Androgen Receptor as a Predictive Marker for Pathologic Complete Response in Hormone Receptor–Positive and HER-2–Negative Breast Cancer with Neoadjuvant Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study investigated pathological complete response (pCR) according to androgen receptor (AR) in breast cancer patients undergoing neoadjuvant chemotherapy and estimated the relationship between AR expression and clinicopathological factors. @*Materials and Methods@#We identified 624 breast cancer patients who underwent surgery after neoadjuvant chemotherapy at the National Cancer Center in Goyang, Korea from April 2016 to October 2019. We retrospectively collected the clinicopathologic information and AR expression results and analyzed the data according to cancer stage, hormonal receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, tumor subtype, and pCR. @*Results@#Among the 624 breast cancer patients, 529 (84.8%) were AR-positive (AR+) patients and 95 (15.2%) were AR-negative (AR–) patients. AR+ patients showed more estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, HER2-positivity, and HR-positive and HER2-negative (HR+/HER2–) subtype. The rate of pCR was 31.4% (196/624). AR– patients had a significantly higher rate of pCR than AR+ patients (AR– 43.2% vs. AR+ 29.3%, p=0.007). The tumor factors associated with pCR were early stage, histologic grade 3, ER-negative, PR-negative, AR-negative, HER2-positive, and high Ki-67 values. In univariable analysis, AR+ significantly decreased the state of pCR (odds ratio, 0.546; 95% confidence interval, 0.349 to 0.853; p=0.008). According to tumor subtype, AR– tumor showed higher pCR rate in HR+/HER2– subtype (AR– 28.6% vs. AR+ 7.3%, p=0.022). @*Conclusion@#AR expression is predominant in the HR+/HER2– subtype. AR– is significantly associated with the pCR rate in breast cancer patients, especially within HR+/HER2– subtype. When determining neoadjuvant chemotherapy for the HR+/HER2– subtype, AR expression can be considered as a pCR predictive marker.

Sentinel Lymph Node Biopsy in Breast Cancer Patients With Pathological Complete Response in the Axillary Lymph Node After Neoadjuvant Chemotherapy / 한국유방암학회지

Purpose@#Sentinel lymph node biopsy (SLNB) alone following neoadjuvant chemotherapy (NAC) remains controversial in patients with breast cancer who are initially lymph nodepositive. The present study aimed to evaluate the impact of SLNB and axillary lymph node dissection (ALND) on breast cancer recurrence and survival in patients who converted from lymph node-positive to pathological node-negative (ypN0) after NAC. @*Methods@#This single-center retrospective study included 223 patients who converted to axillary lymph node-negative status after NAC and underwent breast and axillary surgery between January 2006 and December 2015. This study compared the overall survival (OS), disease-free survival (DFS), ipsilateral axillary lymph node recurrence rates and incidence of postoperative complications, especially, arm lymphedema and shoulder stiffness between SLNB and ALND. @*Results@#This study included 223 patients with axillary pathological complete response (pCR) after NAC and surgery. The SLNB and ALND groups included 94 and 129 patients, respectively. The median follow-up time was 57 (range, 6–155) in the SLNB group and 99 (range 2–159) months in the ALND group. The corresponding 5-year OS and DFS rates were 96.3% and 94.2% (p = 0.392), and 89.2% and 86.4% (p = 0.671), respectively. Four patients (4.3%) in the SLNB group and nine (7.0%) in the ALND group developed locoregional recurrences. Ipsilateral axillary lymph node recurrence and distant metastasis were observed in one (1.1%) and three (2.3%) patients, and in 10 (10.6%) and 11 (8.5%) patients, respectively. Patients in the ALND group were more likely than their SLNB counterparts to experience complications, such as shoulder stiffness (9 [7.0%] vs. 4 [4.3%] patients, p = 0.57). The rate of lymphedema in the ALND group was three times that in the SLNB group (35 [27.1%] vs. 8 [8.5%] patients, p < 0.001). @*Conclusion@#As an alternative to ALND, SLNB has oncological safety in patients with axillary pathological complete response after NAC.

Comparing the Characteristics and Outcomes of Male and Female Breast Cancer Patients in Korea: Korea Central Cancer Registry / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to determine the incidence of male breast cancer (MBC) and its survival outcomes in Korea, and to compare these results to those for female breast cancer (FBC). @*Materials and Methods@#We searched the Korea Central Cancer Registry and identified 227,122 breast cancer cases that were diagnosed between 1999 and 2016. Demographic and clinical characteristics and overall survival (OS) rates were estimated according to sex, age, histological type, and cancer stage. @*Results@#The 227,122 patients included 1,094 MBC cases and 226,028 FBC cases. Based on the age-standardized rate, the male: female ratio was 0.0055:1. The most common ages at diagnosis were 60-69 years for MBC and 40-49 years for FBC (p < 0.001). Male patients were less likely than female patients to receive adjuvant radiotherapy (7.5% vs. 21.8%, p < 0.001) or adjuvant chemotherapy (40.1% vs. 55.4%, p < 0.001). The 5-year OS rates after diagnosis were 88.8% for all patients, although it was significantly lower for MBC than for FBC (76.2% vs. 88.9%, p < 0.001). In both groups, older age (≥ 60 years) was associated with shorter survival. The 5-year OS rates for the invasive histological types were 75.8% for men and 89.0% for women. The 5-year OS rates in both groups decreased with increasing cancer stage. @*Conclusion@#MBC was diagnosed at older ages than FBC, and male patients were less likely to receive radiotherapy and chemotherapy. The survival outcomes were worse for MBC than for FBC, with even poorer outcomes related to older age, the inflammatory histological types, and advanced stage. It is important that clinicians recognize the differences between FBC and MBC when treating these patients.

Comparison of clinical outcomes between sentinel lymph node biopsy and axillary lymph node dissection in a single-center Z0011-eligible breast cancer cohort

Purpose@#The ACOSOG Z0011 trial has proven the oncological safety of sentinel lymph node biopsy (SLBx) for node negative breast cancer. Accordingly, treatment paradigm including axilla surgery was changed. We retrospectively reviewed breast cancer patients to evaluate the clinical effect of paradigm shift in breast cancer surgery after applying the Z0011 criteria. @*Methods@#All women who underwent breast-conserving surgery at the National Cancer Center between January 1, 2000, and December 31, 2015, were enrolled and classified according to the Z0011 criteria. The primary endpoint of the study was the disease-free survival rates, and the secondary was the adverse events, especially arm lymphedema. @*Results@#Total 361 patients were enrolled the study (271 axillary lymph node dissection [ALND] group, 90 SLBx group). After the Z0011 guideline was adopted in our institute, the use of ALND decreased, and lymph node sampling (removing only a few axillary lymph nodes) replaced ALND. The total mean number of retrieved nodes were more in ALND group (13.02) than SLBx group (3.43). However, there was no difference in the mean number of positive nodes between two groups (2.34 in ALND group vs. 1.12 in SLBx group, P=0.001). During follow-up, 25 patients experienced disease recurrence: 22 from the ALND group and three from the SLBx group. All of died seven patients were from the ALND group. The ALND group had more complications than the SLBx group (P=0.02). Arm edema occurred more frequently in the ALND group (29.5%) than in the SLBx group (5.6%), although without statistical significance (P=0.07). @*Conclusion@#In our study, we concluded that SLBx can be used safely in Z0011-eligible cohort without increased risk of locoregional recurrence. Moreover, we found that omission of ALND is favored to reduce some serious complications such as arm lymphedema.

Primary Malignant Melanoma of the Breast: A Report of Two Cases

Primary malignant melanoma of the breast (PMMB) is a rare tumor with only a few case reports available in the literature. We report two cases of PMMB, one derived from the breast parenchyma and the other from the breast skin. The first case consisted of atypical epithelioid cells without overt melanocytic differentiation like melanin pigments. The tumor cells showed diffuse positivity for S100 protein, tyrosinase, and BRAF V600E. However, the tumor cells were negative for cytokeratin, epithelial membrane antigen, and HMB-45. The second case showed atypical melanocytic proliferation with heavy melanin pigmentation. The tumor cells were positive for S100 protein, HMB-45, tyrosinase, and BRAF V600E. These two cases represent two distinct presentations of PMMB in terms of skin involvement, melanin pigmentation, and HMB-45 positivity. Although PMMB is very rare, the possibility of this entity should be considered in malignant epithelioid neoplasms in the breast parenchyma.

Interaction Effect Between Breast Density and Reproductive Factors on Breast Cancer Risk in Korean Population

BACKGROUND: This study was conducted to explore the effect of known risk factors, focusing on risk factors including age at menarche, age at menopause, number of children, family history of breast cancer, and age at first birth according to breast density, in consideration of interaction among East-Asian women. METHODS: Case-control study with 2,123 cases and 2,121 controls with mammographic density was conducted. Using the mammographic film, breast density was measured using Breast Imaging-Reporting and Data System. To identify the association of selected reproductive factors including age at menarche, age at menopause, number of children, family history of breast cancer, and age at first birth according to breast density, stratified analysis was conducted according to breast density groups and interaction effects was assessed. The results were presented with adjusted OR and 95% CIs. RESULTS: Significant interaction effect between age at first birth and breast density on breast cancer (P = 0.048) was observed. Women with age at first birth ≥ 28 years old showed increased breast cancer risk in extremely dense breast group (≥ 75%) (OR = 1.627, 95% CI = 1.190–2.226). However, women with fatty breast (< 50%) and heterogeneously dense breast (50%–75%) did not show an increased association. Age at menarche, age at menopause, number of children, and family history of breast cancer did not show significant interaction with breast cancer and similar risk patterns were observed. CONCLUSIONS: Age at first birth showed significant interaction with breast density on breast cancer risk. Further studies considering biologically plausable model between exposure, intermediate outcomes and breast cancer risk with prospective design need to be undertaken in East Asian women.

Different Patterns of Risk Reducing Decisions in Affected or Unaffected BRCA Pathogenic Variant Carriers / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to investigate decision patterns to reduce the risks of BRCArelated breast and gynecologic cancers in carriers of BRCA pathogenic variants. We found a change in risk-reducing (RR) management patterns after December 2012, when the National Health Insurance System (NHIS) of Korea began to pay for BRCA testing and riskreducing salpingo-oophorectomy (RRSO) in pathogenic-variant carriers. MATERIALS AND METHODS: The study group consisted of 992 patients, including 705 with breast cancer (BC), 23 with ovarian cancer (OC), 10 with both, and 254 relatives of high-risk patients who underwent BRCA testing at the National Cancer Center of Korea from January 2008 to December 2016.We analyzed patterns of and factors in RR management. RESULTS: Of the 992 patients, 220 (22.2%) were carriers of BRCA pathogenic variants. About 92.3% (203/220) had a family history of BC and/or OC,which significantly differed between BRCA1 and BRCA2 carriers (p < 0.001). All 41 male carriers chose surveillance. Of the 179 female carriers, 59 of the 83 carriers (71.1%) with BC and the 39 of 79 unaffected carriers (49.4%) underwent RR management. None of the carriers affected with OC underwent RR management. Of the management types, RRSO had the highest rate (42.5%) of patient choice. The rate of RR surgery was significantly higher after 2013 than before 2013 (46.3% [74/160] vs. 31.6% [6/19], p < 0.001). CONCLUSION: RRSO was the preferred management for carriers of BRCA pathogenic variants. The most important factors in treatment choice were NHIS reimbursement and/or the severity of illness.

Prognostic Impact of Elective Supraclavicular Nodal Irradiation for Patients with N1 Breast Cancer after Lumpectomy and Anthracycline Plus Taxane-Based Chemotherapy (KROG 1418): A Multicenter Case-Controlled Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was conducted to evaluate the impact of supraclavicular lymph node radiotherapy (SCNRT) on N1 breast cancer patients receiving post-lumpectomy whole-breast irradiation (WBI) and anthracycline plus taxane-based (AT) chemotherapy. MATERIALS AND METHODS: We performed a case-control analysis to compare the outcomes of WBI and WBI plus SCNRT (WBI+SCNRT). Among 1,147 patients with N1 breast cancer who received post-lumpectomy radiotherapy and AT-based chemotherapy in 12 hospitals, 542 were selected after propensity score matching. Patterns of failure, disease-free survival (DFS), distant metastasis-free survival (DMFS), and treatment-related toxicity were compared between groups. RESULTS: A total of 41 patients (7.6%) were found to have recurrence. Supraclavicular lymph node (SCN) failure was detected in three patients, two in WBI and one in WBI+SCNRT. All SCN failures were found simultaneously with distant metastasis. There was no significant difference in patterns of failure or survival between groups. The 5-year DFS and DMFS for patients with WBI and WBI+SCNRT were 94.4% versus 92.6% (p=0.50) and 95.1% versus 94.5% (p=0.99), respectively. The rates of lymphedema and radiation pneumonitis were significantly higher in the WBI+SCNRT than in the WBI. CONCLUSION: We did not find a benefit of SCNRT for N1 breast cancer patients receiving AT-based chemotherapy.

Unusual Contralateral Axillary Lymph Node Metastasis in a Second Primary Breast Cancer Detected by FDG PET/CT and Lymphoscintigraphy / 대한핵의학회잡지

Contralateral metastatic axillary lymph nodes in a patient with breast cancer is a rare condition. Here, we present a 55-year-old woman with a second primary breast cancer. The patient underwent ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) for staging work-up. Additionally, preoperative lymphoscintigraphy was performed to detect sentinel lymph nodes. FDG PET/CT demonstrated increased FDG uptake in the left nipple and right axillary lymph nodes. Lymphoscintigraphy identified the right axillary lymph nodes which was consistent with the FDG PET/CT findings. This case emphasizes the usefulness of FDG PET/CT and lymphoscintigraphy for identifying unpredictable contralateral axillary lymph node metastasis from a second primary breast cancer.

Identification of Prognostic Risk Factors for Transient and Persistent Lymphedema after Multimodal Treatment for Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study is to identify risk factors for transient lymphedema (TLE) and persistent lymphedema (PLE) following treatment for breast cancer. MATERIALS AND METHODS: A total of 1,073 patients who underwent curative breast surgery were analyzed. TLE was defined as one episode of arm swelling that had resolved spontaneously by the next follow-up; arm swelling that persisted over two consecutive examinations was considered PLE. RESULTS: At a median follow-up period of 5.1 years, 370 cases of lymphedema were reported, including 120 TLE (11.2%) and 250 PLE (23.3%). Initial grade 1 swelling was observed in 351 patients, of which 120 were limited to TLE (34%), while the other 231 progressed to PLE (66%). All initial swelling observed in TLE patients was classified as grade 1. In multivariate analysis, chemotherapy with taxane and supraclavicular radiation therapy (SCRT) were associated with development of TLE, whereas SCRT, stage III cancer and chemotherapy with taxane were identified as risk factors for PLE (p < 0.05). The estimated incidence of TLE among initial grade 1 patients was calculated using up to three treatment-related risk factors (number of dissected axillary lymph nodes, SCRT, and taxane chemotherapy). The approximate ratios of TLE and PLE based on the number of risk factors were 7:1 (no factor), 1:1 (one factor), 1:2 (two factors), and 1:3 (three factors). CONCLUSION: One-third of initial swelling events were transient, whereas the other two-thirds of patients experienced PLE. Estimation of TLE and PLE based on known treatment factors could facilitate prediction of this life-long complication.

Effect of Time Interval between Breast-Conserving Surgery and Radiation Therapy on Outcomes of Node-Positive Breast Cancer Patients Treated with Adjuvant Doxorubicin/Cyclophosphamide Followed by Taxane / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study evaluated the effect of surgery-radiotherapy interval (SRI) on outcomes in patients treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) and adjuvant four cycles of doxorubicin/cyclophosphamide (AC) followed by four cycles of taxane. MATERIALS AND METHODS: From 1999 to 2007, 397 eligible patients were diagnosed. The effect of SRI on outcomes was analyzed using a Cox proportional hazards model, and a maximal chi-square method was used to identify optimal cut-off value of SRI for each outcome. RESULTS: The median SRI was 6.7 months (range, 5.6 to 10.3 months). A SRI of 7 months was the significant cut-off value for distant metastasis-free survival (DMFS) and disease-free survival (DFS) using a maximal chi-square method. For overall survival, a significant cut-off value was not found. The patients with SRI > 7 months had worse 6-year DMFS and DFS than those with SRI ≤ 7 months on univariate analysis (DMFS, 81% vs. 91%, p=0.003; DFS, 78% vs. 89%, p=0.002). On multivariate analysis, SRI > 7 months did not affect DMFS and DFS. CONCLUSION: RT delayed for more than 7 months after BCS and adjuvant four cycles of AC followed by four cycles of taxane did not compromise clinical outcomes.

Breast Cancer-Related Lymphedema after Neoadjuvant Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The risk for lymphedema (LE) after neoadjuvant chemotherapy (NCT) in breast cancer patients has not been fully understood thus far. This study is conducted to investigate the incidence and time course of LE after NCT. MATERIALS AND METHODS: A total of 313 patients with clinically node-positive breast cancer who underwent NCT followed by surgery with axillary lymph node (ALN) dissection from 2004 to 2009 were retrospectively analyzed. All patients received breast and supraclavicular radiation therapy (SCRT). The determination of LE was based on both objective and subjective methods, as part of a prospective database. RESULTS: At a median follow-up of 5.6 years, 132 patients had developed LE: 88 (28%) were grade 1; 42 (13%) were grade 2; and two (1%) were grade 3. The overall 5-year cumulative incidence of LE was 42%. LE first occurred within 6 months after surgery in 62%; 1 year in 77%; 2 years in 91%; and 3 years in 96%. In a multivariate analysis, age (hazard ratio [HR], 1.66; p < 0.01) and the number of dissected ALNs (HR, 1.68; p < 0.01) were independent risk factors for LE. Patients with both of these risk factors showed a significantly higher 5-year cumulative incidence of LE compared with patients with no or one risk factor (61% and 37%, respectively; p < 0.001). The addition of adjuvant chemotherapy did not significantly correlate with LE. CONCLUSION: LE after NCT, surgery, and SCRT developed early after treatment, and with a high incidence rate. More frequent surveillance of arm swelling may be necessary in patients after NCT, especially during the first few years of follow-up.

A Case of Locally Advanced Breast Cancer Complicated by Pulmonary Tumor Thrombotic Microangiopathy / Journal of the Korean Cancer Association, 대한암학회지

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare, malignancy-related complication that causes marked pulmonary hypertension, right heart failure, and death. We report on a patient with locally advanced breast cancer whose course was complicated by fatal PTTM based on clinical and laboratory findings.

Locoregional Recurrence of Breast Conserving Surgery after Preoperative Chemotherapy in Korean Women with Locally Advanced Breast Cancer / 한국유방암학회지

PURPOSE: Preoperative chemotherapy has been used to increase the rate of breast conserving surgery (BCS) in Caucasian women. However, whether it would also increase the rate of BCS in Korean women has not been verified. The aim of this study was to determine the effectiveness of preoperative chemotherapy to make BCS possible in Korean women who have locally advanced cancer without any increase of locoregional recurrence according to operation methods (BCS vs. mastectomy). METHODS: From August 2002 to April 2005, 205 patients with stage II or III breast cancer were enrolled in a phase III randomized trial of preoperative chemotherapy. Surgeons decided on the type of surgery (mastectomy or BCS) at initial diagnosis. By randomization, patients received four cycles of either docetaxel/capecitabine or doxorubicin/cyclophosphamide followed by surgery and crossover to the other treatment as postoperative chemotherapy. RESULTS: The mean tumor size was 3.29 cm and the mean breast volume was 489 cc at diagnosis. After preoperative chemotherapy, clinical response was shown in 76.0% of the patients. Of the 71 patients planned for a mastectomy at initial diagnosis, 27 patients underwent BCS (38.0%). Clinical T stage after preoperative chemotherapy, pathologic T size and lymphatic invasion were correlated with conversion to BCS. In multivariate analysis, only lymphatic invasion showed statistical significance. Locoregional disease-free survival did not statistically differ between the two operation methods for the patients who were planned for a mastectomy at the initial exam. CONCLUSION: This study showed that preoperative chemotherapy also increased the rate of BCS, while avoiding any increase of locoregional recurrence in Korean women with locally advanced breast cancer.

Charlson Comorbidity Index as a Predictor of Long-Term Survival after Surgery for Breast Cancer: A Nationwide Retrospective Cohort Study in South Korea / 한국유방암학회지

PURPOSE: The aim of this article was to evaluate the impact of the Charlson Comorbidity Index (CCI) on long-term survival after surgery for breast cancer in South Korea. METHODS: The study subjects were 29,562 women patients aged 20 years and older that underwent surgery for breast cancer between 2002 and 2005. The data were obtained from claims submitted to the National Health Insurance. All patients were censored at the follow-up cutoff date of June 30, 2006. Survival curves were estimated by the Kaplan-Meier method. Cox proportional hazards models were used to explore the impact of CCI on all-cause mortality. RESULTS: After a follow-up time of 47 months, higher all-cause mortality was associated with an increasing CCI. In terms of the 4-year survival rate, among patients with CCI=1, it was 91.1%, among patients with CCI=2 it was 87.8%, and those patients with CCI> or =3 it was 80.2%. Multivariate Cox proportional hazard analysis showed that CCI=1 (hazard ratios [HR], 1.10; 95% confidence interval [CI], 0.97-1.25), CCI=2 (HR, 1.61; 95% CI, 1.31-1.97) and CCI> or =3 (HR, 2.27; 95% CI, 1.59-3.24), were associated with long-term survival. CONCLUSION: CCI is a strong predictor of long-term survival after surgery for breast cancer. We recommend the use of a validated comorbidity index in the selection of patients for breast surgery.

Radiation Pneumonitis after Adjuvant Radiotherapy for Breast Cancer: A Volumetric Analysis Using CT Simulator / 한국유방암학회지

PURPOSE: To assess clinical factors and volumetric parameters associated with clinically significant symptomatic radiation pneumonitis (RP), which requires steroid medication after radiotherapy (RT). METHODS: Medical records of 204 irradiated breast cancer patients were reviewed. Percent lung volume (PLV) receiving more than 20 Gy was measured from CT-based treatment plan and was correlated with the central lung distance (CLD) of local and regional fields. PLV was also evaluated as a predictive factor of symptomatic RP, along with other previously reported clinical factors. RESULTS: Average (+/-standard deviation) actual irradiated lung volume and PLV for breast/chest wall irradiation were 169 (+/-50.6) cm3 and 14.9 (+/-3.8)%, respectively. Addition of regional irradiation resulted in increase of 183 (+/-80.2) cm3 in actual irradiated lung volume and 16.5 (+/-6.2)% in PLV. The correlation between CLD of the local fields and PLV was significant, with 1 cm of CLD corresponding to approximately 6% of PLV. CLD of the regional field was also significantly associated with PLV: a CLD of 3 cm corresponds to a PLV of approximately 13%; a CLD of 4 cm, approximately 17%; and a CLD of 5 cm, approximately 21%. RP developed in 11 patients (5.4%). There was an increased incidence of RP among patients who underwent local RT vs local and regional RT (2.4% vs 12.1%, p=0.0192). In terms of PLV, total PLV > or =23% was associated with the development of RP (p=0.0467). Previously reported clinical factors failed to show statistically significant association. CONCLUSION: Correlation between CLD and PLV for local and regional fields was significant on volumetric analysis. Although symptomatic RP requiring steroid medication was a rare complication, regional irradiation increased the incidence of RP, and such relationship can be expressed with a volumetric parameter of PLV.

The Characterization of CpG Methylation of ERalpha and ERbeta Gene in the Breast Cancer / 한국유방암학회지

PURPOSE: Aberrant methylation of promoter cytosine guanine dinucleotide (CpG) islands is known to be responsible for the alteration and silencing of cancer genes. The data presented here show that most methylations of Estrogen Receptoralpha (ERalpha) and ERbeta are found at or near the transcriptional factor binding sites in the breast cancer tissues. METHODS: Fifty archival breast cancer tissues and twenty-five normal tissues were selected and the status of the methylation and the transcription were investigated by bisulfite genomic sequencing and reverse transcription (RT) PCR. RESULTS: Consequently, the hypermethylation of ERalpha and ERbeta genes was found in 66.0% and 50.0% of 50 breast cancers, respectively. In particular, the methylation sites were frequently located near the CCAAT box (-363 and -375) for the ERalpha gene, and at or adjacent to binding sites of GATA (-217, -302) and Sp1 (+224, +227, +160) for the ERbeta gene. The methylations at or near the binding sites were observed in most of the methylated cancers (ERalpha 87.9%, and ERbeta 84.0%). The methylated cases were negatively correlated with the expression of ERalpha and ERbeta RNA (P<0.01). In particular, tumors with CpG methylation of ERalpha and ERbeta at or near the binding sites did not express mRNA, whereas those CpG methylation outside the sites showed moderate expression. Four tumors with methylated ERalpha genes at sites unrelated to the binding sites showed higher levels of protein expression than those with methylation at or near the sites (P=0.01). CONCLUSION: Although the number of samples was relatively small, our results suggest that DNA methylation in ERalpha and ERbeta appears to take significant effect on transcriptional silencing and is most often present in the CpG sites at or near the putative transcriptional factor binding sites. We believe this finding offers a clue to the initiation or spread pattern of CpG methylation in human breast cancer.

Neoadjuvant Chemotherapy Decreases the Identification Rate of Sentinel Lymph Node Biopsy / 한국유방암학회지

PURPOSE: We investigated the feasibility and clinical applicability of sentinel lymph node biopsy (SLNB) in patients with neoadjuvant chemotherapy, tumor size > 2 cm, and privious excisional biopsy. METHODS: 175 patients with 176 breast cancer underwent aLNB between October 2001 and October 2002. Among them twenty-five patients with locally advanced breast cancer underwent SLNB after neoadjuvant chemotherapy. Eighty-nine (50.6%) had primary tumor > 2 cm. The recent biopsy method used before SLNB was excision in thirty-one (17.6%) procedures. The identification rate, false-negative rate, negative prediction value and accuracy of SLNB were determined. RESULTS: SLNB was successful in 164 of 176 cases (detection rate, 93.2%). The identification rate of patients who had neoadjuvant chemotherapy was 68% and lower than that of who had not (97.3%), significantly (P=0.00). However, mapping success was not influenced by large tumor size (> 2 cm) or previous excisional biopsy. The false-negative rate and accuracy were 16.5% and 91.5, respectively. The false negative rate was 21.3% (3/14) in those patients received neoadjuvant chemotherapy compared with a 15.5% in those patents not received neoadjuvant chemotherapy (P> 0.05). In addition, Tumor size > 2 cm and previous excision did not adversely impact the false negative rate and accuracy. CONCLUSION: Neoadjuvant chemotherapy was associated with a lower identification rate for SLNB. But if detected, SLNB after neoadjuvant chemotherapy might reliably predict axillary status. SLNB is feasible and accurate in patients with large tumor (> 2 cm) and previous excision.

Detection of Axillary Lymph Node Micrometastases in Breast Cancer Using RT-PCR Comparison the Results of MUC1, Cytokeratin 19 / 한국유방암학회지

PURPOSE: The detection of axillary lymph-node micrometastases in breast-cancer patients by using the reverse transcriptase-polymerase chain reaction (RT-PCR) may provide a good guide for postoperative therapy. To evaluate effectiveness of RT-PCR for the detection of micrometastasis, we have compared the results of conventional, immunohistochemical (IHC) staining with those of RT-PCR. Breast cancer, Lymph node micrometastases, MUC1, Cytokeratin 19, RT-PCR ] METHODS: We conducted RT-PCR amplifications of MUC1 and cytokeratin (CK) 19 on lymph nodes from 40 breast- cancer patients and conducted IHC staining for cytokeratin. The results of histological examination and cytokeratin IHC staining were compared with the RT-PCR results for the detection of lymph-node micrometastases. RESULTS: Nineteen of 40 cases (47.5%) were lymph-node positive and twenty-one cases (52.5%) were lymph-node negative. Using RT-PCR MUC1 and CK19 expressions were detected in all positive lymph nodes and in 4 (19.0%) and 5 (23.8%), in negative nodes, respectively. Not all positive nodes were stained by IHC (94.7%), and none of the negative lymph nodes were stained by IHC. Thus, IHC staining was ineffective in detecting micrometastases. CONCLUSION: Detection of MUC1 and CK19 by using RT- PCR can be a more accurate and useful method than IHC staining for the detection of axillary lymph-node micrometastases in breast cancer.

Detection of Axillary Lymph Node Micrometastases in Breast Cancer Using RT-PCR: Comparison the Results of MUC1, Cytokeratin 19

PURPOSE: The detection of axillary lymph-node micrometastases in breast-cancer patients by using the reverse transcriptase-polymerase chain reaction (RT-PCR) may provide a good guide for postoperative therapy. To evaluate effectiveness of RT-PCR for the detection of micrometastasis, we have compared the results of conventional, immunohistochemical (IHC) staining with those of RT-PCR. METHODS: We conducted RT-PCR amplifications of MUC1 and cytokeratin (CK) 19 on lymph nodes from 40 breast- cancer patients and conducted IHC staining for cytokeratin. The results of histological examination and cytokeratin IHC staining were compared with the RT-PCR results for the detection of lymph-node micrometastases. RESULTS: Nineteen of 40 cases (47.5%) were lymph-node positive and twenty-one cases (52.5%) were lymph-node negative. Using RT-PCR MUC1 and CK19 expressions were detected in all positive lymph nodes and in 4 (19.0%) and 5 (23.8%), in negative nodes, respectively. Not all positive nodes were stained by IHC (94.7%), and none of the negative lymph nodes were stained by IHC. Thus, IHC staining was ineffective in detecting micrometastases. CONCLUSION: Detection of MUC1 and CK19 by using RT- PCR can be a more accurate and useful method than IHC staining for the detection of axillary lymph-node micrometastases in breast cancer.