Clinicopathological Factors Predicting Pathological Complete Response to Neoadjuvant Anti-HER2 Therapy in HER2-Positive Breast Cancer.

INTRODUCTION: Human epidermal growth factor receptor 2 (HER2)-targeted therapies have shown effectiveness against HER2-positive breast cancer. This makes neoadjuvant chemotherapy (NAC) a valuable option for treating both early and advanced stages of the disease. The tumor's response to HER2-targeted NAC provides crucial prognostic information. Additionally, it allows for tailoring adjuvant treatment strategies for HER2+ breast cancer based on pathological responses. This study aimed to investigate the clinicopathological factors that influence tumor response. METHODS: We retrospectively analyzed 122 patients diagnosed with HER2+ breast cancer. These patients received NAC and HER2-directed therapy between January 2018 and December 2022 at the Pusan National University Yangsan Hospital. Following surgery, tumor response was evaluated, categorizing patients into two groups: pathological complete response (pCR) and non-pCR groups. We analyzed data on various factors, including age, NAC regimen, type of breast and axillary surgery, clinical stage (cTNM), historical grade, and preoperative levels of carcinoembryonic antigen, cancer antigen 15-3 (CA 15-3), estrogen receptor (ER), progesterone receptor (PR), HER2, p53, and KI-67. RESULTS: Out of the 122 patients, 75 achieved pCR, while 47 did not. Most clinicopathological factors showed no significant difference between the pCR and non-pCR groups. However, several factors were associated with a higher pCR rate: normal preoperative CA 15-3 levels (odds ratio [OR]: 3.74, confidence interval [CI]: 1.19-11.72, p = 0.02), preoperative ER positivity (OR: 2.65, CI: 1.25-5.59, p = 0.01), PR negativity (OR: 3.92, CI: 1.82-8.45, p < 0.05), and strong preoperative HER2 immunohistochemistry (IHC) 3+ staining. Multivariate analysis confirmed that PR negativity (OR: 2.8, CI: 1.23-6.42, p = 0.01) and strong preoperative HER2 IHC 3+ staining (OR: 0.18, CI: 0.03-0.84, p = 0.04) were independent predictors of a higher pCR rate. CONCLUSIONS: A pCR after NAC impacts patient prognosis and influences the choice of adjuvant treatment for HER2+ breast cancer. Clinicopathological factors can help predict responses to HER2-targeted NAC. In our study, pre-ER/PR negativity, high pre-HER2 levels, and normal CA 15-3 levels were found to be potential predictors of pCR. These findings may contribute to developing more effective treatment strategies for HER2+ breast cancer.

Comparison of Fused Diffusion-Weighted Imaging Using Unenhanced MRI and Abbreviated Post-Contrast-Enhanced MRI in Patients with Breast Cancer.

Background and Objectives: To determine the percentage of breast cancers detectable by fused diffusion-weighted imaging (DWI) using unenhanced magnetic resonance imaging (MRI) and abbreviated post-contrast-enhanced MRI. Materials and Methods: Between October 2016 and October 2017, 194 consecutive women (mean age, 54.2 years; age range, 28-82 years) with newly diagnosed unilateral breast cancer, who underwent preoperative 3.0 T breast MRI with DWI, were evaluated. Both fused DWI and abbreviated MRI were independently reviewed by two radiologists for the detection of index cancer (which showed the most suspicious findings in both breasts), location, lesion conspicuity, lesion type, and lesion size. Moreover, the relationship between cancer detection and histopathological results of surgical specimens was evaluated. Results: Index cancer detection rates were comparable between fused DWI and abbreviated MRI (radiologist 1: 174/194 [89.7%] vs. 184/194 [94.8%], respectively, p = 0.057; radiologist 2: 174/194 [89.7%] vs. 183/194 [94.3%], respectively, p = 0.092). In both radiologists, abbreviated MRI showed a significantly higher lesion conspicuity than fused DWI (radiologist 1: 9.37 ± 2.24 vs. 8.78 ± 3.03, respectively, p < 0.001; radiologist 2: 9.16 ± 2.32 vs. 8.39 ± 2.93, respectively, p < 0.001). The κ value for the interobserver agreement of index cancer detection was 0.67 on fused DWI and 0.85 on abbreviated MRI. For lesion conspicuity, the intraclass correlation coefficients were 0.72 on fused DWI and 0.82 on abbreviated MRI. Among the histopathological factors, tumor invasiveness was associated with cancer detection on both fused DWI (p = 0.011) and abbreviated MRI (p = 0.004, radiologist 1), lymphovascular invasion on abbreviated MRI (p = 0.032, radiologist 1), and necrosis on fused DWI (p = 0.031, radiologist 2). Conclusions: Index cancer detection was comparable between fused DWI and abbreviated MRI, although abbreviated MRI showed a significantly better lesion conspicuity.

Factors Affecting Pathologic Complete Remission in Patients with Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy.

INTRODUCTION: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is associated with improvement in survival outcomes. This study evaluated the pCR in patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer after NAC. METHODS: We evaluated 417 patients who were diagnosed with invasive breast cancer and treated with NAC followed by curative surgery between January 2007 and December 2020 and analyzed the pCR for HR-positive and HER2-negative breast cancer. RESULTS: The median age at the time of surgery was 45.4 years, and 9.1% of patients (38 of 417) with HR-positive/HER2-negative status had pCR. Among patients with HR-positive/HER2-negative breast cancer, patients with single HR-positivity had a 20.2% pCR rate, and patients with double HR-positivity had a 4.4% pCR rate. Patients with a high Ki-67 index exhibited a higher pCR rate than those with a lower Ki-67 index (14.5% vs. 3.2%). Patients with single HR-positive and high Ki-67 values exhibited a significantly higher pCR rate than those with double HR-positive and low Ki-67 values (27.8% vs. 2.1%; p < 0.001). CONCLUSION: NAC could improve prognosis in patients with HR-positive/HER2-negative breast cancer with a single HR-positive and high Ki-67 values.

Clinicopathological Features of BRCA1/2 Mutation-Positive Breast Cancer.

PURPOSE: The BRCA1/2 gene is the most well-known and studied gene associated with hereditary breast cancer. BRCA1/2 genetic testing is widely performed in high-risk patients of hereditary breast cancer in Korea. This study aimed to investigate the clinicopathological characteristics of BRCA1/2 mutation-positive breast cancer patients. METHODS: The clinical data of 188 Korean breast cancer patients who underwent genetic testing of BRCA1/2 mutation between March 2015 and February 2020 at Pusan National University Yangsan Hospital were retrospectively reviewed. The characteristics of breast cancer according to the expression of BRCA1 and BRCA2 mutations were analyzed using the Health Insurance Review and Assessment Service guideline criteria and other clinicopathological factors. RESULTS: The factor associated with BRCA1/2 gene expression was cancer stage, and mutation expression was significantly decreased in stage I compared to stage 0 (p = 0.033; odds ratio [OR], 0.169; 95% confidence interval [CI], 0.033-0.867), and there was a tendency to increase in stage II (p = 0.780; OR, 1.150; 95% CI, 0.432-3.064). BRCA1 was significantly associated with triple-negative breast cancer (TNBC) (p = 0.004; OR, 5.887; 95% CI, 1.778-19.498). Gene expression of BRCA2 was significantly reduced under 40 years of age (p = 0.040; OR, 0.198; 95% CI, 0.042-0.930). There was no difference in disease-free survival (p = 0.900) and overall survival (p = 0.733) between the BRCA1/2 mutation-positive and -negative groups. CONCLUSION: In this study, the clinicopathological characteristics of breast cancer patients with BRCA1/2 gene mutations were identified. BRCA1 gene expression was highly correlated with TNBC. BRCA1/2 mutation did not have a poor prognosis regarding recurrence and death.

A Prospective Longitudinal Study about Change of Sleep, Anxiety, Depression, and Quality of Life in Each Step of Breast Cancer Patients.

PURPOSE: Quality of sleep (QoS), anxiety, depression, and quality of life (QoL) are common issues among breast cancer patients. Prospective longitudinal studies of QoS, anxiety, depression, and QoL in breast cancer patients are lacking. The aim of this study was to find out whether there is a proper treatment point associated with QoS, anxiety, depression, and QoL during early treatment of breast cancer patients. METHODS: We used 4 self-report questionnaires about QoS, anxiety, depression, and QoL. QoS was measured using the Pittsburgh Sleep Quality Index, anxiety was measured with the Beck Anxiety Inventory, depression was measured with the Beck Depression Inventory, and QoL was measured with the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form. Patients were assessed at the time of surgery, at the beginning of chemotherapy, and at the end of chemotherapy. Clinicopathological information was collected for analysis. RESULTS: Fifty-two patients were enrolled in this study, and 29 completed 3 self-report questionnaires. QoS, anxiety, and depression showed no differences during the early treatment period. However, QoL changed during that period (p = 0.004). Type of breast surgery (total mastectomy vs. breast-conserving surgery) showed a relationship with QoS during the entire treatment period, but with anxiety only at the time of surgery (p = 0.002). Although the sample size was too small, the total mastectomy group showed better results. CONCLUSION: Breast cancer patients experience sleep disturbance, anxiety, depression, and loss of QoL. During the period of treatment, these do not change significantly, but these symptoms are often overlooked. Providing sufficient explanations about the treatment and prognosis of breast cancer and mental support for breast cancer patients prior to treatment will help to improve patients' QoS, anxiety, depression, and QoL.

Ultra-Low-Dose Neck CT With Low-Dose Contrast Material for Preoperative Staging of Thyroid Cancer: Image Quality and Diagnostic Performance.

OBJECTIVE: Although CT has been used as a complementary diagnostic method for the preoperative diagnosis of thyroid cancer, it has the shortcomings of substantial radiation exposure and the use of contrast material (CM). The purpose of this article is to evaluate the image quality and diagnostic performance of 70-kVp thyroid CT with low volumes of CM versus conventional 120-kVp thyroid CT protocol. MATERIALS AND METHODS: Eighty patients referred for preoperative thyroid CT were randomly divided into two groups (group A: 40 patients, 70 kVp, 60 mL of CM; group B: 40 patients, 120 kVp, 100 mL of CM). Quantitative and qualitative image quality and radiation doses for the two groups were compared using the Mann-Whitney U and chi-square tests. Degrees of agreement between preoperative CT staging and pathologic results were evaluated and compared using the Wald statistic. RESULTS: Calculated signal-to-noise ratios of different anatomic structures, calculated contrast-to-noise ratios, overall image quality, subjective noise, and streak artifacts were not significantly different between the two groups (all p > 0.05), and neither were the accuracies of preoperative CT staging (all p > 0.05). The estimated effective doses were significantly lower in group A (mean [± SD], 0.52 ± 0.14 mSv in group A and 2.28 ± 0.29 mSv in group B; p < 0.001). CONCLUSION: Ultra-low-dose 70-kVp CT with a low volume of CM provides sufficient image quality for preoperative staging of thyroid cancer and substantially reduces the radiation dose compared with standard 120-kVp CT.

Enhanced Photosensing and Photodynamic Treatment of Colon Cancer Cells Using Methoxy Poly(ethylene glycol)-Conjugated Chlorin e6.

Nanophotosensitizer composed of methoxy poly(ethylene glycol) (MePEG) and chlorin e6 (Ce6) (abbreviated as Pe6) was synthesized for efficient delivery of Ce6 to the colon cancer cells. Pe6 nanophotosensitizer has small diameter less than 100 nm with spherical shape and core-shell structure. They were activated in aqueous solution while Ce6 was quenched due to its poor aqueous solubility. They showed no intrinsic cytotoxicity against normal cells and colon cancer cells. Pe6 nanophotosensitizers showed enhanced cellular uptake, phototoxicity, and reactive oxygen species (ROS) generation at in vitro cell culture experiment. Furthermore, they showed improved tumor tissue penetration and accumulation in vivo animal studies. We suggested Pe6 nanophotosensitizers as an ideal candidate for PDT of colon cancer.

Patterns of malignant non-mass enhancement on 3-T breast MRI help predict invasiveness: using the BI-RADS lexicon fifth edition.

Background Non-mass enhancements (NME) with invasive components account for 10-42% of total malignant NMEs. The factors associated with invasiveness on magnetic resonance imaging (MRI) could be useful for clinical assessment and treatment. Purpose To evaluate the clinical significances of the distributions and internal enhancement patterns (IEP) of malignant NMEs on 3-T breast MRI. Material and Methods A total of 448 consecutive women with newly diagnosed breast cancer that had undergone preoperative MRI and surgery between February 2013 and March 2016 were identified. After exclusions, 72 malignant NMEs without a mass in 72 women (mean age = 51.5 years) were included. Two readers independently assessed distributions and IEPs of NME, according to the Breast Imaging Reporting and Data System lexicon fifth edition. Collected data included the presence of invasion and histopathologic factors. Results A clustered ring IEP was significantly associated with invasive cancer (75.0%, P = 0.001, Reader1; 72.9%, P < 0.001, Reader 2), absence of necrosis (79.0%, P < 0.001; 72.1%, P < 0.001, respectively), and high Ki-67 expression (74.2%, P = 0.048; 74.2%, P = 0.003, respectively). A clumped IEP was related to ductal carcinoma in situ (33.3%, P = 0.025; 50.0%, P = 0.001, respectively), absence of lymph node metastasis (24.1%, P = 0.029; 31.5%, P = 0.030, respectively), and presence of necrosis (34.5%, P = 0.003; 44.8%, P = 0.001, respectively). Conclusion The presence of a clustered ring IEP in patients with breast cancer was found to be significantly associated with invasive breast cancer and high Ki-67 expression.

Is Beta-Blocker Use Beneficial in Breast Cancer? A Meta-Analysis.

OBJECTIVE: Preclinical studies have proved that beta-blocking agents inhibit several pathways for breast cancer progression and metastasis. We aimed to evaluate the association between beta-blocker use and prognosis of breast cancer. METHODS: A systematic search for studies from MEDLINE and EMBASE (inception to March 2014) was performed using the keywords "breast cancer" and "beta-blocker." In 2 groups of breast cancer patients (beta-blocker users and non-beta-blocker users), overall deaths (ODs), cancer-specific deaths (CSDs), and recurrences were compared. RESULTS: Six studies including 18,118 patients were eligible for this analysis. Two studies with 3,139 patients were included in the analysis of ODs. The random-effects model showed no significant difference in ODs between beta-blocker users and non-beta-blocker users (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.50-1.52, p = 0.49). Four studies with 13,782 patients were included in the measurement of CSDs. The difference in CSDs between beta-blocker users and non-beta-blocker users was not significant using the fixed-effect model (OR 0.93, 95% CI 0.82-1.06, p = 0.29). Three studies with 3,923 patients were included in the calculation of recurrences. Overall, beta-blockers did not affect the incidence of recurrence (OR 0.70, 95% CI 0.25-1.95, p = 0.49). CONCLUSION: Beta-blockers were not beneficial regarding ODs, CSDs, or recurrences. Further studies are needed to evaluate the associations between the effects of beta-blockers and subtypes of breast cancer.

Self-assembled polymeric micelles based on hyaluronic acid-g-poly(D,L-lactide-co-glycolide) copolymer for tumor targeting.

Graft copolymer composed hyaluronic acid (HA) and poly(D,L-lactide-co-glycolide) (PLGA) (HAgLG) was synthesized for antitumor targeting via CD44 receptor of tumor cells. The carboxylic end of PLGA was conjugated with hexamethylenediamine (HMDA) to have amine end group in the end of chain (PLGA-amine). PLGA-amine was coupled with carboxylic acid of HA. Self-assembled polymeric micelles of HAgLG have spherical morphologies and their sizes were around 50-200 nm. Doxorubicin (DOX)-incorporated polymeric micelles were prepared by dialysis procedure. DOX was released over 4 days and its release rate was accelerated by the tumoric enzyme hyaluronidase. To assess targetability of polymeric micelles, CD44-positive HepG2 cells were employed treated with fluorescein isothiocyanate (FITC)-labeled polymeric micelles. HepG2 cells strongly expressed green fluorescence at the cell membrane and cytosol. However, internalization of polymeric micelles were significantly decreased when free HA was pretreated to block the CD44 receptor. Furthermore, the CD44-specific anticancer activity of HAgLG polymeric micelles was confirmed using CD44-negative CT26 cells and CD44-positive HepG2 cells. These results indicated that polymeric micelles of HaLG polymeric micelles have targetability against CD44 receptor of tumor cells. We suggest HAgLG polymeric micelles as a promising candidate for specific drug targeting.

Changing trends in the management of ductal carcinoma in situ in Republic of Korea: a comprehensive analysis using Health Insurance Review and Assessment data [2009-2020].

Background: Increasing rates of diagnosis of ductal carcinoma in situ (DCIS), given the widespread use of mammography, is a global trend. Various attempts have been made in the selection of surgical methods and application of radiation therapy (RT), and the prevalence of infectious diseases has also affected these attempts. This study aimed to investigate evolving treatment patterns and trends in the management of DCIS in South Korea. Methods: We conducted a comprehensive search of the Korean Health Insurance Review and Assessment Service-National Patient Sample (HIRA-NPS) database and selected patients who underwent breast surgery following a DCIS diagnosis between 2009 and 2020. Based on this sample, the analyses were weighted according to the Korean population. We examined annual variations in mastectomy types, reconstructive procedures, and RT utilization from a multidisciplinary perspective. Results: In our weighted sample, 43,780 patients with DCIS underwent surgery, with a consistent annual increase of 10%. The proportion of lumpectomy procedures increased from 56.7% to 65.4%, showing a greater growth rate than that of total mastectomies (TMs). Following the availability of reconstruction data in 2015, shifts have emerged toward a preference for implant-based autologous tissue reconstruction. As we transitioned to the latter part of our study, the trend was marked by the increasing adoption of hypofractionated RT and omission of RT. Of the patients who underwent lumpectomy in 2020, 25.6% adopted hypofractionated RT and 53.8% omitted RT. This transformation was particularly evident among older patients, individuals treated in metropolitan areas, and those treated in small-sized healthcare facilities. Conclusions: Our study sheds light on the changing landscape of DCIS treatment in South Korea incorporating perspectives from surgeons, plastic surgeons, and radiation oncologists. We observed an increase in the rates of lumpectomy and implant-based reconstruction. Adoption of hypofractionated RT and omission of RT showed increasing trends.

3D Superclusters with Hybrid Bioinks for Early Detection in Breast Cancer.

The surface-enhanced Raman scattering (SERS) technique has garnered significant interest due to its ultrahigh sensitivity, making it suitable for addressing the growing demand for disease diagnosis. In addition to its sensitivity and uniformity, an ideal SERS platform should possess characteristics such as simplicity in manufacturing and low analyte consumption, enabling practical applications in complex diagnoses including cancer. Furthermore, the integration of machine learning algorithms with SERS can enhance the practical usability of sensing devices by effectively classifying the subtle vibrational fingerprints produced by molecules such as those found in human blood. In this study, we demonstrate an approach for early detection of breast cancer using a bottom-up strategy to construct a flexible and simple three-dimensional (3D) plasmonic cluster SERS platform integrated with a deep learning algorithm. With these advantages of the 3D plasmonic cluster, we demonstrate that the 3D plasmonic cluster (3D-PC) exhibits a significantly enhanced Raman intensity through detection limit down to 10-6 M (femtomole-(10-17 mol)) for p-nitrophenol (PNP) molecules. Afterward, the plasma of cancer subjects and healthy subjects was used to fabricate the bioink to build 3D-PC structures. The collected SERS successfully classified into two clusters of cancer subjects and healthy subjects with high accuracy of up to 93%. These results highlight the potential of the 3D plasmonic cluster SERS platform for early breast cancer detection and open promising avenues for future research in this field.

Is bone mineral density a prognostic factor in postmenopausal women with luminal A breast cancer?

PURPOSE: Several studies are concerned about the association between bone mineral density (BMD) and the risk of breast cancer in postmenopausal women, but it is controversial. Therefore, we evaluated whether BMD might be a risk factor for recurrences, or metastases in menopausal luminal A breast cancer patients. METHODS: In this retrospective study, data of 348 patients with luminal A breast cancer who received treatment at Pusan National University Yangsan Hospital between 2012 and 2016 were analyzed. Patients were divided into two groups: normal BMD and low BMD including osteopenia or osteoporosis in preoperative examination. Patients were also divided into three groups according to BMD changes: no change in BMD; improvement in BMD, and deterioration in BMD. Events were defined as recurrence, occurrence of contralateral breast cancer, and metastasis to any other organ. RESULTS: Preoperative examination revealed normal BMD in 129 of 348 patients and low BMD in 219 patients. During a median follow-up period of 78 months, only 14 patients (4.0%) experienced recurrences, distant metastases, or occurrences of contralateral breast cancer. Five-year disease-free survival rate was 98.2% for 219 patients with low BMD and 95.0% for 129 patients with normal BMD (P=0.33). Disease-free survival at 5 years was 97.0% for the no change in the BMD group, 94.6% for the BMD improvement group, and 98.4% for the BMD deterioration group (P=0.79). CONCLUSION: In this study, BMD had no statistically significant associations on recurrences, metastases, or incidences of contralateral breast cancer in postmenopausal patients with luminal A breast cancer.

A retrospective study of factors affecting contralateral central-neck lymph node metastasis in unilateral papillary thyroid carcinoma.

BACKGROUND: In 30-40% of papillary thyroid cancer patients, central neck lymph node metastasis occurs. As a result, prophylactic central neck lymph node dissection is performed. The extent of lymph node dissection and prophylactic central neck lymph node dissection is still debatable. The incidence of central neck lymph node metastasis and related factors were investigated in this study, and also the necessity of both central neck lymph node dissections. METHODS: Between December 2017 and December 2019, 482 patients had thyroidectomy at Pusan National University Yangsan Hospital. A retrospective study of 186 patients who had a thyroidectomy with bilateral central neck lymph node dissection for unilateral thyroid carcinoma was done. RESULTS: Ipsilateral and contralateral central neck lymph node metastasis were identified in 40.9% (76/186) and 19.3% (36/186), respectively. Male (p < 0.001), tumor size >1 cm (p = 0.047), extrathyroidal extension (p = 0.002), central neck lymph node metastases >5 (p < 0.001), lateral neck lymph node metastasis (p = 0.012), and ipsilateral central neck lymph node metastasis (p < 0.001) were associated with the contralateral central neck lymph node metastasis in univariate analysis. In a multivariate analysis, extrathyroidal extension (OR, 3.664), more than 5 central neck lymph node metastases (OR, 29.667), ipsilateral central neck lymph node metastasis (OR, 3.911), and male (OR, 5.890) were related to contralateral central neck lymph node metastasis. CONCLUSION: Male, extrathyroidal extension, and ipsilateral central neck lymph node metastasis may be considered for contralateral prophylactic central neck lymph node dissection. In the future, it is thought that more research on the recurrence rate will be required.

Oncologic outcome of breast reconstruction after mastectomy in breast cancer: a systematic review and meta-analysis.

Background: We conducted a comprehensive systematic review of the literature and meta-analysis of the oncologic outcomes of breast reconstruction (BR) after mastectomy and mastectomy only. This study aimed to analyze the impact of BR on the prognosis of patients with breast cancer. Methods: A systematic search of MEDLINE and EMBASE databases was performed using the following keywords: breast cancer, mastectomy, and BR. Inclusion criteria were studies reporting the survival data of patients after mastectomy only and mastectomy with BR. Event-free survival (EFS), breast cancer-specific survival (BCSS), and overall survival (OS) were considered the indicators of oncological outcomes. As all the included studies were non-randomized trials, we used the Newcastle-Ottawa Scale (NOS) for risk of bias assessment. The effect of BR on survival was measured using the effect size of the hazard ratio (HR). Data from each study were analyzed using the Review Manager. Results: Fifteen studies with 20,948 cases of BR and 63,358 cases of mastectomy were included. The pooled HRs for EFS and BCSS were 1.07 [95% confidence interval (CI): 0.78-1.47, P=0.65] and 0.84 (95% CI: 0.64-1.11, P=0.22), respectively. The patients who underwent BR after mastectomy had similar EFS and BCSS scores. Furthermore, patients who received BR had better OS (HR =0.73; 95% CI: 0.61-0.88, P=0.001) than those who underwent mastectomy only. Conclusions: The data showed that BR after mastectomy had similar EFS and BCSS and better OS than mastectomy alone. Our meta-analysis suggests that BR is a practicable and safe treatment option for patients with breast cancer.

Oncologic efficacy of gonadotropin-releasing hormone agonist in hormone receptor-positive very young breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Breast cancer in young women has been shown to have an aggressive behavior and poor prognosis. AIM: To evaluate the outcomes of young hormone receptor (HR)-positive patients with breast cancer treated with neoadjuvant chemotherapy (NAC), and the oncologic efficacy of gonadotropin-releasing hormone (GnRH) agonists. METHODS: This retrospective study involved a prospectively enrolled cohort. We included patients diagnosed with invasive breast cancer who were treated with NAC followed by curative surgery at the Samsung Medical Center and Samsung Changwon Hospital between January 2006 and December 2017. Among patients with HR-positive and human epidermal grow factor 2 (HER2)-negative breast cancer, we analyzed the characteristics and oncology outcomes between the patients equal to or younger than 35 years and the patients older than 35 years. RESULTS: Among 431 patients with NAC and HR-positive/HER2-negative breast cancer, 78 were 35 years old or younger, and 353 patients were older than 35 years. The median follow-up was 71.0 months. There was no statistically significant difference in disease free survival (DFS, P = 0.565) and overall survival (P = 0.820) between the patients equal to or younger than 35 years and the patients older than 35 years. The two groups differed in that the GnRH agonist was used more frequently in the group of patients equal to or younger than 35 years than in the other group (52.4% vs 11.2%, P < 0.001). Interestingly, for the DFS according to the GnRH agonist in the group of patients equal to or younger than 35 years, patients treated with the GnRH agonist had better DFS (P = 0.037). CONCLUSION: Administration of GnRH agonists might improve the DFS rate of HR-positive/HER2-negative breast cancer in the equal to or younger than 35 years group of patients with NAC.

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.

Male metaplastic breast cancer with poor prognosis: A case report.

BACKGROUND: Metaplastic breast cancer (MBC) is a rare subtype of breast cancer. They constitute less than 1% of breast cancer cases and are much rarer in males. There are few reports of MBC because of its rarity. MBC, an aggressive type of cancer, is refractory to common treatment modalities of breast cancer and has a poor prognosis. CASE SUMMARY: We report a case of MBC in a 78-year-old man. He visited our clinic with a palpable mass on the left breast with no masses in the axillary areas. He had previously undergone robot-assisted laparoscopic radical prostatectomy for prostate cancer, but there was no family history of malignancy. The breast mass was visible on ultrasonography, mammography, and magnetic resonance imaging, and chest computed tomography revealed a lung mass in the posterior basal segment of the right lower lobe. The patient was diagnosed with metaplastic carcinoma on core needle biopsy with lung metastasis. Total mastectomy with sentinel lymph node biopsy and video-assisted segmentectomy of the right lung was performed. However, multiple metastases appeared 3 mo after surgery in the brain, chest, and abdomen, and the patient died 5 mo after the initial diagnosis. CONCLUSION: MBC is an aggressive and extremely rare breast cancer type. Further case reports are needed to determine the optimal treatment.

Comparison of mutational profiles between triple-negative and hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancers in T2N0-1M0 stage: Implications of TP53 and PIK3CA mutations in Korean early-stage breast cancers.

Triple-negative breast cancer (TNBC) has higher loco-regional recurrence and visceral metastasis compared to other breast cancer subtypes; however, little is known about the molecular pathogenesis of TNBC. Therefore, we compared the mutation profiles of early TNBC with those of hormone receptor-positive (HR+) and/or human epidermal growth factor receptor 2-negative (HER2-) breast cancer using a customized next-generation sequencing capture panel. DNA was obtained from the primary tumor tissues of 34 patients diagnosed with pT2N0-1M0 HR+/HER2- breast cancer or TNBC. Using SureSelectXT kit (Agilent), next-generation sequencing for 48 breast cancer-associated genes was performed on HiSeq platform (Illumina) with germline confirmation. Also, plasma was collected from 24 patients before surgery, cell-free nucleic acids were extracted, and performed therascreen PIK3CA RGQ PCR assay. Significant mutations were found in TP53, PIK3CA, AR, BRCA1, PTEN, BRCA2, BRIP2, KIT, MET, AKT1, ALK, BARD1, BRAF, CD274, ERBB2, FGFR1, IDH2, NOTCH1, RET, and STK11 (in descending order of occurrence). TP53 mutations were identified in the TNBC group more frequently than in the HR+/HER2- group (P = 0.003). The presence of TP53 mutations was associated with a higher tumor grade (P = 0.008), p53 positivity (P < 0.0001), and a higher Ki-67 index (P = 0.004). PIK3CA was the most frequently mutated gene in HR+/HER2- breast cancer (8/22, 36.4%), but not in TNBC (1/12, 8.3%). The TP53 mutation is associated with higher tumor grade and Ki-67 expression in both groups, and with larger tumor size in TNBC, but not in HR+/HER2- breast cancer. In the foundation of TP53 mutation, concomitant mutation numbers are proportional to tumor size, reflecting clonal progression.

A comparative study of the clinical characteristics and outcomes of HR-positive HER2-negative breast cancer patients over and under 65 years old.

Purpose: The purpose of this study was to compare the clinical characteristics and outcomes of hormone receptor-positive (HR+) human epidermal growth factor 2-negative (HER2-) breast cancer among elderly patients (over 65 years old) and younger patients. Methods: This was a retrospective cohort study of 328 patients who were treated for breast cancer at Pusan National University Yangsan Hospital between January 2009 and December 2014. Tumor characteristics, surgical methods, and survival outcomes were compared between the two age groups (<65 and ≥65 years old). Kaplan-Meier curves for disease-free survival (DFS) and overall survival (OS) were also constructed according to the age groups. Results: Among the 328 patients with HR+ HER2- breast cancer, 184 (56.1%) were <65 years old and 144 (43.9%) were ≥65 years old. Breast cancer stages were similar between the two age groups, but the older patients were treated less often with chemotherapy (81% vs. 66%, P=0.002). During the follow-up period, 17 deaths and 36 cases of recurrence or metastasis were reported. There was no difference in DFS between the two groups (P=0.840); however, the OS of the older age group was significantly lower than that of the younger age group (P=0.015). Conclusion: This study suggested that HR+ HER2- breast cancer patients belonging to the two age groups had no significant difference in DFS. However, older age is an independent factor affecting OS rate. Therefore, even if patients are old, but their physical condition is satisfactory, standard and active treatment may be necessary, similar to that given to younger patients.