Jai Min Ryu

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.

Adjuvant endocrine therapy alone in patients with node-positive, luminal A type breast cancer

Abstract Luminal A breast cancer has a much better prognosis than other subtypes, with a low risk of local or regional recurrence. However, there is controversy around under- versus overtreatment with regard to adjuvant treatment of node-positive, luminal A breast cancer. The purpose of this study was to identify whether adjuvant systemic chemotherapy has any benefit in node-positive, luminal A breast cancer and to evaluate feasibility of endocrine therapy without chemotherapy in this group. This was a retrospective study of 11,025 patients who were surgically treated for invasive breast cancer at Samsung Medical Center between January 2004 and December 2013. Luminal A subtype was defined as ER+, HER2-, and Ki-67 < 14%. We compared AC based (AC: doxorubicin or epirubicin, plus cyclophosphamide) adjuvant chemotherapy versus endocrine therapy without chemotherapy in patients with node-positive, luminal A breast cancer. We performed 1: n matching, with a maximum n of 8 on endocrine therapy group (nu200a=u200a50) to chemotherapy group (nu200a=u200a642). The median age of the patients in each group at the time of surgery was 58.3u200a±u200a9.5 years in the chemotherapy group and 58.7u200a±u200a11.7 in the endocrine therapy only group. The median follow-up time was 51.9 months (range, 1–125 months). In multivariable analysis, omission of adjuvant chemotherapy in luminal A cancer had no influence on OS and DFS. Axillary lymph node metastasis and progesterone receptor (PR) status were significantly different between the endocrine therapy alone group and the chemotherapy group in terms of OS. Nuclear grade, PR status, and adjuvant radiotherapy were significantly different between the endocrine therapy alone group and the chemotherapy group with regard to DFS. In survival analysis, there were no differences in OS (Pu200a=u200a.137) and DFS (Pu200a=u200a.225) between the 2 groups. Adjuvant chemotherapy could provide little benefit to postmenopausal patients with luminal A, node-positive breast cancer, and endocrine therapy alone may help reduce morbidity. Future studies with a large number of patients and longer follow-up time are necessary to determine whether chemotherapy might be avoided in this patient population.

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

Purpose Gonadotropin-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. Methods Among 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. Results Among 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. Conclusion Fifty 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.

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.

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.

A predictive model for high/low risk group according to oncotype DX recurrence score using machine learning

BACKGROUNDnOncotype DX(ODX) is a 21-gene breast cancer recurrence score(RS) assay that aids in decision-making for chemotherapy in early-stage hormone receptor-positive(HR+)breast cancer. We developed a prediction tool using machine learning for high- or low-risk ODX criteria (i.e., RSxa0<xa011 for low-risk; RSxa0>xa025 for high-risk).nnnMETHODSnWe performed a retrospective review of 301 breast cancer patients who underwent surgery between April 2011 and July 2017 and then an ODX test at Samsung Medical Center in Seoul, Korea. Among them, 208 cases were defined as the modeling group and 76 cases were defined as the validation group. We built a supervised machine learning classification model using the Azure ML platform.nnnRESULTSnFor the high RS group, accuracy was 0.903 through Two-class Decision Jungle method in test set. For the low RS group, the accuracy was 0.726 when the Two-class Neural Network method was applied. The AUC of the ROC curve was 0.917 in the high RS group and 0.744 in the low RS group in test set. In addition, we conducted an internal validation using 76 patients who underwent ODX testing between January 2017 and July 2017. The accuracy of validation was 0.880 in the high RS group and 0.790 in the low RS group.nnnCONCLUSIONnWe developed a predictive model using machine learning that could represent a useful and easy-to-access tool for the selection of high ODX RS patients. After additional evaluation with large data and external validation, worldwide use of our model could be expected.

Only estrogen receptor “positive” is not enough to predict the prognosis of breast cancer

PurposeBeginning in 2018, biomarkers including estrogen receptor (ER) status were incorporated in the 8th AJCC staging system. ER expression levels were not considered in these changes. We hypothesized that the levels of ER expression could affect the prognosis of breast cancer.MethodsA retrospective review was conducted to identify all female patients with invasive breast cancer between 2003 and 2012. ER negative (group I), weakly ER-positive (group II), and strongly ER-positive (group III) were defined as Allred total scores of 0–2, 3–5, and 6–8, respectively. We examined a multigene panel, designated the BCT score, which is a newly developed prognostic model for predicting the risk of a distant metastasis.ResultsAmong the 4949 patients enrolled in this study, 1310 (26.5%), 361 (7.3%), and 3277 (66.2%) were categorized as group I, II, and III, respectively. Median F/U duration was 57.8 months. Compared to group III, patients in group II were younger, had larger tumors, and were also more likely to have PR-negative tumors, HER-2 amplification, high Ki-67, and high nuclear grade. Between group II and III, there was a significant difference in OS (Pu2009=u20090.0764, 0.909, and 0.010, respectively). After adjusting for additional factors that may affect OS, the HR for OS showed higher in group II than in group III. The baseline median BCT score indicated that lower ER expression was associated with significantly higher BCT score (Pu2009<u20090.0001) and significantly more likely to have high risk group (Pu2009<u20090.0001) relative to higher levels of ER expression group.ConclusionER expression levels affect the prognosis of breast cancer. The risk for patients with weakly ER-positive breast cancer should not be underestimated.

Conditional disease-free survival among patients with breast cancer.

Abstract Conditional disease-free survival (CDFS) reflects changes over time. Because traditional disease-free survival (DFS) is estimated from the date of diagnosis, it is limited in the ability to predict risk of recurrence in patients who have been disease free. In this study, we determined CDFS of breast cancer patients and estimated the prognostic factors for DFS. We retrospectively reviewed clinical data of 7587 consecutive patients who underwent curative surgery for breast cancer between January 2004 and December 2013 at Samsung Medical Center. Univariate and multivariate analyses were performed to identify risk factors for DFS, which was computed using the Kaplan–Meier method. CDFS rates were based on cumulative DFS estimates. Median follow-up duration was 20.59 months. Three-year DFS was 93.46% at baseline. Three-year CDFS survival estimates for patients who had been disease free for 1, 2, 3, 4, and 5 years after treatment were calculated as 92.84%, 92.37%, 93.03%, 89.41%, and 79.64%, respectively. Three-year CDFS increased continuously each year after 1 year of DFS in hormone receptor (HR)-negative patients but decreased each year in HR-positive patients. In HR-positive patients who are disease free after 3 years, continuous care including surveillance and metastases workup should be considered, although this is not recommended in the current guidelines. On the other hand, the social costs may be reduced in HR-negative patients by extending the surveillance interval. Further studies are needed to identify indicators of DFS prognosis in breast cancer patients.

Comparison of prognosis and specific features according to tumor size in small-sized breast cancer with extensive lymph node involvement.

81 Background: As known, larger tumor size and more extensive lymph node (LN) involvement have been considered an independent factor for poor prognosis of breast cancer. We evaluated if very small tumor size may be a factor of worse prognosis compared to larger tumor in small sized breast cancer with LN involvement.nnnMETHODSnA retrospective analysis was made in a single center of all 1400 patients with small (below 2cm, T1) sized and LN involved (N1~N3) breast cancer without metastasis diagnosed between 2004 and 2014. Their ages ranged from 23 to 88 years (mean age 49.1 ± 9.9 years) and mean follow-up was 31 months. All patients were performed with surgery including axillary LN dissection without neo-adjuvant chemotherapy. We subdivided their tumor size to 4 group (T1m, T1a, T1b and T1c) grading by 7th AJCC cancer staging. The number of patients in each group is as follows: T1m = 17, T1a = 63, T1b = 214, T1c = 1106. The specific features related to mortality were analyzed according to the minor groups and they were compared with one another by Chi-square test and Kaplan-Meier analysis.nnnRESULTSnTotal expired patients were 39 (2.8%) and the number (the rate in each group) of the minor groups is as follows: T1m = 1 (5.9%), T1a = 1 (1.6%), T1b = 7 (3.3%), T1c = 22 (2.0%). Overall survival of smaller sized tumor groups ( ≤ 1cm, T1m+T1a+T1b) are significantly decreased than the other larger sized group T1c in T1N1 staged patients (p = 0.004). There are significant differences in estrogen receptor, progesterone receptor, nuclear grade, recurrence among the 4 minor groups in whole patients group. In the analysis of nuclear grade, the results show higher grade in T1m than T1a, T1m than T1b, T1b than T1c. Especially, recurrence of T1m is significantly more frequent than T1a (17.6% vs 3.2%, P = 0.03) or T1b (17.6% vs 4.2%, p = 0.016).nnnCONCLUSIONSnIn conclusion, this study indicates smaller sized tumor with LN involvement can progress worse compared to larger tumor. This result supports very small size can be another predictive factor for prognosis in small sized breast cancer with LN involvement.