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Purpose Docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) regimen is frequently used to treat early and locally advanced human epidermal growth factor receptor 2 (HER2)–positive breast cancer (BC) in neoadjuvant setting. However, large-scaled real-world evidence did not exist.Materials and Methods We retrospectively reviewed medical records of patients with early or locally advanced HER2-positive BC who underwent neoadjuvant TCHP followed by curative surgery at Samsung Medical Center between January 2016 and August 2020.Results Of 447 patients, 316 (70.7%) received breast-conserving surgery and 131 (29.3%) received total mastectomy. In terms of neoadjuvant chemotherapy response, pathologic complete response (pCR) and residual cancer burden (RCB) score were analyzed. The rate of pCR was 64% a class of RCB 0 was observed in 65% of cases, RCB class I in 12%, RCB class II in 14%, and RCB class III in 2%. The 3-year event-free survival rate was 90.6%, BC with pCR occurred in 92.8%, and BC with non-pCR in 86.3% (p=0.016). In terms of distant metastasis, the 3-year distant recurrence-free survival rate was 93.5%; BC with pCR occurred in 95.9% and BC with non-pCR in 89.2% (p=0.013). Mucositis (85.2%), pain (83.2%), and diarrhea (70.5%) were the most common non-hematologic adverse events. In terms of hematologic adverse events, anemia (89.9%) was the most commonly observed adverse events followed by thrombocytopenia (29.8%).Conclusion Neoadjuvant TCHP therapy had a pCR rate of 64% and a 3-year event-free survival of 90% in real world experience. In terms of toxicity profile, anemia was frequently observed and adequate management including occasional transfusion was required.

Due to the rarity of primary angiosarcoma of the breast, optimal management is based on expert opinion. The aim of this study was to review all primary angiosarcomas of the breast obtained from a single center in terms of clinicopathologic characteristics, treatment, and survival outcomes. From 1997 to 2020, 15 patients with primary angiosarcoma of the breast underwent either mastectomy or wide excision. We analyzed the clinicopathologic data to assess disease-free survival and overall survival. Fifteen women with primary angiosarcoma of the breast were identified. The mean age at diagnosis was 33 years (range: 14–63 years). The overall mean tumor size was 7.7 cm (range 3.5–20 cm). Upon histological grading, there were three cases of low grade, five intermediate grade, six high grade, and one unidentified grade. The five-year disease-free survival rate was 24.4%, and the five-year survival rate was 37.2%. The survival rate of the low-grade patient group was statistically higher than that of the intermediate- or high-grade patient groups (p = 0.024). Primary angiosarcoma of the breast is a rare aggressive tumor characterized by high grade and poor outcome. Histologic grade appears to be a reliable predictor of survival. There are no standard treatment guidelines; thus, optimal R0 surgical resection remains the best approach. The roles of neoadjuvant, adjuvant chemotherapy, and radiotherapy remain unclear.

The American Society of Clinical Oncology and College of American Pathologists guidelines for HER2 testing in breast cancer (BC) have been updated with more stringent criteria regarding immunohistochemistry (IHC) 2 + interpretation. The aim of our study was to determine HER2 status in IHC 2 + cases based on 2013 and 2018 guidelines and to investigate specific histologic characteristics that might predict HER2 status in tumors with equivocal IHC staining. Two hundred eighty BC cases reported as IHC 2 + and 24 cases reported as non-IHC 2 + were reviewed with 12 histologic characteristics. Of the IHC 2 + cases based on 2013 guideline, 21% were reclassified to IHC 1 + when applying the 2018 guidelines. Consequently, it led to an 8% increase of HER2 amplification rate in 2018 IHC 2 + group. Seven characteristics were significantly associated with prediction of HER2 amplification in IHC 2 + BCs, including high tumor-infiltrating lymphocytes (TILs), distinct cellular membrane, no apical snout, large nuclear size, nuclear size variation, high nuclear grade, and tubule formation 10%. Using these criteria, the presence of four or more characteristics significantly indicates HER2 amplification. Moreover, four characteristics among them, including high TILs, distinct cellular membrane, nuclear size variation, and high nuclear grade, were also associated with HER2 amplification in non-IHC 2 + cases, demonstrating their predictive value as complements to IHC. In conclusion, we provide specific morphologic features that will improve pathologist performance in identifying more HER2-positive BCs. We further suggest an algorithm for trastuzumab therapy decisions using a combination of histomorphologic evaluation and the updated 2018 guidelines.

BackgroundThe aim of this study was to develop a machine learning(ML) based model to accurately predict pathologic complete response(pCR) to neoadjuvant chemotherapy(NAC) using pretreatment clinical and pathological characteristics of electronic medical record(EMR) data in breast cancer(BC).Methods The EMR data from patients diagnosed with early and locally advanced BC and who received NAC followed by curative surgery were reviewed. A total of 16 clinical and pathological characteristics was selected to develop ML model. We practiced six ML models using default settings for multivariate analysis with extracted variables. ResultsIn total, 2,065 patients were included in this analysis. Overall, 30.6% (n=632) of patients achieved pCR. Among six ML models, the LightGBM had the highest area under the curve (AUC) for pCR prediction. After hyper-parameter tuning with Bayesian optimization, AUC was 0.810. Performance of pCR prediction models in different histology-based subtypes was compared. The AUC was highest in HR+HER2- subgroup and lowest in HR-/HER2- subgroup (HR+/HER2- 0.841, HR+/HER2+ 0.716, HR-/HER2 0.753, HR-/HER2- 0.653).ConclusionsA ML based pCR prediction model using pre-treatment clinical and pathological characteristics provided useful information to predict pCR during NAC. This prediction model would help to determine treatment strategy in patients with BC planned NAC.

Both skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) have been widely adopted. Although postmastectomy radiation therapy (PMRT) can improve clinical outcomes, it can worsen cosmesis following reconstruction. Therefore, identifying risk factors of ipsilateral breast tumor recurrence (IBTR) could help de-escalate PMRT after NSM/SSM in patients with pT1-2 disease.We retrospectively reviewed patients treated with SSM (N = 400) and NSM (N = 156) in patients with pT1-2N0-1 disease between 2009 and 2016. Seventy-four patients received PMRT with 50-50.4 Gy in 25-28 fractions. The Cox proportional hazards model was used to analyze the prognostic factors of IBTR.With a median follow-up of 66.2 months, 17 IBTR events were observed, with 5-year IBTR-free rate of 97.2%. Although only one IBTR was observed after PMRT, there was no statistical difference in the 5-year IBTR-free rate (PMRT vs. no PMRT, 98.6% vs. 97.0%, p = 0.360). Multivariable analyses demonstrated that age ≤45 years and lymphovascular invasion (LVI) were adverse features of IBTR. The low-risk group (0 risk factor) showed a better 5-year IBTR-free rate than the high-risk group (≥1 risk factor) (100.0% vs. 95.8%, p = 0.003). In the high-risk group, PMRT slightly improved 5-year IBTR-free rate compared with no PMRT (98.6% vs. 95.2%, p = 0.166). In addition, PMRT increased 5-year cumulative incidence of reconstruction failure (10.0% vs. 2.8%, p = 0.001).We identified risk factors (age and LVI) related to IBTR following upfront SSM/NSM with pT1-2 disease. As a hypothesis-generating study, de-escalation of PMRT by omitting chest wall irradiation in selective patients could improve reconstruction-related complications without compromising oncologic outcomes.

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.

Breast-conserving surgery (BCS) has been reported to have better survival rates when compared with total mastectomy (TM) in early breast cancer. We evaluated the long-term outcomes of Korean women with early breast cancer who underwent either BCS plus radiotherapy (RT) or TM. In this population-based study, we evaluated 45,770 patients from the Korean Breast Cancer Registry (KBCR) who were diagnosed with early breast cancer, and divided them into the BCS + RT and TM groups. To minimize bias caused by factors other than the surgical method, we used exact match pairing of prognostic factors. We compared the 10-year overall survival (OS) and breast cancer-specific survival (BCSS) before and after exact matching. As the KBCR is a multicenter, online-based registry program, we used the Asan Medical Center (AMC) database, a single-center database, to validate the results from the KBCR database. In both the KBCR and AMC cohorts, the BCS + RT group showed better OS and BCSS than the TM group, before and after exact matching. For the KBCR cohort after exact matching, the hazard ratios for OS and BCSS were 1.541 (95% confidence interval [CI] 1.392–1.707, p

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

OBJECTIVES To investigate the efficacy of health coaching and a web-based program on survivor physical activity (PA), weight, and distress management among stomach, colon, lung and breast cancer patients. METHODS This randomised, controlled, 1-year trial conducted in five hospitals recruited cancer survivors within 2 months of completing primary cancer treatment who had not met ≥1 of these behavioural goals: (i) conducting moderate PA for at least 150 minutes/week or strenuous exercise for over 75 minutes per week or, in the case of lung cancer patients, low or moderate intensity exercise for over 12.5 MET per week, (ii) maintaining normal weight, and (iii) attaining a score >72 in the Post Traumatic Growth Inventory (PTGI). Participants were randomly assigned to one of three groups: the control group, a web-only group, or a health coaching + web group. The primary endpoint was based on a composite of PA, weight, and PTGI score at 12 months. RESULTS Patients in the health coaching + web group (difference = 6.6%, P = .010) and the web-only group (difference = 5.9%, P = .031) had greater overall improvements across the three-outcome composite than the control group. The health coaching + web group had greater overall improvement in PTGI (difference = 12.6%; P

Objective Demands for genetic counseling with BRCA1/2 examination have markedly increased. Accordingly, the incidence of uninformative results on BRCA1/2 mutation status has also increased. Because most patients examined for BRCA1/2 mutation have a high risk of hereditary breast and/or ovarian cancer, many patients suffer psychological distress even when the BRCA1/2 result is negative. We compared oncological outcomes between BRCA1/2-negative breast cancer with high risk of hereditary breast and/or ovarian cancer and sporadic breast cancer without risk of hereditary breast and/or ovarian cancer. Methods The criteria for high risk for hereditary breast and/or ovarian cancer were defined as family history of breast and/or ovarian cancer in first- or second-degree relative, early onset breast cancer at Results All matching variables were successfully matched. Median follow-up duration was 57.8 months. There was no significant difference between the groups in disease-free survival (log-rank P = 0.197); however, the study group showed significantly better overall survival and breast cancer-specific survival (both P Conclusions BRCA1/2-negative breast cancer patients who had hereditary breast and/or ovarian cancer risk factors showed similar disease-free survival and better overall survival and breast cancer-specific survival compared with those with sporadic breast cancer without hereditary breast and/or ovarian cancer risk factors.

PURPOSE The aim of this study was to translate and linguistically validate a Korean-language version of the US National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). METHODS All 124 PRO-CTCAE items were translated into Korean (PRO-CTCAE-Korean) using International Society for Pharmacoeconomics and Outcomes Research best practices and linguistically validated in a diverse sample of patients undergoing cancer treatment (n = 120) to determine whether the Korean translation captured the original concepts. During the cognitive interviews, participants first completed approximately 60 PRO-CTCAE-Korean questions and were then interviewed to evaluate the conceptual equivalence of the translation to the original PRO-CTCAE English-language source. Interview probes addressed comprehension, clarity, and ease of judgement. Three rounds of interviews were conducted. Items that met the a priori threshold of 10% or more of respondents with comprehension difficulties were considered for rephrasing and retesting. RESULTS A majority of PRO-CTCAE-Korean items were well comprehended in round 1; 14 items posed comprehension difficulties for at least 10% of respondents in round 1. Four symptom terms (mouth and throat sores, feeling like nothing could cheer you up, frequent urination, and pain, swelling, redness at drug injection or intravenous insertion site) were revised and retested in rounds 2 and 3. For the other 10 symptom terms, no suitable alternative phrasing was identified, and the terms were retested in rounds 2 and 3. After rounds 2 and 3, no item presented difficulties in 20% or more of participants. CONCLUSION PRO-CTCAE-Korean has been linguistically validated for use in Korean-speaking populations. Quantitative evaluation of this new measure to establish its measurement properties and responsiveness in Korean speakers undergoing cancer treatment is in progress.

Purpose Double heterozygosity (DH) for BRCA1 and BRCA2 variant is very rare with only a few cases reported, and most those in Caucasians. In this article, we present seven unrelated cases of DH for BRCA1/2 identified from a single institution in Korea, and describe the characteristics and phenotype of DH individuals compared to those with a single BRCA variant.Materials and Methods This study included 27,678 patients diagnosed with breast cancer and surgically treated at Samsung Medical Center (SMC) between January 2008 and June 2020. In total, 4,215 high-risk breast cancer patients were tested for the BRCA1/2 genes, and electronic medical records from 456 cases with pathogenic/likely pathogenic variants (PVs/LPVs) were reviewed.ResultsA younger mean age at diagnosis was associated with DH than a single variant of BRCA1/2. More triple-negative breast cancer (TNBC) and higher nuclear and histologic grade cancer occurred with DH than BRCA2 variant. All 7 cases of DH were unrelated, and their mutation combinations were different. There were no Ashkenazi founder variants detected.ConclusionWe suggest that patients with DH for BRCA1/2 variants develop breast cancer at a younger age, but the histopathologic features are similar to those of BRCA1.

Purpose Little is known about the impact of financial toxicity in disease-free breast cancer survivors. We aim to validate the COmprehensive Score for financial Toxicity in Korean (COST-K) and evaluate financial toxicity among disease-free breast cancer survivors.Materials and Methods We conducted linguistic validation following a standardized methodology recommended by Functional Assessment of Chronic Illness Therapy multilingual translation (FACITtrans). For psychometric validation, we conducted a cross-sectional survey with 4,297 disease-free breast cancer survivors at a tertiary hospital in Seoul, Korea between November 2018 and April 2019. Survivors were asked to complete the COST-K and European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) questionnaires. The test-retest reliability, internal consistency, and validity of the COST-K were assessed using standard scale construction techniques.Results The COST-K demonstrated good internal consistency, with a Cronbach’s α of 0.81. The test-retest analysis revealed an intraclass correlation coefficient of 0.78. The COST-K had moderate correlation (r=–0.60) with the financial difficulty item of the EORTC QLQ-C30 and week correlation with the items on acute and chronic symptom burdens (nausea/vomiting, –0.18; constipation, –0.14; diarrhea, –0.14), showing good convergent and divergent validity. The median COST-K was 27 (range, 0 to 44; mean±standard deivation [SD], 27.1±7.5) and about 30% and 5% of cancer survivors experienced mild and severe financial toxicity, respectively. Younger age, lower education, lower household income was associated with higher financial toxicity.Conclusion The COST-K is a valid and reliable instrument for measuring financial toxicity in disease-free breast cancer survivors. Considering its impact on the health-related quality of life, more studies need to be conducted to evaluate financial toxicity in cancer survivors and design interventions.

Decision to undergo risk-reducing mastectomy (RRM) needs to consider several factors, including patient’s preference, surgeon’s preference, family history, and genetic predisposition. The aim of this study was to examine whether preoperative diagnosis of BRCA1/2 mutation status could influence surgical decision-making in newly diagnosed breast cancer patients. We retrospectively reviewed ipsilateral breast cancer patients with BRCA1/2 mutation who underwent primary surgery between January 2008 and November 2019 at a single institution in Korea. Of 344 eligible patients, 140 (40.7%) patients were aware of their mutation status ‘prior to surgery’, while 204 (59.3%) did not. Contralateral RRM rate was significantly higher in the group with BRCA1/2 mutation status identified ‘prior to surgery’ compared to the group with mutation status identified ‘after surgery’ [45.0% (63/140) vs. 2.0% (4/204)] (p BRCA1/2 testing (p p BRCA1/2 mutation status identified prior to surgery. Although not statistically significant, higher incidence of developing contralateral breast cancer for BRCA1/2 mutation carriers who underwent ipsilateral surgery-only compared to those who underwent contralateral RRM was observed [12.1% (95% CI: 7.7–17.7%)] (p = 0.1618). Preoperative diagnosis of BRCA1/2 mutation could impact surgical decision-making for breast cancer patients to undergo risk-reducing surgery at the time of initial surgery.

To investigate the impact of immediate breast reconstruction (iBR) on patients treated with post-mastectomy radiation therapy (PMRT) using propensity score matching (PSM).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.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%.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.

Background Since April 2015, the Korean National Health Insurance (NHI) has reimbursed breast cancer patients, approximately 50% of the cost of the breast reconstruction (BR) procedure. We aimed to investigate NHI reimbursement policy influence on the rate of immediate BR (IBR) following total mastectomy (TM). Methods We retrospectively analyzed breast cancer data between April 2011 and June 2016. We divided patients who underwent IBR following TM for primary breast cancer into “uninsured” and “insured” groups using their NHI statuses at the time of surgery. Univariate analyses determined the insurance influence on the decision to undergo IBR. Results Of 2,897 breast cancer patients, fewer uninsured patients (n = 625) underwent IBR compared with those insured (n = 325) (30.0% vs. 39.8%, P < 0.001). Uninsured patients were younger than those insured (median age [range], 43 [38–48] vs. 45 [40–50] years; P < 0.001). Pathologic breast cancer stage did not differ between the groups (P = 0.383). More insured patients underwent neoadjuvant chemotherapy (P = 0.011), adjuvant radiotherapy (P < 0.001), and IBR with tissue expander insertion (P = 0.005) compared with those uninsured. Conclusion IBR rate in patients undergoing TM increased after NHI reimbursement., Graphical Abstract

Interleukin-1 (IL1) is a proinflammatory cytokine and promotes cancer cell proliferation and invasiveness in a diversity of cancers, such as breast and colon cancer. Here, we focused on the pharmacological effect of Entelon® (ETL) on the tumorigenesis of triple-negative breast cancer (TNBC) cells by IL1-alpha (IL1A). IL1A enhanced the cell growth and invasiveness of TNBC cells. We observed that abnormal IL1A induction is related with the poor prognosis of TNBC patients. IL1A also increased a variety of chemokines such as CCL2 and IL8. Interestingly, IL1A expression was reduced by the ETL treatment. Here, we found that ETL significantly decreased the MEK/ERK signaling pathway in TNBC cells. IL1A expression was reduced by UO126. Lastly, we studied the effect of ETL on the metastatic potential of TNBC cells. Our results showed that ETL significantly reduced the lung metastasis of TNBC cells. Our results showed that IL1A expression was regulated by the MEK/ERK- and PI3K/AKT-dependent pathway. Taken together, ETL inhibited the MEK/ERK and PI3K/AKT signaling pathway and suppressing the lung metastasis of TNBC cells through downregulation of IL1A. Therefore, we propose the possibility of ETL as an effective adjuvant for treating TNBC.

This study aim was to evaluate efficacy of the combination with cosmetic and psychosocial education program on body image, sexual function, and emotional function among young-onset breast cancer (YBC).An unblended, randomized, controlled trial design was conducted in patients newly diagnosed with stage I-III breast cancer from 2014 to 2015. The intervention group received a structured education program including appearance management and mind control for 4 weeks. The outcome of this study shows effect on body image and sexual functioning and a distress due to altered appearance and anxiety after the intervention and 6 months after intervention.Among 228 eligible patients, 109 (47.8%) agreed to participate in the present study and were randomized to intervention (n = 54) or control (n = 55) groups. After intervention, the intervention group reported significantly better body image compared to the control group (mean score of 75.0 vs. 59.3, respectively; P 0.01). The intervention group also reported significantly lower levels of distress due to altered appearance and higher levels of sexual functioning compared to the control group after the intervention. The effects were maintained even 6 months after intervention.Body image intervention for YBC had effect on improving body image and sexual functioning and a reduction in distress due to altered appearance and anxiety. Trial registration number and date of registration: The study was registered at the Clinical Research Information Service (no. KCT0001191, https://cris.nih.go.kr/cris ) on 23 July 2014.

IL‑1 promotes cancer cell proliferation and invasiveness in various malignancies, such as breast and colorectal cancer. In the present study, the functional roles of IL‑1β (IL1B) and the inhibitory effect of celastrol on IL1B expression were investigated in triple‑negative breast cancer (TNBC) cells. The data revealed that celastrol markedly decreased IL1B expression and suppressed TNBC cell proliferation in a dose‑dependent manner. The levels of IL1B and IL8 mRNA were significantly increased in TNBC cells compared with non‑TNBC cells. In addition, IL1B augmented the expression levels of IL8 as well as matrix metalloproteinases (MMPs), including MMP‑1 and MMP‑9, in TNBC cells. Furthermore, IL1B expression was decreased by a specific MEK1/2 inhibitor, MEK162. Celastrol also promoted IL1B downregulation through the suppression of the MEK/ERK‑dependent pathway. Furthermore, the results also revealed a decrease in IL1B‑induced IL8, MMP‑1, and MMP‑9 expression in response to celastrol treatment. The induction of cellular invasion by IL1B was also markedly decreased by celastrol. Collectively, the present study results suggested celastrol as an effective drug for the treatment of TNBC, involving a reduction in IL1B expression, activity or signaling pathways.

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. 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. 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

Mutations of the p53 gene are the most common genomic alterations associated with triple-negative breast cancer (TNBC) and are reported in 60–88% cases. Despite the high incidence of such mutations, there is no consensus about the clinical application of p53 detection in breast cancer management. This study investigates the prognostic value of immunohistochemically detected p53 in TNBC patients who received adjuvant chemotherapy. We reviewed the clinicopathologic features of 1088 TNBC patients who received curative surgery and adjuvant chemotherapy. Immunohistochemically, nuclear staining of >10% was defined as p53 “positive.” Of the total 1088 TNBC patients, 709 (65.2%) had no lymph node metastasis (N0). Among the N0 patients, 408 (57.5%) were p53- positive (p53+), and 301 (42.5%) were p53- negative (p53-). p53 + tumors showed a tendency for better breast cancer-specific survival (BCSS, p = 0.052) and overall survival (OS, p = 0.079) compared to p53- tumors. In multivariate analysis, p53 + tumors showed significantly better BCSS (p53 + vs. p53-; HR 2.8, 95% confidence interval: 1.1–7.3, p = 0.034); however, in TNBC patients with lymph node metastasis, there was no correlation between p53 status, clinicopathologic characteristics, and survival. Consequently, in TNBC patients who received adjuvant chemotherapy, immunohistochemical p53 expression was associated with better BCSS in N0 patients. Keywords: Triple-negative breast cancer, Chemotherapy, p53, Immunohistochemistry, Survival

Background Interleukin-8 (IL-8) expression is associated with metastasis in a variety of cancer cells. Purpose Here, we investigated the regulatory mechanism of IL-8 expression as well as the pharmacological effect of berberine (BBR) on IL-8 expression in triple-negative breast cancer (TNBC) cells. Methods The clinical value of IL-8 was analyzed by from a public database [Kaplan‑Meier plotter database. IL-8 mRNA and protein expression was analyzed by real-time PCR and ELISA, respectively. Cell invasion was analyzed by Boyden chamber assay. Tumor cell growth was analyzed by colony forming assay. Results Clinically, we observed that breast cancer patients with highly expressed IL-8 are associated with poor outcomes in areas such as relapse-free, overall, and distant metastasis-free survival. We showed that IL-8 expression is higher in TNBC cells than in non-TNBC cells. In addition, the rates of cell invasion were significantly increased by IL-8 treatment. These IL-8 levels were decreased by EGFR (Neratinib and Afatinib) and MEK (PD98059) inhibitors in TNBC cells. Finally, we observed that BBR dramatically suppresses IL-8 expression. In addition, BBR also inhibited cell invasiveness and anchorage-independent growth. Interestingly, our results showed that BBR down-regulates EGFR protein expression and dose-dependently inhibits MEK and ERK phosphorylation. Conclusion Here, we demonstrate that BBR may be a promising drug to suppress cell invasiveness and growth of TNBC through IL-8-related mechanisms.

The value of tumor-infiltrating lymphocytes (TILs) for prediction of pathologic complete response (pCR) in breast cancer (BC) patients treated with neoadjuvant chemotherapy (NAC) has received increasing attention. In human epidermal growth factor receptor 2 (HER2)-positive BC, advances in HER2-targeted therapy have not yet clarified the clinical implications of pre-NAC TILs. Likewise, the prognostic role of TILs for long-term survival is not well established. Pre- and post-NAC TIL levels were evaluated in 248 pair-matched pre-NAC biopsy and post-NAC resection samples, and analyzed for predictive and prognostic significance with other clinicopathologic parameters. Additional 60 pre-NAC biopsy samples of HER2-positive BC treated with a TCHP regimen (docetaxel, carboplatin, and a combination of trastuzumab and pertuzumab) were also assessed. High pre-NAC TILs, clinical nodal stage 0–1 (cN0–1), and negative ER expression were shown to be strong predictive markers for pCR. A nomogram based on these significant clinicopathologic predictors was developed, providing integrated probability of achieving pCR after NAC. The association between high pre-NAC TIL levels and significantly increased pCR rate was also confirmed in HER2-positive BC patients treated with a TCHP regimen. After chemotherapy, increased quantity of post-NAC TILs was shown to have extended BC-specific survival and disease-free survival in univariable and multivariable analyses. High pre-NAC TIL levels were significantly predictive of pCR in BC, and can act as a surrogate marker for predicting therapeutic effects of a TCHP regimen for HER2-positive BC. Post-NAC TILs in residual disease were a new prognostic marker of risk stratification for long-term survival.

Purpose To investigate the effect of body mass index (BMI) on survival in patients with breast cancer according to tumor subtype, metabolic syndrome, and systemic treatment. Patients and Methods We identified 5668 patients who underwent curative surgery for breast cancer between 1996 and 2013 from the clinical data of a single institution. Disease-free survival (DFS) and overall survival (OS) were calculated and compared between the patients with BMI ≥ 25 kg/m2 and Results In all patients, BMI ≥ 25 kg/m2 was an unfavorable factor for OS (P = .030) but not for DFS. In the HR+/HER2− subgroup, DFS and OS were longer in patients with BMI Conclusion BMI ≥ 25 kg/m2 was an unfavorable survival factor, particularly in patients with HR+/HER2− breast cancer.

Background Receipt of a gonadotropin-releasing hormone (GnRH) agonist has been reported to protect against ovarian failure. We sought to determine the oncologic effect of a GnRH agonist with chemotherapy for breast cancer patients. Patients and Methods Data from 1160 patients aged 20 to 40 years with stage I to III breast cancer who received chemotherapy from 5 hospitals in Korea from 2002 to 2012 were reviewed. A GnRH agonist was provided to 406 patients for ovarian protection during chemotherapy, and 754 patients received chemotherapy without ovarian protection. An individual score-matching strategy was used to create sets matched by age, tumor stage, hormone receptor status, neoadjuvant or adjuvant chemotherapy, and institute. Results Survival analysis by Cox regression showed that the GnRH agonist group had better distant metastasis-free survival (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.39-0.89) and disease-free survival (HR, 0.72; 95% CI, 0.52-0.99) than the chemotherapy-alone group. Among patients with hormone receptor–positive breast cancer, the benefit was significant for distant metastasis-free survival (HR, 0.53; 95% CI, 0.29-0.99) and disease-free survival (HR, 0.58; 95% CI, 0.35-0.96). Conclusion Ovarian protection using a GnRH agonist can be safely considered for premenopausal breast cancer patients for whom chemotherapy is planned.

Purpose: To determine prevalence, clinicopathological characteristics, initial treatments, and outcomes associated with low estrogen receptor (ER)–expressing invasive breast cancer.Methods: This retrospective, noninterventional database study included patients undergoing surgery with curative intent for invasive ductal or lobular breast cancer. Patients were treated between January 2003-December 2012. Demographics, clinicopathologic characteristics, initial treatments, and outcomes were abstracted from patient records. Patients were categorized using immunohistochemistry to determine ER, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) levels. ER-positive patients were subclassified as ER-Low (1%–10%) and ER-High (>10%) according to Allred Proportion Score. Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared among groups by log-rank test.Results: 5930 patients were included (median follow-up, 80.9 months). Of all patients included, 117 (2.0%) had ER-Low tumors, 63 (53.8%) of whom had HER2− tumors and 54 (46.2%) HER2+ tumors. Five-year DFS and OS were highest in the ER-High/HER2− cohort (94.0% and 98.6%, respectively) and lowest in the triple-negative breast cancer (TNBC; 81.3% and 90.1%) and ER-Low/HER2− (85.7% and 92.1%) cohorts. Menopausal status, elevated Ki-67, higher nuclear grade, higher tumor stage, presence of lymphovascular invasion, greater regional lymph node involvement, and larger tumor size were all potential prognostic factors for shorter DFS and OS. Conclusion: Patients with ER-Low/HER2− breast cancer had similar clinicopathological characteristics, treatments, and outcomes as patients with TNBC irrespective of disease setting. Further research is needed to understand predictive and prognostic factors associated with ER-Low/HER2− disease.

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)

Objective Previous qualitative studies found cancer stigma was associated with work discrimination and job loss among cancer patients. This study aims to quantify the association between cancer stigma and job loss among cancer survivors. Methods For this study, we used the data from a face-to-face cross sectional survey conducted at 2 cancer hospitals in Seoul and Hwasun in South Korea from October 2017 to March 2018. Cancer stigma was assessed using a validated questionnaire which consists of 12 items in three domains: (a) impossibility of recovery; (b) stereotypes; and (c) discrimination. Multivariable logistic regression was performed to evaluate the association between cancer stigma and job loss adjusting age, sex, marital status, education, job type, residence area, cancer site, stage, comorbidity, time since diagnosis and self-efficacy. Results Among 433 cancer survivors, 24.0% lost their jobs after cancer, and 20.7% experienced discrimination at work. Of total, 21.7% of the survivors agreed that it was difficult to treat cancer regardless of highly developed medical science. Survivors with stigma on impossibility of recovery and stereotypes were 3.10 (95% CI [1.76, 5.44]) and 2.10 (95% CI [1.20, 3.67]) times more likely to lose a job than survivors without cancer stigma. Survivors with discrimination experience at work had 1.98 (95% CI [1.05, 3.74]) times higher risk of losing a job than survivors without it. Conclusions Survivors with cancer stigma were more likely to lose their jobs than survivors without cancer stigma. Considering its social and economic impact on job loss, comprehensive interventions for working cancer survivors as well as public campaigns against cancer stigma would be necessary. This article is protected by copyright. All rights reserved.

Background Immediate breast reconstruction with tissue expander in breast cancer patients who were expected to receive adjuvant therapy, such as chemotherapy or radiotherapy, has been a topic of debate. Postoperative complications from tissue expander procedures can delay the timing of adjuvant treatment and subsequently increase the probability of recurrence. The purpose of this study was to identify the impact of chemotherapy and radiotherapy on postoperative complications in patients who underwent immediate reconstruction (IR) using tissue expander. Methods We conducted a retrospective study of 1081 breast cancer patients who underwent mastectomy and IR using tissue expander insertion between 2012 and 2017 in Samsung Medical Center. The patients were divided into two groups based on complications (complication group vs. no complication group). Complication group was regarded to have surgical removal or conservative treatment based on clinical findings such as infection, capsular contracture, seroma, hematoma, rupture, malposition, tissue viability, or cosmetic problem. The complication group had 59 patients (5.5%) and the no complication group had 1022 patients (94.5%). Results In univariate analysis, adjuvant radiotherapy and adjuvant chemotherapy were significantly associated with postoperative complications. In multivariate analysis, however, only higher pathologic N stage was significantly associated with postoperative complications (p p = 0.775) or radiotherapy (p = 0.825) were not risk factors for postoperative complications. Conclusions IR with tissue expander after mastectomy may be a treatment option even when the patients are expected to receive adjuvant chemotherapy or radiotherapy. These results will aid patients who are concerned about the complications of IR caused by chemotherapy or radiotherapy determine whether or not to have IR. Trial registration Patients were selected and registered retrospectively, and medical records were evaluated.

To elucidate the effects of neoadjuvant chemotherapy (NAC), we conduct whole transcriptome profiling coupled with histopathology analyses of a longitudinal breast cancer cohort of 146 patients including 110 pairs of serial tumor biopsies collected before treatment, after the first cycle of treatment and at the time of surgery. Here, we show that cytotoxic chemotherapies induce dynamic changes in the tumor immune microenvironment that vary by subtype and pathologic response. Just one cycle of treatment induces an immune stimulatory microenvironment harboring more tumor infiltrating lymphocytes (TILs) and up-regulation of inflammatory signatures predictive of response to anti-PD1 therapies while residual tumors are immune suppressed at end-of-treatment compared to the baseline. Increases in TILs and CD8+ T cell proportions in response to NAC are independently associated with pathologic complete response. Further, on-treatment immune response is more predictive of treatment outcome than immune features in paired baseline samples although these are strongly correlated., Neoadjuvant chemotherapy is a therapeutic option for the treatment of breast cancer. Here, the authors characterize changes in the gene expression profiles and immune microenvironment in serial breast cancer biopsies taken before, during and after neoadjuvant chemotherapy.

IMPORTANCE: The potential association between breast implant–related anaplastic large cell lymphoma (BIA-ALCL) and implant texture has raised concerns about the additional unexpected adverse effects of textured implants, including potentially adverse outcomes for other cancers. In addition to the risk of developing BIA-ALCL, breast cancer survivors may worry about whether the type of implant inserted is associated with recurrence of their original cancer—an issue for which little evidence currently exists. OBJECTIVE: To evaluate the oncologic outcomes of breast cancer according to the surface type of implants used for reconstruction and to identify the independent factors associated with breast cancer recurrence and survival, including implant surface type. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted at Samsung Medical Center, a single tertiary referral center in Seoul, South Korea. Patients with breast cancer who underwent total mastectomy and immediate 2-stage tissue expander/implant reconstruction between January 1, 2011, and December 31, 2016, were identified from a prospectively maintained database. Patients were categorized into 2 groups according to the surface type of implant used for their reconstruction (smooth or textured implant). These patients were followed up for at least 2 years after insertion of the implant. Data analysis was performed from February 15, 2020, to March 5, 2020. EXPOSURES: Use of smooth implants vs textured implants at the second-stage operation. MAIN OUTCOMES AND MEASURES: The main outcomes of interest were local and regional recurrence-free survival (LRRFS) and disease-free survival (DFS) rates. Cumulative incidence of oncologic events in the smooth implant and textured implant groups and their respective hazard ratios (HRs) were collected and updated regularly. RESULTS: In total, 650 patients (all women, with a mean [SD] age of 43.5 [7.4] years), representing 687 cases, met the inclusion criteria and were followed up for a median (range) duration of 52 (31-106) months. Of the 687 cases, 274 (39.9%) received a smooth implant and 413 (60.1%) received a textured implant. Patients in these 2 surface texture groups had similar characteristics, including tumor staging (stage I: 102 [37.2%] vs 173 [41.9%]; stage II: 93 [33.9%] vs 119 [28.8%]; stage III: 14 [5.1%] vs 20 [4.8%]; P = .50) and rates of adjuvant radiotherapy (42 [15.3%] vs 49 [11.9%]; P = .19) and chemotherapy (113 [41.2%] vs 171 [41.4%]; P = .97). The 5-year LRRFS was 96.7%, and the 5-year DFS was 95.2%. Compared with the use of a smooth implant, textured implant use was statistically significantly associated with lower DFS, and this difference remained significant after adjusting for estrogen receptor (ER) status and tumor stage (HR, 3.054; 95% CI, 1.158-8.051; P = .02). Similar statistically significant associations were observed on multivariable analysis of patients with ER-positive cancer (HR, 3.130; 95% CI, 1.053-9.307; P = .04) and those with invasive cancer (HR, 3.044; 95% CI, 1.152-8.039; P = .03). The association of textured implant use with recurrence (lower DFS) was more prominent in cases with late-stage (stage II or III) tumor (HR, 8.874; 95% CI, 1.146-68.748; P = .04). The LRRFS did not differ statistically significantly according to implant surface texture. CONCLUSIONS AND RELEVANCE: This cohort study found that use of textured implants in reconstruction appears to be associated with recurrence of breast cancer. Further investigation is required to verify these results.

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 mm(3) in the control group; 160.0 mm(3) in the o-rMETase 100 U group; and 245.3 mm(3) 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

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 4(th) 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 mm(3) in the control group and 450.9 mm(3) in the o-rMETase group (p

Introduction Neoadjuvant endocrine therapy (NET) has demonstrated efficacy in post-menopausal patients with hormone-responsive breast cancer. This trial was designed to compare the efficacy of neoadjuvant chemotherapy (NCT) with NET in pre-menopausal breast cancer. Patients and methods In this prospective, randomised, phase III study, oestrogen receptor (ER)-positive, HER2-negative, and lymph node-positive pre-menopausal breast cancer patients were recruited from 7 hospitals in South Korea. Enrolled patients were randomly assigned (1:1) to receive 24 weeks of either NCT or NET with goserelin and tamoxifen. The primary purpose was to evaluate the non-inferiority of NET compared to NCT using clinical response, assessed by MRI. Besides, pathological complete response rate (pCR), changes in Ki-67 expression, breast conservation surgery (BCS) rate, and quality of life were included as secondary endpoints. Results A total of 187 patients were assigned to receive NCT (n = 95) or NET (n = 92), and 87 patients in each group completed treatments. More NCT patients had complete response or partial response than NET patients using MRI (NCT 83.7% vs. NET 52.9%, 95% CI 17.6–44.0, p p = 0.046). Three NCT patients (3.4%) and one NET patient (1.2%) showed pCR (p p = 0.531) and Ki-67 change (p = 0.114) between the two groups. Nineteen NCT patients had treatment-related grade 3 or worse events compared with none in the NET group. Conclusions Better clinical responses were observed in pre-menopausal patients after 24 weeks of NCT compared to those observed after NET. Trial registration Clinicaltrials.gov, NCT01622361. Registration June 19, 2012.

We investigated the expression profiles of immune genes in patients with triple-negative breast cancer (TNBC) to identify the prognostic value of immune genes and their clinical implications.NanoString nCounter Analysis of 770 immune-related genes was used to measure immune gene expression in patients with TNBC who underwent curative surgery followed by adjuvant chemotherapy at Samsung Medical Center between 2000 and 2004. Statistical analyses were conducted to identify the associations between gene expression and distant recurrence-free survival (DRFS).Of 1189 patients who underwent curative BC surgery, 200 TNBC patients were included and stage was the only clinical factor predictive of DRFS. In terms of immune genes, 155 of 770 genes were associated with DRFS (p 0.01). Further multivariate analysis revealed that 13 genes, CD1B, CD53, CT45A1, GTF3C1, IL11RA, IL1RN, LRRN3, MAPK1, NEFL, PRKCE, PTPRC, SPACA3 and TNFSF11, were associated with patient prognosis (p 0.05). The prognostic value of stage and expression levels of 13 immune genes was analyzed and the area under the receiver operating characteristic curve (AUC) was 0.923. Based on the AUC, we divided patients into three genetic risk groups and DRFS rate was significantly different according to genetic risk groups, even in the same stage (p 0.001).In this study, a 13-gene expression profile in combination with stage precisely predicted distant recurrence of early TNBC. Therefore, this 13-immune-gene signature could help predict TNBC prognosis and provide guidance for treatment as well as the opportunity to develop new targets for immunotherapy in TNBC patients.

WNT5A is abnormally increased in a variety of cancers including breast cancer and has an adverse effect on the prognosis. However, the biological function of WNT5A is not fully known in HER2-positive (HER2+) breast cancer. Using public clinical data, we analyzed disease-free survival (DFS) and distant metastasis-free survival (DMFS). Here, we found that abnormal WNT5A induction is a correlation with the poor prognosis of HER2+ breast cancer. WNT5A expression was also decreased by pan-HER inhibitor neratinib but not by trastuzumab. In addition, WNT5A augmented cell invasiveness of HER2+ breast-cancer cells. To find WNT5A-induced metastatic-related factors, we did a human cytokine array. The levels of GM-CSF and CXCL8 were significantly increased by WNT5A. CXCL8 also accelerated cell invasiveness in HCC1954 breast-cancer cells. The expression of CXCL8 induced by WNT5A has been significantly reduced by MEK inhibitor, binimetinib. Finally, we studied the effect of CXCR2 antagonist, SB225002, to verify the relevance of CXCL8 in WNT5A-induced cell invasion. As expected, we found that WNT5A-induced cell invasion is completely inhibited by SB225002. Taken together, we have demonstrated that WNT5A directly mediates cell invasion through the induction of CXCL8 and ultimately affects the survival rate of HER2+ breast cancer.

TP53 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. A 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. In 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. The 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.

gBRCA1/2 mutations increase the incidence of breast cancer by interrupting the homologous recombination repair (HRR) pathway. Although gBRCA1 and gBRCA2 breast cancer have similar clinical profiles, different molecular characteristics have been observed. In this study, we conducted comprehensive genomic analyses and compared gBRCA1/2 breast cancer. Sanger sequencing to identify gBRCA1/2 mutations was conducted in 2,720 patients, and gBRCA1 (n = 128) and gBRCA2 (n = 126) mutations were analyzed. Within this population, deep target sequencing and matched whole-transcriptome sequencing (WTS) results were available for 46 and 34 patients, respectively. An internal database of patients with breast cancer with wild-type gBRCA was used to compile a target sequencing (n = 195) and WTS (n = 137) reference dataset. Three specific mutation sites, p.Y130X (n = 14) and p.1210Afs (n = 13) in gBRCA1 and p.R294X (n = 22) in gBRCA2, were comparably frequent. IHC subtyping determined that the incidence of triple-negative breast cancer was higher among those with a gBRCA1 mutation (71.9%), and estrogen receptor–positive breast cancer was dominant in those with a gBRCA2 mutation (76.2%). gBRCA1/2 mutations were mutually exclusive with PIK3CA somatic mutations (P < 0.05), and gBRCA1 frequently cooccurred with TP53 somatic mutations (P < 0.05). The median tumor mutation burden was 6.53 per megabase (MB) in gBRCA1 and 6.44 per MB in gBRCA2. The expression of AR, ESR1, and PGR was significantly upregulated with gBRCA2 mutation compared with gBRCA1 mutation. gBRCA1 and gBRCA2 breast cancer have similar clinical characteristics, but they have different molecular subtypes, coaltered somatic mutations, and gene expression patterns. Implications: Even though gBRCA1 and gBRCA2 mutations both alter HRR pathways, our results suggest that they generate different molecular characteristics and different mechanisms of carcinogenesis.

The development and validation of guidelines for breast cancer survivors are of importance due to the increased survival rate for breast cancer. In this cross-sectional study, we aimed to examine the association between adherence to the American Cancer Society (ACS) guidelines for cancer survivors and health-related quality of life (HRQoL). A total of 618 breast cancer survivors aged 30 to 81 years who had been diagnosed with stage I to III primary breast cancer and had surgery at least a year before enrollment were included. The participants completed the 36 Item Short-Form Health Survey (SF-36) to evaluate HRQoL, and adherence scores were calculated based on the Nutrition and Physical Activity Guidelines for Cancer Survivors, which were released by the ACS. Increasing adherence scores were associated with increasing scores on the physical component summary (PCS) and the physical functioning (PF), bodily pain (BP), and vitality (VT) domains (p for trend &lt, 0.001 for PCS and PF, 0.01 for BP, and 0.02 for VT), these scores were mainly driven by the associations among survivors with stage II&ndash, III cancer. Further prospective studies are needed to evaluate whether adherence to these guidelines improves HRQoL scores among breast cancer survivors.

Purpose To evaluate the value of preoperative axillary ultrasonography (US) for preventing unnecessary axillary lymph node dissection after sentinel lymph node (SLN) biopsy in a large series of patients with early-stage breast cancers treated with both breast-conserving surgery and SLN biopsy. Materials and Methods From March 2009 to February 2013, 1802 patients who underwent breast-conserving surgery for clinical T1-2/N0 cancers and SLN biopsy with or without axillary lymph node dissection were included. Preoperative axillary US results and clinical-pathologic variables were compared according to the status of non-SLN metastasis. Multivariate logistic regression analysis was performed to find factors associated with non-SLN metastasis. Results Of 1802 patients, 397 (22.0%) underwent axillary lymph node dissection due to positive SLN biopsy and 76 (4.2%) had non-SLN metastasis at final histopathologic examination. Patients with non-SLN metastasis were younger and showed positive axilla at US and clinical T2 stage more frequently (P < .05). At multivariate analysis, positive axilla at US (P = .001), clinical T2 stage (P = .005), and lymphovascular invasion (P < .001) were significantly associated with non-SLN metastasis. Among 1284 patients with negative axilla at US and clinical T1 stage cancer, 1254 (97.7%) did not have non-SLN metastasis and 30 (2.3%) had non-SLN metastasis. Conclusion Preoperative axillary US results and clinical T stage are associated with the status of non-SLN metastasis in patients with early breast cancer. The results of this study suggest that preoperative axillary US can help select patients at minimal risk of non-SLN metastasis, for whom axillary lymph node dissection can be omitted. © RSNA, 2018 Online supplemental material is available for this article.

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.

Introduction The aim of our study was to analyze the risk of lymphedema (LE) according to the clinicopathologic factors and to investigate the serial change in body weight during neoadjuvant anthracycline plus cyclophosphamide followed by taxane and its correlation with the incidence of LE. Patients and Methods We performed a retrospective 2-center study of 406 patients who had undergone neoadjuvant chemotherapy (NAC) followed by surgery from 2007 to 2014. The regimen included 4 cycles of anthracycline plus cyclophosphamide, followed by 4 cycles of taxane. We investigated the presence and degree of LE using a telephone questionnaire assessment. Weight changes were calculated at each cycle of NAC, and the baseline and preoperative body weights were used to calculate the rate of change to account for the change in weight before and after NAC. Results Of the 406 patients, 270 answered the questionnaires, of whom 97 (35.9%) experienced LE. The increase in body weight was significant during the 4 cycles of taxane, but the change in weight was not significant during the 4 cycles of anthracycline plus cyclophosphamide. The change in body weight was most significant just after the fourth cycle of taxane ( P Conclusion Because a BMI ≥ 25 kg/m 2 was an independent factor of LE occurrence on multivariate analysis, patients with a preoperative BMI ≥ 25 kg/m 2 should be closely monitored for LE given their increased risk, and monitoring and education should be initiated before surgery and continued throughout the course of NAC.

Numerous studies have demonstrated that breast cancer in young women (BCY) has unfavorable prognostic features and more unfavorable subtypes. However, few studies have evaluated the effect of subtype disparities on breast cancer prognosis by age, especially for BCY. We analyzed breast cancer mortality stratified by tumor subtype according to age among patients younger than 50 years. Data from the Korean Breast Cancer Society Registry for patients diagnosed with invasive breast cancer when aged less than 50 years between 2003 and 2010 were reviewed retrospectively. We identified 30,793 patients with breast cancer who were eligible for analysis. Of these, 793 (2.6%) were aged 20–29 and 8926 (28.8%) were aged 30–39. Median follow-up duration was 84 months. Mean age was 42.4 years. Patients in their 20s were more likely to have cancer of advanced stage and higher nuclear grade, present with lymphovascular invasion, and have unfavorable subtypes. Patients in the 20s group showed worse prognosis. In multivariate analysis for overall survival (OS), the hazard ratio (HR) for patients in the 20s group was higher than that for the 30s and 40s groups, and patients with triple-negative breast cancer (TNBC) showed higher HR than patients with HER-2 or luminal subtype (all p

We aimed to investigate the prognostic influence of primary tumor site on the survival of patients with breast cancer.Data of 63,388 patients with primary breast cancer from the Korean Breast Cancer Registry were analyzed. Primary tumor sites were classified into 5 groups: upper outer quadrant, lower outer quadrant, upper inner quadrant, lower inner quadrant (LIQ), and central portion. We analyzed overall survival (OS) and breast cancer-specific survival (BCSS) according to primary tumor site.Central portion and LIQ showed lower survival rates regarding both OS and BCSS compared with the other 3 quadrants (all P .05) and hazard ratios were 1.267 (95% CI, 1.180-1.360, P .001) and 1.215 (95% CI, 1.097-1.345, P .001), respectively. Although central portion showed more unfavorable clinicopathologic features, LIQ showed more favorable features than the other 3 quadrants. Primary tumor site was a significant factor in univariate and multivariate analyses for OS and BCSS (all P .001). For lymph node-negative patients, LIQ showed a worse OS than the other primary tumor sites in the subgroup with no chemotherapy (P .001), but that effect disappeared in the subgroup with chemotherapy (P = .058).LIQ showed a worse prognosis despite having more favorable clinicopathologic features than other tumor locations and it was more prominent for lymph node-negative patients who received no chemotherapy. The hypothesis of possible hidden internal mammary node metastasis could be suggested to play a key role in LIQ lesions.

Purpose We describe a rationale for the re-classification of the BRCA1 c.5539T>C (L1780P) variant using a clinical evidence. Methods A retrospective review was conducted to identify all patients with breast or ovarian cancer and the L1780P variant between 2002 and 2015 at a single institution. Results We identified the BRCA1/2 genetic mutation test results of 1223 breast cancer patients and 174 patients with ovarian cancer. Of the 160 BRCA 1/2 variant unknown significance, 16 (10.0%) patients were identified as having the L1780P variant. Among them, 10 had breast cancer, 4 had ovarian cancer, and 2 had both breast and ovarian cancer. Thirteen (81.3%) patients with this variant had family histories of breast or ovarian cancer. Two (16.7%) also had comorbid ovarian cancer. Two patients with this variant showed that co-segregation of the disease in multiple family members and family histories of breast and ovarian cancer. This variant was found to be either absent or at extremely low frequency in general population databases. Conclusion The L1780P variant might confer to “Likely pathogenic” according to a clinical evidence and the ACMG standards and guidelines. A nation-wide or global survey and a functional analysis are needed to confirm the pathogenicity of the L1780P variant.

Purpose To determine the relationship between tumor heterogeneity assessed by means of magnetic resonance (MR) imaging texture analysis and survival outcomes in patients with primary breast cancer. Materials and Methods Between January and August 2010, texture analysis of the entire primary breast tumor in 203 patients was performed with T2-weighted and contrast material-enhanced T1-weighted subtraction MR imaging for preoperative staging. Histogram-based uniformity and entropy were calculated. To dichotomize texture parameters for survival analysis, the 10-fold cross-validation method was used to determine cutoff points in the receiver operating characteristic curve analysis. The Cox proportional hazards model and Kaplan-Meier analysis were used to determine the association of texture parameters and morphologic or volumetric information obtained at MR imaging or clinical-pathologic variables with recurrence-free survival (RFS). Results There were 26 events, including 22 recurrences (10 local-regional and 12 distant) and four deaths, with a mean follow-up time of 56.2 months. In multivariate analysis, a higher N stage (RFS hazard ratio, 11.15 [N3 stage]; P = .002, Bonferroni-adjusted α = .0167), triple-negative subtype (RFS hazard ratio, 16.91; P.001, Bonferroni-adjusted α = .0167), high risk of T1 entropy (less than the cutoff values [mean, 5.057; range, 5.022-5.167], RFS hazard ratio, 4.55; P = .018), and T2 entropy (equal to or higher than the cutoff values [mean, 6.013; range, 6.004-6.035], RFS hazard ratio = 9.84; P = .001) were associated with worse outcomes. Conclusion Patients with breast cancers that appeared more heterogeneous on T2-weighted images (higher entropy) and those that appeared less heterogeneous on contrast-enhanced T1-weighted subtraction images (lower entropy) exhibited poorer RFS.

Background We evaluated the feasibility and prognostic effect in axillary recurrence or survival of sentinel lymph node biopsy (SLNB) in patients with cytology-proven, node-positive breast cancer after neoadjuvant chemotherapy (NAC). Methods This is a retrospective study of 329 patients who were diagnosed with invasive breast cancer and axillary lymph nodes (ALN) metastasis and treated with NAC followed by curative surgery at Samsung Medical Center between January 2007 and December 2013. We analyzed and compared outcomes including prognoses and survival rates among all groups. Results The median age at the time of surgery was 44.4 years. The median follow-up time was 37 months (range, 1-91 months). The sentinel lymph node (SLN) identification rate was 96.7% (117 of 121 patients). The median number of retrieved SLNs was 4.0 (range, 1-7), and 57 patients had negative SLNs on frozen-section analysis. The false negative rate of SLNB after NAC was 7.8% (5 of 64 patients). In survival analysis, there was no difference in the overall survival (P = .2) and the regional recurrence-free survival (P = .297) among Groups 1, 2, and 4. Conclusion SLNB may be feasible after NAC for node-positive breast cancer and may help reduce surgical morbidity by avoiding the need for standard axillary lymph node dissection in some patients. We suggest that future studies with a large number of patients and a longer follow-up period are necessary to support the use of SLN surgery as an alternative to axillary lymph node dissection in this patient population.

To investigate and compare the effects of mobile health (mHealth) and pedometer with conventional exercise program using a brochure on physical function and quality of life (QOL).The study was a prospective, quasi-randomized multicenter trial where 356 patients whose cancer treatment had been terminated were enrolled. All patients were instructed to perform a 12-week regimen of aerobic and resistance exercise. The mHealth group received a pedometer and a newly developed smartphone application to provide information and monitor the prescribed exercises. Those in the conventional group received an exercise brochure. Physical measurements were conducted at baseline, 6 weeks, and 12 weeks. Self-reported physical activity (international physical activity questionnaire-short form), general QOL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30), and breast cancer-specific QOL (Quality of Life Questionnaire Breast Cancer Module 23) were assessed at baseline and 12 weeks. A user satisfaction survey was assessed in the mHealth group.Basic characteristics were not different between the two groups except for age and previous radiotherapy. Physical function, physical activity, and QOL scores were significantly improved regardless of the intervention method, and changes were not significantly different between the two groups. Additionally, the mean Likert scale response for overall satisfaction with the service was 4.27/5 in the mHealth group.Overall, both the mHealth coupled with pedometer and conventional exercise education using a brochure were effective in improving physical function, physical activity, and QOL. This study provides a basis of mHealth research in breast cancer patients for progressing further developing field, although superiority of the mHealth over the conventional program was not definitely evident.

To investigate variants of uncertain significance (VUS) in BRCA1 and BRCA2, we assessed the multifactorial posterior probability of VUS in BRCA1 and BRCA2 and compared these analyses with interpretations according to the recently released American College of Medical Genetics and Genomics (ACMG) standards and guidelines. The analysis involved 715 Korean patients with breast cancer. The multifactorial probability of a VUS was analyzed using the prior probability and combined likelihoods of personal and family history, the pathologic profile of the breast cancer, and co-occurrence with pathogenic variants. Results were compared with those obtained according to the ACMG standards/guidelines. Sixteen VUS from 51 BRCA1 VUS carriers and 28 VUS from 62 BRCA2 VUS carriers were analyzed. There was a slight agreement between the two analyses, with a kappa value of 0.14 (95% confidence interval (CI) = −0.34 to 0.62) for the BRCA1 VUS and a kappa value of 0.17 (95% CI = −0.10 to 0.49) for the BRCA2 VUS. We propose that genetic counseling should be based on the concordant results between these two analyses. When discrepancies are found, those variants are still considered VUS and careful counseling should be provided. Genet Med 18 12, 1250–1257.

Purpose The purpose of this study was to assess the tumor characteristics and long-term clinical outcomes of adjuvant treatments after surgery with a curative aim for patients with breast cancer who are 65 years and older. Materials and Methods Patients with breast cancer who underwent curative surgery from 2000 to 2009 were analyzed (n=4,388). Tumor characteristics and survival outcome were compared by dividing the patients into two age groups (< 65 and ≥ 65 years old). The Kaplan-Meier method was used for comparison of survival rates by log-rank test, and a Cox regression model was used to examine the effect of variables. Results Among 4,388 patients with invasive breast cancer, 317 patients (7.2%) were 65 years or older and the median age of all patients was 47 years (range, 18 to 91 years). Tumor characteristics were similar between the two age groups, but the older patients were treated less often with adjuvant treatments. During a median follow-up period of 122 months, recurrence-free survival (RFS) was equivalent for patients 65 years and older compared to younger patients, but significantly worse in overall survival (OS) and breast cancer–specific survival (BCSS) (5-year OS, 94.3% vs. 90.5%; p < 0.001 and 5-year BCSS, 94.7% vs. 91.8%; p=0.031). In the multivariate model, age ≥ 65 years old was identified as an independent risk factor for OS and RFS. Conclusion Elderly breast cancer appeared to have worse outcomes with very low prevalence in Korea, despite similar tumor characteristics. More active adjuvant therapies would have a role for aggressive subtypes for fit, elderly patients.