study was conducted among 92 women patients and 122 control subjects. The p53 protein overexpression and loss of p16 protein expression in the tissue sections of patients with breast cancer were determined using immunohistochemistry. RESULTS A total of 26 tumors (28%) demonstrated p53 overexpression and 35 tumors (46%) showed abnormal p16 expression. The heaviest women had a higher risk with p53- and p16+ breast tumors. The odds ratios (OR) adjusted for age, menopausal status, smoking, and drinking revealed a significant gradient of increasing risk of breast cancer with increasing BMI in p53- and p16+ breast cancer. The adjusted ORs for the highest quintile of BMI was 8.51 with p53+ tumors and 14.2 with p53- tumors, and 55.6 with p16+ tumors and 3.72 with p16- tumors.
p53 protein overexpression and the loss of p16 expression did not significantly correlate with nodal status, tumor size, estrogen or progesterone receptor status. CONCLUSION The study concluded that a strong association between p53-/p16+ tumors and BMI suggests the occurrence of p53-/p16+ tumors is related with obesity as compared to p53-/p16+ tumors.