Seok Won Kim

Feasibility of Nipple-Sparing Mastectomy with Immediate Breast Reconstruction in Breast Cancer Patients with Tumor-Nipple Distance Less Than 2.0 cm

AbstractBackground and objectivenDebate continues concerning the oncological risk of nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) if the tumor-nipple distance (TND) is less than 2.0xa0cm. In this retrospective study, we analyzed oncological outcomes after NSM with IBR for the treatment of breast cancer to determine the risk posed by NSM in cases in which magnetic resonance imaging (MRI) showed a TND <2.0xa0cm but intraoperative frozen biopsy results were negative for tumor cells at the nipple base.Materials and methodsnWe conducted a retrospective review of patients with breast cancer who underwent NSM with IBR at Samsung Medical Center between 2008 and 2014. Preoperative MRI was done in all cases to define the TND, and frozen biopsy specimens were obtained intraoperatively.ResultsAmong the 266 NSMs performed, TND was <2.0xa0cm in 145 cases (54.5xa0%) and ≥2.0xa0cm in 121 cases (45.5xa0%). Median follow-up was 25.6xa0months. There were no significant differences between the two patient groups with respect to disease-free survival or local recurrence-free survival.ConclusionOur results suggest that NSM can be a feasible treatment option when the intraoperative frozen biopsy is negative for tumor cells even with a TND <2.0xa0cm in MRI.

Prognostic relevance of biological subtype overrides that of TNM staging in breast cancer: discordance between stage and biology.

Recently, we faced difficult treatment decisions regarding appropriate adjuvant systemic treatment, especially for patients who show discordance between stage and tumor biology. The aim of this study was to compare the prognostic relevance of the TNM staging system with that of intrinsic subtype in breast cancer. We retrospectively identified women patients who received curative surgery for stage I–III breast cancer with available data on immunohistochemistry profiles including hormone receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, and Ki 67 staining at the Samsung Medical Center from January 2004 to September 2008. Primary outcomes were recurrence-free survival (RFS) and overall survival (OS). A total of 1145 patients were diagnosed with breast cancer and received curative surgery. Of these, 463 (40.4xa0%) patients were stage I, and 682 (59.6xa0%) were stage II or III. In addition, 701 (61.2xa0%) patients were HR positive, 239 (20.9xa0%) were HER2 positive, and 205 (20.9xa0%) had triple-negative breast cancer. The 5-year RFS for the patients who were HR positive and HER2 negative with a low Ki 67 staining score (0–25xa0%) was 99xa0%. The 5-year RFS for patients who were HER2-positive or had triple-negative breast cancer were 89 and 83xa0%, respectively (P valueu2009=u2009<0.001). In multivariate analysis, advanced stage (II/III) and unfavorable biology (HER2 positive or triple negative) retained their statistical significance as predictors of decreased RFS and OS. Patients with advanced-stage disease (II or III) but favorable tumor biology (HR positive and HER2 negative and low Ki 67) had better clinical outcomes than those with stage I disease and unfavorable tumor biology in terms of RFS (99 versus 92xa0%, P valueu2009=u20090.011) and OS (99 versus 96xa0%, P valueu2009=u20090.03) at 5xa0years. The current results showed that intrinsic subtype has a greater prognostic impact in predicting clinical outcomes in subpopulations of patients with stage I–III breast cancer who show discordance between stage and biologic subtypes.

Sentinel Lymph Node Biopsy Alone after Neoadjuvant Chemotherapy in Patients with Initial Cytology-Proven Axillary Node Metastasis

Purpose Neoadjuvant chemotherapy (NAC) has been recently used to downstage breast cancer. However, in patients with initial axillary lymph node (ALN) metastasis, ALN dissection regardless of the NAC response remains the standard treatment. The purpose of this study was to identify the feasibility and accuracy of sentinel lymph node biopsy (SLNB) after NAC in patients with ALN metastasis at diagnosis. Methods From January 2007 to August 2013, data of patients who were diagnosed with invasive breast cancer and ALN metastasis and treated with NAC followed by definitive surgery in two centers were collected retrospectively. A total of 386 patients were enrolled and classified into five groups according to surgical procedure for the ALNs and pathologic results. Results At SLNB after NAC, sentinel lymph nodes (SLNs) that stained blue or were hot, including suspicious nodes, were identified; the SLN identification and false-negative rates was 96% and 10%, respectively. There was no difference in the overall survival among the groups. For patients who revealed a pathologic complete node response, there was a significant difference in the disease-free survival rate between the SLNB only and complete ALN dissection groups (p=0.031). However, the rate of axillary recurrence demonstrated no significant differences among the groups (p>0.050). Conclusion SLNB after NAC in breast cancer patients with initial ALN metastasis may help identify downstaging to negative nodal status and thereby reduce the surgical morbidity by avoiding standard ALN dissection.

Frequency of pathogenic germline mutation in CHEK2, PALB2, MRE11, and RAD50 in patients at high risk for hereditary breast cancer

PurposeThis study was performed to evaluate the frequency of mutations in CHEK2, PALB2, MRE11, and RAD50 among Korean patients at high risk for hereditary breast cancer.MethodsA total of 235 Korean patients with hereditary breast cancer who tested negative for BRCA1/2 mutation were enrolled to this study. Entire coding regions of CHEK2, PALB2, MRE11, and RAD50 were analyzed using massively parallel sequencing (MPS). Sequence variants detected by MPS were confirmed by Sanger sequencing.ResultsSix patients (2.5xa0%) were found to have pathogenic variants in CHEK2 (nxa0=xa01), PALB2 (nxa0=xa02), MRE11 (nxa0=xa01), and RAD50 (nxa0=xa02). Among the pathogenic variants, PALB2 c.2257C>T was previously reported in other studies, while CHEK2 c.1245dupC, PALB2 c.1048C>T, MRE11 c.1773_1774delAA, RAD50 c.1276C>T, and RAD50 c.3811_3813delGAA were newly identified in this study. A total of 15 missense variants were found in the four genes among 26 patients; 7 patients had a variant in CHEK2, 11 in PALB2, 2 in MRE11, and 6 in RAD50. When in silico analyses were performed to the 15 missense variants, six variants (CHEK2 c.686A>G, PALB2 c.1492G>T, PALB2 c.3054G>C, MRE11 c.140C>T, RAD50 c.1456C>T, and RAD50 c.3790C>T) were predicted to be deleterious.ConclusionsPathogenic variants in CHEK2, PALB2, MRE11, and RAD50 were detected in a small proportion of Korean patients with features of hereditary breast cancer.

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 (3.6xa0%) 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+xa0group also had lower BCSS for T1b than T1c or T2. In the N1 group of tumors smaller than 10xa0mm, 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.

The Protective Effect of Parity in Hormone Receptor-Positive, Ki-67 Expressing Breast Cancer

AbstractBackgroundnEpidemiologic studies showed that the experience of pregnancy is associated with a reduced risk of breast cancer. We hypothesized that parity may differentially be associated with the development of invasive breast cancer by each subtype.MethodsWe reviewed the clinical, radiological, and pathological records of women diagnosed with invasive ductal carcinoma of the breast at Samsung Medical Center between 2005 and 2009. Clinicopathologic results were assessed by χ2 and Fisher’s exact tests with a Bonferroni correction for categorical variables, and by the Kruskal–Wallis test for nonparametric continuous variables. A multinomial logistic regression model was used for multivariate analysis.ResultsAmong a total of 3,095 patients, 283 (9.14xa0%) patients were nulliparous. Older age, higher pN, and expression of HER2 were associated with parity. In the analysis between parity and molecular subtypes, parity also had a variable influence on breast cancer subtypes (pxa0=xa00.032). Intergroup analysis with multiple comparison showed that luminal B subtype was related to nulliparity compared with HER2-positive subtypes (pxa0=xa00.03).ConclusionsThe effect of parity on the development of breast cancer differed by hormone receptor and HER2 expression. It seems that parity might have a protective effect against hormone receptor-positive breast cancer, especially cancers expressing HR+ and Ki-67. Further basic research to define and understand this result is ongoing.

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 40xa0years. Further follow-up studies are necessary to clarify the role of the impact of ABO blood types on prognosis of breast cancer.

Different prognosis of young breast cancer patients in their 20s and 30s depending on subtype: a nationwide study from the Korean Breast Cancer Society

PurposeNumerous studies have demonstrated that breast cancer in young women (BCY) has unfavorable prognostic features and more unfavorable subtypes. However, few studies have evaluated the effect of subtype disparities on breast cancer prognosis by age, especially for BCY. We analyzed breast cancer mortality stratified by tumor subtype according to age among patients younger than 50xa0years.MethodsData from the Korean Breast Cancer Society Registry for patients diagnosed with invasive breast cancer when aged less than 50xa0years between 2003 and 2010 were reviewed retrospectively.ResultsWe identified 30,793 patients with breast cancer who were eligible for analysis. Of these, 793 (2.6%) were aged 20–29 and 8926 (28.8%) were aged 30–39. Median follow-up duration was 84xa0months. Mean age was 42.4xa0years. Patients in their 20s were more likely to have cancer of advanced stage and higher nuclear grade, present with lymphovascular invasion, and have unfavorable subtypes. Patients in the 20s group showed worse prognosis. In multivariate analysis for overall survival (OS), the hazard ratio (HR) for patients in the 20s group was higher than that for the 30s and 40s groups, and patients with triple-negative breast cancer (TNBC) showed higher HR than patients with HER-2 or luminal subtype (all pxa0<xa00.0001). When stratified by subtype, luminal subtype showed significantly worse prognosis in the 20s group than the 30s and 40s groups, whereas HER-2 and TNBC subtypes showed no significant difference.ConclusionPatients in their 20s with breast cancer had unfavorable characteristics and worse prognosis than patients in their 30s and 40s. When stratified by tumor subtype, patients in their 20s with luminal subtype of breast cancer showed worse prognosis than older patients, whereas HER-2 and TNBC subtypes showed no significant differences.

Genetic Diagnosis before Surgery has an Impact on Surgical Decision in BRCA Mutation Carriers with Breast Cancer

BackgroundThe first aim of our study was to evaluate surgical decision-making by BRCA mutation carriers with breast cancer based on the timing of knowledge of their BRCA mutation status. The second aim was to evaluate breast cancer outcome following surgical treatment.MethodsThis was a retrospective study of 164 patients diagnosed with invasive breast cancer, tested for BRCA mutation, and treated with primary surgery between 2004 and 2015xa0at Samsung Medical Center in Seoul, Korea. We reviewed types of surgery and timing of the BRCA test result. We compared surgical decision- making of BRCA carriers with breast cancer based on the timing of knowledge of their BRCA mutation status.ResultsOnly 15 (9.1%) patients knew their BRCA test results before their surgery, and 149 (90.9%) knew the results after surgery. In patients with unilateral cancer, there was a significant difference between groups whose BRCA mutation status known before surgery and groups whose BRCA status unknown before surgery regarding the choice of surgery (pxa0=xa00.017). No significant difference was observed across surgery types of risk of ipsilateral breast tumor recurrence (pxa0=xa00.765) and contralateral breast cancer (pxa0=xa00.69).ConclusionGenetic diagnosis before surgery has an impact on surgical decision choosing unilateral mastectomy or bilateral mastectomy in BRCA mutation carriers with breast cancer. Knowledge about BRCA mutation status after initial surgery led to additional surgeries for patients with BCS. Thus, providing genetic counseling and genetic testing before surgical choice and developing treatment strategies for patients with a high risk of breast cancer are important.

Clinical Characteristics and Prognosis of Pregnancy-Associated Breast Cancer: Poor Survival of Luminal B Subtype

Background: Pregnancy-associated breast cancer (PABC) is rare and is generally defined as breast cancer diagnosed during pregnancy or within 1 year of delivery. The average ages of marriage and childbearing are increasing, and PABC is expected to also increase. This study is intended to increase understanding of the characteristics of PABC. Methods: A database of 2,810 patients with breast cancer diagnosed when they were less than 40 years of age was reviewed. The clinicopathological factors and survival of PABC (40 patients) were compared to those of patients with young breast cancer (YBC, non-pregnant or over 12 months after delivery; 2,770 patients). Results: PABC had significantly lower estrogen receptor (ER) and progesterone receptor (PR) expression (ER-positive 50.0%, PR-positive 45.0%) and higher HER2 overexpression (38.5%) than YBC. The most common subtype of PABC was triple-negative breast cancer (TNBC; 35.9%), and luminal A subtype represented only 7.7% of cases. In univariate analysis, PABC had significantly worse disease-free survival (DFS) and breast cancer-specific survival (BCSS) compared to YBC. In multivariate analysis, PABC was associated with worse BCSS (HR 4.0, 95% CI 1.2–12.9, p = 0.019) and survival, but there was no difference in DFS between PABC and YBC. In subgroup analysis by subtype, luminal B subtype of PABC showed worse DFS (HR 3.5; 95% CI 1.1–11.2, p = 0.039) and BCSS (HR 10.2, 95% CI 1.2–87.1, p = 0.035), especially with high Ki67. However, no differences were demonstrated in other subtypes. Conclusion: In this study, PABC showed lower expression of ER/PR, higher overexpression of HER2, fewer luminal A subtype, and more TNBC subtype compared to YBC. PABC had worse BCSS, especially luminal B subtype, compared to YBC.