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Background: Studies have shown that the absolute lymphocyte count (ALC) and the neutrophil-to-lymphocyte ratio (NLR) are related to the outcomes in patients with breast cancer receiving specific chemotherapies. However, the reports have focussed on the initial blood test and there is a lack of evidence or data to support that dynamic changes of ALC or NLR are associated with the patients' survival outcomes., Methods: We retrospectively reviewed electronic medical records from patients with breast cancer treated with eribulin from 2015 to 2019 at our institution. Blood test data were available prior to starting eribulin (baseline), and at 1, 3 and 6 months after initiating eribulin. We classified the patients into ALC and NLR high and low groups using the following cut-offs: 1000/µl for ALC and 3 for NLR. We defined ALC and NLR trends as increasing or decreasing compared with the initial data. We assessed the associations between the ALC and NLR with progression-free survival and overall survival., Results: There were 136 patients with breast cancer treated with eribulin. Of these patients, 60 had complete blood tests and follow-up data. Neither a high ALC nor a low baseline NLR was associated with the survival outcome. One month after initiating eribulin treatment, a high ALC and a low NLR were significantly associated with longer progression-free survival (p = 0.044 for each). Three months after initiating eribulin, a high ALC was significantly associated with better overall survival (p = 0.006). A high NLR at 3 or 6 months after initiating eribulin was associated with worse overall survival (p = 0.017 and p = 0.001, respectively). The ALC and NLR trends across times were not associated with survivals., Conclusion: We showed that 1, 3 and 6 months after initiating eribulin, a high ALC and a low NLR may be related to the patients' survival outcomes. The ALC and NLR trends were not associated with survival. Accordingly, we believe patients who maintain a high ALC and a low NLR may have better clinical outcomes after initiating eribulin., (© 2024. The Author(s).)

Introduction: This multicenter, phase II randomized, non-inferiority study reports from the first prospective two-armed randomized control trial that compared the efficacy, safety, and quality of life (QoL) of pegylated liposomal doxorubicin (PLD)-based and epirubicin-based as adjuvant chemotherapy for stage I-II human epidermal growth factor receptor 2 (HER2)-negative breast cancer., Methods: Patients with stage I/II HER2-negative breast cancer received PLD (37.5 mg/m2, Q3W, 5 cycles, LC arm) plus cyclophosphamide (600 mg/m2) or epirubicin (90 mg/m2, Q3W, 4 cycles, EC arm) plus cyclophosphamide (600 mg/m2). Randomization was stratified by lymph node and ER and PR status. The primary endpoint was disease-free survival (DFS), and secondary endpoints were overall survival (OS), safety profiles, and QoL. QoL was assessed using the EORTC-QLQ-C30 and QLQ-BR23 questionnaires., Results: A total of 256 patients were assigned to LC (n = 148) and EC (n = 108). There was no difference in 5-year DFS and OS rate between the two groups. LC-based adjuvant regimens had significantly less alopecia and low-grade 3-4 hematologic adverse events (AEs). Significantly improved QoL was observed in the LC arm during and after treatment for symptoms including fatigue, nausea and vomiting, and systemic therapy side effects., Conclusion: Comparable efficacy and safety between adjuvant PLD and epirubicin for stage I-II HER2-negative breast cancer was observed. There was no difference in the 5-year DFS and OS rates between the two treatment arms. However, low-grade 3-4 AEs and a trend of favorable QoL symptom scales were observed in the LC arm, suggesting that PLD-containing regimen could become a new standard treatment for early-stage HER2-negative breast cancer patients., (© 2024 S. Karger AG, Basel.)

Objective: To compare the clinical and patient-reported outcomes of minimal access and conventional nipple-sparing mastectomy (C-NSM). The secondary outcomes investigated included medical costs and oncological safety., Background: Minimal-access NSM has been increasingly applied in the treatment of patients with breast cancer. However, prospective multicenter trials comparing robotic-assisted NSM (R-NSM) versus C-NSM or endoscopic-assisted NSM (E-NSM) are lacking., Methods: A prospectively designed 3-arm multicenter, nonrandomized trial (NCT04037852) was conducted from October 1, 2019 to December 31, 2021, to compare R-NSM with C-NSM or E-NSM., Results: A total of 73 R-NSM, 74 C-NSM, and 84 E-NSM procedures were enrolled. The median wound length and operation time of C-NSM was (9 cm, 175 minutes), (4 cm, and 195 minutes) in R-NSM, and (4 cm and 222 minutes) in E-NSM. Complications were comparable among the groups. Better wound healing was observed in the minimal-access NSM group. The R-NSM procedure was 4000 and 2600 United States Dollars more expensive than C-NSM and E-NSM, respectively. Wound/scar and postoperative acute pain evaluation favored the use of minimal access NSM over C-NSM. Quality of life in terms of chronic breast/chest pain, mobility, and range of motion of the upper extremity showed no significant differences. The preliminary oncologic results showed no differences among the 3 groups., Conclusions: R-NSM or E-NSM is a safe alternative if compared with C-NSM in terms of perioperative morbidities, especially with better wound healing. The advantage of minimal access groups was higher wound-related satisfaction. Higher costs remain one of the major limiting factors in the widespread adoption of R-NSM., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: This study aimed to compare the time required and concerns raised by various perspectives of participants regarding administering subcutaneous and intravenous trastuzumab for patients with breast cancer (BC)., Design: This observational time-motion study design with mixed-methods research (cross-sectional surveys and semistructured interviews) was conducted. The time spent on preparing or administering trastuzumab by different healthcare professionals (HCPs) was recorded. The data were analysed by descriptive/inferential statistical analyses, followed by thematic analyses., Setting: Outpatient and inpatient administration units of a single medical centre in Taiwan., Participants: The study included patients with early-stage BC who received subcutaneous or intravenous trastuzumab (n=93), and HCPs including two attending physicians, a nurse practitioner, two pharmacists and two nurses., Result: Based on the perspectives of patients and HCPs, the subcutaneous form of trastuzumab was more efficient, less expensive and produced less discomfort in outpatient units than inpatient units. More participants preferred the subcutaneous form over the intravenous form in both outpatient and inpatient units. Pharmacists and nurse practitioners spent threefold more time on patients when preparing and administering the intravenous form in both outpatient and inpatient units. The concerns raised by patients and HCPs varied in certain aspects, including the injection skills, speed, mental distress (eg, needle phobia) and pain associated with the subcutaneous form. Almost all patients preferred receiving the subcutaneous form in outpatient units after the initial COVID-19 outbreak., Conclusion: Patients with early-stage BC preferred receiving subcutaneous trastuzumab in outpatient units rather than inpatient units or the intravenous form before and after the COVID-19 outbreak. Such findings may serve as real-world evidence to facilitate better quality of care regarding administration of subcutaneous or intravenous trastuzumab in medical settings, and its feasible resolutions to balance the quality, concerns and efficiency of anticancer administration during the COVID-19 pandemic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In Taiwan, breast cancer has the highest incidence among all cancers. Although adjunctive traditional Chinese medicine treatment (TCM) have been used to ameliorate the side effects or discomfort caused by cancer treatments, no study has focused on the assessment of the quality of life of patients undergoing adjunctive TCM treatments. This study compared the quality of life between breast cancer patients treated with and without adjunctive TCM. Questionnaires were collected from 7 hospitals with a Chinese medicine clinic in 2018 to 2019. Breast cancer patients who had cancer stages I, II, or III and also underwent resection surgery were included in the study. They were divided into 2 groups: patients receiving cancer treatments with adjunctive traditional Chinese medicine (TCM group) and those receiving cancer treatments without adjunctive traditional Chinese medicine (non-TCM group). A 1:1 matching was used to obtain the study participants. The EQ-5D questionnaire was used to assess the quality of life. Statistical analysis was performed using the t -test and ANOVA to compare the differences between variables. The conditional multiple regression model was applied to explore the factors associated with quality of life in breast cancer patients. A total of 543 participants were surveyed, and 450 participants were included in the study. The EQ-5D score of the TCM group (81.60 ± 11.67) was significantly higher than that of the non-TCM group (78.80 ± 13.10; P  < .05). The results of a conditional multiple regression model showed that the TCM group had a higher (3.45 points) quality of life than non-TCM group ( P  = .002) after adjusting for other related factors. After stratifying by cancer stage, patients with cancer stages II and III scored 5.58 and 4.35 points higher in the TCM group than did those in the non-TCM group ( P  < .05). Breast cancer patients undergoing cancer treatment with adjunctive traditional Chinese medicine have a higher quality of life than those treated without adjunctive traditional Chinese medicine.

Background: This study aimed to examine the effectiveness and safety of eribulin used as an early-line (EL, i.e., first-/second-line) versus late-line (LL, i.e., third-line and beyond) chemotherapy for recurrent advanced or metastatic breast cancer (A/MBC) patients., Methods: This study conducted a retrospective observation of A/MBC patients initiating eribulin between January 1, 2015, and June 30, 2019, using medical database at a university-affiliated teaching hospital in Taiwan. Patients were assigned into either the EL or LL group based on the timing of respective eribulin treatments and were observed for at least 6 months up to December 2019 for progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), disease response, and occurrence of adverse events. The Kaplan-Meier and Cox proportional hazard regression survival analyses were performed., Results: Of 127 patients, 23.6% (n = 30) and 76.4% (n = 97) were assigned to the EL and LL groups, respectively, between which no difference in patient characteristics was noted. Median PFS and TTF were 6.5 months and 5.0 months for the EL and 4.2 months and 3.4 months for the LL, respectively. Median OS could not be estimated in the EL group and was 20.5 months in the LL group. Eribulin as an EL treatment was the only factor associated with longer TTF and OS, whereas the number of metastatic sites was additionally associated with PFS in the multivariate analysis. No complete response was reported in either group, but a partial response was obtained in 6.7% in the EL group and 3.1% in the LL group. The common adverse events between two groups were similar, including leukopenia (80.0%), neutropenia (76.7%), and anemia (60.0%)., Conclusions: The eribulin used as an EL of chemotherapy was effective for A/MBC patients with known toxicities in this study, while eribulin as the LL chemotherapy showed consistent results with previous reports., (© 2022 S. Karger AG, Basel.)

Background: The prognosis of triple-negative breast cancer (TNBC) is worse and a major proportion of TNBC expresses epidermal growth factor receptor (EGFR). Afatinib can inhibit EGFR signal pathway; however, its treatment effect for TNBC is unknown. Thus, we aimed to assess the efficacy and biomarkers of afatinib in combination with paclitaxel in a neoadjuvant setting., Methods: Patients with stage II to III TNBC were enrolled. They received 40 mg of afatinib daily for 14 days, followed by daily afatinib and weekly paclitaxel (80 mg/m 2 ) every 21 days for four to six cycles. To explore the mechanisms of responsiveness and non-responsiveness, 409 cancer-associated genes were sequenced., Results: Twenty-one patients were enrolled and one patient achieved a complete clinical response; however, a 2 mm residual tumor was noted in the surgical specimen. Overall, 33.0% patients were responders. Fifteen patients received molecular testing. No activated mutation of EGFR or Her2 were found. Activated PI3K or JAK2 pathway were trended to associate with non-responder (p = 0.057). Mutation of homologous recombination (HR) genes were correlated with non-responsiveness (p = 0.005). Seven patients did not have altered PI3K, JAK2 or HR pathway; six (85.7%) of them were responder. Patients with the amplified DAXX gene was associated with a favorable trend of response (p = 0.109)., Conclusion: Adding afatinib to neoadjuvant paclitaxel generated a modest effect in TNBC. Exploratory molecular analysis suggested that activated PI3K, JAK2 pathways and mutation of HR genes were associated with therapeutic non-responsiveness, and amplification of DAXX genes was associated with responsiveness to afatinib in combination with paclitaxel., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Purpose: Breast cancer is increasing around the globe, including Asia. We aimed to examine the survival and risk of contralateral breast cancer (CBC) in Asian breast cancer patients with BRCA mutations., Methods: A total of 128 breast cancer patients with germline BRCA mutations and 4,754 control breast cancer patients were enrolled. Data on clinical-pathologic characteristics, survival, and CBC were collected from the medical record. The rates of survival and CBC were estimated by Kaplan-Meier method., Results: The mean age of onset in BRCA mutation carriers was significantly younger than control patients (BRCA vs. Non-BRCA: 43.9 vs. 53.2 years old). BRCA mutation carriers had a higher proportion of triple-negative breast cancer (TNBC) (52%) than control patients (12%, p < 0.001). The risk of CBC was significantly higher in BRCA mutation patients than in control cases (hazard ratio (HR) = 3.95, 95% CI 2.71-5.75); when stratified by genotype, the HRs (95%CI) were 4.84 (3.00-7.82) for BRCA1 and 3.13 (1.78-5.49) for BRCA2 carriers, respectively. Moreover, BRCA1 mutation patients with triple-negative breast cancer (TNBC) as their first breast cancer had the highest risk of CBC (HR = 5.55, 95% CI 3.29-9.34). However, we did not observe any differences in relapse-free survival and overall survival between mutation carriers and control patients., Conclusion: Our study suggest that BRCA patients had a significantly higher risk of developing CBC, particularly for BRCA1 mutation carriers with TNBC as the first breast cancer., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Breast cancer is the most common cancer and the leading cause of cancer-related deaths in women. The estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are the important biomarkers in the prognosis of breast cancer, and their expression is used to categorize breast cancer into subtypes. We aimed to analyze the concordance among ER, PR, and HER2 expression levels and breast cancer subtyping results obtained by immunohistochemistry (IHC, for protein) and reverse transcriptase-polymerase chain reaction (RT-PCR, for mRNA) and to assess the recurrence-free survival (RFS) of the different subtypes as determined by the two methods. We compared biomarker expression by IHC and RT-PCR in 397 operable breast cancer patients and categorized all patients into luminal, HER2, and triple-negative (TN) subtypes. The concordance of biomarker expression between the two methods was 81.6% (κ = 0.4075) for ER, 87.2% (κ = 0.5647) for PR, and 79.1% (κ = 0.2767) for HER2. The κ-statistic was 0.3624 for the resulting luminal, HER2, and TN subtypes. The probability of 5-year RFS was 0.78 for the luminal subtype versus 0.77 for HER2 and 0.51 for TN, when determined by IHC (P=0.007); and 0.80, 0.71, and 0.61, respectively, when determined by the RT-PCR method (P=0.008). Based on the current evidence, subtyping by RT-PCR performs similar to conventional IHC with regard to the 5-year prognosis. The PCR method may thus provide a complementary means of subtyping when IHC results are ambiguous., (© 2022 The Author(s).)

Development of acquired resistance to lapatinib, a dual epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitor, severely limits the duration of clinical response in advanced HER2-driven breast cancer patients. Although the compensatory activation of the PI3K/Akt survival signal has been proposed to cause acquired lapatinib resistance, comprehensive molecular mechanisms remain required to develop more efficient strategies to circumvent this therapeutic difficulty. In this study, we found that suppression of HER2 by lapatinib still led to Akt inactivation and elevation of FOX3a protein levels, but failed to induce the expression of their downstream pro-apoptotic effector p27 kip1 , a cyclin-dependent kinase inhibitor. Elevation of miR-221 was found to contribute to the development of acquired lapatinib resistance by targeting p27 kip1 expression. Furthermore, upregulation of miR-221 was mediated by the lapatinib-induced Src family tyrosine kinase and subsequent NF-κB activation. The reversal of miR-221 upregulation and p27 kip1 downregulation by a Src inhibitor, dasatinib, can overcome lapatinib resistance. Our study not only identified miRNA-221 as a pivotal factor conferring the acquired resistance of HER2-positive breast cancer cells to lapatinib through negatively regulating p27 kip1 expression, but also suggested Src inhibition as a potential strategy to overcome lapatinib resistance., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Aromatase inhibitors (AIs) are standard adjuvant therapy for postmenopausal women with oestrogen receptor-positive, early-stage, and metastatic breast cancer. Although effective, the risk of falls due to AI-associated knee joint pain significantly increased. The aim of this study was to evaluate the therapeutic effects of yoga and massage on AI-associated knee joint pain. Breast cancer survivors were randomly assigned to a 6-week yoga intervention-2-week rest-6-week massage exposure (Yoga first, n = 30) or a 6-week massage intervention-2-week rest-6-week yoga exposure (Massage first, n = 30). Evaluations of the treatment efficacy were made at baseline, post-intervention, and post-exposure using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale, plasma cytokine levels, and changes in meridian energy. The results showed that yoga, superior to massage intervention, significantly reduced AI-associated knee joint pain, as demonstrated by the WOMAC pain score. The yoga intervention improvements were also associated with changes in plasma cytokine levels and meridian energy changes. In conclusion, this study provides scientific evidence that yoga was more effective than massage for reducing AI-associated knee joint pain. Meridian energy changes may provide another scientific, objective, non-invasive way to monitor the therapeutic effects of yoga and investigate another alternative, complementary medicine., (© 2021. The Author(s).)

Purpose: This study aimed to prospectively explore severity and prevalence of chemotherapy-induced peripheral neuropathy (CIPN) and examine the correlation between clinician-assessed (objective) and patient-reported (subjective) CIPN in breast cancer survivors receiving taxane., Methods: This was a prospective, longitudinal study. Purposive sampling was adapted to enroll women newly diagnosed with breast cancer and about to receive taxane. The CIPN was assessed after breast cancer diagnosed and before chemotherapy (T1), before cycle 1 to 4 taxane infusion (T2 to T5), and after chemotherapy completion (T6 to T8). Total Neuropathy Score-clinical version (TNSc), Identification Pain Questionnaire (ID pain), Functional Assessment of Cancer Therapy-Taxane subscale (FACT-Tax), and Peripheral Neuropathy Scale (PNS) were utilized for measuring CIPN. Descriptive statistics, Pearson correlation coefficient, and generalized estimating equation were used to analyze data., Results: A total of 88 participants were included. Both clinician-assessed and patient-reported CIPN gradually increased between T1 and T6 and mildly decreased at T7 and T8. Fifty-five participants (62.5%) experienced CIPN at T8. Weak-to-moderate correlations between subjective and objective CIPN were found at T6 to T8 (r = 0.272-0.533, p < 0.05). The change of TNSc, FACT-Tax, and PNS were significant over time. However, the significant change of neuropathic pain was only found at T6., Conclusion: The change of CIPN prevalence and severity were significant over time in survivors newly diagnosed with breast cancer. Specifically, the severest and highest CIPN was detected at chemotherapy completion. Survivors remained suffering from CIPN 3 months after chemotherapy completion. Besides, mild to moderate correlations between clinician-assessed and patient-reported CIPN were identified.

Background/aim: The current study aimed at evaluating the contribution of IL-13 promoter rs1881457 and rs1800925 genotypes to the risk of breast cancer in Taiwan., Materials and Methods: A total of 1,232 breast cancer cases and 1,232 age-matched controls were genotyped by typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology., Results: As for IL-13 rs1881457, the rates of AA, AC and CC genotypes were 54.8, 37.9 and 7.3% among the cases, and 53.8, 38.7 and 7.5% among the healthy controls, respectively; there were no statistically significant differences between the two groups (p for trend=0.8889). Also, regarding IL-13 rs1800925, there were no statistically significant differences between the two groups either (p for trend=0.6803). Furthermore, the allelic frequencies for IL-13 rs1881457 and rs1800925 were not differentially distributed between the case and control groups (p=0.6515 and 0.8753, respectively)., Conclusion: The rs1881457 and rs1800925 IL-13 promoter polymorphisms may not serve as breast cancer susceptibility determinants for Taiwanese., (Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: TTC-352 is a selective human estrogen receptor (ER) partial agonist developed for treatment of hormone-refractory ER + breast cancer., Methods: This was an accelerated dose escalation study with the primary endpoint of maximum tolerated dose that evaluated five dose levels of TTC-352 in breast cancer progressing after at least two lines of hormonal therapy including one in combination with a CDK4/6 inhibitor. The secondary objectives were to determine treatment tolerability, pharmacokinetics of TTC-352, best response, progression-free survival (PFS), and PKCα expression in tumors., Results: The study enrolled 15 patients. No dose-limiting toxicity was observed. Patients experienced the following grade 3 toxicities: asymptomatic pulmonary embolism, diarrhea, aspartate transaminase elevation, and myalgia, and one grade 4 toxicity of gamma glutamyltransferase elevation. Pharmacokinetic half-life was 7.6-14.3 h. The intra- and inter-individual variability for AUC 0 -∞ hampered assessment of the relationship between dose and AUC 0 -∞. Median PFS was 58 days (95% CI = 28,112). Higher PKCα expression in tumor stroma was associated with a trend toward longer PFS., Conclusions: TTC-352 demonstrates safety and early clinical evidence of antitumor activity against heavily pretreated hormone-refractory breast cancer. Based upon TTC-352 plasma concentrations and tolerability, the 180 mg twice a day is recommended for further testing. (ClinicalTrials.gov Identifier: NCT03201913).

Background/aim: The present study aimed at evaluating the contribution of IL-4 promoter T-1099G (rs2243248), C-589T (rs2243250), C-33T (rs2070874) genotypes to the risk of breast cancer in Taiwanese., Materials and Methods: A total of 1232 breast cancer patients and 1232 age-matched controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology., Results: Genotypic frequencies of IL-4 rs2243248, rs2243250 and rs2070874 were not differentially distributed between case and control groups. Consistently, there was no difference in the distribution of allelic frequencies among patients and controls., Conclusion: IL-4 rs2243248, rs2243250 and rs2070874 do not confer breast cancer susceptibility in Taiwanese., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Hypofractionated whole-breast irradiation is a standard adjuvant therapy for early-stage breast cancer. This study evaluates the plan quality and efficacy of an in-house-developed automated radiotherapy treatment planning algorithm for hypofractionated whole-breast radiotherapy., Methods: A cohort of 99 node-negative left-sided breast cancer patients completed hypofractionated whole-breast irradiation with six-field IMRT for 42.56 Gy in 16 daily fractions from year 2016 to 2018 at a tertiary center were re-planned with an in-house-developed algorithm. The automated plan-generating C#-based program is developed in a Varian ESAPI research mode. The dose-volume histogram (DVH) and other dosimetric parameters of the automated and manual plans were directly compared., Results: The average time for generating an autoplan was 5 to 6 min, while the manual planning time ranged from 1 to 1.5 h. There was only a small difference in both the gantry angles and the collimator angles between the autoplans and the manual plans (ranging from 2.2 to 5.3 degrees). Autoplans and manual plans performed similarly well in hotspot volume and PTV coverage, with the autoplans performing slightly better in the ipsilateral-lung-sparing dose parameters but were inferior in contralateral-breast-sparing. The autoplan dosimetric quality did not vary with different breast sizes, but for manual plans, there was worse ipsilateral-lung-sparing (V 4Gy ) in larger or medium-sized breasts than in smaller breasts. Autoplans were generally superior than manual plans in CI (1.24 ± 0.06 vs. 1.30 ± 0.09, p < 0.01) and MU (1010 ± 46 vs. 1205 ± 187, p < 0.01)., Conclusions: Our study presents a well-designed standardized fully automated planning algorithm for optimized whole-breast radiotherapy treatment plan generation. A large cohort of 99 patients were re-planned and retrospectively analyzed. The automated plans demonstrated similar or even better dosimetric quality and efficacy in comparison with the manual plans. Our result suggested that the autoplanning algorithm has great clinical applicability potential.

The long noncoding RNA HOTAIR plays significant roles in promoting cancer metastasis. However, how it conveys an invasive advantage in cancer cells is not clear. Here we identify the chondroitin sulfotransferase CHST15 (GalNAc4S-6ST) as a novel HOX transcript antisense intergenic RNA (HOTAIR) target gene using RNA profiling and show that CHST15 is required for HOTAIR-mediated invasiveness in breast cancer cells. CHST15 catalyzes sulfation of the C6 hydroxyl group of the N-acetyl galactosamine 4-sulfate moiety in chondroitin sulfate to form the 4,6-disulfated chondroitin sulfate variant known as the CS-E isoform. We show that HOTAIR is necessary and sufficient for CHST15 transcript expression. Inhibition of CHST15 by RNA interference abolished cell invasion promoted by HOTAIR but not on HOTAIR-mediated migratory activity. Conversely, reconstitution of CHST15 expression rescued the invasive activity of HOTAIR-depleted cells. In corroboration with this mechanism, blocking cell surface chondroitin sulfate using a pan-CS antibody or an antibody specifically recognizes the CS-E isoform significantly suppressed HOTAIR-induced invasion. Inhibition of CHST15 compromised tumorigenesis and metastasis in orthotopic breast cancer xenograft models. Furthermore, the expression of HOTAIR closely correlated with the level of CHST15 protein in primary as well as metastatic tumor lesions. Our results demonstrate a novel mechanism underlying the function of HOTAIR in tumor progression through programming the context of cell surface glycosaminoglycans. Our results further establish that the invasive and migratory activities downstream of HOTAIR are distinctly regulated, whereby CHST15 preferentially controls the arm of invasiveness. Thus, the HOTAIR-CHST15 axis may provide a new avenue toward novel therapeutic strategies and prognosis biomarkers for advanced breast cancer., (© 2019 UICC.)

Cancer cells are known to produce and secret extracellular vesicles for intercellular communication through the carried cargos. HOTAIR (HOX transcript antisense intergenic RNA), a well-studied long non-coding RNA (lncRNA), plays a critical role in cancer progression. In several cancer types it has been shown that HOTAIR-containing exosomes are produced by cancer cells. Here we show that circulatory exosomal HOTAIR is present in breast cancer patients and explores the pathological correlation with the disease. Exosomes were isolated by matrix-based precipitation from conditioned media of cultured breast cancer cell lines as well as blood samples of recently recruited breast cancer patients. HOTAIR RNA in exosomes was detected by quantitative reverse transcriptase-mediated polymerase chain reaction (qRT-PCR). Expression of exosomal HOTAIR was positively correlated with status of the receptor tyrosine kinase (RTK) ErbB2 (also known as HER2/neu) in tumor tissues. The causal correlation of ErbB2 and HOTAIR was validated in isogenic breast cancer cell lines with and without ectopic ErbB2 expression. Our finding provides a molecular basis to develop novel liquid biopsy biomarkers and targeted therapies with improved precision for malignant breast cancer., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background/aim: Breast tumor interleukin-6 (IL-6) level increases with tumor grade, and elevated serum IL-6 correlates with poor survival in patients with breast cancer. Epithelial-mesenchymal transition (EMT) phenotypes are associated with enhanced metastasis and unfavorable clinical outcome in breast cancer. Therefore, we examined whether IL-6 induced EMT phenotype characterized in breast cancer cells., Materials and Methods: MCF-7 cells treated with different concentrations (10-50 ng/ml) of IL-6 for 24 and 48 h. Western blotting, flow cytometry, and cell migration assay were used to test whether IL-6 promoted tumor-initiating ability in MCF-7 cells., Results: In this study, we found that the induction of EMT by IL-6 resulted in the acquisition of mesenchymal traits and the increase of tumor-initiating ability in MCF-7 cells. Moreover, we found that 2-phenylnaphthy-ridin-4-one derivatives were able to repress IL-6 induced EMT phenotype and tumor-initiating ability. Among these deriveratives, LYF-11 possessed the most potential inhibitory activity. LYF-11 effectively inhibited IL-6-induced EMT phenotype and tumor-initiating ability via the inhibition of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway., Conclusion: Our results suggest a connection between IL-6 receptor activity and EMT phenotype, and tumor-initiating ability. Moreover, LYF-11 is a potential compound for breast cancer therapy by targeting JAK2/STAT3 signaling pathway., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The family of matrix metalloproteinases (MMPs) are responsible for the homeostasis of extracellular matrix components and their genetic polymorphisms may be associated with cancer susceptibility. The serum levels of MMP-1 have been reported to be lower in breast cancer patients than healthy subjects. In the current study, we aimed at investigating the contribution of a polymorphism in the promoter region of MMP-1 to breast cancer in Taiwan., Materials and Methods: The MMP-1 rs1799705 polymorphic genotypes were genotyped among 1,232 breast cancer patients and 1,232 healthy controls by the typical polymerase chain reaction-restriction fragment length polymorphism methodology., Results: The percentages of 2G/2G, 1G/2G, and 1G/1G for MMP1 -1607 genotypes were 35.4, 40.6 and 24.0% in the breast cancer group and 34.1, 43.6, and 22.3% in the healthy control group (p trend=0.3025), respectively. The odds ratios (ORs) after adjusting for age, smoking and alcohol drinking status for those carrying 1G/2G and 1G/1G genotypes at MMP1 -1607 were 0.93 (95%CI=0.76-1.11, p=0.2390) and 1.01 (95%CI=0.77-1.23, p=0.7377), respectively, compared to those carrying the wild-type 2G/2G genotype. Supporting this finding, the adjusted OR for those carrying the 1G allele at MMP-1 -1607 was 1.03 (95%CI=0.91-1.18, p=0.8860), compared to those carrying the wild-type 2G allele. Our findings suggest that the polymorphic genotypes at MMP1 promoter -1607 investigated in the current study, may not play a major role in determining cancer susceptibility to breast cancer in Taiwan. Other early diagnostic and predictive markers are urgently needed for personalized and precise breast cancer detection and therapy., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The family of matrix metalloproteinases (MMPs) controls homeostasis of the extracellular matrix and their genetic polymorphisms may be associated with personal cancer susceptibility. The serum levels of MMP8 was reported to be higher in patients with breast cancer than in healthy individuals. In this study, we aimed to investigate the contribution of a polymorphism in the promoter region of MMP8 (-799C/T) and two nonsynonymous polymorphisms (Val436Ala and Lys460Thr) to breast cancer., Materials and Methods: MMP8 -799C/T, Val436Ala and Lys460Thr polymorphic genotypes were determined for 1,232 patients with breast cancer and 1,232 healthy controls by polymerase chain reaction-restriction fragment length polymorphism methodology., Results: The odds ratios (ORs) after adjusting for age, gender, smoking and alcohol drinking status for those carrying CT and TT genotypes at the MMP8 promoter C-799T were 1.03 (95% CI=0.88-1.23, p=0.7475) and 1.08 (95% CI=0.91-1.53, p=0.3561), respectively, compared to those carrying the wild-type CC genotype. The OR for the combined T-bearing genotypes were of a similar non-significant level (OR=1.05, 95% CI=0.90-1.26, p=0.5176). Supporting this finding, the adjusted OR for those carrying the T allele at MMP8 C-799T was 1.05 (95% CI=0.86-1.21, p=0.3797), compared to those carrying the wild-type C allele. There was also no significant association of MMP8 Lys460Thr with breast cancer. There was no polymorphic genotype at MMP8 Val436Ala found among any of the investigated individuals., Conclusion: MMP8 -799C/T, Val436Ala and Lys460Thr polymorphisms may only play an indirect role in determining personal cancer susceptibility to breast cancer in Taiwan., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: In this multi-center study, we report the patient selection criteria for and preliminary oncologic outcomes associated with intraoperative radiotherapy (IORT) delivered by the Xoft Axxent® eBx® system for early-stage breast cancer in Taiwan., Methods: Patients with early breast cancer in Taiwan received breast conserving surgery and received IORT with Xoft Axxent® eBx® System during 2013-2015 was search from database of Taiwan IORT study cooperative group (T-IORTSCG). Patients' clinicopathologic characteristics and early post-operative results were collected and reported., Results: During the study period, 26 hospitals in Taiwan performed a total of 261 Xoft IORT procedures for breast cancer. The mean age of them was 52.9 ± 9.8 years (37-72), and tumor size was 1.5 ± 0.8 cm (0.1-4.2 cm) for invasive cancer and 1.2 ± 0.8 cm (range, 0.2-3.0 cm) for ductal carcinoma in situ (DCIS) lesions. Lymph node metastasis was found in 6 (2.3%) patients. The patients received IORT in Taiwan differed markedly from those used in the ELIOT and TARGIT-A studies. Specifically, patients selected for IORT in Taiwan tended to be younger, their tumors tended to be larger and the prevalence of lymph node metastasis tended to be lower. Among these 261 patients, 8 (3.1%) patients required whole breast radiotherapy. During a mean follow up of 15.6 months, locoregional recurrence was observed in 2 (0.8%) patients., Conclusion: In real world experience, patients received IORT differed quite significantly with criteria formulated by trials. The preliminary results of IORT in Taiwan showed it is well acceptable by patients and clinicians.

Background/aim: The matrix metalloproteinase (MMP) family of enzymes are in charge of degradation of various components of the extracellular matrix and their functional genetic polymorphisms may be associated with cancer susceptibility. The functional polymorphisms in the promoter region of MMP7 (A-181G and C-153T) have been reported to influence the binding capacity of nuclear proteins and may contribute to genetic susceptibility to cancer. In this study, we focused on investigating the contribution of the genotypes of MMP7 (A-181G and C-153T) to breast cancer in Taiwan., Materials and Methods: These two polymorphisms were genotyped in 1,232 patients with breast cancer and 1,232 controls by polymerase chain reaction-restriction fragment length polymorphism methodology., Results: The odds ratios (ORs) after adjusting for age, family history of cancer, smoking and alcohol drinking status for those carrying AG and GG genotypes at MMP7 promoter A-181G were 1.22 (95%CI=0.91-1.63, p=0.2235) and 2.84 (95%CI=1.64-7.48, p=0.0007) respectively, compared to those carrying the wild-type AA genotype. Supporting this finding, the adjusted OR for those carrying the G allele at MMP7 promoter A-181G was 1.57 (95%CI=1.29-1.93, p=0.0008), compared to those carrying the wild-type A allele. There was no polymorphic genotype at MMP7 C-153T found among any of the investigated individuals., Conclusion: Our findings suggest that the MMP7 A-181G polymorphisms may play a role in determining personal cancer susceptibility and GG genotype at MMP7 A-181G may serve as a biomarker for early detection and prediction of breast cancer in Taiwanese., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The association of uterine leiomyoma with increased risk of breast cancer is controversial. Therefore, we used the National Health Insurance Research Database of Taiwan to examine breast cancer incidence and mortality among Asian patients with and without uterine leiomyoma. We compared breast cancer incidence and mortality between 22,001 newly diagnosed uterine leiomyoma patients and 85,356 individuals without uterine leiomyoma matched by age and date of diagnosis. Adjusted hazard ratios for breast cancer were estimated using the Cox model. The incidence of breast cancer was 35% higher in the uterine leiomyoma group than the leiomyoma-free group (1.65 vs. 1.22 per 1,000 individuals, p < 0.001), with an adjusted hazard ratio of 1.31 (95% confidence interval = 1.13-1.52). Interestingly, overall mortality was lower (4.12%) in the uterine leiomyoma group (mean followed time, 3.59 ± 2.70 years) than the leiomyoma-free group (8.78%; mean followed time, 3.54 ± 2.67 years) at the endpoint of the study (p <0.05). These findings indicate the incidence of breast cancer is higher in patients with uterine leiomyoma than in those without it, but overall mortality from breast cancer was lower in the patients with uterine leiomyoma.

Background: Breast and cervical cancer are the most common cancers affecting women. The symptom distresses experienced by cancer survivors are critical factors influencing their quality of life (QOL). This study investigated the QOL of breast and cervical cancer survivors, their physical, psychological and social conditions., Methods: The participants were older than 20 years, had been diagnosed with breast or cervical cancer for more than 2 years, and had completed their cancer treatment. The survey incorporated the QOL questionnaires developed by the European Organization of Research and Treatment for Cancer and a self-designed questionnaire., Results: The mean age at diagnosis was 48.89 ± 8.53 years for the breast cancer survivors and 49.00 ± 10.30 years for the cervical cancer survivors. The corresponding QOL scores were 75.33 ± 20.25 and 75.56 ± 17.93. The factors influencing QOL of breast cancer survivors were household income, number of comorbidities, stage of cancer, type of cancer treatment and duration of illness, whereas the factor related to QOL of cervical cancer survivors was only household income., Conclusions: The QOL of the two groups was similar. Healthcare providers should demonstrate greater concern toward breast and cervical cancer survivors.

Aim: Metalloproteinases (MMPs) are a family of enzymes involved in many physiological processes, such as skeletal development, wound healing, and scar formation, as well as carcinogenesis. However, the contribution of MMP1 genotype to breast cancer has not been elucidated. This study aimed to evaluate the contribution of commonly studied MMP1 promoter 1607 genotype to breast cancer risk., Materials and Methods: In this hospital-based case-control study, contribution of MMP1 genotype to breast cancer risk was evaluated among 1,232 patients with breast cancer and 1,232 gender-matched healthy controls., Results: The distribution of 2G/2G, 1G/2G and 1G/1G for MMP1 promoter 1607 genotype was 36.0%, 41.3% and 22.7% in the breast cancer group and 34.2%, 44.5% and 21.3% in the non-cancer group, respectively (p for trend=0.2820). We also analyzed the allelic frequency distributions and found that the variant 1G allele of MMP1 promoter 1607 conferred similar breast cancer susceptibility as the wild-type 2G allele (odds ratio=0.99, 95% confidence interval=0.89-1.11, p=0.8858). There was no interaction between MMP1 promoter 1607 genotype and cigarette smoking or alcohol drinking habits., Conclusion: The genotype of MMP1 promoter 1607 may not be a major determining factor for breast cancer risk. The contribution of MMP1 promoter 1607 genotype to prognosis and subtypes of breast cancer needs further investigation., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Overexpression of cyclooxygenase 2 (COX-2) has been suggested to be associated with breast carcinogenesis. The aim of the present study was to evaluate the contribution of genotypic polymorphisms in COX-2 to breast cancer risk of Taiwanese females. In total, 1,232 breast cancer patients and 1,232 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Six polymorphic variants of COX-2, including G-1195A (rs689466), G-765C (rs20417), T8473C (rs5275), intron 1 (rs2745557), intron 5 (rs16825748) and intron 6 (rs2066826) were examined. The results showed that the GC genotype of COX-2, G-765C was associated with a lower risk compared to the wild-type GG genotype (odds ratio(OR)=0.66, 95% confidence interval(CI)=0.53-0.83, p=0.0005). The C allele of COX-2 G-765C was significantly more frequently found in controls than in cancer patients (p=0.0006). In addition, the OR of the GG/AG+AA, GC/GG and GC/AG+AA at G-765C/Intron 1 combined genotypes compared to wild-type GG/GG genotype were 0.79 (95%CI=0.66-0.96; p=0.0166), 0.61 (95%CI=0.48-0.78; p=0.0001), and 0.71 (95%CI=0.36-1.37; p=0.3040), respectively. As for the combination of G-765C and intron 6, the OR of the GG/AG+AA, GC/GG and GC/AG+AA combined genotypes compared with wild-type GG/GG reference genotype were 0.79 (95%CI=0.62-1.01; p=0.0561), 0.63 (95%CI=0.50-0.81; p=0.0003), and 0.68 (95%CI=0.38-1.21; p=0.1897), respectively. Our results indicate that the C allele of COX-2, G-765C was associated with a decreased risk of breast cancer in Taiwan, and could serve as an early detection and predictive marker for breast cancer risk., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background and Objectives: Patients with node-negative breast cancer (NNBC) usually have a good prognosis, but tumor recurrence still compromises survival. In this study, we sought to identify clinical and pathologic factors that predict recurrence., Methods: A total of 716 patients who were proved with pT1-2N0M0 breast cancer between 2005 and 2009 were enrolled in this study., Results: Forty-seven of the 716 patients developed tumor recurrence during the 47.0 months of median follow-up. The significant risk factors of recurrence were lymphovascular invasion (LVI) (hazard ratio [HR] = 4.60, 95% CI. 2.32-9.10) and Nottingham grade 3 (HR = 4.99, 95% CI. 1.06-23.48); adjuvant radiotherapy (HR = 0.35, 95% CI. 0.14-0.92) prevented tumor recurrence. Furthermore, we investigate the therapeutic impact of adjuvant chemotherapy and radiotherapy on patients with LVI and Nottingham grade 3. The adverse effect of LVI and grade 3 can be abrogated by adjuvant radiotherapy in recurrence-free survival (RFS) (LVI((+)) radiotherapy((+)) , no recurrence; grade 3((+)) radiotherapy((+)) , HR = 0.82, 95% CI. 0.18-3.70). However, adjuvant chemotherapy did not., Conclusions: LVI and Nottingham grade 3 were the independent risk factors predicting tumor recurrence for patients with NNBC. Adjuvant radiotherapy might be considered in NNBC patients with these unfavorable factors to improve the RFS., (© 2013 Wiley Periodicals, Inc.)

Background: The majority of women with breast cancer experience treatment-related fatigue. Fatigue makes patients more inclined to terminate their treatment, which influences patient prognosis and survivorship., Purpose: This study explores the effects of a walking program on fatigue and exercise capacity in women who have undergone breast cancer surgery., Methods: This was a randomized control trial study with measures taken 3 times over 5 weeks. Sixty-six women with breast cancer were recruited from a medical center in central Taiwan. The intervention was a moderate-intensity, home-based walking program. The Functional Assessment for Chronic Illness Treatment-Fatigue and distance walked in a 6-minute period, respectively, were used to score the main outcome measures of fatigue and exercise capacity., Results: For those who accepted chemotherapy, fatigue was significantly higher during chemotherapy than after surgery. Although participants in the walking program achieved gradually reduced fatigue and increased exercise capacity, there was no significant difference in fatigue and exercise capacity between the exercise and control groups at any of the three measured times., Conclusions/implications for Practice: Nurse collaboration with healthcare providers to promote exercise in the breast cancer population may not only improve the health of post-surgery breast cancer women but also enhance the independent functioning of nurses and advance the nursing profession.

Aim: Primary neuroendocrine carcinomas of the breast (PNCB) are very rare and tumor markers for this indication are not well defined. We aim at reporting a case and providing a marker useful for prognosis and prediction of tumor recurrence for patients with PNCB., Case Report: A 75-year-old woman presented with a slight painful lump in her left breast of more than 6 months duration. Prior to surgery, the serum level of carcinoembryonic antigen (CEA) (54.4 ng/ml; normal limit <5.0 ng/ml) was significantly elevated. Ultrasonography identified a hypoechoic lesion. Mammography revealed a hyperdense lesion with a well-circumscribed margin. The patient underwent a modified radical mastectomy with axillary lymph node dissection. Pathology showed tumor cells with neuroendocrine features, with diffuse immunopositivity for chromogranin and synaptophysin. The tumor cells were also strongly positive for progesterone and estrogen receptor, but negative for HER-2/neu expression. The CEA value gradually decreased to the normal range within one month after surgery. Neither recurrence nor distant metastasis has been detected at 20 months after surgery and hormone therapy with letrozole. The serial CEA levels were within normal limits in the follow-up period., Conclusion: The serum CEA level after surgery may be a potential marker for evaluating tumor recurrence or prognosis of patients with PNCB.

Aim: Japanese and American groups reported that single nucleotide variation of caveolin-1 gene (CAV1) plays an important role in breast cancer risk. The aim of this study was to evaluate the association of six polymorphic genotypes of CAV1, which is reported to be overexpressed in tumors, with breast cancer within a Taiwanese population., Patients and Methods: A total of 1232 patients with breast cancer and equal number of healthy controls in central Taiwan were genotyped via polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and six polymorphic variants of CAV1 were analyzed for their association with breast cancer susceptibility., Results: The distribution of genotypes of CAV1 G14713A and T29107A were significantly different between breast cancer and control groups (p=5.6×10(-5) and 1.9×10(-4), respectively), while those for CAV1 C239A, G21985A, T28608A and G32124A were not significant (p>0.05). The percentages of AG genotype of G14713A and TT genotype of T29107A are higher in the cancer group than in the control group. The two single nucleotide polymorphisms were chosen for haplotype analysis and the data showed that compared with GG/TT haplotype of CAV1 G14713A/T29107A, the GG/AT and GG/AA groups have a lower risk of breast cancer (odds ratio, OR=0.69, 95% confidence interval, CI=0.57-0.92). On the contrary, the AG/TT haplotype confers a higher risk of breast cancer (OR=1.50, 95% CI=1.14-2.12)., Conclusion: Our results provide evidence for CAV1 genotypes being involved in predisposition to breast cancer. The association of the potential risk haplotype agrees well with a role of CAV1 genotype in breast cancer risk and the association with tumor progression needs further investigation.

Aim: Alpha B-Crystallin (CRYAB) is purported to be a metastasis suppressor protein, and lack or lower CRYAB expression is a prognostic biomarker for several types of cancer, such as that of the prostate and head and neck. However, the association of genomic variation of CRYAB and breast cancer is not well studied. The aim of this study was to evaluate the association of polymorphic genotypes of CRYAB with breast cancer within a Taiwanese population., Patients and Methods: In this hospital-based study, 1232 patients with breast cancer and an equal number of healthy controls in central Taiwan were genotyped via polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and the association of CRYAB A-1215G (rs2228387), C-802G (rs14133) and intron 2 (rs2070894) polymorphisms with breast cancer risk in a central Taiwanese population was investigated., Results: Those individuals with CRYAB C-802G CG and GG genotypes had 1.50- and 2.22-fold risk for breast cancer than those with the CC genotype. As for the A-1215G and intron 2 polymorphisms, there was no significant association of the genotype with breast cancer risk. In allelic frequency analysis, the G allele CRYAB C-802G conferred a significantly (p=5.63×10(-10)) increased risk of breast cancer. Our results provide evidence that the G allele of CRYAB C-802G is correlated with breast cancer risk and this polymorphism may be a useful marker for early detection of breast cancer in clinical practice.

Background: Accurate intraoperative pathologic examination of sentinel lymph nodes (SLNs) has been an important tool that can reduce the need for reoperations in patients with SLN-positive breast cancer. The objective of the current study was to determine the accuracy of intraoperative frozen section (IFS) of SLNs during breast cancer surgery., Methods: The authors retrospectively reviewed the records of 326 patients with breast cancer who underwent IF analysis of SLNs at a single institution. Then, they conducted a meta-analysis that included 47 published studies of IFS of SLNs in patients with breast cancer., Results: Hematoxylin and eosin (H&E) staining revealed metastasis in SLNs in 99 patients (30.4%), including 61 patients with macrometastasis (MAM) (>2 mm) (the MAM group) and 38 patients with micrometastasis (Mi) or isolated tumor cell (ITC) deposits (the Mi/ITC group). The overall sensitivity of the institutional series was 60.6% (60 of 99 patients), and overall specificity was 100% (227 of 227 true negatives). The sensitivity of IFS was significantly lower in the Mi/ITC group (28.9%) than in the MAM group (80.3%; P < .0001). According to the meta-analysis of published studies and data from the author's institution (47 studies, for a total of 13,062 patients who underwent SLN dissection with IFS of SLNs), the mean sensitivity was 73%, and the mean specificity was 100%. The mean sensitivity was 94% for the MAM group and 40% for the Mi/ITC group., Conclusions: IFS of SLNs was more reliable for detecting MAM than for detecting Mi/ITC deposits. It lacked sufficient accuracy to rule out Mi/ITC deposits., (Copyright © 2010 American Cancer Society.)

Aim: Several epidemiological studies have investigated the association between ataxia telangiectasia mutated (ATM) gene polymorphisms and breast cancer risk. However, published data are still inconclusive and there are no such studies for Taiwan. Thus, the polymorphic variants of ATM were investigated for their association with breast cancer in Taiwan for the first time here., Patients and Methods: In this hospital-based matched case-control study, associations of seven ATM single nucleotide polymorphisms (rs600931, rs652311, rs227060, rs227292, rs624366 and rs189037) with breast cancer risk in a Taiwanese population were investigated. One thousand two hundred and thirty-two patients with breast cancer and the same number of age-matched healthy controls recruited were genotyped and analyzed., Results: There was a slight difference between breast cancer and control groups in the distributions of their genotypic (p = 0.0774) and allelic frequencies (p = 0.0217) in the rs189037 polymorphism. As for the other six polymorphisms there was no differential distribution., Conclusion: Our data indicate that ATM polymorphism is associated with breast cancer, and the A allele of ATM rs189037 is a minor risky biomarker of breast cancer in Taiwan. The gene-gene and gene-environment interactions of ATM with other factors is worthy of further investigation.

Nonsentinel lymph nodes (SLNs) are commonly removed at the time of selective sentinel lymphadenectomy (SSL). Their predictive value for the rest of the nodal basin is unknown. A retrospective review of 436 breast cancer patients who underwent SSL between 12/97 and 04/03 at a single institution. One-hundred nineteen patients had non-SLNs removed at SSL; eight were positive (6.7%). Positive non-SLNs predicted that SLNs would also be positive (p = 0.008). There was no difference in rates of additional positive nodes found on completion axillary node dissection between the non-SLN and SLN positive patients (p = 0.62). After adjustment for covariates, the presence of positive non-SLNs was not associated with poorer disease free survival (p = 0.24), time to systemic recurrence (p = 0.57), or overall survival (p = 0.70). Positive non-SLNs removed during SSL are not a significant risk factor for additional positive nodes on completion axillary nodal dissection (CALND) or for worse survival than positive SLNs.

Background: No consensus exists about the number of sentinel lymph nodes (SLNs) that should be removed based on radioactivity counts in breast cancer, although the "10% rule" is often used. We hypothesized that the node with the highest radioactivity would have the strongest probability of being a positive SLN, and we sought to determine the lowest radioactive count of a node harboring cancer., Study Design: We retrospectively studied 332 breast cancer patients who underwent lymphoscintigraphy by injection of technetium 99m-labeled thiosulfate colloid and sentinel lymphadenectomy (SL) between 1997 and 2006, with intraoperative determination of radioactive counts of nodes by a gamma probe. All SLNs were examined by permanent sections consisting of at least 3 levels of 40- to 100-mum intervals for hematoxylin and eosin evaluation, with or without immunohistochemical staining for cytokeratins., Results: Seventy-four percent of patients had more than 1 SLN removed (mean 2.8 per patient); 23.5% had SLN metastasis. Of the node-positive patients, the hottest SLN was positive in 85.9% (67 of 78). Five of the 78 patients (6.4%) with positive nodes had counts less than 10% of those of the hottest node. The lowest radioactive count of a positive SLN was 4.2% of that of the hottest node. Lymphatic mapping based on the 10% rule could greatly improve the false-negative rates compared with removing only the hottest SLN (14.1% versus 6.4%)., Conclusions: Most positive SLNs had the highest radioactivity. Our institutional experience indicates that to obtain an acceptable false-negative rate, nodes should be removed until the 10% rule is met.