Sae Byul Lee

Metformin increases survival in hormone receptor-positive, HER2-positive breast cancer patients with diabetes

IntroductionMetformin use has recently been observed to decrease both the rate and mortality of breast cancer. Our study was aim to determine whether metformin use is associated with survival in diabetic breast cancer patients by breast cancer subtype and systemic treatment.MethodsData from the Asan Medical Center Breast Cancer Database from 1997 to 2007 were analyzed. The study cohort comprised 6,967 nondiabetic patients, 202 diabetic patients treated with metformin, and 184 diabetic patients that did not receive metformin. Patients who were divided into three groups by diabetes status and metformin use were also divided into four subgroups by hormone receptor and HER2-neu status.ResultsIn Kaplan-Meier analysis, the metformin group had a significantly better overall and cancer specific survival outcome compared with non metformin diabetic group (P <0.005 for both). There was no difference in survival between the nondiabetic and metformin groups. In multivariate analysis, Compared with metformin group, patients who did not receive metformin tended to have a higher risk of metastasis with HR 5.37 (95 % CI, 1.88 to 15.28) and breast cancer death with HR 6.51 (95 % CI, 1.88 to 15.28) on the hormone receptor-positive and HER2-negative breast cancer. The significant survival benefit of metformin observed in diabetic patients who received chemotherapy and endocrine therapy (HR for disease free survival 2.14; 95 % CI 1.14 to 4.04) was not seen in diabetic patients who did not receive these treatments.ConclusionPatients receiving metformin treatment when breast cancer diagnosis show a better prognosis only if they have hormone receptor-positive, HER2-positive tumors. Metformin treatment might provide a survival benefit when added to systemic therapy in diabetic patients.

Patient reporting pain intensity immediately after surgery can be associated with underlying depression in women with breast cancer.

The aims of this study were to determine the prevalence of severe, definite depression symptoms, as measured using the Center for Epidemiological Studies Depression Scale (CES‐D), and the association between high CES‐D scores (i.e., ≥25) and sociodemographic and perioperative factors during perioperative period.

Expansion of tumor-infiltrating lymphocytes and their potential for application as adoptive cell transfer therapy in human breast cancer

Adoptive cell transfer (ACT) of ex vivo expanded tumor-infiltrating lymphocytes (TILs) has been successful in treating a considerable proportion of patients with metastatic melanoma. In addition, some patients with several other solid tumors were recently reported to have benefited clinically from such ACT. However, it remains unclear whether ACT using TILs is broadly applicable in breast cancer, the most common cancer in women. In this study, the utility of TILs as an ACT source in breast cancers was explored by deriving TILs from a large number of breast cancer samples and assessing their biological potentials. We successfully expanded TILs ex vivo under a standard TIL culture condition from over 100 breast cancer samples, including all breast cancer subtypes. We also found that the information about the percentage of TIL and presence of tertiary lymphoid structure in the tumor tissues could be useful for estimating the number of obtainable TILs after ex vivo culture. The ex vivo expanded TILs contained a considerable level of central memory phenotype T cells (about 20%), and a large proportion of TIL samples were reactive to autologous tumor cells in vitro. Furthermore, the in vitro tumor-reactive autologous TILs could also function in vivo in a xenograft mouse model implanted with the primary tumor tissue. Collectively, these results strongly indicate that ACT using ex vivo expanded autologous TILs is a feasible option in treating patients with breast cancer.

BRCA1/ 2-negative, high-risk breast cancers ( BRCAX ) for Asian women: genetic susceptibility loci and their potential impacts

Abstract“BRCAX” refers breast cancers occurring in women with a family history predictive of being a BRCA1/2 mutation carrier, but BRCA1/2 genetic screening has failed to find causal mutations. In this study, we report the findings of the genetic architecture of BRCAX with novel and redefined candidate loci and their potential impacts on preventive strategy. We performed a genome-wide association study involving 1,469 BRCAX cases from the Korean Hereditary Breast Cancer study, and high-risk breast cancer cases (1,482 Asians and 9,902 Europeans) from the Breast Cancer Association Consortium. We also evaluated the previously reported susceptibility loci for their roles in the high-risk breast cancers. We have identified three novel loci (PDE7B, UBL3, and a new independent marker in CDKN2B-AS1) associated with BRCAX, and replicated previously reported SNPs (24 of 92) and moderate/high-penetrance (seven of 23) genes for Korean BRCAX. For the novel candidate loci, evidence supported their roles in regulatory function. We estimated that the common low-penetrance loci might explain a substantial part of high-risk breast cancer (39.4% for Koreans and 24.0% for Europeans). Our study findings suggest that common genetic markers with lower penetrance constitute a part of susceptibility to high-risk breast cancers, with potential implications for a more comprehensive genetic screening test.

Chronological Improvement in Survival of Patients with Breast Cancer: A Large-Scale, Single-Center Study

Purpose This study aimed to chronologically evaluate survival of patients with breast cancer in Korea and investigate the observed changes during the last 20 years. We also sought to determine factors that may influence outcomes and changes in the duration of survival over time. Methods We retrospectively analyzed a total of 10,988 patients with breast cancer who were treated at our institution between January 1993 and December 2008. We divided the study period into three periods (P1, 1993–1997; P2, 1998–2002; and P3, 2003–2008). We retrospectively reviewed the collected data from the Asan database, including age at diagnosis, clinical manifestations, pathology report, surgical methods, types of adjuvant treatment modalities, type of recurrence, and follow-up period. Results At a median follow-up of 8.2 years, we observed that survival outcomes have improved recently. The 5-year breast cancer-specific survival (BCSS) rate also increased from 82.8% in P1 to 92.6% in P3 (p<0.001). The survival rate in patients with tumors at each stage increased in similar patterns in all patients, and, remarkably, there was a significant survival improvement in patients with stage III breast cancer (P1 vs. P3: 5-year BCSS, 57.4% vs. 80.0%, p<0.001). The time period was a significant prognostic factor in multivariate analysis (P1 vs. P2: hazard ratio [HR], 0.83, p=0.035; P1 vs. P3: HR, 0.75, p=0.015). Conclusion The study results suggest an improvement in breast cancer survival in Korea, which is consistent with the development of treatments and early detection.

Comparative Study between Sentinel Lymph Node Biopsy and Axillary Dissection in Patients with One or Two Lymph Node Metastases

Purpose Sentinel lymph node biopsy (SLNB) is a standard axillary surgery in early breast cancer. If the SLNB result is positive, subsequent axillary lymph node dissection (ALND) is a routine procedure. In 2011, the American College of Surgeons Oncology Group Z0011 trial revealed that ALND may not be necessary in early breast cancer with one or two positive sentinel lymph nodes. The purpose of this study was to compare outcomes among Korean patients with one or two positive axillary lymph nodes in the final pathology who did and did not undergo ALND. Methods A total of 131,717 patients from the Korea Breast Cancer Society registry database received breast cancer surgery from January 1995 to December 2014. Inclusion criteria were T stage 1 or 2, one or two positive lymph nodes, and having received breast-conserving surgery (BCS), whole breast radiation therapy, and no neoadjuvant therapy. We analyzed the differences in disease-specific survival (DSS) and overall survival (OS) between patients who received SLNB only and those who underwent SLNB+ALND. Results A total 4,442 patients met the inclusion criteria, with 1,268 (28.6%) in the SLNB group and 3,174 (71.4%) in the SLNB+ALND group. There were no differences in DSS and OS between the two groups (p=0.378 and p=0.925, respectively). The number of patients who underwent SLNB alone for one or two positive lymph nodes increased continuously from 2004 to 2014. Conclusion Korean patients with early breast cancer and 1 or 2 positive axillary lymph nodes who received BCS plus SLNB showed no significant difference in DSS and OS regardless of whether they received ALND. The findings of this retrospective study demonstrate that omitting ALND can be considered when treating selected patients with early breast cancer who have one or two positive lymph nodes.

Differences in prognosis and efficacy of chemotherapy by p53 expression in triple-negative breast cancer

PurposeTP53 mutation is the most common mutation in breast cancer, and it is considered a target marker of triple-negative breast cancer (TNBC). We investigated whether expression of p53 detected by immunochemical staining predicts the chemotherapy response of TNBC.MethodsA total of 11,393 TNBC patients who had between stage I and stage III enrolled in the Korean Breast Cancer Society Registry database from January 1, 2000 to December 31, 2015. There were 6,331 ‘p53-positive (+) TNBC’ patients and 5062 ‘p53-negative (−) TNBC’ patients.ResultsIn univariate analysis, p53(+) TNBC had a worse prognosis than p53(−) TNBC in patients not receiving chemotherapy (P = 0.003). However, there was no difference in prognosis between p53(+) TNBC and p53(−) TNBC for patients receiving chemotherapy. In multivariate analysis adjusted for age and stage, the risk of p53(+) TNBC was 1.84 times higher than that of p53(−) TNBC in the non-chemotherapy group. However, there was no difference between p53(+) TNBC and p53(−) TNBC in patients receiving chemotherapy. In p53(+) TNBC, the risk was 0.6-fold lower when chemotherapy was administered than when chemotherapy was not administered. However, in p53(−) TNBC, there was no risk reduction effect by chemotherapy.ConclusionThe prognosis of p53(+) TNBC has worse than p53(−) TNBC, but the risk for survival was significantly reduced with chemotherapy. It suggests that p53(+) TNBC would be more sensitive to chemotherapy than p53(−) TNBC.

No Association of Positive Superficial and/or Deep Margins with Local Recurrence in Invasive Breast Cancer Treated with Breast-Conserving Surgery

Purpose We evaluated the effect of positive superficial and/or deep margin status on local recurrence (LR) in invasive breast cancer treated with breast-conserving surgery (BCS) followed by radiotherapy. Materials and Methods In total, 3,403 stage 1 and 2 invasive breast cancer patients treated with BCS followed by radiotherapy from January 2000 to December 2008 were included in this study. These patients were divided into three groups according to margin status: clear resection margin status for all sections (group 1, n=3,195); positive margin status in superficial and/or deep sections (group 2, n=121); and positive peripheral parenchymal margin regardless of superficial and/or deep margin involvement (group 3, n=87). The LR-free survival between these three groups was compared and the prognostic role of margin status was analyzed. Results Across all groups, age, tumor size, nodal status, and human epidermal growth factor receptor 2 status did not significantly differ. High grade, positive extensive intraductal component, hormone receptor positivity, hormone therapy received, and chemotherapy not received were more prevalent in groups 2 and 3 than in group 1. Five-year LR rates in groups 1, 2, and 3 were 1.9%, 1.7%, and 7.7%, respectively. Multivariate analysis revealed that group 3 was a significant predictor for LR (hazard ratio [HR], 4.78; p < 0.001), but that positive superficial and/or deep margin was not (HR, 0.66; p=0.57). Conclusion Superficial and/or deep margin involvement following BCS is not an important predictor for LR.

Survival Outcome of Combined GnRH Agonist and Tamoxifen Is Comparable to That of Sequential Adriamycin and Cyclophosphamide Chemotherapy Plus Tamoxifen in Premenopausal Patients with Lymph-Node–Negative, Hormone-Responsive, HER2-Negative, T1-T2 Breast Cancer

Purpose The purpose of this study was to compare treatment outcomes between combined gonadotropin-releasing hormone agonist and tamoxifen (GnRHa+T) and sequential adriamycin and cyclophosphamide chemotherapy and tamoxifen (AC->T) in premenopausal patients with hormone-responsive, lymph-node–negative breast cancer. Materials and Methods In total, 994 premenopausal women with T1-T2, lymph-node–negative, hormone-receptor-positive, HER2-negative breast cancer between January 2003 and December 2008 were included in this retrospective cohort study. GnRHa+T and AC->T were administered to 608 patients (61.2%) and 386 patients (38.8%), respectively. Propensity score matching and inverse probability weighting were applied to the original cohort, and 260 patients for each treatment arm were included in the final analysis. Recurrence-free, cancer-specific, and overall survival was compared between the two treatment groups. Results A total of 994 patients were followed up for a median of 7.4 years (range, 0.5 to 11.4 years). The 5-year follow-up rate was 98.7%, and 13 patients were lost to follow-up. In propensity-matched cohorts (n=520), there was no difference in recurrence-free, cancer-specific, and overall survival rates between the two treatment groups (p=0.306, p=0.212, and p=0.102, respectively), and this was maintained after applying inverse probability weighting. Conclusion GnRHa+T is a reasonable alternative to AC->T in patients with premenopausal, hormone-responsive, HER2-negative, lymph-node–negative, T1-T2 breast cancer.