Minimal Access vs Conventional Nipple-Sparing Mastectomy.

Importance: While nipple-sparing mastectomy (NSM) for breast cancer was only performed using the open method in the past, its frequency using endoscopic and robotic surgical instruments has been increasing rapidly. However, there are limited studies regarding postoperative complications and the benefits and drawbacks of minimal access NSM (M-NSM) compared with conventional NSM (C-NSM). Objective: To examine the differences in postoperative complications between C-NSM and M-NSM. Design, Setting, Participants: This was a retrospective multicenter cohort study enrolling 1583 female patients aged 19 years and older with breast cancer who underwent NSM at 21 university hospitals in Korea between January 2018 and December 2020. Those with mastectomy without preserving the nipple-areolar complex (NAC), clinical or pathological malignancy in the NAC, inflammatory breast cancer, breast cancer infiltrating the chest wall or skin, metastatic breast cancer, or insufficient medical records were excluded. Data were analyzed from November 2021 to March 2024. Exposures: M-NSM or C-NSM. Main Outcomes and Measures: Clinicopathological factors and postoperative complications within 3 months of surgery were assessed. Statistical analyses, including logistic regression, were used to identify the factors associated with complications. Results: There were 1356 individuals (mean [SD] age, 45.47 [8.56] years) undergoing C-NSM and 227 (mean [SD] age, 45.41 [7.99] years) undergoing M-NSM (35 endoscopy assisted and 192 robot assisted). There was no significant difference between the 2 groups regarding short- and long-term postoperative complications (<30 days: C-NSM, 465 of 1356 [34.29%] vs M-NSM, 73 of 227 [32.16%]; P = .53; <90 days: C-NSM, 525 of 1356 [38.72%] vs M-NSM, 73 of 227 [32.16%]; P = .06). Nipple-areolar complex necrosis was more common in the long term after C-NSM than M-NSM (C-NSM, 91 of 1356 [6.71%] vs M-NSM, 5 of 227 [2.20%]; P = .04). Wound infection occurred more frequently after M-NSM (C-NSM, 58 of 1356 [4.28%] vs M-NSM, 18 of 227 [7.93%]; P = .03). Postoperative seroma occurred more frequently after C-NSM (C-NSM, 193 of 1356 [14.23%] vs M-NSM, 21 of 227 [9.25%]; P = .04). Mild or severe breast ptosis was a significant risk factor for nipple or areolar necrosis (odds ratio [OR], 4.75; 95% CI, 1.66-13.60; P = .004 and OR, 8.78; 95% CI, 1.88-41.02; P = .006, respectively). Conversely, use of a midaxillary, anterior axillary, or axillary incision was associated with a lower risk of necrosis (OR for other incisions, 32.72; 95% CI, 2.11-508.36; P = .01). Necrosis occurred significantly less often in direct-to-implant breast reconstruction compared to other breast reconstructions (OR, 2.85; 95% CI, 1.11-7.34; P = .03). Conclusions and Relevance: The similar complication rates between C-NSM and M-NSM demonstrates that both methods were equally safe, allowing the choice to be guided by patient preferences and specific needs.

Clinical characteristics and prognosis of postpartum breast cancer.

PURPOSE: Postpartum breast cancer (PPBC) is a not well-established subset of breast cancer, and only few studies address its poorer prognosis. However, previous studies show that PPBC is associated with worse outcome with higher rates of metastasis than in young women's breast cancer (YWBC). We aimed to analyze the clinical characteristics and prognosis of PPBC based on the diagnosis period of PPBC. METHODS: We retrospectively reviewed 208,780 patients with breast cancer from the Korean Breast Cancer Society registry (KBCSR) database between January 2000 and December 2014. We included premenopausal women aged 20-50 years who underwent breast cancer surgery. The patients were classified by 5-year intervals according to the diagnosis period of breast cancer, from the first birth to the breast cancer diagnosis. RESULTS: Compared with patients in the other groups, patients diagnosed within postpartum 5 years (PPBC < 5 years) group were younger, had a more advanced stage, had lower estrogen receptor (ER) and progesterone receptor (PR) expression, and had a higher human epidermal growth factor receptor 2 (HER2) positive rate. Further, PPBC < 5 years group had a worse survival rate than the nulliparous and other groups (5-year cumulative survival: PPBC < 5 years group, 89%; nulliparous group, 97.3%; 5 ≤ PPBC < 10 years group, 93%). In the multivariate analysis, the PPBC < 5 years group was associated with a worse survival rate (hazard ratio 1.55, 95% confidence interval [CI] 1.148-2.094, p 0.004) after adjustment for age at diagnosis, breast cancer stage, ER and HER2 status, Ki-67 level, and chemotherapy. CONCLUSION: Our findings indicated that patients diagnosed with breast cancer within the first 5 years after delivery had aggressive characteristics and a poor survival rate. It is important to elucidate the pathophysiology of PPBC and establish novel therapeutic strategies to improve the survival rate.

Predictive biological factors for late survival in patients with HER2-positive breast cancer.

The human epidermal growth factor receptor-2 (HER2) enriched subtype of breast cancer is associated with early recurrence, mostly within 5 years. However, anti-HER2 therapies have improved outcomes and their benefits persist in the long term. This study aimed to determine predictive factors for late survival in patients with HER2-positive breast cancer. We analyzed 20,672 patients with HER2-positive stage I-III breast cancer. The patients were divided into two groups based on a follow-up period of 60 months. The multivariate analysis of factors associated with poor overall survival included old age, advanced pathologic tumor size stage (pT), advanced pathologic regional lymph node stage (pN), high histological grade, presence of lymphatic and vascular invasion, and HR-negative status within 60 months. In the breast cancer-specific survival (BCSS) of the > 60 months follow-up group, the hazard ratios (HRa) based on pN-negative were 3.038, 3.722, and 4.877 in pN1 (p = 0.001), pN2 (p < 0.001), and pN3 (p < 0.001), respectively. Only pT4 level was statistically significant in the pT group (HRa, 4.528; p = 0.007). Age (HRa, 1.045, p < 0.001) and hormone receptor-positive status (HRa, 1.705, p = 0.022) were also associated to worse BCSS. Although lymphatic invasion was not significantly associated with BCSS, there was a tendency toward a relationship (p = 0.079) with worse BCSS. In HER2-positive breast cancer patients, node status had a more significant relationship with long-term prognosis than T stage. Patients with HER2-positive breast cancer who have T4 or node-positive should be considered for clinical observation and education beyond 5 years.

Robot-assisted Nipple Sparing Mastectomy: Recent Advancements and Ongoing Controversies.

Purpose of review: The purpose of this review is to summarize the recent technical advancements in RNSM, describe the ongoing teaching programs, and discuss the ongoing controversies. Recent findings: Robot-assisted nipple sparing mastectomy (RNSM) is the newest addition to the armamentarium of surgical techniques for patients who require a mastectomy. The potential benefits of using the da Vinci® Robotic Surgical System (Intuitive Surgical, Sunnyvale, CA) are the small 3D camera and lighting offering superior visualization, the Endowrist robotic instruments offering greater range of motion, and surgeon being at a seated position at the console rendering a more ergonomic operating position. Summary: RNSM can potentially help overcome the technical difficulties of performing a conventional NSM. Further studies are needed to elucidate the oncologic safety and cost-effectiveness of RNSM.

A randomized controlled trial using surgical gloves to prevent chemotherapy-induced peripheral neuropathy by paclitaxel in breast cancer patients (AIUR trial).

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of taxane treatment and can significantly affect patient quality of life. Currently, there are no effective treatments to alleviate symptoms of CIPN; thus, starting with prevention steps in high-risk patients is considered advantageous. However, for these prevention steps to be applicable to all patients, their side effects or accompanying discomforts should be minimal, and the intervention cost-effective. Compression therapy can be considered a prevention intervention, and using surgical gloves is feasible and cost-effective (approximately $0.6 per pair). Although previous studies on compression therapy using surgical gloves have reported decreased incidence of PN, these studies were non-randomized, limited to nab-paclitaxel treatment, and involved the use of small gloves, which may have caused discomfort. Therefore, this study aimed to assess the preventive effects of compression therapy using normal-sized surgical gloves on CIPN in patients treated with paclitaxel. METHODS: This clinical trial is designed to evaluate the preventive effects of compression therapy using surgical gloves on CIPN in women with stage II-III breast cancer who received paclitaxel chemotherapy for at least 12 weeks. This multicenter, randomized-controlled, open-label study will be conducted in six academic hospitals. Patients with medication or a medical history related to neuropathy or hand disease will be excluded. The primary outcome will be the preventive effect of compression therapy using surgical gloves, measured based on changes in the neurotoxicity component of the Functional Assessment of Cancer Therapy-Taxane questionnaire. Furthermore, we will assess the National Cancer Institute's Common Terminology Criteria for Adverse Events grade of CIPN after 6 months. Notably, the estimated sample size, based on a p-value < 0.025 and statistical power of 0.9, will consist of 104 patients (52 per group), accounting for a 10% sample loss. DISCUSSION: This intervention can be easily implemented in clinical practice and may serve as a preventive strategy for CIPNs with strong patient adherence. If successful, this intervention could improve the quality of life and treatment adherence in patients receiving chemotherapy that can induce PN, extending beyond paclitaxel treatment alone. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05771974; Registered on March 16, 2023.

Prognostic factors after isolated ipsilateral local and regional recurrence in HER2-negative luminal breast cancer: a multi-center retrospective study.

BACKGROUND: Although the incidence of isolated ipsilateral local and regional recurrence (IILRR) in human epidermal growth factor 2 (HER2)-negative luminal breast cancer is low, it is important because of its potential risk of distant metastasis and breast cancer related mortality. The aim of this study was to investigate prognostic factor and survival of IILRR using a large multi-center cohort. METHODS: Data on patients with HER2-negative luminal breast cancer between 2005 and 2015 were retrieved. The endpoint was IILRR rate, post-recurrence progression-free survival (P-PFS), and post-recurrence overall survival (P-OS). Prognostic factors for progression and overall survival (OS) after IILRR were assessed by multivariate analysis. RESULTS: Eighty (2.37%) patients experienced IILRR. Of them, 27 (33.7%) experienced a disease progression, including 23 (85.2%) who had distant metastasis. The median DFS was 48.5 months (range, 4-138 months). In 72.5% of cases, the first IILRR occurred after 3 years. Estimated 5-year P-PFS rates were 86.2%, 69.7%, 69.0%, 42.7%, and 82.2% for patients with age < 40 at diagnosis (p = 0.015), T1 stage (p = 0.012), stage I (p < 0.001), lymphovascular invasion (p = 0.003), and patients with post-recurrence endocrine therapy (p < 0.001), respectively. The 5-year Kaplan-Meier P-OS rate for patients was 81.4%. Post-recurrence endocrine therapy was independent factor for progression (HR: 0.176, p < 0.001) and OS (HR: 0.080, p < 0.001). CONCLUSIONS: Although there is no standardized treatment for IILRR yet, endocrine therapy after local resection plays a more important role in improving prognosis than chemotherapy or radiotherapy in HER2-negative luminal breast cancer.

Uncooperative patients suspected of acute stroke ineligible for prehospital stroke screening test by emergency medical service providers: final hospital diagnoses and characteristics.

OBJECTIVE: This study investigated the hospital diagnoses and characteristics of uncooperative prehospital patients suspected of acute stroke who could not undergo a prehospital stroke screening test (PHSST). METHODS: This retrospective observational study was conducted at a single academic hospital with a regional stroke center. We analyzed three scenario-based prehospital stroke screening performances using the final hospital diagnoses: (1) a conservative approach only in patients who underwent the PHSST, (2) a real-world approach that considered all uncooperative patients as screening positive, and (3) a contrapositive approach that all uncooperative patients were considered as negative. RESULTS: Of the 2,836 emergency medical services (EMS)-transported adult patients who met the prehospital criteria for suspicion of acute stroke, 486 (17.1%) were uncooperative, and 570 (20.1%) had a confirmed final diagnosis of acute stroke. The diagnosis in the uncooperative group did not differ from that in the cooperative group (22.0% vs. 19.7%, P=0.246). The diagnostic performances of the PHSST in the conservative approach were as follows: 79.5% sensitivity (95% confidence interval [CI], 75.5%-83.1%), 90.2% specificity (95% CI, 88.8%-91.6%), and 0.849 area under the receiver operating characteristic curve (AUC; 95% CI, 0.829-0.868). The sensitivity and specificity were 83.3% (95% CI, 80.0%-86.3%) and 75.2% (95% CI, 73.3%-76.9%), respectively, in the real-world approach and 64.6% (95% CI, 60.5%-68.5%) and 91.9% (95% CI, 90.7%-93.0%), respectively, in the contrapositive approach. No significant difference was evident in the AUC between the real-world approach and the contrapositive approach (0.792 [95% CI, 0.775-0.810] vs. 0.782 [95% CI, 0.762-0.803], P>0.05). CONCLUSION: We found overestimation (false positive) and underestimation (false negative) in the uncooperative group depending on the scenario-based EMS stroke screening policy for uncooperative prehospital patients suspected of acute stroke.

A nomogram for predicting three or more axillary lymph node involvement before breast cancer surgery.

Based on the American College of Surgeons Oncology Group (ACOSOG)-Z0011, a useful nomogram has been constructed to identify patients who do not require intraoperative frozen sections to evaluate sentinel lymph nodes in the previous study. This study investigated the developed nomogram by ultrasonography (US) and positron emission tomography (PET)/computed tomography (CT) as a modality. In the training set, 89/1030 (8.6%) patients had three or more positive nodes. Larger tumor size, higher grade ultrasonographic ALN classification, and findings suspicious of positive ALN on PET/CT were associated in multivariate analysis. The areas under the receiver operating characteristic curve (AUC) of the nomogram were 0.856 [95% CI 0.815-0.897] in the training set. The AUC in the validation set was 0.866 [95% CI 0.799-0.934]. Application of the nomogram to 1067 patients who met the inclusion criteria of ACOSOG-Z0011 showed that 90 (8.4%) patients had scores above the cut-off and a false-negative result was 37 (3.8%) patients. And the specificity was 93.8%, and the negative predictive value was 96.4%. The upgraded nomogram improved the predictive accuracy, using only US and PET/CT. This nomogram is useful for identifying patients who do not require intraoperative analysis of sentinel lymph nodes and considering candidates for identifying neoadjuvant chemotherapy. The patients consisted of clinical T1-2 and node-negative invasive breast cancer. The training and validation set consisted of 1030 and 781 patients, respectively. A nomogram was constructed by analyzing factors related to three or more axillary lymph node metastases. The patients who matched the ACOSOG-Z0011 criteria were selected and applied to the new nomogram.

Clinicopathologic and Molecular Characteristics of and Diagnostic Dilemmas in Invasive Breast Carcinoma with Choriocarcinomatous Pattern apropos a New Case: A Literature Review with New Findings.

BACKGROUND: Invasive breast carcinoma with a choriocarcinomatous pattern (IBC-CP) is extremely rare, and its molecular basis is yet unclear. The choriocarcinomatous pattern is characterized by the biphasic arrangement of multinucleated syncytiotrophoblast-like cells around clusters of monotypic tumor cells in a hemorrhagic background, along with ß-human chorionic gonadotropin (ß-hCG) expression. The differentiation of IBC-CP from metastatic choriocarcinoma of the breast (MC-B) is difficult due to the histologic similarity. METHODS: Based on a literature review and our own case, the clinicopathologic differences between IBC-CP patients (n = 17) and MC-B patients (n = 8) were analyzed. Moreover, in our case of IBC-CP, next-generation sequencing (NGS) comparative analysis was conducted for both choriocarcinomatous and invasive breast carcinoma (IBC) components. RESULTS: Compared to the MC-B patients, the IBC-CP patients were older (p < 0.001) and less frequently had past histories of gestational trophoblastic disease/pregnancy/abortion (p = 0.001) and distant metastases (p = 0.005). Our case, a 49-year-old female patient, presented with masses in the right breast and axilla. Following neoadjuvant chemotherapy, a radical mastectomy found an 8.5-cm-sized tumor. Microscopically, multinucleated syncytiotrophoblast-like cells were observed around mononuclear tumor cells with hemorrhage and necrosis. Some tumor cells showed ß-hCG immunopositivity, which was compatible with IBC-CP. NGS results showed a missense mutation in exon 5 of the TP53 gene in both the choriocarcinomatous and IBC components. Meanwhile, copy number loss in the PTEN gene was only identified in the choriocarcinomatous components. CONCLUSION: The present IBC-CP case is triple-negative breast cancer with TP53 mutation. The PTEN gene may be associated with choriocarcinomatous differentiation. Obtaining a medical history is mandatory to exclude metastatic lesions.

Clinical significance of HER2 status in T1bN0 breast cancer: a nationwide study from the Korean Breast Cancer Society.

PURPOSE: The prognosis of patients with node-negative T1b tumors according to human epidermal growth factor receptor 2 (HER2) status is not known. This group of patients has not been studied in the available randomized trials. The objective of this study was to evaluate the survival of patients in a monoethnic group diagnosed with T1b lymph node-negative breast cancer depending on HER2 status. METHODS: We analyzed 3110 patients with T1bN0M0 breast cancer whose data were deposited into the Korean Breast Cancer Society Registry database between 2000 and 2009. Overall survival (OS) and breast cancer-specific survival (BCSS) were compared according to HER2 status. RESULTS: Among all patients, 494 (15.9%) had HER2-positive breast cancer. At a mean follow-up of 93 months, 108 deaths and 86 breast cancer-specific deaths were noted among all patients. There was no significant difference in OS between the HER2-negative and HER2-positive groups (p = 0.103). The same result was observed for BCSS. However, in the subgroup of estrogen receptor (ER)-positive women, HER2-negative patients had a better BCSS prognosis than HER2-positive patients (p = 0.025). Multivariate analysis also indicated a significant difference in BCSS in the ER-positive subgroup (HR 2.60; 95% CI 1.15-5.87; p = 0.021). CONCLUSION: This study analyzed a large nationwide and monoethnic cohort and found a significant difference only in BCSS in the ER-positive subgroup according to HER2 status. Anti-HER2 therapy may be considered in HER2-positive and ER-positive patients with small, node-negative breast cancer.

Impact of the COVID-19 Pandemic on the Diagnosis and Surgery of Breast Cancer: A Multi-Institutional Study.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the rates of screening, case identification, and referral for cancer diagnosis. We investigated the diagnosis and surgery status of breast cancer before and after the COVID-19 pandemic at a multi-institutional level. METHODS: We collected breast cancer data from the clinical data warehouse which contained the medical records of patients from six academic institutions in South Korea. Patients were divided into two groups: February to April (period A) and May to July (period B). The data from the two groups were then compared against the same periods in 2019 and 2020. The primary objective was to investigate the differences in breast cancer stages before and after the COVID-19 pandemic. RESULTS: Among 3,038 patients, there was a 9.9% reduction in the number of diagnoses in 2020. This decrease was more significant during period A than period B. The breast cancer stage was not statistically different in period A (p = 0.115), but it was in period B (p = 0.001). In the subset analysis according to age, there was a statistical difference between 2019 and 2020 in period B for patients under the age of 65 years (p = 0.002), but no difference was observed in the other groups. CONCLUSION: The number of breast cancer cases declined during the pandemic, and the staging distribution has changed after the pandemic peak.

A Randomized Controlled Trial for Doing vs. Omitting Intraoperative Frozen Section Biopsy for Resection Margin Status in Selected Patients Undergoing Breast-Conserving Surgery (OFF-MAP Trial).

PURPOSE: Intraoperative frozen section biopsy is used to reduce the margin positive rate and re-excision rate and has been reported to have high diagnostic accuracy. A majority of breast surgeons in the Republic of Korea routinely perform frozen section biopsy to assess margins intraoperatively, despite its long turnaround time and high resource requirements. This study aims to determine whether omitting frozen section biopsy for intraoperative margin evaluation in selected patients is non-inferior to performing frozen section biopsy in terms of resection margin positivity rate. METHODS: This study is a phase III, randomized controlled, parallel-group, multicenter non-inferiority clinical trial. Patients meeting the inclusion criteria and providing written informed consent will be randomized to the "frozen section biopsy" or "frozen section biopsy omission" group after lumpectomy. Patients with clinical stage T1-T3 disease who are diagnosed with invasive breast cancer by core-needle biopsy and plan to undergo breast-conserving surgery will be included in this study. If a daughter nodule, non-mass enhancement, or microcalcification is identified on preoperative imaging, these features must be within 1 cm of the main mass for inclusion in the trial. The target sample size is 646 patients per arm. The primary endpoint will be the resection margin positive rate, and the secondary endpoints include the reoperation rate, operating time, residual cancer after reoperation, residual cancer after re-excision according to the frozen section biopsy result, resection volume, patient quality of life, and cost-effectiveness. DISCUSSION: This is the first randomized clinical trial utilizing frozen section biopsy for intraoperative margin evaluation and aims to determine the non-inferiority of omitting frozen section biopsy in selected patients compared to performing frozen section biopsy. We expect that this trial will help surgeons perform the procedure more efficiently while ensuring patient safety. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03975179; Clinical Research Information Service Identifier: KCT0004606.

Peripheral Pain Modulation of Chrysaora pacifica Jellyfish Venom Requires Both Ca2+ Influx and TRPA1 Channel Activation in Rats.

The venom of jellyfish triggers severe dermal pain along with inflammation and tissue necrosis, and occasionally, induces internal organ dysfunction. However, the basic mechanisms underlying its cytotoxic effects are still unknown. Here, we report one of the mechanisms involved in peripheral pain modulation associated with inflammatory and neurotoxic oxidative signaling in rats using the venom of jellyfish, Chrysaora pacifica (CpV). This jellyfish is identified by brown tentacles carrying nematocysts filled with cytotoxic venom that induces severe pain, pruritus, tentacle marks, and blisters. The subcutaneous injection of CpV into rat forepaws in behavioral tests triggered nociceptive response with a decreased threshold for mechanical pain perception. These responses lasted up to 48 h and were completely blocked by verapamil and TTA-P2, T-type Ca2+ channel blockers, or HC030031, a transient receptor potential cation ankyrin 1 (TRPA1) channel blocker, while another Ca2+ channel blocker, nimodipine, was ineffective. Also, treatment with Ca2+ chelators (EGTA and BaptaAM) significantly alleviated the CpV-induced pain response. These results indicate that CpV-induced pain modulation may require both Ca2+ influx through the T-type Ca2+ channels and activation of TRPA1 channels. Furthermore, CpV induced Ca2+-mediated oxidative neurotoxicity in the dorsal root ganglion (DRG) and cortical neurons dissociated from rats, resulting in decreased neuronal viability and increased intracellular levels of ROS. Taken together, CpV may activate Ca2+-mediated oxidative signaling to produce excessive ROS acting as an endogenous agonist of TRPA1 channels in the peripheral terminals of the primary afferent neurons, resulting in persistent inflammatory pain. These findings provide strong evidence supporting the therapeutic effectiveness of blocking oxidative signaling against pain and cytotoxicity induced by jellyfish venom.

Relationship between Mammographic Density and Age in the United Arab Emirates Population.

OBJECTIVE: Higher breast density is a strong, independent risk factor for breast cancer. Breast density varies by age, ethnicity, and geographic area although dense breast tissue has been associated with younger age and premenopausal status. The relationship between breast density and age in women in the United Arab Emirates (UAE) has not been determined. This study evaluated breast density in the UAE population and its relationship with age. METHODS: Women participating in the national cancer screening program from August 2015 to May 2018 who underwent screening mammography were included. Breast parenchymal density was classified according to the American College of Radiology (ACR) Breast Imaging-Reporting and Data System (BI-RADS) from category a (almost entirely fatty) through d (extremely dense). Subjects were divided into six age groups, and the association between age and breast density was evaluated. RESULTS: Of the 4911 women included, 1604 (32.7%), 2149 (43.8%), 1055 (21.5%), and 103 (2.1%) were classified as having categories a-d breast density, respectively. A significant negative correlation was observed between age and breast density category (p < 0.001). Women of mean age 44 ± 7 years had the highest breast density, whereas those of mean age 56 ± 14 years had the lowest breast density. Comparisons of Emirati women with Lebanese and Western women showed that breast density was lower in Emirati women than in the other populations. CONCLUSIONS: To our knowledge, this is the first study to evaluate the relationship between mammographic breast density and age in UAE women. As in other populations, age was inversely related to breast density, but the proportion of Emirati women with dense breasts was lower than in other populations. Because this study lacked demographic, clinical, and histopathological data, further evaluation is required.

Ki-67 Expression is a Significant Prognostic Factor Only When Progesterone Receptor Expression is Low in Estrogen Receptor-Positive and HER2-Negative Early Breast Cancer.

OBJECTIVE: While the value of Ki-67 has been recognized in breast cancer, controversy also exists. The goal of this study is to show the prognostic value of Ki-67 according to progesterone receptor (PgR) expression in patients who have estrogen receptor- (ER-) positive, human epidermal growth factor receptor 2- (HER2-) negative early breast cancer. METHODS: The records of nonmetastatic invasive breast cancer patients who underwent surgery at a single institution between 2009 and 2012 were reviewed. Primary end point was recurrence-free survival (RFS), and secondary end point was overall survival (OS). Ki-67 and PgR were assessed with immunohistochemistry for the tumor after surgery. RESULTS: A total of 1848 patients were enrolled in this study. 223 (12%) patients had high (≥10%) Ki-67, and 1625 (88%) had low Ki-67 expression. Significantly worse RFS and OS were observed in the high vs. low Ki-67 expression only when the PgR was low (<20%) (p < 0.001 and 0.005, respectively, for RFS and OS). There was no significant difference in RFS and OS according to Ki-67 when the PgR was high (p=0.120 and 0.076). RFS of four groups according to high/low Ki-67 and PgR expression was compared. The low PgR and high Ki-67 expression group showed worst outcome among them (p < 0.001). In a multivariate analysis, high Ki-67 was an independent prognostic factor when the PgR was low (HR 3.05; 95% CI 1.50-6.19; p=0.002). CONCLUSIONS: Ki-67 had a value as a prognostic factor only under low PgR expression level in early breast cancer. PgR should be considered in evaluating the prognosis of breast cancer patients using Ki-67.

Development of screening tool for child abuse in the korean emergency department: Using modified Delphi study.

Mandatory reporting rate of suspected child abuse by health care provider is relatively low in South Korea. The purpose of the study was to develop a screening tool for child abuse and evaluate the feasibility of using this screening tool in emergency department (ED) of South Korea. Injured children younger than 14 years old in the ED were enrolled as subjects to use this screening tool. Candidate items for screening tool were decided after reviewing relevant previous studies by researchers. Using the modified Delphi method, it was judged that the consensus for items of screening tool was achieved in 2 rounds, and the final item of the screening tool was decided through the discussion in the final round. The registry including the developed screening tool was applied to 6 EDs over 10 weeks. Variables of the registry were retrospectively analyzed. A child abuse screening tool called Finding Instrument for Non-accidental Deeds (FIND) was developed. It included 8 questions. One item (suspected signs in physical examination) had 100% agreement; 3 items (inconsistency with development, inconsistent history by caregivers, and incompatible injury mechanism) had 86.7% agreement; and 4 items (delayed visit, inappropriate relationship, poor hygiene, and head or long bone injury in young infants) had 80% agreement. During the period of registry enrollment, the rate of screening with FIND was 72.9% (n = 2815). 36 (1.3%) cases had 1 or more "positive" responses among 8 items. Two (0.07%) cases were reported to the Child Protection Agency. An ED based screening tool for child abuse consisting of 8 questions for injured children younger than 14 years old was developed. The use of screening tools in Korean ED is expected to increase the reporting rate of child abuse. However, further study is necessary to investigate the accuracy of this screening tool using a national child abuse registry.

The Effect of Reproductive Factors on Breast Cancer Presentation in Women Who Are BRCA Mutation Carrier.

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.

Outcome following sentinel lymph node biopsy-guided decisions in breast cancer patients with conversion from positive to negative axillary lymph nodes after neoadjuvant chemotherapy.

PURPOSE: Many breast cancer patients with positive axillary lymph nodes achieve complete node remission after neoadjuvant chemotherapy. The usefulness of sentinel lymph node biopsy in this situation is uncertain. This study evaluated the outcomes of sentinel biopsy-guided decisions in patients who had conversion of axillary nodes from clinically positive to negative following neoadjuvant chemotherapy. METHODS: We reviewed the records of 1247 patients from five hospitals in Korea who had breast cancer with clinically axillary lymph node-positive status and negative conversion after neoadjuvant chemotherapy, between 2005 and 2012. Patients who underwent axillary operations with sentinel biopsy-guided decisions (Group A) were compared with patients who underwent complete axillary lymph node dissection without sentinel lymph node biopsy (Group B). Axillary node recurrence and distant recurrence-free survival were compared. RESULTS: There were 428 cases in Group A and 819 in Group B. Kaplan-Meier analysis showed that recurrence-free survivals were not significantly different between Groups A and B (4-year axillary recurrence-free survival: 97.8 vs. 99.0%; p = 0.148). Multivariate analysis also indicated the two groups had no significant difference in axillary and distant recurrence-free survival. CONCLUSIONS: For breast cancer patients who had clinical conversion of axillary lymph nodes from positive to negative following neoadjuvant chemotherapy, sentinel biopsy-guided axillary surgery, and axillary lymph node dissection without sentinel lymph node biopsy had similar rates of recurrence. Thus, sentinel biopsy-guided axillary operation in breast cancer patients who have clinically axillary lymph node positive to negative conversion following neoadjuvant chemotherapy is a useful strategy.

The treatment outcomes and the use of adjuvant therapies in breast cancer patients with severe co-morbidities.

PURPOSE: Studies have suggested a potential role of patient's co-morbidity in determining the survival outcomes of breast cancer. In this study, we examined the long-term oncologic outcomes in breast cancer patients who underwent curative surgery according to their pre-existing comorbid conditions and analyzed the association between the co-morbidity and the use of adjuvant therapies. METHODS: The medical records of 2,501 patients who underwent surgery for primary breast cancer from June 2006 to June 2010 were reviewed retrospectively. The patients were classified into three groups according to preoperative ASA status determined by the anesthesiologists. Clinico-pathologic characteristics and survival outcomes of the patients were compared among the different co-morbidity groups. RESULTS: There were 1,792 (71.6%), 665 (26.6%), and 44 (1.8%) patients in ASA I, II, and III, respectively. Total 95 (3.8%) deaths and 269 (10.8%) recurrences (loco-regional and distant) occurred during the median follow-up period of 71 months. Patients with high comorbidity showed significantly higher rate of deaths (51 (2.8%), 38 (5.7%) and 6 (13.6%) deaths in ASA I, II and III group, respectively, p<0.001). The ASA 3 patients also showed significantly higher rate of breast cancer recurrence when compared to other groups (180 (10.0%), 80 (12.0%) and 9 (20.5%) in ASA I, II, and III, respectively, p = 0.041). Significantly fewer patients in the high co-morbidity group received adjuvant therapies (77 (4.3%), 44 (6.6%) and 8 (18.2%) in ASA I, II, and III, respectively, p<0.001). The increased recurrence of breast cancer in the high morbidity group was mostly seen in patients who did not receive adjuvant therapies. The incidence of serious adverse effect during the adjuvant therapy did not differ according to the co-morbidity conditions. CONCLUSIONS: In this study, high comorbidity was related to increased risk of death and recurrence in breast cancer. The increased risk of recurrence in high co-morbidity group was mostly seen in patients who did not receive adjuvant therapies. Considering the relatively low rates of serious adverse effects in high co-morbidity patients who received adjuvant therapies, active use of adjuvant therapies in selected patients may improve survival outcomes in breast cancer patients with severe co-morbidities.