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 vacuumassisted 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.

Purpose: Several predictive models have been developed to predict the pathological complete response (pCR) after neoadjuvant chemotherapy (NAC); however, few are broadly applicable owing to radiologic complexity and institution-specific clinical variables, and none have been externally validated. This study aimed to develop and externally validate a machine learning model that predicts pCR after NAC in patients with breast cancer using routinely collected clinical and demographic variables. Methods: The electronic medical records of patients with advanced breast cancer who underwent NAC before surgical resection between January 2017 and December 2020 were reviewed. Patient data from Seoul National University Bundang Hospital were divided into training and internal validation cohorts. Five machine learning techniques, including gradient boosting machine (GBM), support vector machine, random forest, decision tree, and neural network, were used to build predictive models, and the area under the receiver operating characteristic curve (AUC) was compared to select the best model. Finally, the model was validated using an independent cohort from Seoul National University Hospital. Results: A total of 1,003 patients were included in the study: 287, 71, and 645 in the training, internal validation, and external validation cohorts, respectively. Overall, 36.3% of the patients achieved pCR. Among the five machine learning models, the GBM showed the highest AUC for pCR prediction (AUC, 0.903; 95% confidence interval [CI], 0.833–0.972).External validation confirmed an AUC of 0.833 (95% CI, 0.800–0.865). Conclusion Commonly available clinical and demographic variables were used to develop a machine learning model for predicting pCR following NAC. External validation of the model demonstrated good discrimination power, indicating that routinely collected variables were sufficient to build a good prediction model.

The use of neoadjuvant chemotherapy in older patients is increasing. However, chemotherapy should be administered considering the medical comorbidities of the patients and the toxicity of chemotherapeutic agents. Here, we present a case of abdominal wall hematoma with spontaneous inferior epigastric artery injury caused by coughing in a 70-year-old woman who was treated with neoadjuvant chemotherapy. Abdominal computed tomography demonstrated an abdominal wall hematoma with active bleeding. However, angiography with selective embolization of the right inferior epigastric artery and the right internal mammary artery was performed successfully. Scheduled chemotherapy was discontinued over concerns of rebleeding and breast-conserving surgery was performed. When deciding on chemotherapy for older patients, attention should be paid to the various complications.

Purpose: To evaluate the axillary recurrence rate and usefulness of axillary ultrasound (AUS) during supplementary whole-breast ultrasound (US) screening in women with a personal history of breast cancer (PHBC). Methods: A retrospective database search identified consecutive asymptomatic women who underwent postoperative supplemental whole-breast US screening, including that of the bilateral axillae, after negative findings on mammography between January and June 2017. Using the pathologic data or at least 1-year follow-up data as reference standards, the axillary recurrence rate, cancer detection rate (CDR), interval axillary recurrence rate per 1,000 screenings, sensitivity, specificity, and abnormal interpretation rate (AIR) were estimated. Results: From the data of 4,430 women (mean age, 55.0 ± 10.1 years) analyzed in this study, there were five axillary recurrence cases (1.1/1,000) in the median follow-up period of 57.2 months. AUS showed a CDR of 0.2 (1/4,430; 95% confidence interval [CI], 0.01–1.3) and an interval axillary recurrence rate of 0.9 (4/4,402; 95% CI, 0.2–2.3) per 1,000 examinations. The sensitivity and specificity were 20.0% (1/5; 95% CI, 0.5–71.6), and 99.4% (4,398/4,425; 95% CI, 99.1–99.6), respectively, while the AIR was 0.6% (28/4,430; 95% CI, 0.4–0.9%). Conclusion In asymptomatic women with a PHBC and negative findings on mammography, axillary recurrence after breast cancer and axillary treatment was uncommon, and the supplemental AUS screening yielded 0.2 cancers per 1,000 examinations.

Purpose: Hereditary cancer syndrome means that inherited genetic mutations can increase a person's risk of developing cancer. We assessed the frequency of germline mutations using an nextgeneration sequencing (NGS)–based multiple-gene panel containing 64 cancer-predisposing genes in Korean breast cancer patients with clinical features of hereditary breast and ovarian cancer syndrome (HBOC). Materials and Methods: A total of 64 genes associated with hereditary cancer syndrome were selected for development of an NGS-based multi-gene panel. Targeted sequencing using the multi-gene panel was performed to identify germline mutations in 496 breast cancer patients with clinical features of HBOC who underwent breast cancer surgery between January 2002 and December 2017. Results: Of 496 patients, 95 patients (19.2%) were found to have 48 deleterious germline mutations in 16 cancer susceptibility genes. The deleterious mutations were found in 39 of 250 patients (15.6%) who had breast cancer and another primary cancer, 38 of 169 patients (22.5%) who had a family history of breast cancer (≥ 2 relatives), 16 of 57 patients (28.1%) who had bilateral breast cancer, and 29 of 84 patients (34.5%) who were diagnosed with breast cancer at younger than 40 years of age. Of the 95 patients with deleterious mutations, 60 patients (63.2%) had BRCA1/2 mutations and 38 patients (40.0%) had non-BRCA1/2 mutations. We detected two novel deleterious mutations in BRCA2 and MLH1. Conclusion NGS-based multiple-gene panel testing improved the detection rates of deleterious mutations and provided a cost-effective cancer risk assessment.

Purpose: This study was performed to investigate the effect of the interval between the start of gonadotropin-releasing hormone agonist (GnRHa) and the start of chemotherapy on ovarian protection in patients with breast cancer. Methods: This was a prospective observational cohort study that included 136 patients with breast cancer below 40 years who received GnRHa during chemotherapy for fertility preservation. Plasma anti-Müllerian hormone (AMH) levels were measured before chemotherapy (baseline) and after chemotherapy. Subjects were divided into 3 groups according to the interval between the start of GnRHa and the start of chemotherapy for analysis: 1–6 days, 7–13 days, and ≥ 14 days. The ratio of the post-chemotherapy AMH value to the baseline AMH (pcAMH) at each time point were compared among the 3 groups.Ranked analysis of covariance was used for statistical analysis, adjusted for age, body mass index (BMI), and the existence of polycystic ovaries (PCOs). In addition, recovery of ovarian function (AMH ≥ 1 ng/mL) at 12 months was evaluated. Results: The median age of the patients was 32 years. There was no difference in the baseline AMH levels among the 3 groups (mean ± standard error: 5.0 ± 0.4 ng/mL [1–6 days], 5.3 ± 0.7 ng/mL [7–13 days], and 8.1 ± 1.3 ng/mL [≥ 14 days]; p = 0.250). The pcAMH at 3, 6, 12, 24, and 36 months were not significantly different among the 3 groups (p-values were 0.332, 0.732, 0.830, 0.148, and 0.393, respectively). In multivariate analysis, young age (p = 0.024), low BMI (p = 0.013), and the existence of PCO (p = 0.015) were predictors for AMH ≥ 1 ng/mL at 12 months. Conclusion There was no difference in the ovarian protective effect according to the difference in the timing of administration of GnRHa.

Amenorrhea ; Breast Neoplasms ; Breast ; Cohort Studies ; Cyclophosphamide ; Doxorubicin ; Drug Therapy ; Female ; Gonads ; Humans ; Korea ; Menopause ; Multivariate Analysis ; Paclitaxel ; Retrospective Studies ; Tamoxifen

PURPOSE: The oncologic safety of immediate breast reconstruction (IBR) has been demonstrated. However, the outcome of IBR for locally advanced breast cancer (LABC) is still under debate. We compared the survival outcome of LABC patients who underwent IBR vs. mastectomy alone. METHODS: We retrospectively analyzed a total of 248 patients with stage III breast cancer who were treated with mastectomy between 2004 and 2015. The study subjects were divided into 2 groups: patients who received IBR (n=77) or mastectomy alone (MA) (n=171). We compared disease-free survival (DFS) of both groups. RESULTS: Median follow-up duration was 49 months and the mean age of patients was 49 years. Patients in the IBR group were significantly younger and had lower body mass index (BMI) than those in the MA group. In a univariate analysis, IBR group showed better DFS than the MA group (DFS 81.3 months vs. 49.8 months, p<0.001). There was no delay in adjuvant treatment in the IBR group. In a multivariate analysis, IBR was associated with better DFS (hazard ratio (HR) for recurrence: 0.37, 95% CI 0.20–0.69, p=0.002) when adjusted for potential prognostic factors. In a subgroup analysis performed according to disease stage (IIIA and IIIB/IIIC), DFS was significantly better in IBR than MA group in both stage subgroups (p<0.001). CONCLUSION We demonstrated that patients who underwent IBR showed better DFS outcome compared with patients who underwent mastectomy alone. Our results can help surgeons to determine if IBR is an option in patients with LABC.

PURPOSE: Germline mutations in the BRCA1 and BRCA2 genes confer increased risks for breast cancers. However, the clinical presentation of breast cancer among women who are carriers of the BRCA1 or BRCA2 (BRCA1/2 carriers) mutations is heterogenous. We aimed to identify the effects of the reproductive histories of women with the BRCA1/2 mutations on the clinical presentation of breast cancer. METHODS: We retrospectively analyzed clinical data on women with proven BRCA1 and BRCA2 mutations who were recruited to the Korean Hereditary Breast Cancer study, from 2007 to 2014. RESULTS: Among the 736 women who were BRCA1/2 mutation carriers, a total of 483 women had breast cancers. Breast cancer diagnosis occurred at significantly younger ages in women who experienced menarche at ≤14 years of age, compared to those who experienced menarche at >14 years of age (37.38±7.60 and 43.30±10.11, respectively, p<0.001). Additionally, the number of full-term pregnancies was significantly associated with the age of diagnosis, especially in women with the BRCA2 mutation. The prevalence of advanced stages (stage II or III vs. stage I) of disease in parous women was higher than in nulliparous women (68.5% vs. 55.2%, p=0.043). This association was more pronounced in women with the BRCA2 mutation (hazard ratio, 2.67; p=0.014). CONCLUSION: Our results suggest that reproductive factors, such as the age of onset of menarche and the presence of parity, are associated with the clinical presentation patterns of breast cancer in BRCA1/2 mutation carriers.
Age of Onset ; Breast Neoplasms* ; Breast* ; Diagnosis ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Germ-Line Mutation ; Humans ; Menarche ; Parity ; Pregnancy ; Prevalence ; Reproductive History ; Retrospective Studies

PURPOSE: Neoadjuvant chemotherapy (NCT) is a treatment modality that increases the breast-conserving rate in breast cancer. This prospective study was performed to evaluate the actual breast-conserving rate using NCT in a clinical setting in a single institution. METHODS: Between 2014 and 2015, 265 patients who were scheduled to receive NCT and surgery were enrolled in this study. Patients were classified into three groups based on the immunohistochemical results of estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2): ER or PR positive (luminal), ER/PR negative and HER2 positive (HER2+), and triple-negative breast cancer (TNBC). Before starting and immediately after completing NCT, a surgeon decided if breast-conserving surgery (BCS) or total mastectomy (TM) should be performed. We analyzed the rate of type of surgery performed. RESULTS: Before administering NCT, 107 patients (40.4%) and 158 patients (59.6%) were candidates for BCS and TM, respectively. Of the 158 patients, 61 were eligible for BCS after chemotherapy, with a conversion rate of 38.6%. NCT increased the BCS eligible rate from 40.4% to 62.6%. Of the 61 patients, 53 chose to undergo BCS, and BCS was successful in 46 (86.8%). Of the 107 BCS candidates at baseline, 100 patents finally underwent BCS (93.5%). According to the subtype, the conversion rates were 35.4%, 50.0%, and 40.5% for luminal, HER2+, and TNBC groups, respectively. CONCLUSION: NCT increased the eligibility for BCS from 40.4% to 62.6% in a clinical setting. This benefit is similar to that observed in other clinical trials.
Breast Neoplasms* ; Breast* ; Drug Therapy* ; Estrogens ; Humans ; Mastectomy, Segmental ; Mastectomy, Simple* ; Phenobarbital ; Prospective Studies ; Receptor, Epidermal Growth Factor ; Triple Negative Breast Neoplasms