Korean Breast Cancer Research Articles

Frequency of germline patghogenic mutation in breast cancer patients at high risk hereditary cancer.

e13110 Background: Next-generation sequencing technology allows the simultaneous sequencing of multiple target genes. We developed a gene panel containing 64 genes which were associated with various hereditary cancers. This study was performed to evaluate the frequency of pathogenic mutations associated with hereditary cancer among Korean patients at high risk hereditary breast cancer using multi-gene sequencing panel. Methods: A total of 252 breast cancer patients with high-risk hereditary cancer were included. Among them, 179 patients (71.0%) had multiple primary cancers including breast cancer, 27 patients (10.7%) were diagnosed with bilateral breast cancer at age 40 or younger. Thirty-five patients (13.9%) had breast cancer family history of more than 2 relatives. With the 64 gene panel, sequence variants were detected by next-generation sequencing technology. Results: Sixty seven patients (26.8%) were found to have 77 germline pathogenic mutations, 12 in BRCA1, 13 in BRCA2, 9 in CDH1, 3 in FH, 5 in MSH2, 2 in MSH6, 4 in NAT1, 6 in PTCH1, 3 in RAD51, 7 in RET, 4 in SPINK1, 3 in TP53 and one each in ALK, BRIP1, CHEK2, MLH2, MUTYH, and PTEN. In 20 patients (4.0%), 2 (n = 9) or 3 (n = 1) pathogenic mutations were detected. In 227 patients with BRCA1/2 negative, CDH1 (n = 7), RET (n = 7), PTCH1 (n = 5), and MSH2 (n = 5) were the most prevalent pathogenic mutations. Conclusions: The 64 gene panel detected germline pathogenic mutations in 26.8% of Korean breast cancer patients with feature of hereditary cancer. Mutations of BRCA1, BRCA2, CDH1, RET, and PTCH1 were the most prevalent variants.Mutation carriers were considered as high risk to develop malignancy and recommended to receive genetic counseling and intensive cancer screening.

Prognostic value of ABO blood types in young patients with breast cancer; a nationwide study in Korean Breast Cancer Society.

The purpose of this study was to investigate the relationship between ABO blood types and breast cancer survival in young Korean patients. This was a retrospective study of 115,474 patients who were surgically treated for primary breast cancer between 1987 and 2011 in Korea. All data were collected by the Korean Breast Cancer Society (KBCS) online breast cancer registry. Each hospital serologically examined the ABO blood types of patients before surgery. There was no significant difference in overall survival (OS) or breast cancer-specific survival (BCSS) among ABO blood types. Type of surgery; T stage; N stage; histologic grade; status of estrogen receptor, progesterone receptor, and HER2; and chemotherapy were significant prognostic factors of OS and BCSS in univariate analysis and multivariate analyses. Compared to women with blood type O, there was a difference in OS and BCSS for blood type A, blood type B, or blood type AB. Compared to blood group non-O, patients with blood group O were more likely to have favorable prognosis when younger than 40years. Further follow-up studies are necessary to clarify the role of the impact of ABO blood types on prognosis of breast cancer.

Longitudinal patterns and associated factors of postdiagnosis weight changes in Korean breast cancer survivors with normal body mass index.

This study aimed to describe longitudinal patterns of weight changes from diagnosis to within 5years after diagnosis and investigate factors associated with short- and long-term weight changes among Korean breast cancer survivors with initially normal body mass index (BMI). Body weights at diagnosis for 1546 breast cancer survivors were compared with those at 12, 24, 36, 48, and 60months after diagnosis. Absolute weight change (kg) and relative weight changes (%) were analyzed. Logistic regression was used to identify factors associated with short-term (1year) and long-term (5years) weight changes. A significant decrease in mean weight was predominant at 12months postdiagnosis. In subgroup analysis, the younger age group showed significant weight gains after 36months. The older age group and chemotherapy (CT) group showed significant weight losses after 24months. About 40% of weight gainers and 60% of weight losers at 12months returned to their initial weight by 60months postdiagnosis. CT and lower educational levels were associated with short-term weight loss and gain, respectively. For long-term changes, age at diagnosis was the sole associated factor. Korean breast cancer survivors treated with CT mainly experienced postdiagnosis weight loss rather than weight gain. Short-term weight change was independently associated with chemotherapy and educational level. However, long-term weight change was associated with age at diagnosis. Breast cancer survivors with normal BMI may be categorized according to the time-dependent risk for postdiagnosis weight change.

Quality of life on TSU-68: Combination of docetaxel and TSU-68, an oral antiangiogenic agent, in patients with metastatic breast cancer previously treated with anthracycline.

The aim of this study is to investigate whether the addition of TSU-68 would affect on the quality of life (QOL) of Korean metastatic breast cancer patients treated with docetaxel. Sixty-three of 78 patients completed the baseline QOL questionnaires and at least one follow-up questionnaire comprising questions from the Korean Functional Assessment of Cancer Therapy-Breast (FACT-B), hospital anxiety and depression scale (HAD), the shortened form of the profile of mood states (BPOMS), and anticipation and anxiety for treatment scale. Changes in QOL scores from baseline were compared by analysis of covariance at each time point (6, 12 weeks, 9, 12 and 18 months) and at the end of treatment (EOT), and the longitudinal changes over time were evaluated by repeated measure analysis. The two-treatment groups (TSU-68 plus docetaxel [A] vs docetaxel alone [B]) were well balanced regarding sociodemographic characteristics, including age (P = 0.450), religion (P = 1.000), education (P = 0.257), ECOG performance status (P = 0.261), and employment status (P = 0.325). The return rate at EOT was 61.9%. In analyses at each QOL measuring time, A group showed a higher FACT-B total score and FACT-G score than B at 12 months (P = 0.031 and P = 0.024, respectively). The anticipation and anxiety for treatment scale of A group was higher than that of B at 12 weeks and EOT (P = 0.046 and P = 0.022, respectively). However, repeated measure analysis for longitudinal changes over time showed no significant group wise differences. The combination of TSU-68 with docetaxel showed no additional adverse effects on patient QOL during the study period, as compared with docetaxel monotherapy.

P008 - Longitudinal patterns of postdiagnosis weight changes according to adjuvant systemic treatments in Korean breast cancer survivors

P008 - Longitudinal patterns of postdiagnosis weight changes according to adjuvant systemic treatments in Korean breast cancer survivors

P009 - Association between patient beliefs about endocrine therapy and medication adherence in Korean breast cancer survivors

P009 - Association between patient beliefs about endocrine therapy and medication adherence in Korean breast cancer survivors

Abstract P5-16-25: Serum 25-hydroxyvitamin D levels and oncologic outcomes of breast cancer patients receiving neoadjuvant chemotherapy

Abstract Background:According to prior studies, the role of serum vitamin D3 has been inconsistentand clinical implications of 25-hyrdoxyvitamin D (25-OHD) have been little studiedin breast cancer patients receiving neoadjuvant chemotherapy (NCT). Objectives: The aims of study were to investigate changes in 25-OHD levels before and after NCT and to determine the association of 25-OHD and oncologic outcomes including pathological complete response (pCR) in breast cancer patients. Patients and Materials: From January 2010 to December 2013, serum 25-OHD levels at pre- and post-NCT were measured in 377 breast cancer patients. The association of serum 25-OHD levels with clinicopathological data including breast cancer subtypes, pCR and survival were retrospectively analysed. Delta 25-OHD was calculated as serum 25-OHDlevels before minus after NCT. Results: Mean ageof study population was 48.7 yearsand mean follow-up periods were 35.9months.Mean baseline serum 25-OHD concentration was 14.60 ng/mL (standard deviation, 7.44) and more than 80% of patients showed insufficient 25-OHD levels. The mean 25-OHDat post-NCT was 12.16 ng/mL (standard deviation, 6.87).There was a significant decrease in serum 25-OHD after NACT (p<0.001).The pCR rates were 25.7% among study cohort.However, 25-OHD levels at baseline and post-NCT were not related to pCR and survival outcomes. No associations were found between pCR and delta 25-OHD. According to stratification by breast cancer subtypes, however, patients with ≥ -2.67 (median value) of delta 25-OHD revealed a trend of higher achievement of pCR and better survival in luminal A subtype. No associations were found among the other subtypes. Conclusions: Many Korean breast cancer patients showed insufficient serum 25-OHD levels at diagnosis of malignancy and a significant decrease in serum vitamin D3 after NACT was observed.No significant association of 25-OHD 3 with pCR and survival was found. Therefore, correction or maintenance of appropriate serum 25-OHD levels should be focused for bone health as comprehensive management of breast cancer during NCT.In addition, possible oncological aspects of 25-OHD should further researched individually considering breast subtypes. Citation Format: Park S, Lee JS, Kim JH, Lim SM, Park HS, Kim SI. Serum 25-hydroxyvitamin D levels and oncologic outcomes of breast cancer patients receiving neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-25.

Abstract P5-13-15: Longitudinal patterns of postdiagnosis weight changes according to adjuvant systemic treatments in Korean breast cancer survivors

Abstract This abstract was withdrawn by the authors.

Education Level Is a Strong Prognosticator in the Subgroup Aged More Than 50 Years Regardless of the Molecular Subtype of Breast Cancer: A Study Based on the Nationwide Korean Breast Cancer Registry Database.

PurposeThis study investigated the role of the education level (EL) as a prognostic factor for breast cancer and analyzed the relationship between the EL and various confounding factors.Materials and MethodsThe data for 64,129 primary breast cancer patients from the Korean Breast Cancer Registry were analyzed. The EL was classified into two groups according to the education period; the high EL group (≥ 12 years) and low EL group (< 12 years). Survival analyses were performed with respect to the overall survival between the two groups.ResultsA high EL conferred a superior prognosis compared to a low EL in the subgroup aged > 50 years (hazard ratio, 0.626; 95% confidence interval [CI], 0.577 to 0.678) but not in the subgroup aged ≤ 50 years (hazard ratio, 0.941; 95% CI, 0.865 to 1.024). The EL was a significant independent factor in the subgroup aged > 50 years according to multivariate analyses. The high EL group showed more favorable clinicopathologic features and a higher proportion of patients in this group received lumpectomy, radiation therapy, and endocrine therapy. In the high EL group, a higher proportion of patients received chemotherapy in the subgroups with unfavorable clinicopathologic features. The EL was a significant prognosticator across all molecular subtypes of breast cancer.ConclusionThe EL is a strong independent prognostic factor for breast cancer in the subgroup aged > 50 years regardless of the molecular subtype, but not in the subgroup aged ≤ 50 years. Favorable clinicopathologic features and active treatments can explain the main causality of the superior prognosis in the high EL group.

Poor Prognosis of Lower Inner Quadrant in Lymph Node–negative Breast Cancer Patients Who Received No Chemotherapy: A Study Based on Nationwide Korean Breast Cancer Registry Database

BackgroundWe aimed to investigate the prognostic influence of primary tumor site on the survival of patients with breast cancer. Patients and MethodsData of 63,388 patients with primary breast cancer from the Korean Breast Cancer Registry were analyzed. Primary tumor sites were classified into 5 groups: upper outer quadrant, lower outer quadrant, upper inner quadrant, lower inner quadrant (LIQ), and central portion. We analyzed overall survival (OS) and breast cancer–specific survival (BCSS) according to primary tumor site. ResultsCentral portion and LIQ showed lower survival rates regarding both OS and BCSS compared with the other 3 quadrants (all P < .05) and hazard ratios were 1.267 (95% CI, 1.180-1.360, P < .001) and 1.215 (95% CI, 1.097-1.345, P < .001), respectively. Although central portion showed more unfavorable clinicopathologic features, LIQ showed more favorable features than the other 3 quadrants. Primary tumor site was a significant factor in univariate and multivariate analyses for OS and BCSS (all P < .001). For lymph node–negative patients, LIQ showed a worse OS than the other primary tumor sites in the subgroup with no chemotherapy (P < .001), but that effect disappeared in the subgroup with chemotherapy (P = .058). ConclusionLIQ showed a worse prognosis despite having more favorable clinicopathologic features than other tumor locations and it was more prominent for lymph node–negative patients who received no chemotherapy. The hypothesis of possible hidden internal mammary node metastasis could be suggested to play a key role in LIQ lesions.

Fertility Rates in Young Korean Breast Cancer Patients Treated with Gonadotropin-Releasing Hormone and Chemotherapy.

PurposeGonadotropin-releasing hormone (GnRH) agonists have been used with adjuvant chemotherapy to protect ovarian function. However, there are no data on the actual pregnancy rates among young breast cancer patients receiving GnRH agonists and concurrent chemotherapy in Korea.MethodsAmong patients who underwent surgery from January 2002 to April 2012, premenopausal patients aged between 20 and 40 years were included in the analysis. We retrospectively reviewed clinicopathologic features (e.g., age, obstetric and menstruation history), recurrence, and survival status. The rate of resumption of menstruation was calculated in all patients. In the married group, pregnancy and delivery rates were also recorded.ResultsAmong 101 patients, 19 were lost to follow-up and 82 were eligible for the analysis. Among them, 31 were married, 10 of 51 got married, and 41 remained unmarried through the follow-up period. Among the married patients, 15 became pregnant and gave birth to 19 babies, whereas 26 did not become pregnant. The pregnancy rate in the married group was 50.0% (15/30). Three of 15 pregnancies (20.0%) were multiparous. Most of the delivered babies were healthy and 80.0% of patients had no problems breastfeeding (12/15). More than half the patients in all groups recovered menstrual status within 12 months.ConclusionFifty percent of young breast cancer patients who attempted pregnancy succeeded in pregnancy after adjuvant chemotherapy and GnRH agonists. Further studies that include control groups are required to confirm whether the use of GnRH agonists improves pregnancy.

Development of second primary cancer in Korean breast cancer survivors.

PurposeBreast cancer survivors have slightly increased the risk of second primary cancers. Breast, colon, uterine, and ovarian cancers are common secondary cancers in breast cancer survivors. In this study, we assessed the development of second primary cancers of breast cancer survivors in Korea.MethodsMedical records of patients with breast cancer in 3 tertiary medical institutions were reviewed retrospectively. We evaluated secondary malignancy diagnosed at least 2 months after the breast cancer diagnosis. Based on the International Classification of Disease-9 codes of malignancies, secondary primary breast cancer records were evaluated with person-year adjustment. The standardized incidence ratio (SIR) was assessed using national cancer incidence.ResultsA total of 3,444 treatment records were included from 3 medical centers. The cumulative incidence of overall second primary cancers was 2.8% (n = 93). The SIR was significantly higher in all sites (1.56; 95% confidence interval [CI], 1.26–1.91), endometrial cancer (5.65; 95% CI, 2.06–12.31), biliary tract cancer (3.96; 95% CI, 1.19–8.60), and thyroid cancer (2.29; 95% CI, 1.67–3.08).ConclusionThe incidence of cancer was higher in breast cancer survivors compared to general population. Surveillance of secondary cancer in this group should be recommended individually considering the benefit related to the prognosis of primary breast cancer.

Clinicopathologic Characteristics of Pregnancy-Associated Breast Cancer: Results of Analysis of a Nationwide Breast Cancer Registry Database

PurposeThis study aimed to evaluate the clinicopathological characteristics of pregnancy-associated breast cancer (PABC) in comparison with non-pregnancy associated breast cancer (non-PABC).MethodsA total of 344 eligible patients with PABC were identified in the Korean Breast Cancer Society Registry database. PABC was defined as ductal carcinoma in situ, invasive ductal carcinoma, or invasive lobular carcinoma diagnosed during pregnancy or within 1 year after the birth of a child. Patients with non-PABC were selected from the same database using a 1:2 matching method. The matching variables were operation, age, and initial stage.ResultsPatients with PABC had significantly lower survival rates than patient with non-PABC (10-year survival rate: PABC, 76.4%; non-PABC, 85.1%; p=0.011). PABC patients had higher histologic grade and were more frequently hormone receptor negative than non-PABC patients. Being overweight (body mass index [BMI], ≥23 kg/m2), early menarche (≤13 years), late age at first childbirth (≥30 years), and a family history of breast cancer were more common in the PABC group than in the non-PABC group. Multivariate analysis showed the following factors to be significantly associated with PABC (vs. non-PABC): early menarche (odds ratio [OR], 2.165; 95% confidence interval [CI], 1.566–2.994; p<0.001), late age at first childbirth (OR, 2.446; 95% CI, 1.722–3.473; p<0.001), and being overweight (OR, 1.389; 95% CI, 1.007–1.917; p=0.045).ConclusionEarly menarche, late age at first childbirth, and BMI ≥23 kg/m2 were more associated with PABC than non-PABC.

Basic Facts of Breast Cancer in Korea in 2014: The 10-Year Overall Survival Progress.

We, the Korean Breast Cancer Society (KBCS), present the facts and the trends of breast cancer in Korea in 2014. Data on the total number of newly diagnosed patients was obtained from the Korea Central Cancer Registry database, other data were collected from the KBCS online registry database, and the overall survival data of patients were updated from Statistics Korea. A total of 21,484 female patients were newly diagnosed with breast cancer in 2014. The crude incidence rate and the age-standardized incidence rate (ASR) of breast cancer in female patients, including carcinoma in situ, were 83.4 cases and 63.9 cases per 100,000 women, respectively. The ASR showed an annual increase of 6.1% from 1999 to 2014; however, although the increase of the ASR had slowed since 2008, the incidence rate itself continuously increased. The proportion of early breast cancer increased consistently, and the pathological features changed accordingly. While breast-conserving surgery was mainly performed, the proportion of total mastectomy was slightly increased. The total number of breast reconstruction surgeries increased rapidly. The 5-year and 10-year overall survival rates for all stages of breast cancer patients were 91.2% and 84.8%, respectively. The overall survival rate of Korean patients with breast cancer was extremely high, compared with other developed countries. Thus, we consider that the clinical characteristics of breast cancer have changed over the past decade. A nationwide registry data will contribute to a better understanding of the characteristics of breast cancer in Korea.

Meeting Highlights: The Second Consensus Conference for Breast Cancer Treatment in Korea.

The Korean clinical practice guideline recently developed by the Korean Breast Cancer Society to address the national clinical situation is currently under revision ahead of a seventh recommendation. A second consensus conference was held to further develop this guideline by soliciting opinions regarding important issues related to surgery, radiotherapy, and medical oncology. Several issues were discussed, and the discussion progressed to pros and cons in the context of cases in various clinical situations. The panels discussed and voted on issues regarding surgical treatment for non-axillary regional lymph nodes, regional nodal irradiation of pN1 disease, and ovarian functional suppression (OFS) as an adjuvant treatment in premenopausal patients with hormone receptor-positive breast cancer. Regarding the surgical treatment of non-axillary regional lymph node, most panelists agreed with the recommendation of preoperative chemotherapy and postoperative radiotherapy for patients with biopsy-diagnosed metastases, whereas surgery or radiotherapy of non-axillary regional lymph nodes was suggested for clinical partial responders. Discussions on radiotherapy addressed the need for adjuvant radiotherapy and radiation field of regional lymph node in the context of various N1 breast cancer cases. The participants reached a consensus to recommend that N1 patients should receive regional nodal irradiation for a large tumor burden (e.g., three positive nodes, perinodal extension, or large primary tumor). Finally, the panels favored OFS in addition to endocrine therapy for premenopausal women with high risk factors such as a large tumor size, involvement of more than three nodes, and a high histologic grade.

유방암 생존자들의 자가관리에 대한 현상학적 연구: 비약물적 접근방법을 중심으로

본 연구는 현상학적 방법을 적용하여 유방암 생존자들의 비약물적 추후 관리 경험에 대한 본질적 구조와 의미에 대해 심도 있게 파악하는 것을 목적으로 한다. 이번 연구에서 총 참여자는 10명으로 S시 E병원 외래에 정기적으로 내원하는 유방암 생존자로 수술, 화학요법, 방사선요법을 완료한 자들이었다. 자료수집 기간은 2014년 8월부터 2015년 2월까지로 수집된 자료는 심층면담 후 Colaizzi의 방법 적용하여 분석하였다. 연구결과, 7개의 주제와 16개의 하위범주가 도출되었다. 7개의 주제는 '1. 증상을 완화하기 위해 용이한 방법을 적용함, 2. 변화된 신체 상태를 위해 움직이려 함, 3. 재발 방지를 위해 특정 식용 작물을 섭취함, 4. 건강을 유지하기 위한 식생활 양식이 있음, 5. 보완대체요법에 대해 항상 예의주시함, 6. 주치의 처방외 필요한 치료가 있음, 7. 자연친화적인 환경에서의 삶을 지향함' 이었다. 이번 연구는 유방암 생존자들이 치료 후에 일상생활에서 어떻게 추후관리를 하는지 심도있게 파악하는 데 도움을 줄 것이다. 나아가 본 결과는 향후 유방암 생존자들에게 실제 관리 양식에 근거한 실행 가능한 지침과 프로그램을 제공하는데 있어 기초자료로써 제공될 것이다. The purpose of this study was to understand the essential structure and meaning of self-management intervention for breast cancer survivors by using non-pharmacological approaches. The study participants were 10 breast cancer survivors who were completing cancer treatment that involved surgery, chemotherapy, and radiation therapy. Data collected between August 2014 and February 2015 at E Hospital in S city were analyzed by using Colaizzi's phenomenological method. Outcomes were classified into seven essential themes: 1) application of comfort measures to alleviate ongoing symptoms, 2) movement to change physical conditions, 3) special herbal intake to prevent recurrence, 4) a specially designed diet plan for health self-management, 5) constant awareness of complementary and alternative medicine, 6) unmet needs treated by one's own doctor's prescription, and 7) future life toward a nature-friendly environment. The study results contribute to a deeper understanding of self-management interventions in the daily lives of Korean breast cancer survivors. In addition, results provide an essential resource, based on actual self-management styles, that will help survivors to obtain guidance and participate in appropriate programs.

Detection of Human Papillomavirus in Korean Breast Cancer Patients by Real-Time Polymerase Chain Reaction and Meta-Analysis of Human Papillomavirus and Breast Cancer.

BackgroundHuman papillomavirus (HPV) is a well-established oncogenic virus of cervical, anogenital, and oropharyngeal cancer. Various subtypes of HPV have been detected in 0% to 60% of breast cancers. The roles of HPV in the carcinogenesis of breast cancer remain controversial. This study was performed to determine the prevalence of HPV-positive breast cancer in Korean patients and to evaluate the possibility of carcinogenic effect of HPV on breast.MethodsMeta-analysis was performed in 22 case-control studies for HPV infection in breast cancer. A total of 123 breast cancers, nine intraductal papillomas and 13 nipple tissues of patients with proven cervical HPV infection were tested by real-time polymerase chain reaction to detect 28 subtypes of HPV. Breast cancers were composed of 106 formalin-fixed and paraffin embedded (FFPE) breast cancer samples and 17 touch imprint cytology samples of breast cancers.ResultsThe overall odds ratio between breast cancer and HPV infection was 5.43 (95% confidence interval, 3.24 to 9.12) with I² = 34.5% in meta-analysis of published studies with case-control setting and it was statistically significant. HPV was detected in 22 cases of breast cancers (17.9%) and two cases of intaductal papillomas (22.2%). However, these cases had weak positivity.ConclusionsThese results failed to serve as significant evidence to support the relationship between HPV and breast cancer. Further study with larger epidemiologic population is merited to determine the relationship between HPV and breast cancer.

Association between basal-like phenotype and BRCA1/2 germline mutations in Korean breast cancer patients.

BRCA mutation testing allows index patients and their families to be provided with appropriate cancer risk-reduction strategies. Because of the low prevalence of BRCA mutations in unselected breast cancer patients and the high cost of genetic testing, it is important to identify the subset of women who are likely to carry BRCA mutations. In the present study, we examined the association between BRCA1/2 germline mutations and the immunohistochemical features of breast cancer. In a retrospective review of 498 breast cancer patients who had undergone BRCA testing at Seoul National University Bundang Hospital between July 2003 and September 2012, we gathered immunohistochemical information on estrogen receptor (er), progesterone receptor (pr), her2 (human epidermal growth factor receptor 2), cytokeratin 5/6, egfr (epidermal growth factor receptor), and p53 status. Among the 411 patients eligible for the study, 50 (12.2%) had germline mutations in BRCA1 or BRCA2. Of the 93 patients with triple-negative breast cancer (tnbc), 25 with BRCA1/2 mutations were identified (BRCA1, 20.4%; BRCA2, 6.5%). On univariate analysis, er, pr, cytokeratin 5/6, egfr, and tnbc were found to be related to BRCA1 mutations, but on multivariate analysis, only tnbc was significantly associated with BRCA1 mutations. Among patients with early-onset breast cancer or with a family history of breast or ovarian cancer, BRCA1 mutations were significantly more prevalent in the tnbc group than in the non-tnbc group. In the present study, tnbc was the only independent predictor of BRCA1 mutation in patients at high risk of hereditary breast and ovarian cancers. Other histologic features of basal-like breast cancer did not improve the estimate of BRCA1 mutation risk.

Clinically Significant Unclassified Variants in BRCA1 and BRCA2 genes among Korean Breast Cancer Patients.

PurposeUnclassified variants (UVs) of BRCA1 and BRCA2 genes are not defined as pathogenic for breast cancer, and their clinical significance currently remains undefined. Therefore, this study was conducted to identify potentially pathogenic UVs by comparing their prevalence between breast cancer patients and controls.Materials and MethodsA total of 328 breast cancer patients underwent BRCA1/2 genetic screening at the National Cancer Center of Korea. Genetic variants of BRCA genes that were categorized as unclassified according to the Breast Cancer Information Core database were selected based on allelic frequency, after which candidate variants were genotyped in 421 healthy controls. We also examined family members of the study participants. Finally, the effects of amino acid substitutions on protein structure and function were predicted in silico.ResultsGenetic tests revealed 33 UVs in BRCA1 and 47 in BRCA2. Among 15 candidates genotyped in healthy controls, c.5339T>C in BRCA1 and c.6029T>G, c.7522G>A in BRCA2 were not detected. Moreover, the c.5339T>C variant in the BRCA1 gene was detected in four patients with a family history of breast cancer. This nonsynonymous variant (Leu1780Pro) in the BRCA1 C-terminal domain was predicted to have an effect on BRCA1 protein structure/function.ConclusionThis study showed that comparison of genotype frequency between cases and controls could help identify UVs of BRCA genes that are potentially pathogenic. Moreover, ourfindings suggest that c.5339T>C in BRCA1 might be a pathogenic variant for patients and their families.

Breast cancer-specific mortality in small-sized tumor with node-positive breast cancer: a nation-wide study in Korean breast cancer society.

Tumor size and number of lymph node (LN) metastases are well known as the most important prognostic factors of breast cancer. We hypothesized that very small breast cancers with LN metastasis represent a progressive biologic behavior and evaluated tumor size stratified by LN metastasis. Data between 1990 and 2010 were obtained retrospectively from the Korean Breast Cancer Society Registry with inclusion criteria of female, non-metastatic, unilateral, and T1/2 breast cancer. We collected the following variables: age at surgery, tumor size, number of LN metastases, nuclear grade (NG), lymphovascular invasion (LVI), estrogen receptor status, progesterone receptor status, and epidermal growth factor receptor-2 status. Patient characteristics were compared by means of independent t-tests for continuous variables and the Chi-square or Fisher's exact test for categorical variables. Kaplan-Meier curves, with corresponding results of log-rank tests, were constructed for breast cancer-specific survival (BCSS). Five- and eight-year breast cancer-specific mortality (BCSM) was obtained in groups of 300 patients, followed by smoothing according to the confidence interval using the lowess method. We identified 39,826 breast cancer patients who met the inclusion criteria. Among them, 1433 (3.6%) patients died due to breast cancer. The median follow-up duration was 63.4 (3-255) months. In the multivariate analysis, age at surgery, NG, LVI, subtype, and tumor size-nodal interactions were independently associated with BCSM. The N1 group had lower BCSS for T1a than T1b. The N2+group also had lower BCSS for T1b than T1c or T2. In the N1 group of tumors smaller than 10mm, 5- and 8-year BCSM decreased with larger tumor size. Patients with very small tumors with LN metastasis have decreased BCSM according to increase tumor size. Small tumors with LN metastasis could have aggressive biological behavior.