Tailored radiation dose according to margin width for patients with ductal carcinoma in situ after breast-conserving surgery.

A 2 mm resection margin is considered adequate for ductal carcinoma in situ (DCIS). We assessed the effectiveness of a tailored radiation dose for margins < 2 mm and the appropriate margin width for high-risk DCIS. We retrospectively evaluated 137 patients who received adjuvant radiotherapy after breast-conserving surgery for DCIS between 2013 and 2019. The patients were divided into three- positive, close (< 2 mm), and negative (≥ 2 mm) margin groups. Radiation dose to the tumor bed in equivalent dose in 2 Gy fractions were a median of 66.25 Gy, 61.81 Gy, and 59.75 Gy for positive, close, and negative margin groups, respectively. During a median follow-up of 58 months, the crude rates of local recurrence were 15.0%, 6.7%, and 4.6% in the positive, close, and negative margin groups, respectively. The positive margin group had a significantly lower 5-year local recurrence-free survival (LRFS) rate compared to the close and negative margin groups in propensity-weighted log-rank analysis (84.82%, 93.27%, and 93.20%, respectively; p = 0.008). The difference in 5-year LRFS between patients with the high- and non-high-grade tumors decreased as the margin width increased (80.4% vs. 100.0% for margin ≥ 2 mm, p < 0.001; 92.3% vs. 100.0% for margin ≥ 6 mm, p = 0.123). With the radiation dose tailored for margin widths, positive margins were associated with poorer local control than negative margins, whereas close margins were not. Widely clear margins (≥ 2 mm) were related to favorable local control for high-grade DCIS.

Oncologic efficacy of gonadotropin-releasing hormone agonist in hormone receptor-positive very young breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Breast cancer in young women has been shown to have an aggressive behavior and poor prognosis. AIM: To evaluate the outcomes of young hormone receptor (HR)-positive patients with breast cancer treated with neoadjuvant chemotherapy (NAC), and the oncologic efficacy of gonadotropin-releasing hormone (GnRH) agonists. METHODS: This retrospective study involved a prospectively enrolled cohort. We included patients diagnosed with invasive breast cancer who were treated with NAC followed by curative surgery at the Samsung Medical Center and Samsung Changwon Hospital between January 2006 and December 2017. Among patients with HR-positive and human epidermal grow factor 2 (HER2)-negative breast cancer, we analyzed the characteristics and oncology outcomes between the patients equal to or younger than 35 years and the patients older than 35 years. RESULTS: Among 431 patients with NAC and HR-positive/HER2-negative breast cancer, 78 were 35 years old or younger, and 353 patients were older than 35 years. The median follow-up was 71.0 months. There was no statistically significant difference in disease free survival (DFS, P = 0.565) and overall survival (P = 0.820) between the patients equal to or younger than 35 years and the patients older than 35 years. The two groups differed in that the GnRH agonist was used more frequently in the group of patients equal to or younger than 35 years than in the other group (52.4% vs 11.2%, P < 0.001). Interestingly, for the DFS according to the GnRH agonist in the group of patients equal to or younger than 35 years, patients treated with the GnRH agonist had better DFS (P = 0.037). CONCLUSION: Administration of GnRH agonists might improve the DFS rate of HR-positive/HER2-negative breast cancer in the equal to or younger than 35 years group of patients with NAC.

Effect of high-dose radiation therapy on positive margins after breast-conserving surgery for invasive breast cancer.

PURPOSE: Positive margins after breast-conserving surgery are associated with poor oncological outcomes and warrant additional surgery. This study aimed to evaluate the effectiveness of high-dose radiation therapy for positive margins by comparing local recurrence between patients with positive and negative margins. METHODS: We retrospectively evaluated 550 patients treated with adjuvant radiation therapy after breast-conserving surgery for invasive breast cancer between 2013 and 2019. The total equivalent dose in 2 Gy fractions (EQD2) to the tumor bed ranged from 65.81 to 66.25 Gy for positive margins and 59.31-61.81 Gy for negative margins. The differences in local recurrence between the positive and negative margin groups were analyzed. RESULTS: After a median follow-up of 58 months, the crude local recurrence rate was 7.3% in the positive margin group (n = 55) and 2.4% in the negative margin group (n = 495). Positive margins were associated with higher local recurrence without statistical significance in the entire cohort (p = 0.062). Among patients aged <60 years, those with positive margins had a significantly lower 5-year local recurrence-free survival rate than those with negative margins (89.16% vs. 97.57%, respectively; p = 0.005). In contrast, there was no significant difference in the 5-year local recurrence-free survival rate between patients with positive and negative margins among those aged ≥60 years (100.00% vs. 94.38%, respectively; p = 0.426). CONCLUSION: In this study, positive margins were not associated with poor local control in older patients after a high-dose boosts. Further prospective studies are needed to verify our findings.

The efficacy and safety of an indocyanine green-hyaluronic acid mixture (LuminoMark™) for localization in patients with non-palpable breast lesions: A multicenter, randomized, open-label, parallel phase 3 clinical trial.

Purpose: The incidence of early tumor detection is increasing due to popularization of breast cancer screening and the development of imaging techniques. Thus, suitable preoperative localization is required for proper diagnosis and treatment of non-palpable breast lesions. The purpose of this study was to evaluate the efficacy and safety of indocyanine green (ICG)-hyaluronic acid (HA) mixture for lesion localization compared to activated charcoal. Methods: This was a multicenter, randomized, open-label, parallel phase 3 clinical trial performed at four centers in Korea. Female patients scheduled for surgery to remove non-palpable breast lesions were enrolled. One hundred and nine patients were randomly assigned to a control group (activated charcoal: 0.3. - 1 mL) or a study group (ICG-HA mixture, 0.2 mL) for the localization of a breast lesion. The primary endpoint was the accuracy of resection. Secondary endpoints included the technical success rate, histopathological accuracy, skin pigmentation rate, and adverse event rate. Results: A total of 104 patients were eligible for per-protocol analysis (control group, n = 51; study group, n = 53). The accuracy of resection in the study group was not inferior to that of the control group (90.57% vs. 98.04%, 95% confidence interval (CI): -2.31 - 18.91, p = 0.21). There was no statistically significant difference in technical success rate between the two groups (marking on breast skin: p = 0.11, marking on the excised specimen: p = 0.12). However, there were statistically significant differences in histopathological accuracy (0.26 ± 0.13 vs. 0.33 ± 0.17, p = 0.01) and skin pigmentation rate (0.00% vs. 30.77%, p< 0.01). Adverse events were not reported in either group. Conclusions: When localization was performed using ICG-HA, the accuracy of resection was not inferior to that of activated charcoal. However, skin pigmentation rate was significantly lower. In conclusion, ICG-HA is effective and safe for localizing of non-palpable breast lesions.

Robotic versus endoscopic transoral thyroidectomy in papillary thyroid cancer: A comparative analysis of surgical outcomes in 240 consecutive patients.

BACKGROUND: This study compared the surgical outcomes of transoral endoscopic thyroidectomy vestibular approach (TOETVA) and transoral robotic thyroidectomy (TORT) in papillary thyroid cancer (PTC). METHODS: The TOETVA and TORT groups comprised 119 and 121 patients between November 2016 and May 2022. Clinico-surgical outcomes and operation times were retrospectively reviewed. RESULTS: The TORT group showed a higher number of retrieved central compartment lymph nodes, shorter hospital stays, and lower pain score after 48 h than the TOETVA group. No significant difference was observed in the other postoperative complications, including permanent vocal cord palsy. Total operation, working space creation, and endoscopic or robotic surgery times of the TORT group were longer than those of the TOETVA group. CONCLUSIONS: TORT and TOETVA are feasible and safe. TORT may have some advantages, such as central compartment node dissection, shorter hospital stays, and pain score after 48 h in PTC, despite a longer operative time.

Is Pathologic Axillary Staging Valid If Lymph Nodes Are Less than 10 with Axillary Lymph Node Dissection after Neoadjuvant Chemotherapy?

Introduction: The aim of this study was to evaluate the prognostic value of the number of lymph nodes removed in breast cancer patients who undergo axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC). Methods: We included patients who were diagnosed with invasive breast cancer and cytology with proven involved axillary node metastasis at diagnosis and treated with NAC followed by curative surgery at Samsung Medical Center between January 2007 and December 2015. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Results: Among 772 patients with NAC and ALND, there were 285 ypN0, 258 ypN1, 135 ypN2, and 94 ypN3 cases. The median follow-up duration was 69.0 months. The group with less than 10 lymph nodes number (<10 nodes group) included 123 patients and the group with 10 or more lymph nodes number (≥10 nodes group) included 649 patients. There were no significant differences in DFS (p = 0.501) or OS (p = 0.883) between the two groups. In the ypN0 subgroup, the <10 nodes group had worse DFS than ≥10 nodes group (p = 0.024). In the ypN1 subgroup, there were no significant differences in DFS (p = 0.846) or OS (p = 0.774) between the two groups. In the ypN2 subgroup, the <10 nodes group had worse DFS (p = 0.025) and OS (p = 0.031) than ≥10 nodes group Conclusion: In ypN0 and ypN2 subgroups, breast cancer patients with less than 10 lymph nodes number in ALND after NAC might be considered for additional staging or closer surveillance when compared to patients with 10 or more than lymph node.

Factors Affecting Pathologic Complete Remission in Patients with Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy.

INTRODUCTION: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is associated with improvement in survival outcomes. This study evaluated the pCR in patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer after NAC. METHODS: We evaluated 417 patients who were diagnosed with invasive breast cancer and treated with NAC followed by curative surgery between January 2007 and December 2020 and analyzed the pCR for HR-positive and HER2-negative breast cancer. RESULTS: The median age at the time of surgery was 45.4 years, and 9.1% of patients (38 of 417) with HR-positive/HER2-negative status had pCR. Among patients with HR-positive/HER2-negative breast cancer, patients with single HR-positivity had a 20.2% pCR rate, and patients with double HR-positivity had a 4.4% pCR rate. Patients with a high Ki-67 index exhibited a higher pCR rate than those with a lower Ki-67 index (14.5% vs. 3.2%). Patients with single HR-positive and high Ki-67 values exhibited a significantly higher pCR rate than those with double HR-positive and low Ki-67 values (27.8% vs. 2.1%; p < 0.001). CONCLUSION: NAC could improve prognosis in patients with HR-positive/HER2-negative breast cancer with a single HR-positive and high Ki-67 values.

Relationship Between Breast and Axillary Pathologic Complete Response According to Clinical Nodal Stage: A Nationwide Study From Korean Breast Cancer Society.

PURPOSE: We evaluated the relationship between breast pathologic complete response (BpCR) and axillary pathologic complete response (ApCR) after neoadjuvant chemotherapy (NACT) according to nodal burden at presentation. As the indications for NACT have expanded, clinicians have started clinical trials for the omission of surgery from the treatment plan in patients with excellent responses to NACT. However, the appropriate indications for axillary surgery omission after excellent NACT response remain unclear. METHODS: Data were collected from patients in the Korean Breast Cancer Society Registry who underwent NACT followed by surgery between 2010 and 2020. We analyzed pathologic axillary nodal positivity after NACT according to BpCR stratified by tumor subtype in patients with cT1-3/N0-2 disease at diagnosis. RESULTS: A total of 6,597 patients were identified. Regarding cT stage, 528 (9.5%), 3,778 (67.8%), and 1,268 (22.7%) patients had cT1, cT2, and cT3 disease, respectively. Regarding cN stage, 1,539 (27.7%), 2,976 (53.6%), and 1,036 (18.7%) patients had cN0, cN1, and cN2 disease, respectively. BpCR occurred in 21.6% (n = 1,427) of patients, while ApCR and pathologic complete response (ypCR) occurred in 59.7% (n = 3,929) and ypCR 19.4% (n = 1,285) of patients, respectively. The distribution of biologic subtypes included 2,329 (39.3%) patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative disease, 1,122 (18.9%) with HR-positive/HER2-positive disease, 405 (6.8%) with HR-negative/HER2-positive disease, and 2,072 (35.0%) with triple-negative breast cancer . Among the patients with BpCR, 89.6% (1,122/1,252) had ApCR. Of those with cN0 disease, most (99.0%, 301/304) showed ApCR. Among patients with cN1-2 disease, 86.6% (821/948) had ApCR. CONCLUSION: BpCR was highly correlated with ApCR after NACT. In patients with cN0 and BpCR, the risk of missing axillary nodal metastasis was low after NACT. Further research on axillary surgery omission in patients with cN0 disease is needed.

Robot-assisted Nipple-sparing Mastectomy With Immediate Breast Reconstruction: An initial Experience of the Korea Robot-endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG).

OBJECTIVE: The aim of this study was to present the results of early experience of robot-assisted nipple sparing mastectomy (RANSM). BACKGROUND: RANSM improves cosmetic outcomes over conventional nipple-sparing mastectomy. However, data on the feasibility and safety of the RANSM are limited. METHODS: Patients who underwent RANSM with immediate breast reconstruction as part of the Korea Robot-endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) from November 2016 to January 2020 were enrolled. clinicopathologic characteristics, perioperative complications, and operation time were collected. RESULTS: Overall, 73 women underwent 82 RANSM procedures conducted by 11 breast surgeons at 8 institutions. The median patient age was 45.5 years old (20-66 years), and 52 (63.4%) patients were premenopausal. Invasive breast cancer was noted in 55 cases (40 cases were stage i, 11 cases were stage ii, and 4 cases were stage iii, respectively) and ductal carcinoma in-situ was recorded in 20 cases. Of those, 3 patients with BRCA1/2 mutation carriers underwent contralateral risk-reducing RANSM. The median length of hospitalization was 12.0 days (5.0-24.0 days). The incision location was the mid-axillary line and the median incision length was 50.0 mm (30.0-60.0 mm). Median total operation time, median total mastectomy time, and median reconstruction time was 307.0 minutes (163.0-796.0 minutes), 189.5 minutes (97.5-325.0 minutes), and 119.5 minutes (45.0-689.0 minutes). Only 2 cases (2.5%) required reoperation. Nipple ischemia was found in 9 cases (10.9%) but only 1 case (1.2%) required nipple excision given that 8 cases (9.7%) resolved spontaneously. Skin ischemia was observed in 5 cases (6.1%) and only 2 (2.4%) cases needed skin excision whereas 3 cases (3.6%) resolved spontaneously. There was no conversion to open surgery orcases of mortality. The mean time for mastectomy among surgeons who performed more than 10 cases was 182.3 minutes (± 53.7, minutes) and 195.4 minutes (± 50.4, minutes). CONCLUSION: This was the first report of RANSM conducted in the KoREa-BSG. RANSM is technically feasible and acceptable with a short learning curve. Further prospective research to evaluate surgical and oncologic outcomes is needed.

Is Sentinel Lymph Node Biopsy for Breast Cancer with Cytology-Proven Axillary Metastasis Safe? A Prospective Single-Arm Study.

The purpose of this study was to evaluate pathologic lymph node metastasis in breast cancer with cytology-proven axillary metastasis. This study was designed prospectively. We performed axillary lymph node dissections (ALND) after lymphatic mapping by near-infrared (NIR) fluorescence imaging with Indocyanine Green (ICG). We evaluated 72 breast cancer patients with cytology-proven axillary metastasis by curative surgery at the Samsung Medical Center between May of 2016 and December of 2017. Among the 72 patients with cytology-proven axillary metastasis, 14 of 39 patients (35.9%) with one or two sentinel lymph nodes containing metastases were metastasized to post-sentinel lymph node. Thirteen of fourteen patients had additional non-sentinel lymph node metastases, seven of thirteen patients also had additional level II lymph node metastases, and one patient had only one additional level II lymph node metastasis. Of T1 or T2 stage patients, 10 of 33 patients (30.3%) with one or two sentinel lymph nodes containing metastases were metastasized to post-sentinel lymph node. Even in patients without SLN metastasis, 50% of the patients had at least three LN metastases, and 40% in the T1 or T2 stage patients. Sentinel lymph node biopsy without ALND might be not safe for patients with cytology-proven axillary metastasis.

Effect of Poloxamer-Based Thermo-Sensitive Sol-Gel Agent on Upper Limb Dysfunction after Axillary Lymph Node Dissection: A Double-Blind Randomized Clinical Trial.

PURPOSE: Restricted shoulder motion is a major morbidity associated with a lower quality of life and disability after axillary lymph node dissection (ALND) in patients with breast cancer. This study sought to evaluate the antiadhesive effect of a poloxamer-based thermosensitive sol-gel (PTAS) agent after ALND. METHODS: We designed a double-blind, multicenter randomized controlled study to evaluate the clinical efficacy and safety of PTAS in reducing upper-limb dysfunction after ALND. The primary outcome was the change in the range of motion (ROM) of the shoulder before surgery and 4 weeks after ALND (early postoperative period). Secondary outcomes were shoulder ROM at six months, axillary web syndrome, and lymphedema (late postoperative period). RESULTS: A total of 170 patients with planned ALND were randomly assigned to one of 2 groups (poloxamer and control) and 15 patients were excluded. In the poloxamer group (n = 76), PTAS was applied to the surface of the operative field after ALND. ALND was performed without the use of poloxamer in the control group (n = 79). Relative to the control group, the poloxamer group had significantly lower early postoperative restrictions in total shoulder ROM at four weeks (-30.04 ± 27.76 vs. -42.59 ± 36.79; p = 0.0236). In particular, the poloxamer group showed greater reductions in horizontal abduction at four weeks (-3.92 ± 9.80 vs. -10.25 ± 15.42; p = 0.0050). The ROM of the shoulder at 24 weeks, axillary web syndrome, and lymphedema were not significantly different between the two groups. No adverse effects were observed in either group. CONCLUSION: We suggest that poloxamer might improve the early postoperative shoulder ROM in patients with breast cancer who have undergone ALND. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02967146.

The efficacy and safety of indocyanine green-hyaluronic acid mixture (LuminoMark™) for localization in patients with non-palpable breast lesions: a multi-center open-label parallel phase-2 clinical trial.

BACKGROUND: Increasing rates of breast cancer screening have been associated with an increasing frequency of non-palpable breast lesions detection. Preoperative breast lesion localization is essential for optimizing excision accuracy. This study aimed to evaluate the efficacy and safety of indocyanine green (ICG) hyaluronic acid injection as a novel mixture for localization. METHODS: We performed a prospective clinical trial with female patients who underwent surgery for non-palpable breast lesions. All patients were sequentially assigned to the control group (localization with activated charcoal), Test Group 1 (ICG-hyaluronic acid mixture 0.1 mL), or Test Group 2 (ICG-hyaluronic acid mixture 0.2 mL) by 1:1:1 ratio. RESULTS: A total of 44 patients were eligible for this study (Control Group = 14, Test Group 1 = 15, Test Group 2 = 15 patients). Fibroadenoma (n = 17, 38.6%) accounted for the largest proportion of diagnoses, and five patients (11.4%) were diagnosed with malignancies. There were no statistically significant differences in baseline characteristics among the three groups. The marking rate was over 86% in all groups, with no significant intergroup differences. Skin pigmentation was only observed in the control group. The mean accuracy of resection (the greatest diameter of the excised specimen divided by the greatest diameter of the preoperative lesion as observed using ultrasonography, with values closer to 1 reflecting a higher accuracy) was 3.7 in the control group, 2.2 in Test Group 1, and 2.1 in Test Group 2 (p = 0.037 between Controls and Test Group 1, p = 0.744 between Test Group 1 and Test Group 2, and p = 0.026 between Controls and Test Group 2). CONCLUSION: ICG-hyaluronic acid injection is a novel method that was shown to accurately localize non-palpable breast lesions and was associated with no skin pigmentation. Further research is required to apply this method to malignant breast lesions. Trial registration "A Multicenter Open-label, Parallel, Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of LuminoMark™ Inj. (Conc. for Fluorescence) Localization in Patients with Non-palpable Breast Lesions" was prospectively registered as a trial (ClinicalTrials. gov Identifier: NCT03743259, date of registration: May 29, 2018, https://clinicaltrials.gov/ct2/show/NCT03743259 ).

Breast radiologic complete response is associated with favorable survival outcomes after neoadjuvant chemotherapy in breast cancer.

BACKGROUND: The aim of this study was to examine the accuracy of radiologic complete response (rCR) in predicting pathologic complete response (pCR), and determine whether rCR is a predictor of favorable survival outcomes. MATERIALS AND METHODS: We retrospectively reviewed breast cancer patients treated with neoadjuvant chemotherapy (NAC) followed by surgery from September 2007 to June 2016. Breast lesions and axillary nodes were measured by MRI and categorized into either disappeared (breast rCR) or residual disease (breast non-rCR) and either normalized (axillary rCR) or abnormal findings (axillary non-rCR) in the axillary nodes. Correlation between rCR and pCR were compared using Cohen's Kappa statistics, and the recurrence-free survival (RFS) and overall survival (OS) rates were calculated by the Kaplan-Meier method. RESULTS: Out of the 1017 eligible patients, 287 (28.2%) achieved breast pCR, 165 (16.2%) achieved breast rCR, 529 (52.0%) had axillary pCR, and 274 (26.9%) achieved axillary rCR. The correlation between a breast rCR and pCR showed a Cohen's Kappa value of 0.459, and between axillary rCR and pCR, the value was 0.384. During a median follow-up time of 48.0 months, the 5-year RFS rates were 90.6% for breast rCR, and 69.2% for breast non-rCR. The 5-year RFS rates were 82.3% for axillary rCR, and 68.8% for axillary non-rCR. Patients without breast rCR had a 2.4-fold significant increase in the risk of recurrence (p = 0.004) compared to patients with breast rCR. CONCLUSION: Although rCR correlated with pCR by only moderate to fair degrees, breast rCR was a strong predictor for a favorable RFS outcome.

Response of Triple-negative Breast Cancer Liver Metastasis to Oral Recombinant Methioninase in a Patient-derived Orthotopic Xenograft (PDOX) Model.

BACKGROUND/AIM: The aim of this study was to establish a patient-derived orthotopic xenograft (PDOX) mouse model of liver metastasis of triple-negative breast cancer (TNBC) and examine the efficacy of oral recombinant methioninase (o-rMETase) on the liver metastasis. MATERIALS AND METHODS: TNBC from a patient was implanted in the left hepatic lobe of nude mice to simulate liver metastasis in a PDOX model. Ten days later, all mice underwent laparotomy to measure tumor size and were randomized to three groups: control; o-rMETase 100 U once daily (qd); and o-rMETase 200 U qd. After 9 days of treatment, all mice were sacrificed. RESULTS: At the end of the treatment period for the liver metastasis, the size of liver metastases was 372.6 mm3 in the control group; 160.0 mm3 in the o-rMETase 100 U group; and 245.3 mm3 in the o-rMETase 200 U group. All mice had ascites and 12 out of 14 mice in all groups had mesenteric lymph-node metastasis, as re-metastasis. The mean body-condition score was 1.5 in the control group; 2.4 in the o-rMETase 100 U group; and 2.6 in the o-rMETase 200 U group (control group vs. o-rMETase 200 U group, p<0.05). CONCLUSION: The TNBC liver metastasis was highly aggressive resulting in re-metastasis and ascites. o-rMETase tended to inhibit the liver metastasis and significantly improved the mouse body-condition score. This new PDOX model of TNBC liver metastasis will be useful for identifying effective agents for this recalcitrant disease.

Oral Methioninase Inhibits Recurrence in a PDOX Mouse Model of Aggressive Triple-negative Breast Cancer.

BACKGROUND/AIM: The aim of the study was to use a triple-negative breast cancer (TNBC) patient-derived orthotopic xenograft (PDOX) model to examine the efficacy of oral recombinant methioninase (o-rMETase) against this recalcitrant disease. MATERIALS AND METHODS: The TNBC tumor from a patient was implanted in the right 4th inguinal mammary fat pad of nude mice. Two weeks later, the mice underwent tumorectomy with grossly-negative surgical margins. Two days after tumorectomy the mice were divided in two groups: one control and one treated with o-rMETase. RESULTS: Tumors recurred in all mice. On day 11, the mean recurrent tumor volumes were 936.7 mm3 in the control group and 450.9 mm3 in the o-rMETase group (p<0.05). On day 15, the mean recurrent tumor volumes were 3392.5 mm3 in the control group and 1603.5 mm3 in the o-rMETase group. The mean recurrent tumor weights were 2.1 g in the control group and 1.1 g in the o-rMETase group on day 15. CONCLUSION: o-rMETase is an effective adjuvant treatment for aggressive TNBC.

Serum Vitamin Levels and Their Relationships with Other Biomarkers in Korean Breast Cancer Patients.

Numerous studies have shown that vitamins reduce the risk of cancers, but the relationship between serum vitamin levels and breast cancer is still controversial. In this study, we evaluated serum levels of vitamins in Korean patients with benign breast disease or breast cancer and investigated their associations with clinical and laboratory parameters. Concentrations of vitamin A, D, and E, together with homocysteine and methylmalonic acid as biomarkers of vitamin B12 deficiency, were measured by high-performance liquid chromatography (HPLC) or liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the serum of 104 breast cancer patients, 62 benign breast disease patients, and 75 healthy Korean females. We further assessed possible associations between vitamin levels and breast cancer subtypes, the presence of lymph node metastasis, and tumor stages. Serum concentrations of vitamins A and E were significantly lower in breast cancer patients and in benign breast disease patients than in healthy controls. Severe vitamin D deficiency was more prevalent in breast cancer patients than in healthy controls. Vitamin D level was significantly lower in breast cancer patients with estrogen receptor-negative or triple-negative subtypes than in those with other subtypes. Further research with a larger study population is required to elucidate the role of vitamins in breast cancer.

A Single Low Dose of Eribulin Regressed a Highly Aggressive Triple-negative Breast Cancer in a Patient-derived Orthotopic Xenograft Model.

BACKGROUND/AIM: In the present study, the breast cancer patient-derived orthotopic xenograft (PDOX) model was used to identify an effective drug for a highly aggressive triple negative breast cancer (TNBC). MATERIALS AND METHODS: The TNBC tumor from a patient was implanted in the right 4th inguinal mammary fat pad of nude mice to establish a PDOX model. Three weeks later, 19 mice were randomized into the untreated-control group (n=10) and the eribulin treatment group (n=9, eribulin, 0.3 mg/kg, i.p., day 1). RESULTS: On day 8, eribulin significantly inhibited tumor volume compared to the control group (p<0.01). Eribulin regressed tumors in 3 mice (33.3%) and apparently eradicated them in 6 mice (66.7%). At day 14, tumor regrowth was observed in 2 mice of the eribulin group, which was undetectable on day 8. However, 44.4% (4 out of 9) of the mice in the eribulin group were tumor-free on day 14. CONCLUSION: A single low-dose eribulin was efficacious on a highly aggressive TNBC. The breast cancer PDOX model can be used to identify highly effective drugs for TNBC.

EGFR is a Therapeutic Target in Hormone Receptor-Positive Breast Cancer.

BACKGROUND/AIMS: Despite effective therapeutic strategies for treating hormone receptor-positive (HR+) breast cancer, resistance to endocrine therapy that is either de novo or acquired still occurs. We investigated epidermal growth factor receptor (EGFR) as a therapeutic target for overcoming endocrine resistance in HR+ breast cancer models. METHODS: Using clinical data from 2,166 patients who had HR+ breast tumors and received tamoxifen, we analyzed survival rates. Levels of mRNA and protein expression were analyzed by real-time PCR and western blotting, respectively. Cell viability was analyzed by MTT assays and anchorage-independent growth by soft agar colony-formation assays. Efficacy of tamoxifen and/or gefitinib was analyzed using orthotopic xenograft mouse models. RESULTS: EGFR expression was significantly associated with more advanced stage and higher grade. EGFR expression was different in luminal A-like (Lum A, 1.3%) versus luminal B-like (Lum B, 11.4%) subtypes. On multivariate analyses for survival Lum B subtype EGFR+ tumors showed a hazard ratio (HR) of 5.22 (95% CI, 1.29-21.15, P = 0.020) for overall survival (OS) and HR of 2.91 (95% CI, 1.35-6.28, P = 0.006) for disease-free survival (DFS). Levels of EGFR inversely correlated with ER-α expression. Basal ER-α level was completely blocked by TGFA or EGF treatment. With TGFA pretreatment, ER+ breast cancer cells were resistant to 4-hydroxytamoxifen (4-OHT). Conversely, downregulation of ER-α by TGFA was reversed by gefitinib with recovered sensitivity to 4-OHT. Tumorigenicity of EGFR and ER+ breast cancer cells were significantly decreased by combined tamoxifen and gefitinib. CONCLUSION: Aberrant EGFR expression was associated with poor prognosis in ER+ breast cancers, especially the Lum B subtype. Loss of ER by EGFR activation induced tamoxifen resistance. Therefore, EGFR could be a therapeutic target for overcoming recurrence of ER+ breast cancer with high EGFR expression.

Prediction of axillary pathologic response with breast pathologic complete response after neoadjuvant chemotherapy.

PURPOSE: Many breast cancer patients receive sentinel lymph node biopsy after neoadjuvant chemotherapy (NAC). We evaluated the axillary pathologic complete response (pCR) in relation to achievement of breast pCR. METHODS: We evaluated 1044 patients who were diagnosed with invasive breast cancer and were treated with NAC followed by curative surgery at the Samsung Medical Center between January 2008 and December 2016. The pathologic node-positive rates in breast pCR patients were compared for different breast cancer subtypes and clinical nodal stages. RESULTS: Axillary pCR was achieved in 51.9% of the patients after NAC. In this case, the axillary pCR was associated with a biologic subtype (P < 0.0001), initial clinical tumor stage (P < 0.0001), clinical nodal stage (P = 0.0071), and breast pCR (P < 0.0001). In particular, axillary pCR correlated more than 80% with breast pCR (87.1%) or clinical nodal stage N0 (81.0%). Patients with breast pCR had 96.4% axillary pCR in clinical nodal stage N0, 86.1% in N1, and 84.7% in N2/N3. CONCLUSION: Our study may help to predict node-positive rates in patients with breast pCR after NAC according to clinical node stage. Patients with a high probability of achieving pCR might be suitable candidates for more minimal surgery.

Nomogram for accurate prediction of breast and axillary pathologic response after neoadjuvant chemotherapy in node positive patients with breast cancer.

PURPOSE: Many patients with cytology proven node-positive breast cancer receive a neoadjuvant chemotherapy (NAC) treatment. We developed a nomogram to predict the breast and axillary pathologic complete responses (pCR) in patients with a cytologically proven axillary node positive breast cancer with NAC. METHODS: We selected 995 patients who were diagnosed with an invasive breast cancer and axillary lymph nodes metastasis, and who were treated with NAC followed by a curative surgery at the Samsung Medical Center between January 2007 and December 2014. The baseline patient and tumor characteristics, chemotherapy regimen, and tumor and nodal responses were thoroughly analyzed and reviewed. A nomogram was developed using a binary logistic regression model with a cross validation. RESULTS: Axillary pCR was achieved in 47.3% and breast pCR was achieved in 24.3% of the patients after NAC. In this case, the both pCR was associated with an initial clinical tumor stage, negative progesterone receptor status, positive human epidermal growth factor receptor 2 status, and clinical radiologic nodal responses. A nomogram was developed based on the clinical and statistically significant predictors. It had good discrimination performance (area under the curve [AUC], 0.868; 95% confidence interval, 0.84-0.89) and calibration fit as noted in that case. The cross validation had an average AUC 0.853 (0.837-0.869). CONCLUSION: Our nomogram might help to predict breast and axillary pCRs after NAC in patients with an initially node-positive breast cancer. Minimal surgery might be acceptable in patients for whom the nomogram indicates a high probability of achieving pCRs.