Development and External Validation of a Machine Learning Model to Predict Pathological Complete Response After Neoadjuvant Chemotherapy in Breast Cancer / 한국유방암학회지

Purpose@#Several predictive models have been developed to predict the pathological complete response (pCR) after neoadjuvant chemotherapy (NAC); however, few are broadly applicable owing to radiologic complexity and institution-specific clinical variables, and none have been externally validated. This study aimed to develop and externally validate a machine learning model that predicts pCR after NAC in patients with breast cancer using routinely collected clinical and demographic variables. @*Methods@#The electronic medical records of patients with advanced breast cancer who underwent NAC before surgical resection between January 2017 and December 2020 were reviewed. Patient data from Seoul National University Bundang Hospital were divided into training and internal validation cohorts. Five machine learning techniques, including gradient boosting machine (GBM), support vector machine, random forest, decision tree, and neural network, were used to build predictive models, and the area under the receiver operating characteristic curve (AUC) was compared to select the best model. Finally, the model was validated using an independent cohort from Seoul National University Hospital. @*Results@#A total of 1,003 patients were included in the study: 287, 71, and 645 in the training, internal validation, and external validation cohorts, respectively. Overall, 36.3% of the patients achieved pCR. Among the five machine learning models, the GBM showed the highest AUC for pCR prediction (AUC, 0.903; 95% confidence interval [CI], 0.833–0.972).External validation confirmed an AUC of 0.833 (95% CI, 0.800–0.865). @*Conclusion@#Commonly available clinical and demographic variables were used to develop a machine learning model for predicting pCR following NAC. External validation of the model demonstrated good discrimination power, indicating that routinely collected variables were sufficient to build a good prediction model.

Detection of Germline Mutations in Breast Cancer Patients with Clinical Features of Hereditary Cancer Syndrome Using a Multi-Gene Panel Test / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Hereditary cancer syndrome means that inherited genetic mutations can increase a person's risk of developing cancer. We assessed the frequency of germline mutations using an nextgeneration sequencing (NGS)–based multiple-gene panel containing 64 cancer-predisposing genes in Korean breast cancer patients with clinical features of hereditary breast and ovarian cancer syndrome (HBOC). @*Materials and Methods@#A total of 64 genes associated with hereditary cancer syndrome were selected for development of an NGS-based multi-gene panel. Targeted sequencing using the multi-gene panel was performed to identify germline mutations in 496 breast cancer patients with clinical features of HBOC who underwent breast cancer surgery between January 2002 and December 2017. @*Results@#Of 496 patients, 95 patients (19.2%) were found to have 48 deleterious germline mutations in 16 cancer susceptibility genes. The deleterious mutations were found in 39 of 250 patients (15.6%) who had breast cancer and another primary cancer, 38 of 169 patients (22.5%) who had a family history of breast cancer (≥ 2 relatives), 16 of 57 patients (28.1%) who had bilateral breast cancer, and 29 of 84 patients (34.5%) who were diagnosed with breast cancer at younger than 40 years of age. Of the 95 patients with deleterious mutations, 60 patients (63.2%) had BRCA1/2 mutations and 38 patients (40.0%) had non-BRCA1/2 mutations. We detected two novel deleterious mutations in BRCA2 and MLH1. @*Conclusion@#NGS-based multiple-gene panel testing improved the detection rates of deleterious mutations and provided a cost-effective cancer risk assessment.

Contralateral Breast Cancer and Ipsilateral Breast Tumor Recurrence in BRCA1/2 Carriers and Non-Carriers at High-Risk of Hereditary Breast Cancer / 한국유방암학회지

Axillary Lymph Node to Primary Breast Tumor Standardized Uptake Value Ratio from FDG-PET/CT Imaging for Predicting the Necessity for Nodal Dissection in Primary Breast Tumors

PURPOSE: Accurate preoperative detection by radiologic assessment is necessary to specifically identify patients with at least three positive nodes, who can directly undergo axillary lymph node (ALN) dissection, and avoid unnecessary surgical procedures. We evaluated the usefulness of the standardized uptake value (SUV) ratio of ALN in primary breast tumor, using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) and magnetic resonance imaging (MRI) to predict the necessity of ALN dissection during breast cancer surgery. METHODS: In this retrospective study we enrolled 316 consecutive patients with invasive breast cancer. The SUV ratio of ALN to primary breast tumor uptake was calculated. Optimal cutoff values were determined by receiver operating characteristic curve analysis for predicting the presence of ≥3 ALN metastases. Diagnostic performance of FDG-PET and MRI features for the prediction of ≥3 ALN metastases were determined by sensitivity, specificity, and diagnostic odds ratio (DOR). A subgroup analysis for FDG-avid tumors was also performed. RESULTS: Of the 316 patients, 36 (11.4%) showed involvement of ≥3 ALNs, with 101 (32%) having at least one metastatic lymph node. Axillary 18F-FDG uptake was positive in 75 patients (23.7%), and the optimal ratio of maximum SUV of axillary lymph node and primary tumor for determining ALN dissection was 0.3. MRI scans revealed suspicious ALN involvement in 147 patients (46.6%). The sensitivity and specificity of MRI detection were 88.9% and 56.2%, respectively, while for SUVLN/T ratio, they were 69.4% and 86.8%, respectively. DOR values for MRI and SUVLN/T ratio were 10.37 and 9.7, respectively. The area under the curve (AUC) was improved to 0.896 (95% confidence interval [CI], 0.817–0.975) for the SUVLN/T ratio in patients with FDG-avid primary tumors (FDG ≥3.9, n=108), but the MRI AUC was worsened (0.681; 95% CI, 0.569–0.793). The DOR, sensitivity, and specificity for the SUVLN/T ratio of FDG-avid cancers were 25.68, 89.0% and 86.0%, respectively. CONCLUSION: SUVLN/T ratio outperformed MRI features in predicting the need for ALN dissection in FDG-avid primary breast cancer. PET/CT may be a potential noninvasive diagnostic technique for identifying the presence of ≥3 ALN metastases.

Patients with Concordant Triple-Negative Phenotype between Primary Breast Cancers and Corresponding Metastases Have Poor Prognosis / 한국유방암학회지

PURPOSE: We investigated the prognostic impact of discordance between the receptor status of primary breast cancers and corresponding metastases. METHODS: A total 144 patients with breast cancer and distant metastasis were investigated. The estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status of primary tumor and corresponding metastases were assessed. Tumor phenotype according to receptor status was classified as triple-negative phenotype (TNP) or non-TNP. Concordance and discordance was determined by whether there was a change in receptor status or phenotype between primary and metastatic lesions. RESULTS: The rates of discordance between primary breast cancer and metastatic lesions were 18.1%, 25.0%, and 10.3% for ER, PR, and HER2, respectively. The rates of concordant non-TNP, concordant TNP and discordant TNP were 65.9%, 20.9%, and 13.2%, respectively. Patients with concordant ER/PR-negative status had worse postrecurrence survival (PRS) than patients with concordant ER/PR-positive and discordant ER/PR status (p=0.001 and p=0.021, respectively). Patients who converted from HER2-positive to negative after distant metastasis had worst PRS (p=0.040). Multivariate analysis showed that concordant TNP was statistically significant factor for worse PRS (p<0.001). CONCLUSION: Discordance in receptor status and tumor phenotype between primary breast cancer and corresponding metastatic lesions was observed. Patients with concordant TNP had worse long-term outcomes than patients with concordant non-TNP and discordant TNP between primary and metastatic breast cancer. Identifying the receptor status of metastatic lesions may lead to improvements in patient management and survival.

Relapse of Biphenotypic Acute Leukemia as a Breast Mass / 한국유방암학회지

In acute leukemia, leukemic infiltration of the breast is extremely rare. We report a case of biphenotypic acute leukemia (BAL) that presented as a breast mass. A 30-year-old woman presented with a 4-month history of a right breast mass with nipple discharge and easy fatigue. She had received chemotherapy and peripheral blood stem cell transplantation for BAL and had been in complete remission for the last 2 years. Core needle biopsy of the breast mass revealed monomorphous infiltrates of blast cells with round nuclei and fine chromatin, consistent with leukemic infiltration. Subsequent bone marrow biopsy showed diffuse infiltration of immature cells. However, bone marrow karyotyping showed 46, XY, suggesting complete engraftment of transplanted donor cells. This is the report of BAL recurring as a breast mass. In the differential diagnosis of a breast mass, extramedullary relapse should be considered when the patient has a history of leukemia.

Reliability of Core Needle Biopsy in Evaluating Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2, and Ki-67 Status

PURPOSE: The preoperative determination of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), and Ki-67 expression status is crucial because these factors influence the therapeutic response to endocrine therapy, chemotherapy, and HER2-targeted therapy and help in the selection of adjuvant or neoadjuvant treatment. To evaluate the accuracy of core needle biopsy (CNB) in determining ER, PR, and HER2 status, and Ki-67 level status, we compared the results of CNB with those of surgical specimens. METHODS: We retrospectively reviewed data from 191 patients with breast cancer whose ER, PR, and HER2 status, and Ki-67 level status was analyzed using both CNB and surgical specimens between 2013 and 2015. Patients who received neoadjuvant chemotherapy were excluded from this study. ER, PR, and Ki-67 were detected using immunohistochemistry (IHC) and reported as the percentage of positively stained cells. The cutoff point was 1% for ER and PR, and 14% for Ki-67. HER2 was determined by IHC and/or fluorescence in situ hybridization (FISH). HER2 positivity was defined as IHC 3+ or FISH (+). RESULTS: In correlation analysis, Pearson correlation coefficients were 0.950 for ER expression, 0.813 for PR expression, 0.847 for HER2 grade, and 0.817 for Ki-67 expression level (p<0.0001). According to criteria for ER, PR, HER2, and Ki-67, the sensitivities of ER, PR, HER2, and Ki-67 assessment in CNB were 92.6%, 88.8%, 100%, and 80.6%, respectively. The specificities of ER, PR, HER2, and Ki-67 assessments in CNB were 90.7%, 86.0%, 99.1%, and 88.7%, respectively. CONCLUSION: The ER, PR, HER2, and Ki-67 status in CNB specimens correlated well with their status in surgical specimens. The HER2 status was the most accurately assessed factor in CNB specimens when compared to its assessment in surgical specimens. However, Ki-67 levels in CNB specimens were lower than those in surgical specimens.

Analysis of the Relationship between Body Mass Index and Breast Cancer Incidence in Korean Women

PURPOSE: Obesity in women has been shown to have correlation with breast cancer incidence. The proportion of Korean women who are obese has increased recently. However, there is no large-scale study evaluating the relationship between obesity and breast cancer incidence in Korea. In this study, we tried to identify the relationship between obesity and breast cancer incidence in Korean women by using body mass index (BMI). METHODS: A retrospective analysis was performed using single-center data of 28,631 patients screened with breast ultrasonography or mammography between January 2009 to December 2013 in Seoul National University Hospital Healthcare System Gangnam Center. Their clinical characteristics were evaluated. The correlations between breast cancer incidence with BMI and other factors were analyzed using univariate and multivariate logistic regression models. RESULTS: A total of 28,631 patients were enrolled; 67 patients were diagnosed with breast cancer. Among patients without breast cancer, the proportion of patients with BMI under 23 was 68.1%, whereas it was 56.7% among patients with breast cancer (p=0.036). In univariate analysis, patients with a BMI over 25 had an odds ratio of 2.09 for breast cancer compared with those with a BMI under 23 (p=0.012). In addition, patients with a waist circumference over 85 cm had an odds ratio of 1.69 for breast cancer compared with the others (p=0.042). In multivariate analysis, BMI also had significant correlation with breast cancer incidence (odds ratio=1.87, p=0.035). CONCLUSION: An increase in BMI has positive correlation with breast cancer incidence in Korean women. However, a multi-centered prospective study is needed for further evaluation.

Trends in the Use of Chemotherapy before and after Radical Cystectomy in Patients with Muscle-invasive Bladder Cancer in Korea

We investigated trends in perioperative chemotherapy use, and determined factors associated with neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC) use in Korean patients with muscle-invasive bladder cancer (MIBC). We recruited 1,324 patients who had MIBC without nodal invasion or metastases and had undergone radical cystectomies (RC) between 2003 and 2013. The study's cut-off time for AC was three months after surgery, and the study's timespan was divided into three periods based on NAC use, namely, 2003-2005, 2006-2009, and 2010-2013. Complete remission was defined as histologically confirmed T0N0M0 after RC. NAC and AC were administered to 7.3% and 18.1% of the patients, respectively. The median time interval between completing NAC and undergoing RC was 32 days and the mean number of cycles was 3.2. The median time interval between RC and AC was 43 days and the mean number of cycles was 4.1. Gemcitabine and cisplatin were most frequently used in combination for NAC (49.0%) and AC (74.9%). NAC use increased significantly from 4.6% between 2003 and 2005 to 8.4% between 2010 and 2013 (P < 0.05), but AC use did not increase. Only 1.9% of patients received NAC and AC. Complete remission after NAC was achieved in 12 patients (12.5%). Multivariable modeling revealed that an advanced age, the earliest time period analyzed, and clinical tumor stage < or = cT2 bladder cancer were negatively associated with NAC use (P < 0.05). While NAC use has slowly increased over time, it remains an underutilized therapeutic approach in Korean clinical practice.

Low Rates of Additional Cancer Detection by Magnetic Resonance Imaging in Newly Diagnosed Breast Cancer Patients Who Undergo Preoperative Mammography and Ultrasonography / 한국유방암학회지

PURPOSE: We evaluated the efficacy of breast magnetic resonance imaging (MRI) for detecting additional malignancies in breast cancer patients newly diagnosed by breast ultrasonography and mammography. METHODS: We retrospectively reviewed the records of 1,038 breast cancer patients who underwent preoperative mammography, bilateral breast ultrasonography, and subsequent breast MRI between August 2007 and December 2010 at single institution in Korea. MRI-detected additional lesions were defined as those lesions detected by breast MRI that were previously undetected by mammography and ultrasonography and which would otherwise have not been identified. RESULTS: Among the 1,038 cases, 228 additional lesions (22.0%) and 30 additional malignancies (2.9%) were detected by breast MRI. Of these 228 lesions, 109 were suspected to be malignant (Breast Imaging-Reporting and Data System category 4 or 5) on breast MRI and second-look ultrasonography and 30 were pathologically confirmed to be malignant (13.2%). Of these 30 lesions, 21 were ipsilateral to the main lesion and nine were contralateral. Fourteen lesions were in situ carcinomas and 16 were invasive carcinomas. The positive predictive value of breast MRI was 27.5% (30/109). No clinicopathological factors were significantly associated with additional malignant foci. CONCLUSION: Breast MRI was useful in detecting additional malignancy in a small number of patients who underwent ultrasonography and mammography.

Validation of a Scoring System for Predicting Malignancy in Patients Diagnosed with Atypical Ductal Hyperplasia Using an Ultrasound-Guided Core Needle Biopsy / 한국유방암학회지

PURPOSE: The need for surgical excision in patients with ultrasound-guided core needle biopsy (CNB)-diagnosed atypical ductal hyperplasia (ADH) remains an issue of debate. The present study sought to validate a scoring system (the U score, for underestimation) that we have previously developed for predicting malignancy in CNB-diagnosed ADH. METHODS: The study prospectively enrolled 85 female patients with CNB-diagnosed ADH who underwent subsequent surgical excision. Underestimation was defined as a surgical specimen having malignant foci. RESULTS: The overall underestimation rate was 37% (31/85). Multivariate analysis showed that a clinically palpable mass, microcalcification on imaging, size >15 mm and a patient age of > or =50 years were independently associated with underestimation. When applied to the scoring system, the validation score was significant (p<0.001; area under the curve, 0.852). No patient with a U score <3.5 had an underestimated lesion. CONCLUSION: The present study successfully validated the efficacy of our scoring system for predicting malignancy in CNB-diagnosed ADH. A U score of < or =3.5 indicates that surgical excision may not be necessary.

Clinical Significance of Annexin A1 Expression in Breast Cancer / 한국유방암학회지

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.

Clinicopathological Characteristics and Factors Affecting Recurrence of Ductal Carcinoma In Situ in Korean Women / 한국유방암학회지

PURPOSE: As breast cancer screening becomes more popular in Korea, incidence of ductal carcinoma in situ (DCIS) of breast has increased to more than 10% of all breast cancer diagnosed. We aimed to show the clinicopathological characteristics and factors affecting recurrence of DCIS in Korean women. METHODS: We retrospectively reviewed 152 DCIS patients who underwent breast conserving surgery in Seoul National University Hospital between January 1995 and December 2005. RESULTS: Mean age at diagnosis was 46.7 years (24 to 66 years). Mean follow up duration of the patients was 73.82 months (0.80 to 168.43 months). Recurrence of disease occurred in 19 (12.5%) patients: 2 in contralateral breast, 15 in ipsilateral breast, and 2 in axilla. One patient showed ipsilateral breast recur after excision of axillary metastasis. Eight (42.11%) of all recurrence was infiltrating ductal carcinoma and one of them showed bone metastasis during follow up. In an multivariate analysis of factors affecting recurrence, younger age at diagnosis and omission of radiotherapy had significant association with recurrence (p=0.005 and p=0.002, respectively). However, tumor size (p=0.862), microinvasion (p=0.988), histologic grade (p=0.157), estrogen receptor status (p=0.401) and resection margin status (p=0.112) were not significantly correlated with recurrence. There was no breast cancer associated mortality. CONCLUSION: In this study, we found that the younger age at diagnosis and omission of adjuvant radiotherapy are independent predictors of recurrence in Korean DCIS patients.

Laparoscopic Removal of a Vertebral Foreign Body / 대한내시경복강경외과학회지

We report a case of laparoscopic removal of a retained foreign body, a broken surgical instrument, after posterior lumbar decompression and interbody fusion (PLIF) for infection control of the vertebrae. The surgical instrument was broken during PLIF surgery. However, the orthopedic surgeon could not remove the broken instrument because of bleeding and a poor operative view; the surgeon finished the operation leaving the broken surgical instrument in the vertebral body. Plain films revealed a metallic pin-like material at the anterior side of the lumbar vertebral body. Six days later, through a laparoscopic approach, the broken surgical instrument was removed without complication, and the orthopedic surgeon completed the planned operation successfully.

Experience with Enterostomy Closure in Very Low Birth Weight Infants

The survival of Very Low Birth Weight (VLBW) infants has been improved with the advancement of neonatal intensive care. However, the incidence of accompanying gastrointestinal complications such as necrotizing enterocolitis has also been increasing. In intestinal perforation of the newborn, enterostomy with or without intestinal resection is a common practice, but there is no clear indication when to close the enterostomy. To determine the proper timing of enterostomy closure, the medical records of 12 VLBW infants who underwent enterostomy due to intestinal perforation between Jan. 2004 and Jul. 2007 were reviewed retrospectively. Enterostomy was closed when patients were weaned from ventilator, incubator-out and gaining adequate body weight. Pre-operative distal loop contrast radiographs were obtained to confirm the distal passage and complete removal of the contrast media within 24-hours. Until patients reached oral intake, all patients received central-alimentation. The mean gestational age of patients was 26(+2) wks (24(+1)~33(+0) wks) and the mean birth weight was 827 g (490~1450 g). The mean age and the mean body weight at the time of enterostomy formation were 15days (6~38 days) and 888 g (590~1870 g). The mean body weight gain was 18 g/day (14~25 g/day) with enterostomy. Enterostomy closure was performed on the average of 90days (30~123 days) after enterostomy formation. The mean age and the mean body weight were 105 days (43~136 days) and 2487 g (2290~2970 g) at the time of enterostomy closure. The mean body weight gain was 22 g/day after enterostomy closure. Major complications were not observed. In conclusion, the growth in VLBW infants having enterostomy was possible while supporting nutrition with central-alimentation and the enterostomy can be closed safely when the patient's body weights is more than 2.3 kg.

3 Cases of Spontaneous Pregnancies and Deliveries in Turner's syndrome / 대한산부인과학회잡지

Spontaneous pregnancy in Turner's syndrome is very rare because of ovarian dysgenesis and subsequent streak gonads. Recently we experienced 3 cases of pregnancies and deliveries in Turner's syndrome, so we report with a brief review of literature.

3 Cases of Primary Hepatocellular Carcinoma First Detected During Pregnancy / 대한산부인과학회잡지

No abstract available.

The efficacy of fetal genetic diagnosis using fetal nucleated erythrocytes in maternal blood / 대한산부인과학회잡지

OBJECTIVE: The conventional methods to determine fetal genetic status, such as amniocentesis or chorionic villi sampling(CVS) have small procedure-related risk of abortion. Recently, several researchers reported that fetal genetic status, such as sex, can be confirmed by fetal nucleated erythrocytes in maternal blood and this method might reduce such risk. Therefore, in this study, we attempted to determine the basic fetal genetic status, sex, with fetal nucleated erythrocytes. METHODS: In twelve pregnant women who undertook amniocentesis or CVS, 20 ml of venous blood was drawn immediately before the procedure and the nucleated erythrocytes were recovered by magnetic activated cell sorting(MACS). After MACS, DNA was extracted from 200 microliter of sample and single nucleated erythrocyte was obtained by additional procedure, immunostaining, and microdissection. After recovery of nucleated erythrocytes by microdissection, nested polymerase chain reaction(PCR) and fluorescent PCR of amelogenin gene were performed to identify the fetal gender. RESULTS: The DNA of enriched erythrocytes after MACS could identify the fetal gender in the 58.3% of the samples by nested PCR. After the recovery of single nucleated erythrocyte by MACS, immunostaining and microdissection, the minute DNA in a single cell could be amplified by primer extension preamplification(PEP), nested PCR, and fluorescent PCR. Fetal genders were correctly identified in 8 out of 12 (66.7 %). CONCLUSION: Through this study, we could conclude that fetal nucleated erythrocytes in maternal blood might be sufficient sample to determine fetal sex. And single cell isolation by microdissection could get the better results than nested PCR after MACS only. However, in spite of the pregnancy of male fetus, female specific bands were obtained after nested PCR of amelogenin in several cells, which might suggest that part of nucleated erythrocytes in maternal blood might be maternal origin. Therefore, to determine fetal genetic condition by nucleated erythrocytes in maternal blood, further improvements of methods to identify the nucleated erythrocytes of fetal origin are needed.

A Cytogenetic Survey of 1788 Genetic Amniocenteses / 대한산부인과학회잡지

No abstract available.

Clinical Mnaifestations, Management and Obstetrical Outcome of the Pregnant Women with Aplastin Anemia / 대한주산의학회잡지

BACKGROUND: Aplastic anemia is an uncommon disease characterized by marrow hypocellularity, resulting in a reduction of the counts of circulating red blood cells, neutrophils, and platelets. The etiology of aplastic anemia remains unknown in the majority of cases. An association of aplastic anemia with pregnancy has been reported but the strength of such a relationship remains somewhat controversial. OBJECTIVE: To evaluate the association of aplastic anemia with pregnancy and the optimal management of patients with aplastic anemia during pregnancy. METHODS: This retrospective study was done by review of medical records of 18 patients with aplastic anemia, of whom 8 patients were diagnosed before pregnancy and 10 patients were diagnosed during pregnancy, who had a total of 25 pregnancies after the diagnosis from January, 1990 to October, 1997 at the Seoul National University Hospital, RESULTS: The incidence of aplastic anemia during pregnancy was one in 806 persons(18/14, 507) in this study. During pregnancy, the circulating blood cell levels decreased in all pregnancies. In all 7 cases that showed a relapse during pregnancy the remission occurred following the termination of pregnancy. 12 patients presenting with severe aplastic anemia during pregnancy had poorer hematological improvement than patients with mild aplastic anemia after termination of pregnancy. CONCLUSION: In all patients with aplastic anemia during pregnancy the circulating blood cell levels decreased. The successful outcome in these cases illustrates the benefit of modern supportive care in the management of such patients. The present observations suggest that a pregnancy which occurs during the long-term remission of aplastic anemia may be allowed to progress to birth.