Dong Young Noh

The Estimation of Breast Cancer Disease-Probability by Difference of Individual Susceptibility

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.

Oncologic Safety of Immediate Breast Reconstruction for Invasive Breast Cancer Patients: A Matched Case Control Study

Purpose The purpose of this study was to compare locoregional recurrence-free survival (LRFS) and disease-free survival (DFS) between patients undergoing mastectomy and immediate breast reconstruction (IBR) and those undergoing mastectomy alone. Methods A retrospective review of patients who underwent mastectomy and immediate breast reconstruction for resectable invasive breast cancer between 2002 and 2010 at a single center was conducted. These cases were matched to patients who underwent mastectomy alone in the same time period, performed by 1:2 matching. Matching control variables included age, tumor size, axillary lymph node metastasis, and estrogen receptor status. Overall, 189 patients were identified in the IBR group, and 362 patients were matched to this group. Results In the IBR group, 75 patients (39.7%) underwent conventional total mastectomy, 78 (41.3%) underwent skin-sparing mastectomy (SSM), and 36 (19.0%) underwent nipple-sparing mastectomy (NSM). The IBR group was significantly younger than the control group (41.9 and 45.1 years, respectively) (p=0.032), in spite of matching between three age groups. The DFS rates were similar between the IBR group and mastectomy alone group, at 92.0% and 89.9%, respectively, at 5-year follow-up (log-rank test, p=0.496). The 5-year LRFS was 96.2% in the IBR group and 96.4% in the mastectomy alone group (log-rank test, p=0.704), similar to data from previous reports. Subgroup analyses for SSM or NSM patients showed no differences in LRFS and DFS between the two groups. Additionally, in stage III patients, IBR did not cause an increase in recurrence. Conclusion IBR after mastectomy, including both SSM and NSM, had no negative impact on recurrence or patient survival, even in patients with advanced disease.

Risk Factors Associated with Distant Metastasis and Survival Outcomes in Breast Cancer Patients with Locoregional Recurrence

Purpose To decide the optimal treatment for breast cancer patients with locoregional recurrence (LRR), it is important to determine which group has the highest risk of subsequent distant metastasis (DM). We aimed to investigate the factors associated with DM in patients with LRR. Methods We reviewed the data of 208 patients with LRR as the first event after primary surgery for breast cancer at our institution between 1997 and 2010, to identify significant factors associated with DM. Subsequently, Kaplan-Meier curves and the Cox regression method were used to analyze the correlation between clinical factors and survival. Results DM occurred in 33.2% (68/208) of LRR patients. The median DM-free interval was 23 months. Some clinical factors were associated with DM in univariate analysis, including the type of primary surgery (p=0.026), tumor size (p=0.005), nodal status (p=0.011), and administration of initial adjuvant chemotherapy (p=0.001). In addition, regional rather than local recurrence and a disease-free interval (DFI; duration between primary surgery and LRR) ≤30 months were also significant (p<0.001 for both). However, only a shorter DFI reached significance in multiple logistic regression analysis. Cox regression analysis of DM-free survival showed that both a shorter DFI and regional recurrence were significant factors with hazard ratios of 2.1 (95% confidence interval [CI], 1.21-3.65) and 1.85 (95% CI, 1.04-3.28), respectively. Conclusion DFI was the most important factor associated with subsequent DM in patients with LRR as a first event of failure.

Prognostic Influence of BCL2 on Molecular Subtypes of Breast Cancer

Purpose We aimed to reveal the prognostic influence of B-cell CLL/lymphoma 2 (BCL2) on molecular subtypes of breast cancer. Methods We analyzed 9,468 patients with primary breast cancer. We classified molecular subtypes according to the National Comprehensive Cancer Network (NCCN) and St. Gallen guidelines, mainly on the basis of the expression of hormonal receptor (HR), human epidermal growth factor receptor 2 (HER2), and Ki-67. Results Regarding NCCN classification, BCL2 was a strong favorable prognostic factor in the HR(+)/HER2(–) subtype (p<0.001) and a marginally significant favorable prognosticator in the HR(+)/HER2(+) subtype (p=0.046). BCL2 had no prognostic impact on HR(–)/HER2(+) and HR(–)/HER2(–) subtypes. In relation to St. Gallen classification, BCL2 was a strong favorable prognosticator in luminal A and luminal B/HER2(–) subtypes (both p<0.001). BCL2 was a marginally significant prognosticator in the luminal B/HER2(+) subtype (p=0.046), and it was not a significant prognosticator in HER2 or triple negative (TN) subtypes. The prognostic effect of BCL2 was proportional to the stage of breast cancer in HR(+)/HER2(–), HR(+)/HER2(+), and HR(–)/HER2(–) subtypes, but not in HR(–)/HER2(+) subtype. BCL2 was not a prognostic factor in TN breast cancer regardless of epidermal growth factor receptor expression. Conclusion The prognostic influence of BCL2 was different across molecular subtypes of breast cancer, and it was largely dependent on HR, HER2, Ki-67, and the stage of cancer. BCL2 had a strong favorable prognostic impact only in HR(+)/HER2(–) or luminal A and luminal B/HER2(–) subtypes, particularly in advanced stages. Further investigations are needed to verify the prognostic influence of BCL2 on molecular subtypes of breast cancer and to develop clinical applications for prognostication using BCL2.

Prognostic Significance of Inner Quadrant Involvement in Breast Cancer Treated with Neoadjuvant Chemotherapy

Purpose In the present study, we aimed to evaluate the initial tumor location as a prognostic factor in breast cancer patients treated with neoadjuvant chemotherapy (NAC). Methods Between March 2002 and January 2007, a total of 179 patients with stage II/III breast cancer underwent NAC followed by breast surgery. Using physical and radiologic findings, patients were grouped by their initial tumor location into inner/both quadrant (upper/lower inner quadrant involvement +/− multicentric tumor involving outer quadrant; n=97) and outer quadrant (n=82) tumor groups. All patients received neoadjuvant docetaxel/doxorubicin chemotherapy. One hundred two patients underwent modified radical mastectomy and 77 patients underwent breast-conserving surgery. Adjuvant radiotherapy (RT) and hormonal therapy were administered after surgery when indicated. While 156 patients underwent postoperative RT, 23 did not. The median follow-up duration was 61.1 (12–106) months. Results The 5-year disease-free survival (DFS) and overall survival rates of all patients were 74.8% and 89.9%, respectively. Patients with inner/both quadrant tumors had lower 5-year DFS than those with outer quadrant tumors (67.7% vs. 83.4%, respectively; hazard ratio [HR]=1.941, p=0.034). A nodal ratio >25% was also an independent adverse prognostic factor for DFS (HR=3.276; p<0.001). There was no significant difference in DFS (p=0.592) after RT on the internal mammary node (IMN). Treatment failed in 44 out of 179 patients (24.6%), of which 27 patients had inner/both quadrant tumors. Twenty-one out of 27 patients had distant failures. Conclusion Among breast cancer patients treated with NAC, those with inner/both quadrant tumors had lower DFS than those with outer quadrant tumors. More aggressive neoadjuvant and/or adjuvant chemotherapy with IMN RT is required for improved disease control and long-term survival.

Glutathione S-transferase P1 Genetic Polymorphisms and Breast Cancer Risk.

PURPOSE To evaluate the potential association between the GSTP1 genotype and the development of breast cancer, a hospital based case-control study was conducted in South Korea. MATERIALS AND METGODS: The study population consisted of 171 histologically confirmed incidents of breast cancer cases, and 171 age-matched controls with no present, or previous, history of cancer. A PCR method was used for the genotyping analyses, and statistical evaluation was performed by an unconditional logistic regression model. RESULTS No association was observed in the study subjects, or the premenopausal women group with GSTP1 Val allele. However, postmenopausal women with GSTP1 Val allele had a reduced risk of breast cancer (OR=0.3, 95% CI=0.1~0.7). When the data were stratified, by the known risk factors of breast cancer, a significant interaction was observed between the GSTP1 genotype and alcohol consumption (p for interaction = 0.01); women with GSTP1 Val allele, that drank regularly, had a 3.0-fold increased risk of breast cancer (95% CI=1.1~7.9), whereas women with GSTP1 Val allele, that never drink, had protective effects (OR=0.4, 95% CI=0.2~0.8). CONCLUSION Our findings suggest that GSTP1 Ile105Val polymorphism influences the individual susceptibility to breast cancer, and that this effect may be modified by alcohol consumption.

Risk Reduction of Breast Cancer by Childbirth,Breastfeeding, and Their Interaction in Korean Women: Heterogeneous Effects Across Menopausal Status, Hormone Receptor Status, and Pathological Subtypes

Objectives The purpose of this study was to examine the associations of childbirth, breastfeeding, and their interaction with breast cancer (BC) risk reduction, and to evaluate the heterogeneity in the BC risk reduction effects of these factors by menopause, hormone receptor (HR) status, and pathological subtype. Methods BC patients aged 40+ from the Korean Breast Cancer Registry in 2004-2012 and controls from the Health Examinee cohort participants were included in this study after 1:1 matching (12 889 pairs) by age and enrollment year. BC risk according to childbirth, breastfeeding, and their interaction was calculated in logistic regression models using odds ratios (ORs) and 95% confidence intervals (CIs). Results BC risk decreased with childbirth (3+ childbirths relative to 1 childbirth: OR, 0.66; 95% CI, 0.56 to 0.78 and OR, 0.80; 95% CI, 0.68 to 0.95 in postmenopausal and premenopausal women, respectively); and the degree of risk reduction by the number of children was heterogeneous according to menopausal status (p-heterogeneity=0.04), HR status (p-heterogeneity<0.001), and pathological subtype (p-heterogeneity<0.001); whereas breastfeeding for 1-12 months showed a heterogeneous association with BC risk according to menopausal status, with risk reduction only in premenopausal women (p-heterogeneity<0.05). The combination of 2 more childbirths and breastfeeding for ≥13 months had a much stronger BC risk reduction of 49% (OR, 0.51; 95% CI, 0.45 to 0.58). Conclusions This study suggests that the combination of longer breastfeeding and more childbirths reduces BC risk more strongly, and that women who experience both 2 or more childbirths and breastfeed for ≥13 months can reduce their BC risk by about 50%.

Abstract P1-12-13: Factors associated with adherence to adjuvant endocrine therapy in patients with hormone receptor positive breast cancer

Background/Purpose Adjuvant endocrine therapy in patients with hormone receptor positive breast cancer reduces recurrence and mortality, but many patients are non-adherent to anti-hormonal medication. In order to increase the adherence, it is important to know about factors associated with adherence. So we investigated factors associated with adherence to anti-hormonal medication using variable questionnaires. Methods We carried out a cross-sectional survey of a sample of women who underwent surgery due to breast cancer in the Seoul National University Hospital Breast Care Center from 2007 to 2011 and treated with anti-hormonal medication. Questionnaires were sent to 1,000 patients. The questionnaire booklet included the Medication Adherence Report Scale-5(MARS-5), Women’s Health Questionnaire(WHQ), Beliefs about Medicine Questionnaire(BMQ), Satisfaction with Information about Medicines Scale(SIMS). And to identify patient’s clinical characteristics, we reviewed electronic medical records, retrospectively. Result The response rate of questionnaire was 40.8%(408/1000). Of the answered patients, 263 patients were treated with tamoxifen and 145 patients were treated with aromatase inhibitors(AIs). 197 of 408 answered patients(48.3%) were classified as non-adherence. The rate of non-adherence was 132/263(50.1%) and 65/145(44.8%) in patients treated with tamoxifen and AIs. Of the all answered patients, non-adherent patients had more depressed mood (p Conclusion This study showed associations between depressive mood of breast cancer patients treated with anti-hormonal therapy and adherence. And beliefs and satisfaction with information about medication also associated with adherence. To improve adherence, we should evaluate and correct patient’s mood. And we should provide proper information about medications. Citation Format: Jongjin Kim, Wonshik Han, Hyeong-Gon Moon, Min Kyoon Kim, Eunshin Lee, Tae-Kyung Yoo, Han-Byoel Lee, Young Joon Kang, Yun-Gyoung Kim, Tae Ryung Kim, Dong Young Noh. Factors associated with adherence to adjuvant endocrine therapy in patients with hormone receptor positive breast cancer [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 P1-12-13.

Ultrasound Assessment of Invasive Breast Cancer: Correlation with Histologic Grade.

Purpose: To correlate the final assessment of ultrasound and histologic grade in patients with invasive breast cancer. Materials and Methods: The study consisted of one hundred eighty-six women with breast masses that were evaluated by ultrasound and subsequently found to have invasive ductal carcinoma not previously diagnosed. Two radiologists prospectively analyzed the results of the ultrasounds and issued an American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) assessment category which indicates the probability of malignancy. The histologic grade of the 186 invasive ductal carcinomas were separated as follows, low grade in 22 lesions (9%), intermediate grade in 91 lesions (50%), and high grade in 73 lesions (41%). Results: In the 186 invasive ductal carcinomas not previously diagnosed, a circumscribed margin was seen in 4% (three of 73) of high-grade tumors compared to none in intermediate-grade and low-grade tumors. A spiculated margin was seen in 59% (13 of 22) of low-grade tumors compared, to 20% (18 of 91) in intermediate-grade and 7% (five of 73) in high-grade tumors. Posterior acoustic enhancement was seen in 33% (24 of 73) of high-grade tumors compared, to 20% (18 of 91) in intermediate-grade and none in low-grade tumors. Posterior acoustic shadowing was seen in 59% (13 of 22) of low-grade tumors compared, to 34% (31 of 91) in intermediate-grade and 15% (11 of 73) in high-grade tumors. The final BI-RADS assessment of the 186 cases separated as follows, three lesions (2%) were category 3 probably benign, 115 lesions (62%) were category 4 suspicious, and 68 lesions (37%) were category 5 highly suggestive of malignancy. The three cases misclassified as probably benign were high-grade tumors. Conclusion: Breast cancer showing a spiculated margin and posterior acoustic shadowing on ultrasound were mainly low-grade tumors whereas breast cancer showing benign features were high-grade tumors.