Comparison of initial and sequential salvage brain-directed treatment in patients with 1-4 vs. 5-10 brain metastases from breast cancer (KROG 16-12).

PURPOSE: We aimed to compare the initial and salvage brain-directed treatment and overall survival (OS) between patients with 1-4 brain metastases (BMs) and those with 5-10 from breast cancer (BC). We also organized a decision tree to select the initial whole-brain radiotherapy (WBRT) for these patients. METHODS: Between 2008 and 2014, 471 patients were diagnosed with 1-10 BMs. They were divided into two groups based on the number of BM: 1-4 BMs (n = 337) and 5-10 BMs (n = 134). Median follow-up duration was 14.0 months. RESULTS: Stereotactic radiosurgery (SRS)/fractionated stereotactic radiotherapy (FSRT) was the most common treatment modality (n = 120, 36%) in the 1-4 BMs group. In contrast, 80% (n = 107) of patients with 5-10 BMs were treated with WBRT. The median OS of the entire cohort, 1-4 BMs, and 5-10 BMs was 18.0, 20.9, and 13.9 months, respectively. In the multivariate analysis, the number of BM and WBRT were not associated with OS, whereas triple-negative BC and extracranial metastasis decreased OS. Physicians determined the initial WBRT based on four variables in the following order: number and location of BM, primary tumor control, and performance status. Salvage brain-directed treatment (n = 184), mainly SRS/FSRT (n = 109, 59%), prolonged OS by a median of 14.3 months. CONCLUSION: The initial brain-directed treatment differed notably according to the number of BM, which was chosen based on four clinical factors. In patients with ≤ 10 BMs, the number of BM and WBRT did not affect OS. The major salvage brain-directed treatment modality was SRS/FSRT and increased OS.

Immediate breast reconstruction has no impact on the oncologic outcomes of patients treated with post-mastectomy radiation therapy: a comparative analysis based on propensity score matching.

PURPOSE: To investigate the impact of immediate breast reconstruction (iBR) on patients treated with post-mastectomy radiation therapy (PMRT) using propensity score matching (PSM). METHODS: After a retrospective review of patients treated with PMRT between 2008 and 2017, we included 153 patients who underwent iBR and 872 patients who did not undergo iBR. Among the 153 patients who underwent iBR, 34 received one-stage iBR with autologous tissue and 119 received two-stage iBR. Conventional fractionated PMRT with a total dose of 50-50.4 Gy in 25-28 fractions was performed in all patients. Propensity scores were calculated via logistic regression. RESULTS: Patients who underwent iBR were younger, had early stage disease, and had more frequent hormone receptor-positive tumor than those who did not undergo iBR. After PSM, 127 patients from each group with well-balanced characteristics were selected. With a median follow-up of 67.5 months, iBR led to better 6-year disease-free survival rates compared to no iBR before PSM (84.8% vs. 71.4%, p = 0.003); after PSM, there was no significant difference (84.8% vs. 75.5%, p = 0.130). On multivariable analysis in the matched cohort, iBR was not associated with inferior disease-free survival (hazard ratio, 0.67; p = 0.175). In the sensitivity analysis, iBR was not associated with a lower disease-free survival across all prognostic groups. The 5-year cumulative incidence of iBR failure was 15.0%. CONCLUSION: In patients with adverse pathologic factors planning to receive PMRT, iBR did not compromise oncologic outcomes. In addition, iBR can be considered in patients treated with PMRT with several clinicopathologic risk factors.

Determining Which Patients Require Preoperative Pelvic Radiotherapy Before Curative-Intent Surgery and/or Ablation for Metastatic Rectal Cancer.

BACKGROUND: The aim of this study is to determine the optimal indications for preoperative pelvic radiotherapy (RT) in patients with metastatic rectal cancer who underwent curative-intent surgical resection and/or ablation. METHODS: Between January 2000 and October 2019, 246 patients who met our inclusion criteria were enrolled. Preoperative RT was performed in 22 patients (8.9%). Lower margin below the peritoneal reflection (p < 0.001), mesorectal fascia (MRF) invasion (p = 0.02), and lateral pelvic lymph node (LPLN) involvement (p = 0.005) were more frequent in the preoperative RT group. RESULTS: During the median follow-up period of 13.3 months (interquartile range [IQR]: 6.0-36.3 months), local recurrence (LR) was identified in 60 patients (24.4%). It was the first site of recurrence in 45 of them (18.3%). Among them, three patients were in the preoperative RT group. On multivariable analysis, lower margin below the peritoneal reflection, MRF invasion, LPLN involvement, carcinoembryonic antigen (CEA) level ≥ 10 ng/mL before treatment, and preoperative RT were significant prognostic factors for LR-free survival (LRFS). In the patient group without any risk factors, the 2-year LRFS rate was 94.9% without preoperative RT. In the patient group with one or more risk factors, the 2-year LRFS was 64.4% without and 95.2% with preoperative RT. CONCLUSION: LR developed in about 25% of patients within 2 years. Preoperative RT should be considered, especially in patients with a risk factor for LR, including lower margin below the peritoneal reflection, MRF invasion, LPLN involvement, or CEA ≥ 10 ng/mL before treatment.

Dynamics of circulating tumor DNA during postoperative radiotherapy in patients with residual triple-negative breast cancer following neoadjuvant chemotherapy: a prospective observational study.

BACKGROUND: This study was performed to evaluate circulating tumor DNA (ctDNA) kinetics during postoperative radiotherapy (PORT) in patients with residual triple-negative breast cancer (TNBC) at surgery following neoadjuvant chemotherapy (NAC). METHODS: Stage II/III patients with post-NAC residual TNBC who required PORT were prospectively included in this study between March 2019 and July 2020. For 11 TNBC patients, next-generation sequencing targeting 38 genes was conducted in 55 samples, including tumor tissue, three plasma samples, and leukocytes from each patient. The plasma samples were collected at three-time points; pre-PORT (T0), after 3 weeks of PORT (T1), and 1 month after PORT (T2). Serial changes in ctDNA variant allele frequency (VAF) were analyzed. RESULTS: Somatic variants were found in the tumor specimens in 9 out of 11 (81.8%) patients. Mutated genes included TP53 (n = 7); PIK3CA (n = 2); and AKT1, APC, CSMD3, MYC, PTEN, and RB1 (n = 1). These tumor mutations were not found in plasma samples. Plasma ctDNA variants were detected in three (27.3%) patients at T0. Mutations in EGFR (n = 1), CTNNB1 (n = 1), and MAP2K (n = 1) was identified with ctDNA analysis. In two (18.2%) patients, the ctDNA VAF decreased through T1 and T2 while increasing at T2 in one (9.1%) patient. After a median follow-up of 22 months, no patient showed cancer recurrence. CONCLUSION: Among patients with post-NAC residual TNBC, more than a quarter exhibited a detectable amount of ctDNA after curative surgery. The ctDNA VAF changed variably during the course of PORT. Therefore, ctDNA kinetics can serve as a biomarker for optimizing adjuvant treatment.

New brain metastases after whole-brain radiotherapy of initial brain metastases in breast cancer patients: the significance of molecular subtypes (KROG 16-12).

PURPOSE: To identify the risk factors leading to new brain metastases (BM) following brain-directed treatment for initial BM resulting from breast cancer (BC). METHODS: In this multi-institutional study, 538 BC patients with available follow-up imaging after brain-directed treatment for initial BM were analyzed. Tumor molecular subtypes were classified as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-, n = 136), HER2-positive (HER2+, n = 253), or triple-negative BC (TNBC, n = 149). RESULTS: In 37.4% of patients, new BM emerged at a median of 10.5 months after brain-directed treatment for initial BM. The 1-year actuarial rate of new BM for HR+/HER2-, HER2+, and TNBC were 51.9%, 44.0%, and 69.6%, respectively (p = 0.008). Initial whole-brain radiotherapy (WBRT) reduced new BM rates (22.5% reduction at 1 year, p < 0.001) according to molecular subtype (HR+/HER2-, 42% reduction at 1 year, p < 0.001; HER2+, 18.5%, p = 0.004; TNBC, 16.9%, p = 0.071). Multivariate analysis revealed an increased risk of new BM for the following factors: shorter intervals between primary BC diagnoses and BM (p = 0.031); TNBC (relative to HR+/HER2-) (p = 0.016); presence of extracranial metastases (p = 0.019); number of BM (>4) (p < 0.001); and BM in both tentorial regions (p = 0.045). Anti-HER2 therapy in HER2+ patients (p = 0.013) and initial use of WBRT (p < 0.001) significantly lowered new BM development. CONCLUSIONS: Tumor molecular subtypes were associated with both rates of new BM development and the effectiveness of initial WBRT. Anti-HER2 therapy in HER2+ patients significantly lowered new BM occurrence.

Chronological Skin Changes Through Postmastectomy Radiotherapy Based on Radiotherapy Techniques: Using Quantitative Dermatological Measurements.

BACKGROUND: There has been few research on how to measure skin status quantitatively throughout the course of radiotherapy (RT). We evaluated the changes in the skin induced by 2 different RT techniques using objective measurements in breast cancer patients. METHODS: In this prospective study, between August 2015 and March 2019, serial measurements of the dermatological factors during and after postmastectomy radiotherapy (PMRT) were made in 40 breast cancer patients. PMRT was performed using the conventional photon tangential technique (PTT) or patient-tailored bolus technique (PTB). We analyzed these measurements using a mixed effect model and compared the clinically evaluated radiation dermatitis and patient-reported outcomes (PROs). RESULTS: The trend of changes in melanin and erythema was significantly different between the PTB and PTT groups (p = 0.045 and 0.016, respectively). At the 3-month follow-up erythema intensity and melanin were higher in the PTB group than in PTT group (both p < 0.001). Eight patients (40% in the PTB group) reported grade 2 radiation dermatitis and 1 patient (5% in the PTB group) reported grade 3 radiation dermatitis. No grade 2 or higher radiation dermatitis was found in the PTT group. Ten patients (50%) in the PTB group and 3 patients (15%) in the PTT group reported severe erythema likely due to questionable clinical evaluation, but hyperpigmentation was rarely reported at the follow-up visits. CONCLUSION: The PTB group showed higher intensity of erythema at the end of RT than the PTT group and the increase in melanin lasted until the 3-month follow-up visits in the PTB group. Moreover, patients subjectively appealed more severe symptoms following PTB in PROs.

Determining whether postoperative chemoradiotherapy is required in patients with pathologic T3N0 rectal cancer with negative resection margin.

PURPOSE: This study aimed to identify the risk factors for locoregional recurrence (LR) and determine possible candidates for postoperative concurrent chemoradiotherapy (CCRT) in pathologic T3N0 (pT3N0) rectal cancer patients with a negative resection margin after total mesorectal excision (TME). METHOD: Data from 365 patients who had pT3N0 rectal cancer between 2003 and 2012 in the Samsung Medical Center were reviewed. All patients underwent upfront surgery without preoperative treatment. Postoperative management involved either no adjuvant therapy (n = 122), chemotherapy alone (n = 100), or CCRT (n = 143). RESULTS: The median follow-up duration was 71 months. The 5-year overall survival, disease-free survival, and LR-free survival (LRFS) rates were 95.9%, 86.9%, and 96.3%, respectively. When comparing the three groups (surgery alone [n = 122], chemotherapy alone [n = 100], and CCRT [n = 143]), there was no significant difference in LRFS among them (94.0%, 93.4%, and 99.2%, respectively; p = 0.20). However, when patients were stratified by risk factors (distance from anal verge ≤ 5 cm and distal resection margin [DRM] ≤ 2 cm), the 5-year LRFS improved by more than 10% by adding CCRT (98.9% with CCRT vs. 87.4% without CCRT, p = 0.006) in those with more than one risk factor. Postoperative CCRT did not affect the 5-year LRFS (100% with CCRT vs. 99.0% without CCRT, p = 0.66) in patients with no risk factors. CONCLUSION: Postoperative CCRT significantly decreased LR in patients with pT3N0 rectal cancer with a negative resection margin but having a distance from the anal verge ≤ 5 cm or DRM ≤ 2 cm.

Comamonas flocculans sp. nov., a Floc-Forming Bacterium Isolated from Livestock Wastewater.

A Gram-negative, aerobic, non-motile, rod-shaped, floc-forming, and non-spore-forming bacterium, designated as NLF-7-7T, was isolated from the biofilm of a sample collected from a livestock wastewater treatment plant in Nonsan, Republic of Korea. Strain NLF-7-7T, forms a visible floc and grows in the flocculated state. Cells of strain NLF-7-7T grew optimally at pH 6.5 and 30 °C and in the presence of 0.5% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain NLF-7-7T belonged to the family Comamonadaceae, and was most closely related to Comamonas badia DSM 17552T (95.8% similarity) and Comamonas nitrativorans 23310T (94.0% similarity). The phylogenetic and phenotypic data indicate strain NLF-7-7T is clearly distinguished from the Comamonas lineage. The major cellular fatty acids were C10:0 3OH, C16:0, and summed feature 3 (C16:1 ω6c/C16:1 ω7c). The respiratory quinone was Q-8. The polar lipids were composed of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, and an unidentified aminolipid. The DNA G+C content of strain NLF-7-7 was 68.0 mol%. Based on the phenotypic, chemotaxonomic, and phylogenetic properties, strain NLF-7-7T represents a novel species of the genus Comamonas, for which the name Comamonas flocculans sp. nov. is proposed. The type strain is C. flocculans NLF-7-7T (=KCTC 62943T). The GenBank/EMBL/DDBJ accession number for the 16S rRNA gene sequence of Comamonas flocculans NLF-7-7T is MN527436. The whole-genome shotgun BioProject Number is PRJNA555370 with the Accession Number CP042344.

Checkpoint Kinase 1 (CHK1) Inhibition Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to Proton Irradiation via Rad51 Downregulation.

Due to a superior dose conformity to the target, proton beam therapy (PBT) continues to rise in popularity. Recently, considerable efforts have been directed toward discovering treatment options for use in combination with PBT. This study aimed to investigate the targeting of checkpoint kinase 1 (CHK1), a critical player regulating the G2/M checkpoint, as a promising strategy to potentiate PBT in human triple-negative breast cancer (TNBC) cells. Protons induced cell-cycle arrest at the G2/M checkpoint more readily in response to increased CHK1 activation than X-rays. A clonogenic survival assay revealed that CHK1 inhibition using PF-477736 or small interfering RNA (siRNA) enhanced the sensitivity toward protons to a greater extent than toward X-rays. Western blotting demonstrated that PF-477736 treatment in the background of proton irradiation increased the pro-apoptotic signaling, which was further supported by flow cytometry using annexin V. Immunofluorescence revealed that proton-induced DNA double-strand breaks (DSBs) were further enhanced by PF-477736, which was linked to the downregulation of Rad51, essential for the homologous recombination repair of DSBs. Direct inactivation of Rad51 resulted in enhanced proton sensitization. Collectively, these data suggest that targeting CHK1 may be a promising approach for improving PBT efficacy in the treatment of TNBC.

Germline BRCA Mutation and Clinical Outcomes in Breast Cancer Patients Focusing on Survival and Failure Patterns: A Long-Term Follow-Up Study of Koreans.

Background and Objectives: This study aimed to evaluate the effect of a BRCA mutation on survival and failure patterns, focusing on the risk of ipsilateral recurrence and contralateral breast cancer in patients. Materials and Methods: We retrospectively reviewed medical records of 300 patients with breast cancer who underwent genetic screening for BRCA1/2 genes and were treated at Samsung Medical Center between 1 January 2000 and 31 December 2010. Ultimately, clinical outcomes of 273 patients were analyzed. Results: The median follow-up duration was 102 months (range, 1 to 220 months). Patients with BRCA1/2-mutated tumors had a shorter 10-year disease-free survival (DFS) rate compared to those with non-mutated tumors (62.8% vs. 80.0%, p = 0.02). Regarding failure patterns, patients with BRCA1/2-mutated tumors showed a higher incidence of contralateral breast cancer than those with non-mutated tumors (BRCA1/2 non-mutated vs. mutated tumors: 4.9% vs. 26.0%, p < 0.001). BRCA mutation status remained a significant prognostic factor for contralateral breast recurrence-free survival (HR: 4.155; 95% CI: 1.789-9.652; p = 0.001). Korean patients with a BRCA mutation showed inferior DFS compared to those without a BRCA mutation. Conclusions: BRCA mutation status is a strong predictor of recurrence in contralateral breast cancer. Strategies such as prophylactic treatment and active surveillance should be discussed with breast cancer patients who have a BRCA mutation.

Prevalence and oncologic outcomes of BRCA 1/2 mutations in unselected triple-negative breast cancer patients in Korea.

PURPOSE: Triple-negative breast cancer (TNBC) accounts for 10-20% of all diagnosed BCs and it is enriched in BRCA1 mutation. Guidelines for Western countries suggest that BRCA 1/2 genetic testing should be done for patients with TNBC diagnosed less than 60 years, but there is lack of evidence supporting genetic testing in Asian populations. We determined the prevalence of germline BRCA 1/2 mutations among unselected Korean patients with TNBC and analyzed oncologic outcomes. METHODS: From among 1628 women with TNBC who underwent surgery at Samsung Medical Center (SMC) between Jul 2008 and Jan 2016, 999 samples were available in the SMC biobank for testing germline BRCA 1/2 mutations using next-generation DNA sequencing. RESULTS: Overall, 131 Korean patients (13.1%) had BRCA 1/2 mutations: 97 (9.7%) were in BRCA 1, and 35 (3.5%) were in BRCA 2. One patient had both BRCA 1 and BRCA 2 mutations. Overall, 68 distinct pathologic or likely pathogenic variants (43 BRCA1 and 25 BRCA2) were found. Among those diagnosed at ≤ 60 years, the prevalence of BRCA 1/2 mutation was 14.5%. The mean age of diagnosis of BRCA1/2 mutation carriers was significantly younger than that of non-carriers (45.6 vs. 50.1 years, p < 0.0001). The median follow-up duration was 53.6 months. There were no significant differences in disease-free survival, overall survival, or breast cancer-specific survival (p = 0.799, 0.092, and 0.124, respectively) between BRCA 1/2 carriers and non-carriers, although BRCA 1/2 carriers showed significantly worse contralateral breast cancer-free survival (p < 0.0001) than non-carriers. CONCLUSION: In unselected TNBC patients, we found BRCA 1/2 mutations in 13.1% of overall patients and 14.5% of patients ≤ 60 years. We suggest that Korean women with TNBC diagnosed at ≤ 60 years should be tested for BRCA1/2 mutation.

Heart-sparing radiotherapy with three-dimensional printing technology after mastectomy for patients with left breast cancer.

The purpose of this study was to analyze the effectiveness of electron beam therapy (EBT) with patient-tailored bolus (PTB) using three-dimensional printing technology to reduce heart and lung doses during post-mastectomy radiotherapy (PMRT). For 28 patients with left breast cancer, we designed customized virtual bolus for PMRT to compensate for surface irregularities on computed tomography images and developed optimized plans for EBT. As comparison between the PTB and tangential plans, the PTB plan reduced unnecessary exposure to heart and ipsilateral lung with better target coverage compared with the tangential technique.

The association between non-breast and ovary cancers and BRCA mutation in first- and second-degree relatives of high-risk breast cancer patients: a large-scale study of Koreans.

BACKGROUND: As a large-scale study of Koreans, we evaluated the association between BRCA mutation and the prevalence of non-breast and ovary cancers in first- and second-degree relatives of high-risk breast cancer patients. METHODS: We organized familial pedigrees of 2555 patients with breast cancer who underwent genetic screening for BRCA1/2 in Samsung Medical Center between January 2002 and May 2018. Families with a member that had a history of cancer other than of the breast or ovary were regarded positive for other primary cancer. RESULTS: The median age of the population was 40 years (range, 19 to 82 years). BRCA mutation was detected in 377 (14.8%) of the patients. The BRCA-positive group had a higher frequency of family history of breast or ovarian cancer (p <  0.001), bilateral breast cancer (p = 0.021), and the male gender (p = 0.038). There were 103 (27.3%) patients who had multiple risk factors in the BRCA-positive group, while there were 165 (7.6%) patients who had multiple risk factors in the BRCA-negative group (p <  0.001). BRCA mutation was detected in 215 (11.7%) of the 1841 families without history of other primary cancers. Among the 714 families with histories of other primary cancers, 162 (22.7%) had BRCA mutation, and this was significantly more frequent (p < 0.001) than in those without a history. The occurrence of other primary cancers in families of high-risk patients was associated with a younger age at diagnosis (p = 0.044), bilateral breast cancer (p = 0.006), and BRCA mutations (p < 0.001). The most common site for the occurrence of another type of primary cancer was the stomach. In the BRCA-positive group, the proportional incidences of stomach, pancreas, colorectal, lung, and uterine cancer were 13.8, 4.0, 7.7, 8.8, and 5.0%, respectively; these were all relatively higher than those in the BRCA-negative group. CONCLUSIONS: We confirmed that BRCA mutation was associated with having multiple risk factors and an increased prevalence of non-breast and ovary cancers in first- and second-degree relatives of high-risk breast cancer patients. Due to the possibility of inherited cancer risk, genetic counseling with options for risk assessment and management should be provided to both patients and families of BRCA mutation carriers.

Cyclin D1 is Associated with Radiosensitivity of Triple-Negative Breast Cancer Cells to Proton Beam Irradiation.

Proton therapy offers a distinct physical advantage over conventional X-ray therapy, but its biological advantages remain understudied. In this study, we aimed to identify genetic factors that contribute to proton sensitivity in breast cancer (BC). Therefore, we screened relative biological effectiveness (RBE) of 230 MeV protons, compared to 6 MV X-rays, in ten human BC cell lines, including five triple-negative breast cancer (TNBC) cell lines. Clonogenic survival assays revealed a wide range of proton RBE across the BC cell lines, with one out of ten BC cell lines having an RBE significantly different from the traditional generic RBE of 1.1. An abundance of cyclin D1 was associated with proton RBE. Downregulation of RB1 by siRNA or a CDK4/6 inhibitor increased proton sensitivity but not proton RBE. Instead, the depletion of cyclin D1 increased proton RBE in two TNBC cell lines, including MDA-MB-231 and Hs578T cells. Conversely, overexpression of cyclin D1 decreased the proton RBE in cyclin D1-deficient BT-549 cells. The depletion of cyclin D1 impaired proton-induced RAD51 foci formation in MDA-MB-231 cells. Taken together, this study provides important clues about the cyclin D1-CDK4-RB1 pathway as a potential target for proton beam therapy in TNBC.

Malignant and borderline phyllodes tumors of the breast: a multicenter study of 362 patients (KROG 16-08).

PURPOSE: To identify risk factors for local recurrence (LR) and investigate roles of adjuvant local therapy for malignant and borderline phyllodes tumors of the breast. METHODS: From 1981 to 2014, 362 patients with malignant (n = 235) and borderline (n = 127) phyllodes tumors were treated by breast-conserving surgery (BCS) or total mastectomy (TM) at 10 centers. Thirty-one patients received adjuvant radiation therapy (RT), and those who received adjuvant chemotherapy were excluded from the study. RESULTS: Median follow-up was 5 years. LR developed in 60 (16.6%) patients. Regional recurrence occurred in 2 (0.6%) patients and distant metastasis (DM) developed in 19 (5.2%) patients. Patients receiving BCS (p = 0.025) and those not undergoing adjuvant RT (p = 0.041) showed higher LR rates. For malignant subtypes, local control (LC) rates at 5 years for BCS alone, BCS with adjuvant RT, TM alone, and TM with adjuvant RT were 80.7, 93.3, 92.4, and 100%, respectively (p = 0.033). Multivariate analyses revealed BCS alone, tumor size ≥ 5 cm, and positive margins as independent risk factors for LR. Margin-positive BCS alone showed poorest LC regardless of tumor size (62.5%, p = 0.007). For margin-negative BCS alone, 5-year LC rates for tumors ≥ 5 cm versus those < 5 cm were 71.8% versus 89.5% (p = 0.012). For borderline subtypes, only positive margins (p = 0.044) independently increased the risk of LR. DM developed exclusively in malignant subtypes and a prior LR event increased the risk of DM by sixfold (HR 6.2, 95% CI 1.6-16.1, p = 0.001). CONCLUSIONS: Malignant and borderline phyllodes tumors with positive margins after surgery have high LR rates. After treatment by margin-negative BCS alone, patients with large malignant phyllodes tumors ≥ 5 cm also have heightened risk of LR. Thus, such patients should be considered for additional local therapy.

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

PURPOSE: This 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. METHODS: A 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. RESULTS: Six patients (2.5 %) were found to have pathogenic variants in CHEK2 (n = 1), PALB2 (n = 2), MRE11 (n = 1), and RAD50 (n = 2). 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. CONCLUSIONS: Pathogenic variants in CHEK2, PALB2, MRE11, and RAD50 were detected in a small proportion of Korean patients with features of hereditary breast cancer.

Recurrence outcomes after omission of postoperative radiotherapy following breast-conserving surgery for ductal carcinoma in situ of the breast: a multicenter, retrospective study in Korea (KROG 16-02).

PURPOSE: To evaluate the loco-regional recurrence (LRR) rate after breast-conserving surgery without postoperative radiotherapy (RT) for ductal carcinoma in situ (DCIS) of the breast. METHODS: Between 2000 and 2010, 311 DCIS patients from 9 institutions were analyzed retrospectively. The median age was 47 (range, 20-82). The median tumor size was 7 mm (range, 0.01-76). Margin width was <1 cm in 85 patients (27.3%), and nuclear grade was high in 37 patients (11.9%). Two hundred and three patients (65.3%) received tamoxifen. RESULTS: With a median follow-up of 74 months (range, 5-189), there were 11 local recurrences (invasive carcinoma in 6 and DCIS in 5) and 1 regional recurrence. The 7-year LRR rate was 3.8%. On univariate analysis, age and margin width were significant risk factors influencing LRR (p = 0.017 and 0.014, respectively). When age and margin width were combined among 211 patients whose margin width were available, the 7-year LRR rates were as follows (p < 0.001): (1) 0% in patients with age >50 years and any margin width status (n = 64), (2) 1.2% in age ≤50 years and margin width ≥1 cm (n = 93), (3) 13.1% in age ≤50 years and margin width <1 cm (n = 54). CONCLUSIONS: The LRR rate was very low in selected DCIS patients treated with breast-conserving surgery without postoperative RT. However, adjuvant RT should be considered for those with age ≤50 years and margin width <1 cm.

Patient-reported symptoms of radiation dermatitis during breast cancer radiotherapy: a pilot study.

PURPOSE: To find out which symptoms most frequently and severely affect breast cancer patients during radiotherapy and how patients manage the symptoms and unmet needs. METHODS: A cross-sectional survey was conducted with 111 patients who receive radiotherapy for breast cancer from January to April 2015 at Samsung Medical Center in Seoul, South Korea. Participants were asked about symptoms and discomfort due to radiotherapy, management methods for radiation dermatitis, unmet needs for radiation dermatitis care, and clinical and socio-demographic information. RESULTS: Of total, 108 out of 111 patients (97.3%) reported symptoms related to radiation dermatitis. Hyperpigmentation was the most commonly reported uncomfortable symptom followed by erythema. On average, patients reported 8.6 radiotherapy-induced skin problems (range, 0-11). Of total, 59 (53.2%) patients stated that they wanted care for radiation dermatitis, and 80.0, 59.4, and 51% of patients searched for information, used products, and visited the hospital to manage radiotherapy-related skin problems. Patients who experienced dryness, burning feelings, irritation, roughness, and hyperpigmentation were 11.73, 7.02, 5.10, 4.27, and 2.80 times more likely to have management needs than patients without those symptoms, respectively, adjusting age, current cycle of radiation therapy, chemotherapy, and type of surgery. CONCLUSIONS: Most of the breast cancer patients experience multiple symptoms associated with radiation dermatitis. Hyperpigmentation was the most common and uncomfortable symptom followed by erythema. Majority of patients wanted management for radiation dermatitis and patients who experienced dryness, burning feelings, irritation, roughness, and hyperpigmentation had higher needs for radiation dermatitis management.

Does internal mammary node irradiation affect treatment outcome in clinical stage II-III breast cancer patients receiving neoadjuv ant chemotherapy?

The purpose of this study is to assess the value of internal mammary node irradiation (IMNI) in patients receiving postoperative radiotherapy after neoadjuvant chemotherapy (NAC) using modern systemic therapy. Between 2001 and 2009, 521 consecutive patients with clinical stage II-III breast cancer received NAC and postoperative radiotherapy. With a consistent policy, the treating radiation oncologist either included (N = 284) or excluded (N = 237) the internal mammary node in the treatment volume. Anthracycline- and taxane-based chemotherapy was provided to 482 (92.5 %) patients. To account for the unbalanced characteristics between the two groups, we performed propensity score matching and covariate adjustment using the propensity score. The median follow-up duration was 71 months (range 31-153 months). The 5-year disease-free survival (DFS) with and without IMNI was 81.8 and 72.7 %, respectively (p = 0.019). The benefit of IMNI varied according to patient characteristics such that it was more apparent in patients with N1-2 disease, inner/central location, and triple-negative subtype. After adjusting for all potential confounding variables, IMNI was independently associated with improved DFS (p = 0.049). The significant effect of IMNI on DFS was sustained after propensity score matching (p = 0.040) and covariate adjustment using the propensity score (p = 0.048). Symptomatic radiation pneumonitis developed in 9 (3.2 %) patients receiving IMNI. Our results indicated that IMNI was associated with a significant improvement in DFS with low toxicity rate for breast cancer patients receiving NAC. Further prospective studies are warranted to confirm the effect of IMNI in the NAC setting.

Is Chemoradiotherapy Beneficial for Stage IV Rectal Cancer?

PURPOSE: The aim of this study was to investigate the oncologic impact of preoperative or postoperative chemoradiotherapy on stage IV rectal cancer. METHODS: A total of 140 consecutive patients with locally advanced mid-to-lower rectal cancer and resectable stage IV disease were prospectively enrolled. In total, 69 patients received chemoradiotherapy (26 preoperatively and 43 postoperatively); in contrast, 71 did not. Survival curves were constructed using the Kaplan-Meier method, and a multivariate analysis was performed to identify independent prognostic factors. RESULTS: According to the multivariate analysis, radiation therapy was not an independent factor associated with either survival or recurrence. The overall survival curves revealed that patients who underwent radiotherapy tended to have a better survival compared with patients who did not undergo radiotherapy; however, this trend was not statistically significant (p = 0.057). The disease-free, local recurrence-free, and distant metastasis-free survival curves did not differ significantly between the two groups. The local recurrence-free survival rates for patients who underwent preoperative radiotherapy were significantly higher than those for patients who underwent postoperative radiotherapy (p = 0.042). CONCLUSION: Preoperative radiotherapy, rather than postoperative radiotherapy, may improve local control of stage IV rectal cancer. However, chemoradiotherapy did not improve the survival of patients with stage IV rectal cancer in this study.