No axillary surgical treatment for lymph node-negative patients after ultra-sonography [NAUTILUS]: protocol of a prospective randomized clinical trial.

BACKGROUND: Following sentinel lymph node biopsy (SLNB), the axillary recurrence rate is very low although SLNB has a false-negative rate of 5-10%. In the ACOSOG Z0011 trial, non-sentinel positive-lymph nodes were found in more than 20% of the axillary dissection group; the SLNB only group did not have a higher axillary recurrence rate. These findings raised questions about the direct therapeutic effect of the SLNB. SLNB has post-surgical complications including lymphedema. Considering advances in imaging modalities and adjuvant therapies, the role of SLNB in early breast cancer needs to be re-evaluated. METHODS: The NAUTILUS trial is a prospective multicenter randomized controlled trial involving clinical stage T1-2 and N0 breast cancer patients receiving breast-conserving surgery. Axillary ultrasound is mandatory before surgery with predefined imaging criteria for inclusion. Ultrasound-guided core needle biopsy or needle aspiration of a suspicious node is allowed. Patients will be randomized (1:1) into the no-SLNB (test) and SLNB (control) groups. A total of 1734 patients are needed, considering a 5% non-inferiority margin, 5% significance level, 80% statistical power, and 10% dropout rate. All patients in the two groups will receive ipsilateral whole-breast radiation according to a predefined protocol. The primary endpoint of this trial is the 5-year invasive disease-free survival. The secondary endpoints are overall survival, distant metastasis-free survival, axillary recurrence rate, and quality of life of the patients. DISCUSSION: This trial will provide important evidence on the oncological safety of the omission of SLNB for early breast cancer patients undergoing breast-conserving surgery and receiving whole-breast radiation, especially when the axillary lymph node is not suspicious during preoperative axillary ultrasound. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04303715 . Registered on March 11, 2020.

Characteristics and prognosis of breast cancer after liver or kidney transplantation.

PURPOSE: Immunoediting is crucial in cancer development and progression. This study compared the characteristics and prognosis of post-transplant breast cancer (PTBC) patients receiving immunosuppressants and general breast cancer patients. METHODS: Data from the Asan Medical Center Breast Cancer (AMCBC), kidney transplantation, and liver transplantation databases recorded during 1989-2013 were retrospectively analyzed. Four controls of AMCBC cohort per one case of PTBC cohort were selected based on tumor size, lymph node metastasis, and age. RESULTS: After a median of 61 and 90.8 months after liver and kidney transplantation, respectively, 8 and 16 patients were diagnosed with breast cancer, respectively (p = 0.178). Mean age at breast cancer diagnosis was 51.9 (±8.7) and 45.2 (±4.5) years in liver and kidney transplantation patients, respectively. Age at diagnosis was significantly younger in kidney transplantation patients than in general breast cancer patients (45.2 ± 4.5 vs. 48.5 ± 10.1 years; p = 0.008). Cancer was detected via asymptomatic screening in 41.7% of the PTBC cohort but 30.6% of the control cohort (p = 0.241). In the PTBC cohort, 7 (29.2%) patients had stage 0 breast cancer compared with 1704 (9.7%) in the control cohort (p = 0.022); 22 (91.7%) patients had lymph node-negative cancer compared with 11,704 (66.8%) in the control cohort (p = 0.01). Estrogen receptor, progesterone receptor, and HER2 positivity did not differ between cohorts. Immunosuppressant use was not a poor prognostic factor for breast cancer patients. CONCLUSIONS: Age at breast cancer diagnosis was younger in patients who received kidney transplants; the subtype and prognosis of breast cancer were comparable with that in the general cohort. Immunosuppressants do not adversely affect breast cancer prognosis.

Spontaneous formation of periodic nanostructures by localized dynamic wrinkling.

Micro/nanoscale periodic structures are widely used in display, optics and bio industries as key functional elements. We present a novel nanopatterning method, localized dynamic wrinkling (LDW), which creates micro/nanoscale metal gratings continuously by simply sliding a flat edge of a hard material over a thin metal surface coated on a polymer layer. The LDW process presented in this paper is an etching- and template-free nanopatterning technology based on nanoscale wrinkling phenomenon. This simple process enables spontaneous formation of large-area metal gratings with controllable periodicity from micrometer down to 120 nm.

Association of shared decision-making with type of breast cancer surgery: a cross-sectional study.

BACKGROUND: Although some studies examined the association between shared decision-making (SDM) and type of breast cancer surgery received, it is little known how treatment decisions might be shaped by the information provided by physicians. The purpose of this study was to identify the associations between shared decision making (SDM) and surgical treatment received. METHODS: Questionnaires on SDM were administered to 1,893 women undergoing primary curative surgery for newly diagnosed stage 0-II localized breast cancer at five hospitals in Korea. Questions included being informed on treatment options and the patient's own opinion in decision-making. RESULTS: Patients more likely to undergo mastectomy were those whose opinions were respected in treatment decisions (adjusted odds ratio, aOR), 1.40; 95% confidence interval (CI), 1.14-1.72) and who were informed on chemotherapy (aOR, 2.57; CI, 2.20-3.01) or hormone therapy (aOR, 2.03; CI, 1.77-2.32). In contrast, patients less likely to undergo mastectomy were those who were more informed on breast surgery options (aOR, 0.34; CI, 0.27-0.42). In patients diagnosed with stage 0-IIa cancer, clinical factors and the provision of information on treatment by the doctor were associated with treatment decisions. In patients diagnosed with stage IIb cancer, the patient's opinion was more respected in treatment decisions. CONCLUSION: Our population-based study suggested that women's treatment decisions might be shaped by the information provided by physicians, and that women might request different information from their physicians based on their preferred treatment options. These results might need to be confirmed in other studies of treatment decisions.

Dynamic nanoinscribing for continuous and seamless metal and polymer nanogratings.

Nanoscale grating structure can be utilized in many practical applications in optics, flat-panel displays, and biosensors. We present a dynamic nanoinscribing (DNI) technique for directly creating large-area, truly continuous nanograting patterns in a variety of metal or polymer materials with feature size down to sub-50 nm and at very high speed (10 cm/sec). DNI is carried out under either ambient temperature or with a brief heating time on the order of 10 micros, which minimizes damage on UV or thermosensitive functional materials. We also demonstrated future applications of the DNI process into the simple, one-step fabrication of split-ring resonator (SRR) structures for negative index materials.

Large-area roll-to-roll and roll-to-plate nanoimprint lithography: a step toward high-throughput application of continuous nanoimprinting.

A continuous roll-to-roll nanoimprint lithography (R2RNIL) technique can provide a solution for high-speed large-area nanoscale patterning with greatly improved throughput; furthermore, it can overcome the challenges faced by conventional NIL in maintaining pressure uniformity and successful demolding in large-area imprinting. In this work, we demonstrate large-area (4 in. wide) continuous imprinting of nanogratings by using a newly developed apparatus capable of roll-to-roll imprinting (R2RNIL) on flexible web and roll-to-plate imprinting (R2PNIL) on rigid substrate. The 300 nm line width grating patterns are continuously transferred on either glass substrate (roll-to-plate mode) or flexible plastic substrate (roll-to-roll mode) with greatly enhanced throughput. In addition, the film thickness after the imprinting process, which is critical in optical applications, as a function of several imprinting parameters such as roller pressure and speed, is thoroughly investigated, and an analytical model has been developed to predict the residual layer thickness in dynamic R2RNIL process.

Association of clinical experiences with patient-reported outcomes among breast cancer surgery patients: breast cancer quality care study.

BACKGROUND: We aimed to clarify the association of breast cancer patients' clinical experiences with patient-reported outcomes (PRO) of satisfaction with care, choice of the same type of surgery again, and health-related quality of life (HRQOL). METHODS: There were 2,403 (25.9%) of 9,283 eligible women who had undergone primary curative surgery for breast cancer in one of five selected hospitals between 1993 and 2002 who responded to a survey questionnaire including information about care experiences, satisfaction with care, and HRQOL. RESULTS: Treatment satisfaction was independently associated with cancer recurrence, problems obtaining surgery, receiving adjuvant hormonal therapy, being involved in treatment decisions, having opinions reflected in treatment decisions, experiencing treatment toxicity, or being hospitalized for treatment toxicity (P <0.01). Breast-conserving surgery with radiotherapy, receiving adjuvant hormone therapy, being involved in treatment decisions, having opinion reflected in treatment decisions, having no treatment toxicity, and receiving regular follow-up care were associated with choosing the same treatment over again (P < 0.01). Good care experiences, except for regular follow-ups, were significantly associated with good HRQOL in most functioning subscales (P < 0.01). CONCLUSIONS: Our findings suggest that timely referral for treatment, reflection of the patient's opinions in treatment decisions, and prevention of treatment toxicity might be important to HRQOL.

Trends in breast cancer treatment in Korea and impact of compliance with consensus recommendations on survival.

Although some studies suggest that conformity with consensus recommendations for breast cancer therapy is associated with increased survival, the data are not clear. We identified patients in four hospital-based breast cancer registries in Korea who had undergone primary curative surgery (stage 0-III) from 1993 through 2002 (n = 8,407). We collected demographic and clinical characteristics such as age, stage, treatment, and hormone receptor status. We gathered 1993-2004 mortality data by linkage to the National Statistical Office. During the follow-up period of 43,145 person-years (mean, 5.13 years), we identified 899 deceased cases. We used the standard Poisson regression model to estimate the hazard ratio (HR) for survival in relation to conformity with guidelines for chemo-, hormone, and locoregional therapy. Guideline compliance for systemic therapy increased from 24.0% in 1993 to 83.8% in 2002. Among mastectomy patients with <4 positive lymph nodes and tumors <5 cm, post-mastectomy radiotherapy was associated with poor survival (HR 2.07; 95% CI: 1.53-2.81). Tamoxifen use was associated with better survival among patients with hormone receptor-positive tumors (HR 0.57; 95% CI: 0.45-0.73) and with poorer survival among hormone receptor-negative patients who had affected nodes (HR 1.58; 95% CI: 1.01-2.44). Relative to conformity, non-conformity with both chemo- and hormone therapy guidelines was associated with a 76% higher risk of death. Compliance with consensus recommendations for chemo- and hormone therapy is significantly associated with better survival. Overuse of post-mastectomy radiotherapy and tamoxifen beyond the consensus recommendations may be harmful.

Immunohistochemical and clinicopathologic characteristics of invasive ductal carcinoma of breast with micropapillary carcinoma component.

CONTEXT: A micropapillary carcinoma (MC) component is generally considered to behave aggressively. Although several reports have described the prognostic significance of MC in breast carcinomas, immunohistochemical findings of MC, especially as compared to non-MC, are rarely described. OBJECTIVE: We compared clinicopathologic and immunohistochemical findings between 38 cases of invasive breast carcinoma with an MC component (IMC) and 217 cases of invasive breast carcinoma without an MC component (NIMC). DESIGN: We constructed a tissue microarray from 38 cases of IMC and performed immunohistochemical stainings for cytokeratin (CK) 7, CK20, estrogen receptor, progesterone receptor, p53, c-Erb-B2, CD34, CK5, epidermal growth factor receptor, and c-Kit in both MC and non-MC components. RESULTS: Cases with IMC were associated with greater tumor size, more frequent lymphovascular invasion, nodal metastases, greater mean numbers of positive lymph nodes, and higher stage than those with NIMC, but were not associated with poorer survival rates. On immunohistochemistry, only p53 reactivity was statistically different between MC and non-MC components in IMC cases. Estrogen receptor positivity tended to be lower in MC than non-MC, but the difference was not significant. Most of the MCs and non-MCs in IMC cases were positive for CK7, but none of them were positive for CK20, CK5, epidermal growth factor receptor, or c-Kit. CONCLUSIONS: Based on the frequent nodal metastases and association with higher stage found in IMC as compared with NIMC cases, as well as higher p53 positivity and lower frequency of estrogen receptor expression, MC could be considered an aggressive histologic type of breast carcinoma. In both MC and non-MC components in IMC cases, no basallike immunostaining pattern was detected.

BRCA1 and BRCA2 germline mutations in Korean patients with sporadic breast cancer.

In order to evaluate the role of BRCA1 and BRCA2 germline mutations in Korean patients with sporadic breast cancer, 97 patients with sporadic breast cancer were analyzed for mutations in the BRCA1 and BRCA2 coding regions, by using a combination of fluorescent-conformation sensitive gel electrophoresis (F-CSGE) and direct sequencing. Fifty-five distinct sequence variants were detected, which included three pathogenic truncating mutations, 15 missense mutations, 16 polymorphisms, and 21 intronic variants. Twenty-six of these variants have never been previously reported and may be of Korean-specific origin. Two pathogenic BRCA1 mutations (c.922_924delinsT, c.5445G>A) and one pathogenic BRCA2 mutation (c.2259delT) were observed, and two of these (BRCA1 c.5445G>A and BRCA2 c.2259delT) are novel. The total prevalence of germline pathogenic mutations in BRCA1 and/or BRCA2 in Korean sporadic breast cancer is estimated to be about 3.1%. Considering that the majority of breast cancer cases are sporadic, the present study will be helpful in the evaluation of the need for the genetic screening of germline BRCA mutations in sporadic breast cancer patients. Further study using a larger sample size is required to determine the merits of genetic diagnosis and counseling in breast cancer patients.

Estrogen receptor alpha gene polymorphisms and breast cancer risk.

We conducted a hospital-based case-control study to evaluate the association between the XbaI and PvuII restriction fragment length polymorphisms (RFLPs) in intron I of the estrogen receptor alpha (ER alpha) gene and breast cancer risk. The study population consisted of 205 histologically confirmed incident breast cancer cases and 205 age-matched controls with no present and previous history of cancer. The PvuII genotype distribution did not show any difference between cases and controls, but the adjusted odds ratio (OR) for the XbaI X allele containing genotypes was 0.4 (95% CI: 0.3-0.6) compared with the xx genotype. The decrease in the OR appeared to be more attributable to the postmenopausal women; the ORs were 0.3 (95% CI: 0.1-0.5) and 0.5 (95% CI: 0.3-0.9) for postmenopausal and premenopausal women, respectively. Our results therefore suggest that the ER alpha XbaI polymorphism modifies individual susceptibility to breast cancer in Korean women.

hOGG1 Ser326Cys polymorphism and breast cancer risk among Asian women.

To evaluate the potential association between breast cancer risk and Ser326Cys polymorphism of hOGG1 gene, encoding for an enzyme involved in the base excision repair of 8-hydroxyguanine, hospital based case-control studies were conducted in two Asian populations consisting of 475 breast cancer cases (271 Korean and 204 Japanese) and 500 controls (314 Korean and 186 Japanese). PCR-based methods were employed for the genotyping analyses and the statistical evaluations were performed by unconditional logistic regression model. The frequency of hOGG1 Ser/Ser, Ser/Cys, and Cys/Cys genotypes were 22.5, 48.7, and 28.8% in all cases, and 23.7, 52.1, and 24.1% in the controls. No statistically significant associations between the genotypes and breast cancer risk were observed, neither when the ethnic groups were examined separately nor when the total study population was included. Neither did stratification by menopausal status reveal any association between hOGG1 genotypes and breast cancer. Our novel findings therefore suggest that hOGG1 Ser326Cys polymorphism is unlikely to play a modifying role in individual susceptibility to breast cancer among Asian women.

Reproductive factors, glutathione S-transferase M1 and T1 genetic polymorphism and breast cancer risk.

We conducted a hospital-based case-control study to evaluate the interactive effect of reproductive factors and glutathione S-transferase (GST) M1 and T1 genetic polymorphisms in individual susceptibility to breast cancer. The study population consisted of 189 incident breast cancer cases and 189 age-matched controls with no known malignant diseases. GSTM1/T1 genotypes were determined by a multiplex polymerase chain reaction (PCR) method, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by conditional logistic regression model. The parity factors were grouped as (1) high-risk status defined as nullipara or para with experience of first full-term pregnancy (FFTP) at or over 30 years, and (2) low-risk status defined as para with experience of FFTP under 30 years. A significant multiplicative interaction was observed between GSTM1 and GSTT1 null genotypes and high-risk status of parity factor in all women and in premenopausal women (P < or = 0.01), but not in postmenopausal women (P > 0.05). The interaction between the combined genotypes of GSTM1 and GSTT1 and status of parity factor was also significant in all women and in premenopausal women (P < 0.01). Our findings suggest that genetic polymorphisms GSTM1/T1 could modify estrogen-related breast cancer risk.

Epidemiology of breast cancer in Korea: occurrence, high-risk groups, and prevention.

Breast cancer ranks second or third to uterine cervix cancer and stomach cancer as a cause of death in women, and as a common site of primary cancer. The large difference in its incidence between Westernized and non-Westernized countries is remarkable. There is a linear increase with age that is observed in Western countries, which are high-incidence areas, on the contrary to the inverted V shape curve seen in Asian countries. Epidemiologic studies conducted in Korea have shown that an older age, a family history of breast cancer, early menarche, late menopause, late full-term pregnancy, and never having had a breast-fed child are primary risk factors in the development of breast cancer. The estrogen-augmented-by-progesterone hypothesis explains the roles of these factors to some extent. On the other hand, recent molecular studies have revealed the existence of novel gene environmental interactions. Epidemiological features suggest that the breast cancer incidence rate in Korea will increase, but the age specific curve would not be changed in keeping with what is observed in Western countries. Strategies aimed at controlling breast cancer that include the screening guidelines and the identification of individual predispositions may give us further insights into both the etiology and the prevention of breast cancer.

Glutathione S-transferase P1 Genetic Polymorphisms and Breast Cancer Risk.

PURPOSE: To evaluate the potential association between the GSTP1 genotype and the development of breast cancer, a hospital based case-control study was conducted in South Korea. MATERIALS AND METGODS: The study population consisted of 171 histologically confirmed incidents of breast cancer cases, and 171 age-matched controls with no present, or previous, history of cancer. A PCR method was used for the genotyping analyses, and statistical evaluation was performed by an unconditional logistic regression model. RESULTS: No association was observed in the study subjects, or the premenopausal women group with GSTP1 Val allele. However, postmenopausal women with GSTP1 Val allele had a reduced risk of breast cancer (OR=0.3, 95% CI=0.1~0.7). When the data were stratified, by the known risk factors of breast cancer, a significant interaction was observed between the GSTP1 genotype and alcohol consumption (p for interaction = 0.01); women with GSTP1 Val allele, that drank regularly, had a 3.0-fold increased risk of breast cancer (95% CI=1.1~7.9), whereas women with GSTP1 Val allele, that never drink, had protective effects (OR=0.4, 95% CI=0.2~0.8). CONCLUSION: Our findings suggest that GSTP1 Ile105Val polymorphism influences the individual susceptibility to breast cancer, and that this effect may be modified by alcohol consumption.