Omission of Breast Surgery in Predicted Pathologic Complete Response after Neoadjuvant Systemic Therapy: A Multicenter, Single-Arm, Non-inferiority Trial.

PURPOSE: Advances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies. METHODS: The Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuum-assisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years. DISCUSSION: This study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05505357. Registered on August 17, 2022. Clinical Research Information Service Identifier: KCT0007638. Registered on July 25, 2022.

A prospective randomized controlled trial to determine the safety and efficacy of extracorporeal shock waves therapy for primary prevention of subclinical cardiotoxicity in breast cancer patients without a cardiovascular risk treated with doxorubicin.

Background: Doxorubicin is a highly effective anti-cancer drug that causes left ventricular (LV) dysfunction and induces late-onset cardiomyopathy. However, an effective and clinically applicable preventive treatment is yet to be discovered. Objective: Cardiac-Extracorporeal shockwave therapy (C-ESWT) has been suggested to treat inflammatory and ischemic diseases and protect cardiomyocytes from doxorubicin-induced cardiomyopathy. This study aims to assess the safety and efficacy of C-ESWT in the prevention of subclinical cardiotoxicity. Methods: We enrolled 64 breast cancer patients. C-ESWT group 33 patients were treated with our C-ESWT (200 shots/spot at 0.09 mJ/mm2 for 20 spots, 3 times every six weeks). The efficacy endpoints were the difference in left ventricular global longitudinal strain (LVGLS) change by 2D speckle tracking echocardiography and chemotherapy-related cardiac dysfunction (CTRCD). Echocardiography was performed on the baseline line and every 4 cycles of chemotherapy, followed by a follow-up 3,6 months after chemotherapy to compare the incidence of cardiomyopathy of subclinical LV dysfunction due to chemotherapy between the two groups. Results: Participants averaged 50 ± 9 years in age, 100% female. In the results of follow-up 6 months after the end of chemotherapy, there was a significant difference in delta LVGLS between the C-ESWT group and the control group (LVGLS; -1.1 ± 10.9% vs. -11.5 ± 11.6% p-value; <0.001). A total of 23% (15 patients) of patients developed CTRCD (Control group; 13 vs. C-ESWT group; (2). C-ESWT was performed safely without any serious adverse events. Conclusion: In this prospective study, C-ESWT established efficacy in preventing subclinical cardiotoxicity, especially in breast cancer patients using doxorubicin chemotherapy, and the safety of C-ESWT. Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT05584163).

An observational, prospective, open label, multicenter study to evaluate the safety and effectiveness of pegfilgrastim as secondary prophylaxis to decrease the incidence of febrile neutropenia in Korean female patients with breast cancer.

PURPOSE: Pegfilgrastim is a widely used long-acting granulocyte colony-stimulating factor (G-CSF) that prevents febrile neutropenia (FN) in patients with breast cancer receiving chemotherapy. This study aimed to evaluate the incidence of chemotherapy-related FN events and other adverse events (AEs) during chemotherapy in Korean patients with breast cancer treated with pegfilgrastim as secondary prophylactic support. MATERIALS AND METHODS: This was a multicenter, open-label, prospective, observational study. A total of 1255 patients were enrolled from 43 institutions. The incidence of FN was evaluated as the primary endpoint. The secondary endpoints included (1) incidence of bone pain, (2) proportion of patients with a relative dose intensity (RDI) of ≥85%, and (3) proportion of patients with AE. RESULTS: Pegfilgrastim administration reduced FN by 11.8-1.6%. The highest incidence of bone pain was observed at the time point of the 1st day after the administration and mild bone pain was the most common of all bone pain severity. The mean RDI was 98.5 ± 7.3%, and the proportion of the patients with and RDI≥85% was 96.9% (1169/1233). AEs were reported in 52.6% of the patients, and serious drug reactions occurred in only 0.7%. CONCLUSION: The use of pegfilgrastim as secondary prophylaxis was effective and safe for preventing FN in patients with breast cancer who were treated with chemotherapy.

Estrogen Effects Differ Between Medium Maintenance and Replacement from Transcriptional and Clinical Perspectives in T47D Breast Cancer Cells.

BACKGROUND/AIM: Our most recent study revealed that the responsiveness of hormone receptor-positive breast cancer (HR+ BC) cells to estrogen or endocrine therapy can be altered by certain cell culture or ambient environmental conditions. Nevertheless, we were unable to investigate the relevant molecular mechanism and clinical relevance. Therefore, this study was planned as a follow-up. MATERIALS AND METHODS: RNA sequencing was mainly used with T47D cells treated with or without 17ß-estradiol (E2) under medium maintenance (MTN; conventional culture method) and medium exchange (EXC; daily replacing the existing medium with fresh medium). RESULTS: The role of E2 in transcription differed between MTN and EXC, and E2 played more important roles in transcription in terms of cancer development under EXC than under MTN, consistent with the previous functional effects of EXC. The novel concept of the "estrogen-responsive and proliferation-related gene (ERPG)" was introduced. The expression of ERPGs, which were distinguished from typical estrogen-responsive genes, was correlated with that of prognostic and predictive factors for HR+ BC. The transcriptional induction of ERPGs and typical estrogen-responsive genes regardless of E2 treatment under MTN was reminiscent of constitutive estrogen receptor (ER) activation. Additionally, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) inhibitors were more effective under EXC than under MTN. CONCLUSION: This study, demonstrating the more important roles of estrogen in terms of cancer development under EXC than under MTN, supports the use of our research model in future studies to overcome endocrine resistance in HR+ BC.

Adding Ovarian Suppression to Tamoxifen for Premenopausal Women With Hormone Receptor-Positive Breast Cancer After Chemotherapy: An 8-Year Follow-Up of the ASTRRA Trial.

PURPOSE: To determine the updated long-term outcomes of the Addition of Ovarian Suppression to Tamoxifen in Young Women With Hormone-Sensitive Breast Cancer Who Remain Premenopausal or Regain Vaginal Bleeding After Chemotherapy (ASTRRA) trial. PATIENTS AND METHODS: This study is a post-trial follow-up of the ASTRRA trial, involving 1,483 premenopausal women younger than 45 years treated with definitive surgery after completing adjuvant or neoadjuvant chemotherapy for estrogen receptor-positive breast cancer. Patients were randomly assigned in a 1:1 ratio to complete 5 years of tamoxifen (TAM) alone (TAM-only) or 5 years of TAM with ovarian function suppression (OFS) for 2 years (TAM + OFS). The primary end point was disease-free survival (DFS), and the secondary end point was overall survival (OS). RESULTS: At 106.4 months of median follow-up, there was a continuous significant reduction in the DFS event rate in the TAM + OFS group. The 8-year DFS rate was 85.4% in the TAM + OFS group and 80.2% in the TAM-only group (hazard ratio [HR], 0.67; 95% CI, 0.51 to 0.87). There were no significant differences in OS between the two groups. The OS rate was 96.5% in the TAM + OFS group and 95.3% in the TAM-only group (HR, 0.78; 95% CI, 0.49 to 1.25). CONCLUSION: Adding OFS for 2 years to adjuvant TAM with a longer follow-up resulted in consistent DFS benefits, suggesting that adding OFS to TAM should be considered for patients who remain in a premenopausal state or resume ovarian function after chemotherapy.

A New Culture Model for Enhancing Estrogen Responsiveness in HR+ Breast Cancer Cells through Medium Replacement: Presumed Involvement of Autocrine Factors in Estrogen Resistance.

Hormone receptor-positive breast cancer (HR+ BC) cells depend on estrogen and its receptor, ER. Due to this dependence, endocrine therapy (ET) such as aromatase inhibitor (AI) treatment is now possible. However, ET resistance (ET-R) occurs frequently and is a priority in HR+ BC research. The effects of estrogen have typically been determined under a special culture condition, i.e., phenol red-free media supplemented with dextran-coated charcoal-stripped fetal bovine serum (CS-FBS). However, CS-FBS has some limitations, such as not being fully defined or ordinary. Therefore, we attempted to find new experimental conditions and related mechanisms to improve cellular estrogen responsiveness based on the standard culture medium supplemented with normal FBS and phenol red. The hypothesis of pleiotropic estrogen effects led to the discovery that T47D cells respond well to estrogen under low cell density and medium replacement. These conditions made ET less effective there. The fact that several BC cell culture supernatants reversed these findings implies that housekeeping autocrine factors regulate estrogen and ET responsiveness. Results reproduced in T47D subclone and MCF-7 cells highlight that these phenomena are general among HR+ BC cells. Our findings offer not only new insights into ET-R but also a new experimental model for future ET-R studies.

Prediction of breast cancer using blood microbiome and identification of foods for breast cancer prevention.

The incidence of breast cancer (BC) is increasing in South Korea, and diet is closely related to the high prevalence of BC. The microbiome directly reflects eating habits. In this study, a diagnostic algorithm was developed by analyzing the microbiome patterns of BC. Blood samples were collected from 96 patients with BC and 192 healthy controls. Bacterial extracellular vesicles (EVs) were collected from each blood sample, and next-generation sequencing (NGS) of bacterial EVs was performed. Microbiome analysis of patients with BC and healthy controls identified significantly higher bacterial abundances using EVs in each group and confirmed the receiver operating characteristic (ROC) curves. Using this algorithm, animal experiments were performed to determine which foods affect EV composition. Compared to BC and healthy controls, statistically significant bacterial EVs were selected from both groups, and a receiver operating characteristic (ROC) curve was drawn with a sensitivity of 96.4%, specificity of 100%, and accuracy of 99.6% based on the machine learning method. This algorithm is expected to be applicable to medical practice, such as in health checkup centers. In addition, the results obtained from animal experiments are expected to select and apply foods that have a positive effect on patients with BC.

Number of Tumor Foci as a Risk Factor for Recurrence in Papillary Thyroid Carcinoma: Does It Improve Predictability?

Multifocality in papillary thyroid carcinoma (PTC) increases the risk of recurrence. Some recent studies have suggested that multifocality-related parameters, such as the number of tumor foci, total tumor diameter (TTD), and bilaterality, are more useful for predicting recurrence than multifocality. However, it is still unclear if these factors can improve the accuracy of the recurrence prediction model. Between 2012 and 2019, 1288 patients with PTC underwent total thyroidectomy at Ewha Womans University Medical Center. The 5-year disease-free survival rate was 91.2% in patients with >3 tumor foci, 95.1% with 3 foci, and 97.6% with 2 foci; conversely, those with a unifocal tumor showed a 5-year recurrence-free survival rate of 98.0%. Cox proportional hazards analysis indicated that the number of tumor foci (HR for >3 foci, 3.214; HR for 3 foci, 2.473), bilaterality (HR, 2.530), or TTD (HR for >3 cm, 5.359; HR for 2−3 cm, 3.584) could be an independent predictor of recurrence. However, models using the number of tumor foci, bilaterality, and TTD did not show better overall predictability of recurrence than models based on multifocality. In conclusion, a simpler prediction model based on multifocality may be sufficient.

Effect of radiotherapy sequence on long-term outcome in patients with node-positive breast cancer: a retrospective study.

The optimal sequence of chemotherapy (CT) and radiotherapy (RT) after surgery in breast cancer patients is unclear. There is a lack of literature on RT given between anthracycline and taxane administration. We evaluated the effect of RT sequence on long-term outcome in breast cancer. Two hundred patients who underwent surgery between January 2009 and December 2012 for node-positive breast cancers were evaluated retrospectively. All patients were treated with doxorubicin and cyclophosphamide (AC) followed by taxane. Sandwich RT group that received RT between AC and taxane was compared to the group that received RT after CT. The mean follow-up period was 105.4 months. The locoregional recurrence (LRR) rate was lower in sandwich RT group (P = 0.012) and there was no significant difference in distant metastasis between the two groups. The RT sequence was an important predictor for LRR in multivariable analysis (P = 0.017). For luminal A subtype, disease-free survival (DFS) was better in sandwich RT group than in CT followed by RT group (P = 0.001). The overall survival did not correlated with RT sequence regardless of subtype. Sandwich RT can offer DFS benefit in luminal A subtype breast cancer. A tailored approach of sequencing chemotherapy and radiotherapy would be needed considering the factors that can influence outcome.

Staphylococcus aureus-Derived Extracellular Vesicles Enhance the Efficacy of Endocrine Therapy in Breast Cancer Cells.

The microbiome involved in the human estrogen metabolism is known as the estrobolome. This study aimed to show that the estrobolome can be used in breast cancer treatment. We first analyzed the blood microbiome composition of healthy controls and patients with breast cancer. In particular, we investigated the bacteria producing ß-glucuronidase and/or ß-galactosidase, which are involved in estrogen metabolism in the human body. Staphylococcus species were more abundant in healthy controls than in breast cancer patients and therefore were selected for further analyses. The effect of Staphylococcus aureus on endocrine therapy was analyzed by a combination treatment with tamoxifen. Analysis of the microbiome of blood samples showed that species producing ß-glucuronidase were more abundant in breast cancer patients than in healthy controls. Further experiments confirmed that the efficacy of tamoxifen increased when administered in conjugation with the extracellular vesicles (EVs) of S. aureus. Based on our results, we deduced that S. aureus EVs could potentially be used as adjuvants for breast cancer treatment in the future.

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.

Selenium inhibits growth of trastuzumab-resistant human breast cancer cells via downregulation of Akt and beclin-1.

The response rate to treatment with trastuzumab (Tz), a recombinant humanized anti-HER2 monoclonal antibody, is only 12-34% despite demonstrated effectiveness on improving the survival of patients with HER2-positive breast cancers. Selenium has an antitumor effect against cancer cells and can play a cytoprotective role on normal cells. This study investigated the effect of selenium on HER2-positive breast cancer cells and the mechanism in relation to the response of the cells to Tz. HER2-positive breast cancer cell lines, SK-BR-3 as trastuzumab-sensitive cells, and JIMT-1 as Tz-resistant cells were treated with Tz and sodium selenite (selenite). Cell survival rates and expression of Her2, Akt, and autophagy-related proteins, including LC3B and beclin 1, in both cell lines 72 h after treatment were evaluated. Significant cell death was induced at different concentrations of selenite in both cell lines. A combined effect of selenite and Tz at 72 h was similar to or significantly greater than each drug alone. The expression of phosphorylated Akt (p-Akt) was decreased in JIMT-1 after combination treatment compared to that after only Tz treatment, while p-Akt expression was increased in SK-BR-3. The expression of beclin1 increased particularly in JIMT-1 after only Tz treatment and was downregulated by combination treatment. These results showed that combination of Tz and selenite had an antitumor effect in Tz-resistant breast cancer cells through downregulation of phosphorylated Akt and beclin1-related autophagy. Selenite might be a potent drug to treat Tz-resistant breast cancer by several mechanisms.

The Comparison of Breast Reconstruction Using Two Types of Acellular Dermal Matrix after Breast-Conserving Surgery.

Breast reconstruction during breast-conserving surgery (BCS) can improve the breast shape. This study introduces breast reconstruction in BCS with two types of acellular dermal matrix (ADM). The study included 134 patients who underwent BCS due to breast cancer from February 2018 to May 2021. This study was conducted by one surgeon, and is the result of a three-year study. The patient group who underwent BCS using ADM was mainly targeted at patients with minor to severe defects after the operation. The average age of the patients was 51.8 years, and the body mass index (BMI) was 23.8 kg/m. The specimen weight was 30-120 g. The average surgical time, including reconstruction, was 100.4 min, combined with reconstruction. There were minor complications in six patients. The advantage of using ADM is that it can quickly correct the shape of the breast after conventional BCS surgery. Pellet-type ADM, rather than sheet-type, can create a breast shape similar to that before surgery. Breast reconstruction using ADM can be an easy and convenient method for making a better shape from BCS.

Response to neoadjuvant chemotherapy based on pathologic complete response in very young patients with ER-positive breast cancer: a large, multicenter, observational study.

BACKGROUND: In estrogen receptor (ER)-positive breast cancer (BC), young age is associated with poor prognosis. While very young patients respond better to chemotherapy, chemotherapy is less effective in ER-positive tumors than in ER-negative tumors. The authors tried to evaluate chemotherapy response of very young patients with ER-positive BC by pathologic complete response (pCR) after neoadjuvant chemotherapy excluding the effect of endocrine treatment to the extent possible. METHODS: We collected individual patient data from 1992 to 2013 from the Korean Breast Cancer Society (KBCS). Total 1048 ER-positive and 797 ER-negative patients aged < 50 years who had been treated with neoadjuvant chemotherapy were included for analysis. We compared pCR rate between patients aged < 35 years with ER-positive tumors and the other groups. RESULTS: The proportion of patients aged < 35 years was 14.0% of patients with ER-positive BC in this cohort of under 50 years old, and 16.8% of patients with ER-negative BC in this cohort of under 50 years old. Although most characteristics of tumors according to age were comparable, tumors with high Ki-67 expression were more common in patients aged < 35 years than in patients aged 35-49 years in both ER-positive and -negative group (P = 0.001). Breast conservation rates were not significantly different according to age (44.2% vs. 46.8% in ER-positive group, 55.2% vs. 48.0% in ER-negative group). pCR rate was not different according to age in ER-positive group (P = 0.71) but significantly better in patients aged < 35 years in ER-negative group (P = 0.009). After adjusting for confounding variables, young patients maintained the higher probability of pCR than older patients in ER-negative tumors. However, pCR rate did not differ according to age in ER-positive tumors. In multivariate analysis, young age (< 35 years) was correlated with poor overall survival (P = 0.003, HR = 1.98) and there was only one event in a few patients achieved pCR in ER-positive group. CONCLUSIONS: Chemotherapy response based on pCR was not better in young patients (< 35 years) with ER-positive BC than in older premenopausal patients with non-metastatic ER-positive BC. Young age cannot be a predictive factor of response to neoadjuvant chemotherapy in ER-positive BC. Different biological characteristics such as high proliferative index should be considered. TRIAL REGISTRATION: Retrospectively registered.

Efficacy of erector spinae plane block with opioid-sparing analgesic technique in breast-conserving surgery.

PURPOSE: Breast-conserving surgery (BCS) is a surgical method designed to minimize intraoperative tissue injury. Although this technique is minimally invasive, it can cause significant postoperative pain and may be a risk factor for persistent pain. Erector spinae plane block (ESPB) is an easy interfascial plane block for analgesia in patients undergoing breast surgery. The primary outcome was the numeric rating scale scores measured separately on the breast and axilla. Secondary outcomes included correlation between pain score and skin sensitivity test. METHODS: Forty patients were divided into 2 groups (ESPB group and control group). Patients in the ESPB group received an ESPB 30 minutes before the induction of general anesthesia, whereas patients in the control group did not receive any regional analgesia during the perioperative period. RESULTS: Median pain scores of the breast were significantly lower in the ESPB group than that in the control group at 12, 24, and 48 hours after surgery. However, the median pain scores of the axilla were not significantly different between the groups, and the pain score was unrelated to skin sensitivity. CONCLUSION: ESPB can effectively alleviate acute postoperative pain with an opioid-sparing analgesic technique in patients undergoing BCS, and a strong correlation is lacking between pain scores and skin sensitivity test.

Accuracy of Digital Breast Tomosynthesis for Detecting Breast Cancer in the Diagnostic Setting: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare the accuracy for detecting breast cancer in the diagnostic setting between the use of digital breast tomosynthesis (DBT), defined as DBT alone or combined DBT and digital mammography (DM), and the use of DM alone through a systematic review and meta-analysis. MATERIALS AND METHODS: Ovid-MEDLINE, Ovid-Embase, Cochrane Library and five Korean local databases were searched for articles published until March 25, 2020. We selected studies that reported diagnostic accuracy in women who were recalled after screening or symptomatic. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A bivariate random effects model was used to estimate pooled sensitivity and specificity. We compared the diagnostic accuracy between DBT and DM alone using meta-regression and subgroup analyses by modality of intervention, country, existence of calcifications, breast density, Breast Imaging Reporting and Data System category threshold, study design, protocol for participant sampling, sample size, reason for diagnostic examination, and number of readers who interpreted the studies. RESULTS: Twenty studies (n = 44513) that compared DBT and DM alone were included. The pooled sensitivity and specificity were 0.90 (95% confidence interval [CI] 0.86-0.93) and 0.90 (95% CI 0.84-0.94), respectively, for DBT, which were higher than 0.76 (95% CI 0.68-0.83) and 0.83 (95% CI 0.73-0.89), respectively, for DM alone (p < 0.001). The area under the summary receiver operating characteristics curve was 0.95 (95% CI 0.93-0.97) for DBT and 0.86 (95% CI 0.82-0.88) for DM alone. The higher sensitivity and specificity of DBT than DM alone were consistently noted in most subgroup and meta-regression analyses. CONCLUSION: Use of DBT was more accurate than DM alone for the diagnosis of breast cancer. Women with clinical symptoms or abnormal screening findings could be more effectively evaluated for breast cancer using DBT, which has a superior diagnostic performance compared to DM alone.

Next-Generation Sequencing-Based Biomarkers in Breast Cancer.

For the realization of precision medicine in cancer treatment, discovery, and validation of clinically useful biomarker is the most important prerequisite. Biomarkers are needed and used for evaluation of cancer susceptibility, cancer screening (early detection), cancer subtyping, prediction of prognosis, decision of appropriate adjuvant therapy and duration of therapy, and for monitoring of recurrence. Biomarkers are also needed for decision of target therapy in metastatic cancer and monitoring of their response during follow-up. Now is the era of Next-Generation Sequencing (NGS). NGS technology can detect almost all kind of genomic changes that occur in cancer that is different from normal condition. The cost also is now reasonably low to use in routine clinical practice.This chapter will review four kinds of NGS-based biomarkers that are already being used in clinical practice although the routine use is controversial, and that are promising and under active investigation focusing on studies done in Seoul National University Hospital (SNUH).

Bacterial extracellular vesicles affect endocrine therapy in MCF7 cells.

BACKGROUND: : The microbiome is important in the development and progression of breast cancer. This study investigated the effects of microbiome derived from Klebsiella on endocrine therapy of breast cancer using MCF7 cells. The bacterial extracellular vesicles (EVs) that affect endocrine therapy were established through experiments focused on tamoxifen efficacy. METHODS: : The microbiomes of breast cancer patients and healthy controls were analyzed using next-generation sequencing. Among microbiome, Klebsiella was selected as the experimental material for the effect on endocrine therapy in MCF7 cells. MCF7 cells were incubated with tamoxifen in the absence/presence of bacterial EVs derived from Klebsiella pneumoniae and analyzed by quantitative real-time polymerase chain reaction and Western blot. RESULTS: : Microbiome derived from Klebsiella is abundant in breast cancer patients especially luminal A subtype compared to healthy controls. The addition of EVs derived from K pneumoniae enhances the anti-hormonal effects of tamoxifen in MCF7 cells. The increased efficacy of tamoxifen is mediated via Cyclin E2 and p-ERK. CONCLUSION: : Based on experiments, the EVs derived from K pneumoniae are important in hormone therapy on MCF7 cells. This result provides new insight into breast cancer mechanisms and hormone therapy using Klebsiella found in the microbiome.

Feasibility and safety of breast-conserving surgery via a periareolar incision for cancers located far from the nipple-areolar complex: a retrospective study.

PURPOSE: We performed breast-conserving surgery (BCS) using periareolar incisions for cancers located far from the nipple-areolar complex (NAC) and examined if BCS via a periareolar incision maximized cosmesis and maintained oncologic safety. One of the most important goals of BCS is to improve cosmesis after surgery and quality of life, but the skin incision can affect cosmesis based on the tumor location. METHODS: Fifty-five patients with breast cancers located far from the NAC underwent BCS via periareolar incisions between January 2017 and April 2018. If a sentinel lymph node biopsy was required, another skin incision was created in the axilla using the conventional technique. Medical records of patients were reviewed retrospectively. RESULTS: The mean patient age was 48.1 ± 10.6 years. The mean tumor size was 1.8 ± 1.0 cm (range 0.2-4.5 cm) on preoperative magnetic resonance imaging (MRI); the mean distance from the NAC to the tumor was 5.9 ± 1.9 cm (range 4.0-12.3 cm). Patients with cancers in the subareolar area were excluded even though the distance from the nipple was > 4 cm on MRI. Negative microscopic margins were obtained in all patients. There was no surgical complication such as seroma, bleeding, or infection. Re-operation was not needed. All patients received whole breast radiation therapy. After surgery and radiation therapy, periareolar incision scars were nearly invisible. CONCLUSION: For cancers located far from the NAC, BCS via periareolar incisions is feasible and leads to superior cosmesis in selective patients. Moreover, BCS seems oncologically safe, although long-term outcomes need to be evaluated.

Pure hemi-periareolar incision versus conventional lateral radial incision mastectomy and direct-to-implant breast reconstructions: comparison of indocyanine green angiographic perfusion and necrosis of the nipple.

BACKGROUND: This study evaluated the feasibility of direct-to-implant breast reconstruction after nipple-sparing mastectomy using pure hemi-periareolar incision without extension and with the aid of indocyanine green angiographic evaluation on the mastectomy skin flap. METHODS: Patients who underwent immediate direct-to-implant breast reconstruction from December 2018 to February 2020 were included. After nipple-sparing mastectomy, indocyanine green angiographic evaluation of perfusion to nipple-areola complex was performed by video recording with a near infrared camera, and nipple perfusion time and perfusion pattern were analyzed. Patients were divided into a pure hemi-periareolar incision group and conventional lateral radial incision groups to compare nipple perfusion and surgical outcomes. RESULTS: A total of 61 breasts in 56 patients were included. Pure hemi-periareolar incision was used in 41 breasts, and conventional lateral radial incisions were used in 20 breasts. Nipple perfusion time was significantly increased in the pure hemi-periareolar incision group (79.6±65.8 vs. 43.2±49.8 seconds, P=0.031). While minor nipple-areola complex necrosis was significantly increased in the pure hemi-periareolar incision group (19.5% versus 0%; P=0.044), major nipple-areola complex necrosis (2.4% versus 5.0%; P>0.999) was not significantly different between the two groups. The rates of nipple-areola complex necrosis were 0%, 16.7%, and 63.6% in rapid, delayed, and no perfusion groups, respectively (P<0.001). No nipple perfusion pattern was a significant predictor for nipple-areola complex necrosis in univariable and multivariable analyses (P<0.001). There was no case of reconstruction failure. CONCLUSIONS: Immediate direct-to-implant breast reconstruction after nipple-sparing mastectomy using pure hemi-periareolar incision can be safely performed using indocyanine green angiographic evaluation on the mastectomy skin flap.