Chan Heun Park

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

BackgroundNeoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer.Methods/DesignPatients meeting the inclusion criteria and providing written informed consent will be randomized to 24xa0weeks of neoadjuvant treatment with letrozole (2.5xa0mg/day) and either metformin (2000xa0mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively.DiscussionThis study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer.Trial registrationClinicalTrials.gov Identifier NCT01589367

Conventional laparoscopic adrenalectomy versus laparoscopic adrenalectomy through mono port.

A standard procedure for single-port laparoscopic adrenal surgery has not been established. We retrospectively investigated intraoperative and postoperative outcomes after laparoscopic adrenalectomy through mono port (LAMP) and conventional laparoscopic adrenalectomy to assess the feasibility of LAMP. Between March 2008 and December 2009, 22 patients underwent adrenalectomy at the Department of Surgery, Kangbuk Samsung Hospital. Twelve patients underwent conventional laparoscopic adrenalectomy and 10 patients underwent LAMP. The same surgeon performed all the surgeries. The 2 procedures were compared in terms of tumor size, operating time, time to resumption of a soft diet, length of hospital day, and postoperative complications. The 2 groups were similar in terms of tumor size (30.08 vs. 32.50 mm, P=0.796), mean operating time (112.9 vs. 127 min, P=0.316), time to resumption of a soft diet (1.25 vs. 1.30 d, P=0.805), and length of hospital day (4.08 vs. 4.50 d, P=0.447). Despite 1 patient in the LAMP group experiencing ipsilateral pleural effusion as a postoperative complication, this parameter was similar for the 2 groups (P=0.195). Perioperative mortality, blood transfusion, and conversion to open surgery did not occur. Perioperative outcomes for LAMP were similar to those for conventional laparoscopic adrenalectomy. LAMP appears to be a feasible option for adrenalectomy.

Feasibility of Preoperative Axillary Lymph Node Marking with a Clip in Breast Cancer Patients Before Neoadjuvant Chemotherapy: A Preliminary Study

BackgroundThe aim of this study was to determine the feasibility of image-guided marker-clip placement in axillary lymph nodes (ALNs) for breast cancer upon initial presentation and to assess the reliability of this method with sentinel lymph node biopsy (SLNB) for axillary restaging after neoadjuvant chemotherapy (NAC).MethodsBetween June 2015 and August 2016, a marker clip was placed at a clinically positive ALN under ultrasonography (US) guidance before initiation of NAC in 20 patients. Preoperative localization of marker-clipped LNs was performed, and the localized LNs were removed by SLNB. We compared the postoperative results of the marker-clipped LNs, SLNs and ALNs.ResultsImage-guided marker-clip placements and localization of marker-clipped LNs were performed successfully in 20 patients. A total of 24 marker clips were inserted, and 23 marker-clipped LNs were successfully retrieved during surgery (identification rate, 23/24, 95.8%). In the 11 patients with pathologically confirmed metastatic marker-clipped LNs, four became negative after NAC, and seven maintained metastatic residues on the marker-clipped LNs. Three of the seven patients had metastatic residues on the ALNs, and two of the three patients also had negative SLNs. Marker-clipped nodes accurately predicted the axillary nodal status in these two patients compared with SLNs alone.ConclusionImage-guided marker-clip placement on positive ALNs before NAC and removal with SLNB is technically feasible. This technique can improve the accuracy of the residual disease evaluation on the axilla, especially in patients with negative SLNB results, and can identify candidates for limited axillary surgery after NAC.

The Optimal Approach for Laparoscopic Adrenalectomy through Mono Port regarding Left or Right Sides: A Comparative Study.

Introduction. Several studies have shown the feasibility and safety of both transperitoneal and posterior retroperitoneal approaches for single incision laparoscopic adrenalectomy, but none have compared the outcomes according to the left- or right-sided location of the adrenal glands. Materials and Methods. From 2009 to 2013, 89 patients who received LAMP (laparoscopic adrenalectomy through mono port) were analyzed. The surgical outcomes attained using the transperitoneal approach (TPA) and posterior retroperitoneal approach (PRA) were analyzed and compared. Results and Discussion. On the right side, no significant differences were found between the LAMP-TPA and LAMP-PRA groups in terms of patient characteristics and clinicopathological data. However, outcomes differed in which LAMP-PRA group had a statistically significant shorter mean operative time (84.13 ± 41.47u2009min versus 116.84 ± 33.17u2009min; P = 0.038), time of first oral intake (1.00 ± 0.00 days versus 1.21 ± 0.42 days; P = 0.042), and length of hospitalization (2.17 ± 0.389 days versus 3.68 ± 1.38 days; P ≤ 0.001), whereas in left-sided adrenalectomies LAMP-TPA had a statistically significant shorter mean operative time (83.85 ± 27.72 min versus 110.95 ± 29.31u2009min; P = 0.002). Conclusions. We report that LAMP-PRA is more appropriate for right-sided laparoscopic adrenalectomies due to anatomical characteristics and better surgical outcomes. For left-sided laparoscopic adrenalectomies, however, we propose LAMP-TPA as a more suitable method.

Expression Pattern of Smad4/GATA3 as a Predictor of Survival in Invasive Ductal Carcinoma of the Breast

Background: Smad4 and GATA3 proteins are known prognostic markers in various cancers. Smad4 is a mediator linked to both tumour suppression and progression. GATA3 is a regulator of development and morphogenesis of the mammary gland. We assessed and compared the predictive performance of Smad4 and GATA3 for clinical outcomes in patients with breast cancer. Methods: The combined expression pattern based on Smad4+/- and GATA3+/- was evaluated by immunostaining using breast cancer tissue microarray, and the relationships between protein expression and clinicopathological variables were analysed. Results: Smad4 expression was only associated with an ill-defined tumour border, whereas GATA3 was associated with several good prognostic factors. On analysis of combined markers, there was a significant difference in the expression of fascin (an important factor for cancer invasiveness) between the Smad4+/GATA3- and Smad4-/GATA3+ groups. Smad4+/GATA3- was correlated with worse clinicopathological parameters, relapse-free survival (RFS), and overall survival (OS), compared to Smad4-/GATA3+. Conclusion: Combined markers of Smad4/GATA3 showed a superior performance compared to single markers for predicting RFS and OS in patients with breast cancer.

The effect of adjuvant chemotherapy on survival in Korean patients with node negative T1c, triple negative breast cancer

Background The present study investigated the prognostic role of adjuvant systemic chemotherapy in patients with node negative, T1c triple negative breast cancer (TNBC) from a nationwide cohort. In addition, the prognostic effect between 3 different chemotherapy regimens were compared in node-negative T1c TNBC patients by subgroup analysis. Methods From the Korean breast cancer registry database, 1,151 T1c node negative TNBC patients were included in this study. Patients were categorized into four treatment groups according to chemotherapy regimen: (1) no chemotherapy, (2) adriamycin plus cyclophosphamide (AC), (3) adriamycin/epirubicin plus cyclophosphamide plus 5-FU (FAC/FEC), and (4) cyclophosphamide plus 5-FU plus methotrexate (CMF). Overall survival (OS) was evaluated between each patient group. Results Of the 1,151 T1c node negative TNBC patients, 1,006 received adjuvant chemotherapy, while 145 received no chemotherapy. Among the patients receiving adjuvant chemotherapy the distribution of regimens was: 586 AC, 168 FAC/FEC (126 FAC, 42 FEC), and 252 CMF. The mean follow-up time of the full study cohort was 87.98 ± 33.56 months (range = 6–192 months). Patients in the no chemotherapy group showed significantly worse OS compared to each chemotherapy regimen group. However, when OS was compared between each chemotherapy regimen, no significant difference was found. Conclusions This study showed that adjuvant systemic chemotherapy improved OS in T1c node negative TNBC patients, regardless of chemotherapy between AC, FAC/FEC, and CMF regimens.

Chronologically changing patterns in the survival of korean patients with breast cancer and related clinical factors: a nationwide registry-based study

PurposeAdvances in breast cancer treatment have contributed to marked improvements in patient outcomes over the past three decades. This study aims to chronologically evaluate the survival of patients with breast cancer and investigate the observed changes over time.MethodsStatistics from the Korean National Cancer Registry, based on all 60,571 patients with invasive breast cancer during the 21xa0year period, were analyzed. We divided the study interval into four periods (P1: 1988–1992, P2: 1993–1997, P3: 1998–2002, P4: 2003–2008).ResultsThe patients treated during P4 showed significantly better 5-year overall survival (OS) than did those treated during P1 (5Y OS; P1u2009=u200979.0 vs. P4u2009=u200992.2, pu2009<u20090.001). In the multivariate analyses, younger age, mastectomy, high stage, high tumor grade, lymphovascular invasion, and hormone receptor negativity were poor prognostic factors. The multivariate analysis demonstrated that diagnosis periods significantly and independently associated with OS in the overall group of patients. In our analysis of age-period-interaction models, the hazard ratio (HR) for death for patients who were under 35xa0years of age, compared to those who were older, tended to decrease over time (HR of ageu2009<u200935 vs. 35u2009~u200950; P1u2009=u20090.739, pu2009=u20090.007; P2u2009=u20090.744, pu2009<u20090.001; P3u2009=u20090.886, pu2009=u20090.041; P4u2009=u20090.983, pu2009=u20090.813). The survival rate of patients who underwent breast conserving surgery (BCS) has recently gotten better than that of mastectomy (HR of mastectomy vs. BCS; P1u2009=u20090.957, pu2009=u20090.790; P2u2009=u20090.542, pu2009<u20090.001; P3u2009=u20090.543, pu2009<u20090.001; P4u2009=u20090.425, pu2009<u20090.001).ConclusionsThe clinical factors related to the changes in breast cancer survival have improved and increased patient OS over the past 20xa0years in Korea. In addition, we provided new insights into the effects of age and surgery methods on prognosis in each period.

The prognostic and predictive value of tumor-infiltrating lymphocytes and hematologic parameters in patients with breast cancer

BackgroundCarcinogenesis and tumor growth are associated with chronic inflammation and the host immune system. Here, we investigated the clinical significance and relationship between tumor-infiltrating lymphocytes (TILs) and hematologic parameters in patients with breast cancer.MethodsInvasive ductal breast cancer patients (Nu2009=u2009145) who underwent surgery were retrospectively evaluated. Samples were obtained using a core needle biopsy for CD8+, FOXP3+ TIL assessment. Blood lymphocytes, neutrophils, monocytes, and platelets were obtained by peripheral venous punctures.ResultsCD8u2009+u2009TILs were significantly associated with absolute lymphocyte count (ALC) and the absolute monocyte count (AMC). Low LMR (ALC/AMC) (cut-off - 5.3, rangeu2009=u20090.73–12.31) was associated with poor overall survival (OS) (pu2009=u20090.010), disease-free survival (DFS) (pu2009=u20090.005). However, in subgroup analysis, LMR did not have any value as a prognostic factor in HER2-positive breast cancers. TILs had different prognostic impacts across breast cancer subtypes, although they were not statistically significant. The treatment response after NAC tended to improve in breast cancer patients with high FOXP3+ TILs, low NLR (neutrophil count/ALC) (FOXP3 p for trendu2009=u20090.006, NLR p for trendu2009=u20090.063).ConclusionsA relevance between TILs and hematologic parameters in breast cancer was demonstrated. The influence of the immune system on breast cancer progression may differ by subtype.

Expression of epithelial–mesenchymal transition driver brachyury and status of tumor-infiltrating CD8+ and FOXP3+ lymphocytes in predicting treatment responses to neoadjuvant chemotherapy of breast cancer:

Brachyury has been characterized as a driver of epithelial–mesenchymal transition process which is regarded as an important mechanism of cancer cell invasion and metastatic progression. The status of tumor-infiltrating lymphocytes has been proposed to predict response to neoadjuvant chemotherapy in breast cancer. We investigated the clinical significance and value of tumor-infiltrating lymphocytes and brachyury as biomarkers to predict treatment responses to neoadjuvant chemotherapy in breast cancer. We also examined the correlation of the Neo-Bioscore with tumor-infiltrating lymphocytes and brachyury to indirectly predict long-term outcome. This retrospective study included a series of 44 consecutive patients treated between January 2011 and December 2015. All patient samples were obtained using core needle biopsy before neoadjuvant chemotherapy. The relationship of expression of Brachyury and tumor-infiltrating lymphocyte subsets (CD8+, forkhead box protein 3 tumor-infiltrating lymphocytes) with clinicopathological factors was assessed to identify its predictive role with respect to tumor response to neoadjuvant chemotherapy and the outcome. Of 44 patients, 6 showed no response, 31 had partial response, and 7 demonstrated pathological complete response. Forkhead box protein 3 was significantly higher in the response group than in the no response group (no responseu2009=u20092.6, partial responseu2009=u20097.0, complete responseu2009=u20099.7, pu2009=u20090.020). Brachyury expression was inversely associated with response to neoadjuvant chemotherapy, but the difference was not statistically significant (pu2009=u20090.62). We also observed a significant association between forkhead box protein 3 (pu2009=u20090.001) and the Neo-Bioscore, while only a marginal difference was observed with CD8+ expression (pu2009=u20090.074). This study demonstrated that forkhead box protein 3 expression has value as the only independent marker that predicts a good response to neoadjuvant chemotherapy and that it is related with a good prognosis according to the Neo-Bioscore. Brachyury was significantly associated with estrogen receptor positive and human epidermal growth factor receptor 2 negative status; further study would be needed to clarify how it affects treatment prognosis.