Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer.

PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042). Also, the disease-free survival periods were prolonged following treatment of hyperlipidemia (p = 0.047, hazard ratio: 0.399) and statin administration (p = 0.028, hazard ratio: 0.328). CONCLUSION: In cT1 breast cancer, the results suggest that oral statin therapy may contribute to favorable outcomes.

Eribulin Treatment Promotes Re-expression of Estrogen Receptor in Endocrine Therapy-resistant Hormone Receptor-positive Breast Cancer Cells.

BACKGROUND/AIM: Hypoxia is significantly associated with the development of drug resistance, and endocrine therapy is ineffective against hormone receptor (HR)-positive breast cancer in hypoxic tumor environments. Eribulin has a unique anticancer effect in breast cancer cells and improves tumor hypoxia by vascular remodeling. Therefore, we investigated the effect of eribulin on HR-positive breast cancer cells that were resistant to endocrine blockade. MATERIALS AND METHODS: We established hypoxia-resistant breast cancer cell lines by continuous culture in a hypoxic environment. Parental and hypoxia-resistant cell lines were treated with eribulin and/or tamoxifen, and estrogen receptor (ER)-, epithelial-mesenchymal transition-, and hypoxia-related gene and protein expression changes in each surviving cell line were assessed. In addition, proliferation was assessed after eribulin treatment in the parental and hypoxia-resistant cell lines. We also assessed the effect of eribulin in vivo using subcutaneous xenograft models. RESULTS: Hypoxia-resistant cell lines showed significantly decreased expression of epithelial and ER-related markers and exhibited a higher level of resistance to tamoxifen. Conversely, eribulin treatment increased epithelial and ER-related gene and protein expression in hypoxia-resistant cell lines and enhanced the anticancer effect of tamoxifen. In in vivo xenograft models, eribulin treatment of hypoxia- and tamoxifen-resistant tumors slightly induced the re-expression of ER. In addition, hypoxia-resistant tumors treated with eribulin tended to respond better to tamoxifen. CONCLUSION: Eribulin ameliorated the aggressive behavior caused by hypoxia and induced the re-expression of ER in hypoxia-resistant breast cancer cells. Eribulin treatment of HR-positive breast cancer may resensitize cells to hormone blockade.

Prognostic Impact of Smoking on Bevacizumab Combination Chemotherapy for Advanced Breast Cancer.

BACKGROUND/AIM: Smoking has been a proven carcinogenic risk factor for various cancers, including breast cancer. Furthermore, smoking has been recognized as a prognostic factor of breast cancer. Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) used in combination with chemotherapy to treat breast cancer. We, herein, investigated the effect of smoking on the prognosis of unresectable breast cancer patients who received bevacizumab plus weekly paclitaxel. PATIENTS AND METHODS: From April 2011 to June 2022, 131 patients received bevacizumab plus weekly paclitaxel for unresectable breast cancer. At their first visit to our hospital, smoking status (i.e., period of smoking and amount of smoking per day) was evaluated by interview, and packs-years were calculated. RESULTS: Time to treatment failure (TTF) was significantly longer in the high packs-years group than the low packs-years group (p=0.010, log-rank). The log-rank test showed that the high packs-years group had a significantly longer overall survival than the low packs-years group (p=0.049, log-rank). Multivariate analysis of TTF revealed that progesterone receptor (p=0.005, HR=0.408) and packs-years (p=0.007, HR=0.391) were independent factors. CONCLUSION: A history of smoking may impact prognosis of combination chemotherapy with bevacizumab for advanced breast cancer treatment.

Factor Analysis of Intraoperative Bleeding Loss and its Impact on Prognosis in Breast Cancer.

BACKGROUND/AIM: Intraoperative blood loss (IBL) during the surgical treatment of various cancers affects complication rates and prognosis. However, few studies have examined the importance of minimal IBL in breast cancer surgery. We used factor analysis to examine the prognostic importance of IBL in breast cancer. PATIENTS AND METHODS: One hundred ninety-seven patients who underwent mastectomy plus axillary lymph node dissection (level II) after preoperative chemotherapy between June 2007 and June 2021 were included. Pearson's Chi-square test was used to confirm the relationships between different factors. Kaplan-Meier survival curves and the log-rank test were used to examine prognosis. Logistic regression was performed using a Cox proportional hazards model. RESULTS: The median IBL was 55.0 g (range=5.0-420.0 g). IBL was <100 g in 143 patients (72.5%), 100-200 g in 39 patients (19.8%), and >200 g in 15 patients (7.6%). Logistic regression analysis showed that patients with IBL ≥200 g had a significantly worse prognosis (disease-free survival: p=0.003, log-rank test; overall survival: p<0.001, log-rank test). Factor analysis revealed that HER2-negative status (p=0.015), non-pathological complete response (p=0.031), obesity (p=0.001), heavy smoking (p=0.047), and diabetes mellitus (p=0.004) were significantly associated with increased IBL. CONCLUSION: IBL in breast cancer was correlated with various clinicopathological factors associated with a poor prognosis, suggesting that increased IBL may be associated with poor prognosis in breast cancer as well.

Clinical Verification on the Predictors for Febrile Neutropenia in Breast Cancer Patients Treated With Neoadjuvant Chemotherapy.

BACKGROUND/AIM: Febrile neutropenia (FN) is a potentially life-threatening complication of chemotherapy. In this study, we evaluated the predictors for FN according to neoadjuvant chemotherapy (NAC) in all breast cancer subtypes. PATIENTS AND METHODS: We examined 327 patients with breast cancer treated with NAC. The correlation between the development of FN and clinicopathological features, including systemic inflammatory markers, and prognosis was evaluated retrospectively. RESULTS: There were no significant differences between patients with and without FN in terms of disease-free survival or overall survival (p=0.562, p=0.149, log-rank, respectively). Low body mass index (BMI) (p<0.001), white blood cells (WBC) at baseline (p=0.008), and NAC regimen (p=0.026) significantly related with FN in all patients with breast cancer. Moreover, among patients with hormone receptor-positive/human epidermal growth factor receptor 2-positive breast cancer, low WBC (p=0.007) and low absolute lymphocyte counts (ALC) at baseline (p=0.039) were significantly associated with FN, and overall survival was significantly worse in patients with FN development (p=0.039, log-rank). CONCLUSION: Poor immune activity-related factors, low ALC or BMI, may be useful to predict the development of FN in patients with breast cancer.

The Effect of Smoking on Endocrine Therapy for Stage IV Hormone Receptor Positive Breast Cancer.

BACKGROUND/AIM: Smoking worsens breast cancer prognosis. It has been reported that tobacco components directly reach the mammary gland tissue, causing smoking-related DNA damage and biological effects. We hypothesized that smoking may have characteristics that affect the therapeutic effect and clinical course in patients with stage IV hormone receptor-positive breast cancer (HRBC) who received endocrine therapy as the first-line treatment. PATIENTS AND METHODS: Fifty-six patients diagnosed with stage IV HRBC were treated with endocrine therapy as the first-line treatment. Before treatment, the period and amount of smoking were confirmed through patient interviews, and each pack-year was recorded. RESULTS: Disease progression with new metastases was more frequent in smokers than non-smokers during endocrine therapy as first-line treatment (p=0.034). Furthermore, as the pack-year increased, new metastases tended to appear [pack-year ≤15; hazard ratio (HR)=1.929, p=0.507; pack-year 15-30, HR=3.857, p=0.223; pack-year >30, HR=7.714, p=0.028]. CONCLUSION: In stage IV HRBC, smoking increases the metastatic potential of breast cancer, suggesting that changes in its biology may lead to poor prognosis.

Validation of the Optimum Timing of Assessment of Tumor Infiltrating Lymphocytes During Preoperative Chemotherapy for Breast Cancer.

BACKGROUND/AIM: Tumor microenvironment (TME) assessment is considered to play an important role in the prediction of prognosis and therapeutic response following breast cancer treatment. No consensus has been reached regarding evaluation methods despite reports on the utilization of tumor-infiltrating lymphocytes (TILs) for immune TME (iTME) monitoring. Optimum timing of iTME assessment has not yet been established. PATIENTS AND METHODS: Two hundred thirty-nine patients were treated with neoadjuvant chemotherapy (NAC). During the period from diagnostic needle biopsy to NAC initiation for breast cancer, the optimal evaluation timing was examined using a receiver operating characteristic (ROC) curve analysis. RESULTS: A significant correlation between TILs and pathological complete response (pCR) was only observed in the short-term group (≤35 days) (p=0.033). Prognostic analysis revealed that in the short-term group, patients with high TIL levels had a significantly better survival prognosis relative to those with low TIL levels (>35 days) [disease-free survival (DFS): p=0.001, overall survival (OS): p=0.021]. TILs were identified as an independent factor affecting DFS in a multivariate analysis (p=0.008, hazard ratio=0.130). CONCLUSION: TIL assessment during NAC for breast cancer is a prognostic predictor only when performed at ≤35 days before NAC initiation.

[A Case of Liver Abscess during Treatment for Abemaciclib-Induced Interstitial Lung Disease].

The patient was a 64-year-old woman. The patient was operated for left breast cancer(pT2N0M0, stage ⅡA, Luminal A). Eight years after surgery, CT findings revealed lung metastasis in the S8 and S9 areas of the left lung. The patient was treated with a combination of abemaciclib and letrozole, which resulted in a partial response(PR). One year after treatment, the lung metastases remained small, but multiple interstitial shadows appeared in both lower lung fields. The patient was diagnosed with drug-induced interstitial lung disease(Grade 1), and abemaciclib withdrawal and steroid therapy were initiated. After 3 months of treatment with prednisolone at 30 mg/day, the interstitial shadows tended to improve on CT, but a liver abscess was found in the S8 area of the right lobe of the liver. Prednisolone was tapered and abemaciclib was resumed at a dose of 200 mg/day, resulting in scarring of the lung injury and resolution of the liver abscess. The patient's PR was maintained for 18 months after relapse. We report a case of liver abscess during treatment of abemaciclib-induced interstitial lung disease.

Lifestyle changes during the coronavirus disease 2019 pandemic impact metabolic dysfunction-associated fatty liver disease.

BACKGROUND AND AIMS: The coronavirus disease 2019 (COVID-19) pandemic precipitated lifestyle changes. We aimed to clarify whether COVID-19-induced lifestyle changes affected the development of metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: This retrospective longitudinal study included 973 participants who underwent health check-ups between 2018 and 2020. We used data from the MedCity21 health examination registry. Participants' clinical characteristics and lifestyle habits were investigated. Independent lifestyle predictors of MAFLD development before the pandemic (2018-2019) and during the pandemic (2019-2020) were identified using logistic regression analysis. RESULTS: In 2018, 261 (27%) patients were diagnosed with MAFLD. Before the pandemic, 22 patients developed new MAFLD. During this time, routine late-night meals were identified as an independent lifestyle predictor of MAFLD development (hazard ratio [HR] 2.54, 95% confidence interval [CI] 1.02-6.36, P = .046). In contrast, 44 patients developed new MAFLD during the pandemic. During this time, higher daily alcohol intake was identified as an independent lifestyle predictor of MAFLD development (HR 1.03, 95% CI 1.01-1.05, P = .008). In participants aged <60 years, daily alcohol intake and the proportion of participants who ate 2 times/day were significantly higher in patients who developed MAFLD during the pandemic than in those who did not. In participants aged ≥60 years, no lifestyle habits were associated with MAFLD development before or during the pandemic. CONCLUSIONS: New MAFLD diagnoses increased during the COVID-19 pandemic. Changes in lifestyle factors, particularly in those aged <60 years, must be monitored and addressed as the pandemic continues.

[Experience with BD EleVationTM in Vacuum-Assisted Biopsy].

For qualitative diagnosis of breast mass, core needle biopsy(CNB)and fine-needle aspiration biopsy cytology(FNAC)are widely used. Overseas, vacuum-assisted biopsy(VAB)is often the first choice for qualitative diagnosis, and its proper use has become a clinical issue. In addition, with the progress of diagnostic imaging in recent years, the chances of finding micro-lesions such as ductal carcinoma in situ(DCIS)are increasing. Since a sufficient amount of tissue sample is required for these diagnoses and abundant biopsy materials are required, tissue biopsy by VAB may be desirable. The advantage of tissue biopsy with VAB is that accurate definitive diagnosis is possible by collecting a sufficient amount of tissue to obtain pretreatment tissue information. On the other hand, there is concern that patient stress may occur, such as hematoma formation after puncture and invasion by a thick puncture needle. It is lightweight and has an ergonomic design that provides stable grip. New technological innovations in this device may contribute to the reduction of patient stress, and are expected to be used in the future. We outline the experience of using BD EleVationTM in breast suction tissue biopsy at our institution.

Treatment of anaplastic thyroid cancer with tyrosine kinase inhibitors targeted on the tumor vasculature: initial experience in clinical practice.

Anaplastic thyroid cancer (ATC) is a rarely occurring refractory disease. While recent clinical trials have demonstrated the efficacy of tyrosine kinase inhibitor (TKI) therapy for ATC, evidence is scarce in clinical practice. In this study, we reviewed our initial experiences with TKI treatment in ATC patients with the aim of revealing the efficacy and safety of the same in clinical practice. We retrospectively reviewed our experiences with TKI treatment use in ATC patients diagnosed at our institute from 2014 to 2019. Changes in the patients' neutrophil-to-lymphocyte ratio (NLR) by TKI therapy introduction as well as their clinical factors to indicate the efficacy were examined. Seven patients showed no indication for TKI treatment, while 13 (65%) received treatment. The median duration of TKI treatment was 1.9 months. All patients died, and the overall survival period from diagnosis was 4.7 (95% confidence interval: 2.0-11.5) months. Adverse events ≥Grade 3 were observed commonly (92.3%), and resulted in the termination of TKI treatment in six cases (46.1%). Existence of multiple unfavorable characteristics (higher Prognostic Index) was associated with poor survival. The NLR decreased after the introduction of TKIs and increased again when treatment failed. The response rate to TKI among the ATC patients were approximately 30% in practice. Although the duration of the response was short, several patients demonstrated long survival durations when TKI treatment was provided after successful multidisciplinary treatment to control local disease. Decreases in high NLR values during treatment may suggest the continued effect of TKIs.

[Clinical Significance of Inflammatory Markers in Recombinant Human-Soluble Thrombomodulin Therapy for DIC in Solid Tumors].

BACKGROUND: The peripheral blood neutrophil-lymphocyte ratio(NLR), platelet-lymphocyte ratio(PLR), and lymphocyte- monocyte ratio(LMR)of cancer patients have been proposed as indicators of systemic inflammatory response. Recombinant human-soluble thrombomodulin(rTM)has also been reported its efficacy in DIC associated with solid tumors. In this study, we investigated the clinical significance of inflammatory markers in rTM therapy for DIC associated with solid tumors. PATIENTS AND METHOD: A retrospective study of 63 patients with solid tumors with DIC was performed. We examined the correlation between NLR, LMR, PLR and DIC withdrawal rate and 28-day survival rate. RESULTS: The DIC withdrawal rate was not correlated in LMR(p=0.655), and significantly higher in low NLR and low PLR cases(p=0.037, p=0.024). Furthermore, 28-day survival rate was not correlated in LMR(p=0.632), and significantly higher in low NLR and low PLR cases(p= 0.046, p=0.014). CONCLUSIONS: It was suggested that NLR and PLR may be useful as predictive markers of DIC withdrawal rate and 28-day survival rate in rTM therapy for DIC associated with solid tumors.

[A Case of Metastatic Invasive Lobular Carcinoma of the Breast Initially Presenting with Periorbital Swelling].

The patient was 54 years old, female. She was aware of gradually worsening right peri-eyelid swelling 2 years before the first presentation to our dermatology department. She underwent biopsy of eyelid skin 2 times. Nevertheless, definitive diagnosis was not obtained. Two months after the initial examination, right anterior thoracic swelling appeared, and right axillary, right subclavian, and interpectoral lymphadenopathy were detected. She was referred to our department for diagnosing metastatic breast cancer. Ultrasonography showed hypoechoic lesion with distortion(largest lesion>2 cm)in right breast, which was suspected to be a breast cancer. The results of breast core needle biopsy, the third time's eyelid skin biopsy and additional imaging studies confirmed T2N3M1, Stage Ⅳ right mammary invasive lobular carcinoma with metastasis to the eyelid skin, right axillary lymph nodes, right subclavian lymph nodes and the subcutaneous tissue of the right back. Immunohistochemical studies showed ER-positive, PgR-negative, HER2-negative, and low Ki-67 expression. Endocrine therapy with letrozole was initiated, which maintained stable disease without compromising the quality of life.

[A Case of Dermatitis Caused by Metronidazole Gel That Needed to Be Differentiated from Breast Cancer Skin Metastasis].

Seventy years old woman noticed a mass in her right breast before 3 years. Since she had ulcer bleeding, she visited our hospital. In physical findings, a hemorrhagic about 8 cm mass with an ulcer was found in the upper right breast. Breast ultrasonography revealed a large tumor of approximately 8 cm in the right A area, and needle biopsy revealed invasive ductal carcinoma(ER positive, PgR positive, HER2 positive, Ki-67 low expression). Right axillary lymph node metastasis was confirmed, but no clear distant metastasis was observed. Pretreatment diagnosis was right breast cancer, cT4bN1M0, Stage ⅢB, Luminal HER. Chemotherapy was started with pertuzumab, trastuzumab, and docetaxel, and the tumor was reduced after 6 cycles. Due to side effects, the drug was changed to a molecular targeted drug only and the treatment was continued. However, redness was observed in the entire right breast, and breast cancer skin metastasis was suspected. Since the dermatitis caused by metronidazole gel was also distinguished, the redness was improved when the application was stopped. When confirmed by a patch test, a reaction to metronidazole gel was observed, leading to the diagnosis of dermatitis caused by metronidazole gel.

[Effectiveness of Atezolizumab Combination Therapy for PD-L1(SP142)Positive Lung and Breast Double Cancer-A Case Report].

The anti-PD-L1 antibody atezolizumab has become the standard of immunochemotherapy with the results of the international phase Ⅲ trials in lung cancer and breast cancer. We report a case in which atezolizumab was efficiency in PD-L1 (SP142)-positive lung and breast double cancer. A 56-years-old woman. She noticed a lump in her right breast and visited a nearby doctor, who referred her to our hospital for close examination and treatment. Ultrasonography revealed about 5 cm mass on the right mammary gland and axillary lymph nodes swelling. Core-needle biopsy was confirmed invasive ductal carcinoma( ER negative, PgR negative, HER2 negative, Ki-67 high expression). CT findings showed right mammary mass, right axillary lymph nodes swelling, liver mass, and lung tumor with mediastinal lymph nodes swelling. Therefore, a bronchoscopic biopsy was performed and a diagnosis of primary lung cancer was obtained. Pretreatment diagnosis was lung adenocarcinoma, cT2a, N2/3, M1b/1c(HEP, OSS), Stage ⅢA/B or ⅣA/B(PD-L1 positive), and right breast cancer, T4b, N2, M0/1 (HEP, OSS, LYM), Stage ⅢB or Ⅳ triple-negative(PD-L1 positive)double cancer. We underwent surgery(mastectomy with axillar lymph nodes dissection), followed by immunochemotherapy(atezolizumab, carboplatin, paclitaxel)and it was efficiency.

[A Case of Cervical Metastasis from Breast Cancer].

A 59-year-old female was performed a left mastectomy with axillary lymph node dissection. Final diagnosis of the surgical specimen was left breast cancer pT2N1M0, Stage ⅡB, Luminal type. She was treated with adjuvant endocrine therapy, however, chest wall recurrence was identified at 1 year and 3 months after surgery, and curative resection of this tumor and radiotherapy were performed. Nine months later, she was admitted to the hospital for cervical pain and dyspnea, and magnetic resonance imaging showed bone metastasis in cervical vertebra which compressed spinal cord. Although cervical fusion therapy was performed, she died 39 days later. Metastasis spinal cord compression in breast cancer patients may result in irreversible spinal cord injury if treatment is delayed. Rapid diagnosis and systemic treatment for oncologic emergency are significant.

[A Case in Which Re-Administration of Pertuzumab/Trastuzumab with Eribulin Therapy Was Useful for Recurrent HER2 Breast Cancer].

Pertuzumab plus trastuzumab plus docetaxel regimen is the first choice for the initial treatment of HER2-positive recurrent breast cancer. However, docetaxel causes many adverse events. A 48-year-old woman was admitted to our hospital for a left breast tumor and was diagnosed with left breast cancer(T1N0M0, Stage Ⅰ, Luminal A). We performed a breast-conserving surgery and sentinel lymph node biopsy, followed by irradiation of the remaining parts of the mammary gland and adjuvant therapy with tamoxifen. Three and a half years after the first surgery, she underwent local resection due to chest wall recurrence of breast cancer. The recurrent tumor was HER2-positive, and we administered fluorouracil, epirubicin, cyclophosphamide( FEC)and paclitaxel plus trastuzumab. Liver metastases were confirmed on completion of cycle 11 of trastuzumab administration, and the regimen was changed to pertuzumab plus trastuzumab plus docetaxel. A partial response was seen following this regimen. The next line of treatment was the administration of 5 cycles of T-DM1, which resulted in stabilizing the disease. The liver metastases progressed, and the regimen was changed to pertuzumab plus trastuzumab plus eribulin. Partial response was seen following this regimen for liver metastases without serious adverse events(20 cycles).

Sorafenib inhibits vascular endothelial cell proliferation stimulated by anaplastic thyroid cancer cells regardless of BRAF mutation status.

Anaplastic thyroid cancer (ATC) is a rare refractory disease, frequently associated with BRAF mutations and aberrant vascular endothelial growth factor (VEGF) secretion. The antitumor effects of sorafenib were evaluated, and its mechanisms of action were investigated. Four human ATC cell lines were used: OCUT­4, which possesses a BRAF mutation; OCUT­6 and ACT­1, which carry NRAS mutations; and OCUT­2, which possesses mutations in BRAF and PI3KCA. The viability of Sorafenib was evaluated by MTT assay. In order to examine the inhibitory effect of Sorafenib on intracellular signal transduction, expression of mitogen­activated protein kinase kinase was examined by western blotting. In addition, cell cycle analysis was performed using flow cytometry. The inhibitory effects of sorafenib on the growth of ATC cells and human umbilical vein endothelial cells (HUVECs) stimulated with conditioned media from ATC cells were examined. Sorafenib inhibited the viability of OCUT­4 more effectively than other ATC cell lines; these effects may have been mediated cytostatically by suppressing mitogen­activated protein kinase kinase phosphorylation. Conversely, similar suppression was not observed in OCUT­6 cells, which possess an NRAS mutation. The four cell lines secreted different quantities of VEGF, and the proliferation of HUVECs was differentially stimulated by their conditioned media. Both anti­VEGF antibody and sorafenib prevented this stimulation of proliferation. In conclusion, sorafenib more effectively inhibited RAF­generated growth signals in ATC cells compared with signals generated by its upstream gene, RAS. ATC cells stimulated the growth of HUVECs via humoral factors, including VEGF; this effect was clearly inhibited by sorafenib. The present findings highlighted the potential of sorafenib for the treatment of ATC and provided insight into its mechanism of action.

Continuous intraoperative neuromonitoring for thyroid cancer surgery: A prospective study.

OBJECTIVE: We evaluated the utility of continuous intraoperative neuromonitoring (CIONM) during surgery for thyroid cancer (TC) in an educational university hospital. STUDY DESIGN: Prospective observational study. METHODS: During the period April 2016 to March 2017, 43 patients who underwent standardized surgery with CIONM were prospectively included: 5 men and 38 women, 24-87 years old (median 52 years); 23 lobectomies and 20 total thyroidectomies with node dissection were conducted. Thirty-six operations were performed by a supervising surgeon, and seven were performed by trainees. RESULTS: Temporal vocal cord paresis (VCP) was identified in 9 of 63 nerves at risk (14.3%) by postoperative laryngoscopy. VCP was not related to clinical factors including the surgeon's experience or the severe nerve stress demonstrated by CIONM. A significant relation only between VCP and loss of signal (LOS) was demonstrated (P = .002). The recovery of VCP was rapid (<1 month) in patients with global injury even when LOS was demonstrated, but was prolonged in patients demonstrating obvious segmental nerve injury and LOS. CONCLUSION: The present standard protocol of CIONM was useful to some extent to protect prolonged VCP, but not enough to detect every nerve stress causing VCP during TC surgery. On the other hand, CIONM is a promising method that could contribute surgical education at training hospitals enabling the instant confirmation of the procedure safely. LEVELS OF EVIDENCE: 3b.

De-escalated neoadjuvant therapy with nanoparticle albumin-bound paclitaxel and trastuzumab for low-risk pure HER2 breast cancer.

PURPOSE: Neoadjuvant trastuzumab combined with anthracycline and taxane is now considered a standard regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. A less toxic, non-anthracycline regimen has been considered as a treatment option for patients with node-negative small tumors. Estrogen receptor-negative and HER2-positive (pure HER2) tumors are more likely to achieve a pathological complete response (pCR). This study evaluates the activity and safety of neoadjuvant nanoparticle albumin-bound paclitaxel (nab-PTX) plus trastuzumab for pure HER2 breast cancer in patients with low risk of relapse. METHODS: We treated patients with tumors measuring ≤ 3 cm, node-negative, pure HER2 breast cancer using neoadjuvant nab-PTX 260 mg/m2 with trastuzumab every 3 weeks for four cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, disease-free survival, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery conversion rate, safety, and disease-free survival. Depending on the pathological findings of surgical specimens, the administration of adjuvant anthracycline could be omitted. RESULTS: Eighteen patients were enrolled. No patient required dose delays or reductions; none showed disease progression, and all patients underwent surgery as scheduled. Of the 18 patients, 66.7% achieved pCR, and the adjuvant anthracycline regimen was omitted for all patients. The incidence of severe adverse events was quite low. CONCLUSION: This less toxic, anthracycline-free regimen appears to be a significantly effective neoadjuvant therapy for patients with pure HER2 breast cancer at low relapse risk.