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A series of successes in RNA interference (RNAi) therapies for liver diseases using lipid nanoparticles and N-acetylgalactosamine have heralded a current era of RNA therapeutics. However, alternative delivery strategies are required to take RNAi out of the comfort zone of hepatocytes. Here we report SIRPα IgV/anti-CD47 siRNA (vS-siCD47) conjugates that selectively and persistently disrupt the antiphagocytic CD47/SIRPα axis in solid tumors. Conjugation of the SIRPα IgV domain protein to siRNAs enables tumor dash through CD47-mediated erythrocyte piggyback, primarily blocking the physical interaction between CD47 on cancer cells and SIRPα on phagocytes. After internalization of the vS-siCD47 conjugates within cancer cells, the detached free-standing anti-CD47 siRNAs subsequently attack CD47 through the RNAi mechanism. The dual-action approach of the vS-siCD47 conjugate effectively overcomes the "don't eat me" barrier and stimulates phagocyte-mediated tumor destruction, demonstrating a highly selective and potent CD47-blocking immunotherapy. This delivery strategy, employing IgV domain protein-siRNA conjugates with a dual mode of target suppression, holds promise for expanding RNAi applications beyond hepatocytes and advancing RNAi-based cancer immunotherapies for solid tumors.
Subject(s)
CD47 Antigen , RNA, Small Interfering , Receptors, Immunologic , CD47 Antigen/metabolism , CD47 Antigen/chemistry , Humans , RNA, Small Interfering/chemistry , Animals , Mice , Receptors, Immunologic/metabolism , Neoplasms/therapy , Neoplasms/genetics , Neoplasms/pathology , Antigens, Differentiation , Cell Line, TumorABSTRACT
PURPOSE: This research aimed to clarify the impact of residual ductal carcinoma in situ(DCIS) in surgical specimens obtained after neoadjuvant chemotherapy(NAC) for breast cancer on the associated prognosis outcomes. METHODS: This retrospective study was performed on a cohort of 1,009 patients who achieved pCR following NAC for breast cancer and underwent subsequent breast surgery at a single institution between January 2008 and December 2019. Overall survival, local recurrence-free survival, distant metastasis-free survival, and disease-free survival of the residual and non-residual DCIS groups were the outcomes compared, with further subgroup analysis performed according to hormone receptor status. RESULTS: 260 individuals (25.8%) presented with residual DCIS. Based on a median follow-up of 54.0 months, no significant differences in outcomes were observed between the two groups. Patients with residual DCIS and hormone receptor-negative (HR-) breast cancer demonstrated a significant decrease in distant metastasis-free survival (p = 0.030) compared to those without residual DCIS. In the HR + cohort, no significant difference was observed between the two groups. Multivariate analysis of the HR- cohort demonstrated a significant association between residual DCIS and an elevated risk for distant recurrence (hazard ratio = 2.3, 95% confidence interval = 1.01-5.20, p = 0.047). CONCLUSIONS: Residual DCIS following NAC may impact breast cancer outcomes, particularly with respect to the occurrence of distant metastasis in HR- patients. Therefore, clinicians must vigilantly monitor patients with residual DCIS after NAC, and further research is needed to expand our understanding of the clinical implications of residual DCIS.
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Purpose: Tumescent in nipple-sparing mastectomy (NSM) has been reported to increase the risk of necrosis by impairing blood flow to the skin flap and nipple-areolar complex. At our institution, we introduced a tumescent-free robotic NSM using the da Vinci single-port system (Intuitive Surgical, Inc.). Methods: We conducted a retrospective analysis of patients who underwent tumescent-free robotic NSM between October 2020 and March 2023 at Asan Medical Center (Seoul, Korea). Clinicopathological characteristics, adverse events, and operative time were evaluated. Results: During the study period, 118 patients underwent tumescent-free robotic NSM. Thirty-one patients (26.3%) experienced an adverse event. Five patients (4.2%) were classified as grade III based on the Clavien-Dindo classification and required surgery. The mean total operative time was 467 minutes for autologous tissue reconstruction (n = 49) and 252 minutes for implants (n = 69). No correlation was found between the cumulative number of surgical cases and the breast operative time (P = 0.30, 0.52, 0.59 for surgeons A, B, C) for the 3 surgeons. However, a significant linear relationship (P < 0.001) was observed, with the operative time increasing by 13 minutes for every 100-g increase in specimen weight. Conclusion: Tumescent-free robotic NSM is a safe procedure with a feasible operative time and few adverse events.
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BACKGROUND: Current guidelines recommend against the use of routine imaging tests to detect distant metastasis in asymptomatic breast cancer patients. However, recent advancements in effective therapeutics and diagnostic accuracy have raised the need to reassess the clinical efficacy of intensive metastasis surveillance. We report the results of a multicenter retrospective study to investigate the association between intensive imaging studies and survival outcomes. PATIENTS AND METHODS: We retrospectively reviewed the data of 4130 patients who underwent surgery from 11 hospitals in Korea between January 2010 and December 2011. Patients were divided into two groups on the basis of the intensity of metastasis imaging studies during their disease-free period. The types and intervals of the imaging studies were based on each physician's decisions. RESULTS: High-intensive screening showed a shorter distant metastasis-free survival [p < 0.001, hazard ratio (HR) 1.62; 95% confidence interval (CI) 1.29-2.04], especially for patients in whom bone or lung was the first site of metastasis. With a median follow-up period of 110.0 months, the 5-year breast cancer-specific survival (BCSS) rate was 96.5%. The high-intensity screening group showed significantly poorer BCSS compared with the low-intensity screening group (p < 0.001, HR 3.13; 95% CI 2.32-4.21). However, both multivariable analysis and propensity score matching analysis showed no significant association between the screening intensity and BCSS. CONCLUSIONS: Frequent imaging studies to detect distant metastasis were associated with earlier detection of distant metastasis, especially for lung and bone metastasis. However, intensive surveillance showed no apparent association with BCSS despite the use of currently available treatments.
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Rationale: Growing evidence has demonstrated that miRNA-21 (miR-21) upregulation is closely associated with tumor pathogenesis. However, the mechanisms by which miR-21 inhibition modulates the immunosuppressive tumor microenvironment (TME) and improves tumor sensitivity to immune checkpoint blockade therapies remain largely unexplored. In this study, we demonstrate the precise delivery of anti-miR-21 using a PD-L1-targeting peptide conjugate (P21) to the PD-L1high TME. Methods: Investigating miR-21 inhibition mechanisms involved conducting quantitative real-time PCR, western blot, flow cytometry, and confocal microscopy analyses. The antitumor efficacy and immune profile of P21 monotherapy, or combined with anti-PD-L1 immune checkpoint inhibitors, were assessed in mouse models bearing CT26.CL25 tumors and 4T1 breast cancer. Results Inhibition of oncogenic miR-21 in cancer cells by P21 efficiently activates tumor suppressor genes, inducing autophagy and endoplasmic reticulum stress. Subsequent cell-death-associated immune activation (immunogenic cell death) is initiated via the release of damage-associated molecular patterns. The in vivo results also illustrated that the immunogenic cell death triggered by P21 could effectively sensitize the immunosuppressive TME. That is, P21 enhances CD8+ T cell infiltration in tumor tissues by conferring immunogenicity to dying cancer cells and promoting dendritic cell maturation. Meanwhile, combining P21 with an anti-PD-L1 immune checkpoint inhibitor elicits a highly potent antitumor effect in a CT26.CL25 tumor-bearing mouse model and 4T1 metastatic tumor model. Conclusions: Collectively, we have clarified a miR-21-related immunogenic cell death mechanism through the precise delivery of anti-miR-21 to the PD-L1high TME. These findings highlight the potential of miR-21 as a target for immunotherapeutic interventions.
Subject(s)
B7-H1 Antigen , Immunogenic Cell Death , Immunotherapy , MicroRNAs , Tumor Microenvironment , MicroRNAs/genetics , MicroRNAs/metabolism , Animals , Mice , B7-H1 Antigen/metabolism , B7-H1 Antigen/antagonists & inhibitors , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Immunogenic Cell Death/drug effects , Cell Line, Tumor , Immunotherapy/methods , Female , Mice, Inbred BALB C , Humans , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Autophagy/drug effects , Breast Neoplasms/immunology , Breast Neoplasms/therapy , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/geneticsABSTRACT
Introduction: Male breast cancer (MBC) is a rare condition, and recent research has underscored notable distinctions between MBC and breast cancer in women. This study aimed to assess and contrast the long-term survival outcomes and disease patterns of MBC patients with those of their female counterparts. Methods: We analyzed data from 113,845 patients diagnosed with breast cancer who had undergone curative surgery from the Korean Breast Cancer Registry (KBCR) between January 1990 and August 2014 in Seoul, Korea. The five-year overall survival was analyzed according to clinicopathological characteristics. Results: Among 113,845 patients with breast cancer, 473 MBC cases were included. The median duration of follow-up was 72 months. The median age at diagnosis was 60 and 48 years for MBC and female breast cancer, respectively. Most male patients (92.6%) underwent total mastectomy, while 50.4% of female patients underwent breast-conserving surgery. Among MBC, 63.2% received chemotherapy, and 83.9% of hormone receptor-positive male patients received endocrine therapy. In survival analysis, MBC demonstrated distinct 5-year overall survival patterns compared with female breast cancer, according to age at diagnosis. In women with breast cancer, the younger age group (≤40 years) demonstrated worse 5-year overall survival than did the older age group (>40 years) (91.3% vs 92.7%, p <0.05). While in MBC, the younger age group (≤40 years) demonstrated better 5-year overall survival than did the older age group (>40 years) (97.4% vs 86.4%, p <0.05). Discussion: In conclusion within this extensive cohort, we have revealed unique survival patterns in MBC that diverge from those observed in women with breast cancer. This study enhances our comprehension of MBC prognosis and can potentially shed light on unresolved questions, paving the way for future research in the realm of MBC.
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Animal models of retinal degeneration are critical for understanding disease and testing potential therapies. Inducing degeneration commonly involves the administration of chemicals that kill photoreceptors by disrupting metabolic pathways, signaling pathways, or protein synthesis. While chemically induced degeneration has been demonstrated in a variety of animals (mice, rats, rabbits, felines, 13-lined ground squirrels (13-LGS), pigs, chicks), few studies have used noninvasive high-resolution retinal imaging to monitor the in vivo cellular effects. Here, we used longitudinal scanning light ophthalmoscopy (SLO), optical coherence tomography, and adaptive optics SLO imaging in the euthermic, cone-dominant 13-LGS (46 animals, 52 eyes) to examine retinal structure following intravitreal injections of chemicals, which were previously shown to induce photoreceptor degeneration, throughout the active season of 2019 and 2020. We found that iodoacetic acid induced severe pan-retinal damage in all but one eye, which received the lowest concentration. While sodium nitroprusside successfully induced degeneration of the outer retinal layers, the results were variable, and damage was also observed in 50% of contralateral control eyes. Adenosine triphosphate and tunicamycin induced outer retinal specific damage with varying results, while eyes injected with thapsigargin did not show signs of degeneration. Given the variability of damage we observed, follow-up studies examining the possible physiological origins of this variability are critical. These additional studies should further advance the utility of chemically induced photoreceptor degeneration models in the cone-dominant 13-LGS.
Subject(s)
Retinal Cone Photoreceptor Cells , Retinal Degeneration , Sciuridae , Tomography, Optical Coherence , Animals , Retinal Degeneration/chemically induced , Retinal Degeneration/pathology , Retinal Cone Photoreceptor Cells/pathology , Retinal Cone Photoreceptor Cells/drug effects , Disease Models, Animal , Intravitreal Injections , Ophthalmoscopy , Nitroprusside/pharmacology , Female , MaleABSTRACT
PURPOSE: To select patients who would benefit most from sentinel lymph node biopsy (SLNB) by investigating the characteristics and risk factors of axillary lymph node metastasis (ALNM) in microinvasive breast cancer (MIBC). METHODS: This retrospective study included 1688 patients with MIBC who underwent breast surgery with axillary staging at the Asan Medical Center from 1995 to 2020. RESULTS: Most patients underwent SLNB alone (83.5%). Seventy (4.1%) patients were node-positive, and the majority had positive lymph nodes < 10 mm, with micro-metastases occurring frequently (n = 37; 55%). Node-positive patients underwent total mastectomy and axillary lymph node dissection (ALND) more than breast-conserving surgery (BCS) and SLNB compared with node-negative patients (p < 0.001). In the multivariate analysis, independent predictors of ALNM included young age [odds ratio (OR) 0.959; 95% confidence interval (CI) 0.927-0.993; p = 0.019], ALND (OR 11.486; 95% CI 5.767-22.877; p < 0.001), number of lymph nodes harvested (≥ 5) (OR 3.184; 95% CI 1.555-6.522; p < 0.001), lymphovascular invasion (OR 6.831; 95% CI 2.386-19.557; p < 0.001), presence of multiple microinvasion foci (OR 2.771; 95% CI 1.329-5.779; p = 0.007), prominent lymph nodes in preoperative imaging (OR 2.675; 95% CI 1.362-5.253; p = 0.004), and hormone receptor positivity (OR 2.491; 95% CI 1.230-5.046; p = 0.011). CONCLUSION: Low ALNM rate (4.1%) suggests that routine SLNB for patients with MIBC is unnecessary but can be valuable for patients with specific risk factors. Ongoing trials for omitting SLNB in early breast cancer, and further subanalyses focusing on rare populations with MIBC are necessary.
Subject(s)
Axilla , Breast Neoplasms , Lymph Nodes , Lymphatic Metastasis , Sentinel Lymph Node Biopsy , Humans , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Female , Middle Aged , Lymphatic Metastasis/pathology , Retrospective Studies , Risk Factors , Adult , Aged , Lymph Nodes/pathology , Lymph Nodes/surgery , Lymph Node Excision , Neoplasm Invasiveness , Mastectomy , Aged, 80 and overABSTRACT
PURPOSE: To compare the oncological safety of nipple-sparing breast-conserving surgery (BCS) versus central lumpectomy for centrally located breast cancer (CLBC). METHODS: Patients who underwent BCS for CLBC at Asan Medical Center from 2007 to 2018 were reviewed retrospectively. The oncological outcomes of nipple-sparing BCS (NS-BCS) and central lumpectomy were compared using univariate and multivariate Cox regression analyses and compared again after 1:1 propensity score matching (PSM). RESULTS: The study included 306 patients who underwent NS-BCS and 106 patients who underwent central lumpectomy (median follow-up: 111 months). On multivariate analysis, central lumpectomy had a lower risk of local recurrence compared to NS-BCS, albeit without statistical significance (HR 0.14, 95% CI 0.02-1.24; p = 0.077). There was no significant difference in the risk of death (HR 0.14, 95% CI 0.01-1.68, p = 0.12). After PSM, each group had 106 patients. The 5-year and 10-year local recurrence-free survival rates were 94.2% and 92.9% for NS-BCS, and 99.1% and 99.1% for central lumpectomy, respectively (p = 0.031). There were no significant differences in overall survival, regional recurrence-free survival, or distant recurrence-free survival. Fifteen patients (4.9%) who underwent NS-BCS had ipsilateral breast tumor recurrence (IBTR), of which 40% were in the nipple-areolar complex and previous surgical sites. One patient (0.9%) who underwent central lumpectomy experienced an IBTR in a different quadrant. CONCLUSION: NS-BCS showed more local recurrence than central lumpectomy. When deciding whether to spare the nipple during BCS in CLBC, patients should be sufficiently informed about the risk of IBTR.
Subject(s)
Breast Neoplasms , Mastectomy, Segmental , Neoplasm Recurrence, Local , Nipples , Propensity Score , Humans , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Breast Neoplasms/mortality , Female , Middle Aged , Nipples/surgery , Mastectomy, Segmental/methods , Retrospective Studies , Adult , Aged , Treatment Outcome , Organ Sparing Treatments/methods , Follow-Up StudiesABSTRACT
OBJECTIVE: This study aimed to determine whether sentinel lymph node biopsy (SLNB) alone could afford oncological outcomes comparable with axillary lymph node dissection (ALND) in patients with early breast cancer without palpable lymphadenopathy who underwent total mastectomy (TM) and were SLN-positive. METHODS: This study analyzed clinical data of 6747 patients with breast cancer who underwent TM between 2014 and 2018 in two tertiary hospitals in Korea. Overall, 643 clinical stage T1-3 N0 patients who did not receive neoadjuvant therapy and had one to two metastatic SLNs at the time of surgery were included. Propensity score matching was performed between the SLNB alone and ALND groups, adjusting for clinical T stage and number of metastatic SLNs. In total, 237 patients were allocated to each group. RESULTS: Mean number of metastatic SLNs was 1.2 for the SLNB group and 1.6 for the ALND group. With a median follow-up of 65.0 months, 5 year disease-free survival was 90.8% for the SLNB group and 93.9% for the ALND group (hazard ratio [HR] 1.35, 95% confidence interval [CI] 0.70-2.58; p = 0.36). 5 year ipsilateral locoregional recurrence-free survival (LRRFS) was not significantly different between the two groups (95.1% and 98.3% for the SLNB and ALND groups, respectively) [HR 1.86, 95% CI 0.69-5.04; p = 0.21]. In the SLNB group, patients who received radiation therapy (RT) showed superior 5 year LRRFS than patients who did not receive RT (100% vs. 92.9%; p = 0.02). CONCLUSION: Collectively, our findings suggest that SLNB could afford comparable outcomes to ALND in patients with early breast cancer and one to two metastatic SLNs who underwent TM. Importantly, RT could decrease locoregional recurrence in patients who underwent SLNB alone.
Subject(s)
Breast Neoplasms , Lymphadenopathy , Sentinel Lymph Node , Humans , Female , Breast Neoplasms/pathology , Mastectomy, Simple , Mastectomy , Neoplasm Recurrence, Local/pathology , Lymph Node Excision , Sentinel Lymph Node Biopsy , Lymph Nodes/pathology , Lymphadenopathy/surgery , Axilla/pathology , Sentinel Lymph Node/surgery , Sentinel Lymph Node/pathologyABSTRACT
This study investigated the effects of subcritical water (SW) temperatures on the hydrolysis pattern and characteristics of hydrolysates prepared with strong rice (SR) and floury rice (FR). The characteristics of the hydrolysates were generally dependent on the rice cultivar in the SW temperature range of 150-250 °C, while the cultivar dependence was diminished at temperatures greater than 300 °C. Based on brix and reducing sugar content, an optimal production of rice hydrolysates was obtained at a SW temperature range of 200-250 °C. However, thermal conversion of sugar into acids, 5-hydroxymethylfurfural (HMF) and furfural was manifested at 250 °C. The rice hydrolysates prepared at 250 â¼ 300 °C had the highest antioxidant activity with strong umami intensity, but they suppressed the growth of prebiotics. Therefore, the present study demonstrated that controlling the SW temperature is crucial to improve rice hydrolysis efficiency and to regulate the physiological activity of the hydrolysates.
Subject(s)
Oryza , Hydrolysis , Temperature , Water , Carbohydrates , Antioxidants , Flour , SugarsABSTRACT
PURPOSE: This study aimed to investigate the frequency of BRCA testing and related factors among young breast cancer patients (age < 40 years) in South Korea. MATERIALS AND METHODS: We conducted a nationwide retrospective cohort study using data from the Health Insurance Review and Assessment claims. Newly diagnosed breast cancer patients younger than 40 were included. Annual BRCA testing ratios (number of BRCA test recipients/the number of patients undergoing breast cancer surgery in each year) were analyzed by region and health care delivery system. We investigated the location of breast cancer diagnosis and BRCA testing. RESULTS: From January 2010 to December 2020, there were 25,665 newly diagnosed young breast cancer patients, of whom 12,186 (47.5%) underwent BRCA testing. The BRCA testing ratios increased gradually from 0.084 (154/1,842) in 2010 to 0.961 (1,975/2,055) in 2020. Medical aid (vs. health insurance) and undergoing surgery in metropolitan cities or others (vs. Seoul), general hospitals, and clinics (vs. tertiary hospitals) were associated with a lower likelihood of BRCA testing. While 97.8% of the patients diagnosed in Seoul underwent BRCA testing in Seoul, 22.9% and 29.2% of patients who were diagnosed in metropolitan areas and other regions moved to Seoul and underwent BRCA testing, respectively. CONCLUSION: The frequency of BRCA testing has increased over time in South Korea, with Seoul showing a particularly high rate of testing. About one-quarter of patients diagnosed with breast cancer outside of Seoul moved to Seoul and underwent BRCA testing.
Subject(s)
BRCA1 Protein , BRCA2 Protein , Breast Neoplasms , Genetic Testing , Humans , Female , Breast Neoplasms/genetics , Breast Neoplasms/epidemiology , Breast Neoplasms/diagnosis , Republic of Korea/epidemiology , Adult , Genetic Testing/statistics & numerical data , Genetic Testing/methods , Retrospective Studies , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Young Adult , Genetic Predisposition to DiseaseABSTRACT
Background: Pulmonary rehabilitation is well known to improve clinical symptoms (including dyspnea), quality of life, and exercise capacity in patients with chronic obstructive pulmonary disease (COPD). However, researchers have reported difficulties in practicing center-based pulmonary rehabilitation. Recently, mobile app-based pulmonary rehabilitation has become available in clinical practice. We investigated the clinical outcomes of mobile app-based pulmonary rehabilitation in patients with COPD. Objective: The objective of our study was to evaluate the clinical efficacy of mobile app-based pulmonary rehabilitation versus conventional center-based pulmonary rehabilitation for patients with COPD, using a systematic review and meta-analysis. Methods: A systematic search of the literature published between January 2007 and June 2023 was performed, using the PubMed, Embase, Cochrane, and CINAHL databases to identify relevant randomized controlled trials involving patients with COPD. Pulmonary rehabilitation programs needed to provide an exercise program on a smartphone app. Study outcomes, including exercise capacity, symptom scores, quality of life, and hospitalization, were evaluated. The meta-analysis evaluated mean differences in 6-minute walk test distances (6MWDs), COPD Assessment Test (CAT) scores, modified Medical Research Council (mMRC) dyspnea scale scores, St. George Respiratory Questionnaire (SGRQ) scores, and risk ratios for hospitalization resulting from disease exacerbation. Results: Of the 1173 screened studies, 10 were included in the systematic review and 9 were included in the meta-analysis. Further, 6 studies were multicenter studies. There were a total of 1050 participants, and most were aged ≥65 years. There were discrepancies in the baseline participant characteristics, smartphone apps, interventions, and study outcomes among the included studies. In the meta-analysis, 5 studies assessed 6MWDs (mean difference 9.52, 95% CI -3.05 to 22.08 m), 6 studies assessed CAT scores (mean difference -1.29, 95% CI -2.39 to -0.20), 3 studies assessed mMRC dyspnea scale scores (mean difference -0.08, 95% CI -0.29 to 0.13), 2 studies assessed SGRQ scores (mean difference -3.62, 95% CI -9.62 to 2.38), and 3 studies assessed hospitalization resulting from disease exacerbation (risk ratio 0.65, 95% CI 0.27-1.53). These clinical parameters generally favored mobile app-based pulmonary rehabilitation; however, a statistically significant difference was noted only for the CAT scores (P=.02). Conclusions: Despite some discrepancies in the baseline participant characteristics and interventions among studies, mobile app-based pulmonary rehabilitation resulted in favorable exercise capacity, symptom score, quality of life, and hospitalization outcomes when compared with conventional pulmonary rehabilitation. In the meta-analysis, the CAT scores of the mobile app-based pulmonary rehabilitation group were significantly lower than those of the control group (P=.02). In real-world practice, mobile app-based pulmonary rehabilitation can be a useful treatment option when conventional center-based pulmonary rehabilitation is not feasible.
Subject(s)
Mobile Applications , Pulmonary Disease, Chronic Obstructive , Humans , Quality of Life , Pulmonary Disease, Chronic Obstructive/therapy , Treatment Outcome , Disease Progression , Dyspnea/rehabilitationABSTRACT
PURPOSE: To estimate the diagnostic yield (DY) of abdominal staging CT for detecting breast cancer liver metastasis (BCLM) in patients with initially diagnosed breast cancer and to determine the indications for abdominal staging CT. METHODS: Patients with newly diagnosed breast cancer who underwent abdominal CT as an initial staging work-up between January 2019 and December 2020 were retrospectively analyzed. DY was calculated and analyzed according to patient age, type of treatments, histologic type, histologic grade, lymphovascular invasion, Ki-67 status, hormone receptor status, subtype, and the American Joint Committee on Cancer anatomical staging. RESULTS: A total of 2056 patients (mean age, 51 ± 11 years) were included. The DY of abdominal staging CT for detecting BCLM was 1.1 % (22 of 2056). DY was significantly higher in stage III than in stage I or II cancers (3.9 % [18 of 467] vs. 0 % [0 of 412] or 0.4 % [4 of 1158], respectively, p < .001), and in human epidermal growth factor receptor-2 (HER2)-enriched cancers than in luminal or triple negative cancers (2.9 % [16 of 560] vs. 0.4 % [4 of 1090] or 0.5 % [2 of 406], respectively, p < .001). CONCLUSIONS: The DY of abdominal staging CT for detecting BCLM was low among all patients with initially diagnosed breast cancer. However, although abdominal staging CT for detecting BCLM is probably unnecessary in all patients, it can be clinically useful in patients with stage III or human epidermal growth factor receptor-2-enriched breast cancers.
Subject(s)
Breast Neoplasms , Liver Neoplasms , Humans , Adult , Middle Aged , Female , Breast Neoplasms/metabolism , Neoplasm Staging , Retrospective Studies , Liver Neoplasms/pathology , Receptor, ErbB-2/metabolism , Tomography, X-Ray ComputedABSTRACT
The prognostic role of the recurrence score (RS) based on the 21-gene expression assay in premenopausal women is not well delineated, and we investigated the association of outcomes and the RS in premenopausal patients who had 21-gene expression assay at Asan Medical Center, Seoul, Korea, between June 2005 and July 2018. Invasive breast cancer-free survival (IBCFS) by STEEP version 2.0 was compared according to the RS and clinical risk factors. A total of 554 patients were included in our study and 116 patients (20.9%) had age <40 years, 238 patients (43.0%) had luminal B subtype (Ki67 ≥ 20%), and 83 patients (15.0%) had RS >25. All patients received adjuvant tamoxifen ± chemotherapy. Overall, patients with RS >25 showed trend toward worse IBCFS from multivariable analysis (adjusted HR 1.89 [95% CI: 0.95-3.73], P = .069). When comparing outcomes according to age and luminal subtypes, patients with luminal B subtype and age <40 years (n = 60) showed significantly worse outcomes compared to the others (luminal A or luminal B + age ≥40 years, n = 494; adjusted HR 2.95 [95% CI: 1.49-5.82], log-rank P < .001). Among patients with luminal B subtype and age <40 years, there was no significant association observed between IBCFS and the RS (log-rank P = .51). In conclusion, while RS >25 showed association with poor outcomes in premenopausal women, it may have less prognostic significance among those with luminal B subtype and age <40 years.
Subject(s)
Breast Neoplasms , Humans , Female , Adult , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/complications , Prognosis , Tamoxifen , Risk Factors , Gene Expression Profiling , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Receptors, Progesterone/genetics , Receptors, Progesterone/metabolism , Neoplasm Recurrence, Local/geneticsABSTRACT
PURPOSE: Sentinel lymph node biopsy (SLNB) has yet to be accepted as the standard staging procedure in node positive (cN1) breast cancer patients who had clinical complete response in the axilla (cN0) following neoadjuvant chemotherapy (NAC), due to the presumed high false negative rate associated with SLNB in such scenario. This study aimed to determine whether there is a significant difference in the axillary recurrence rate (ARR) and long-term survival in this group of patients, receiving SLNB alone versus axillary lymph node dissection (ALND). METHODS: A retrospective cohort of cN1 patients who were rendered cN0 by NAC from January 2014 to December 2018 were identified from the Asan Medical Center database. Patients' characteristics and outcomes were collected and analyzed. RESULTS: 902 cN1 patients treated with NAC and turned cN0 were identified. 477 (52.9%) patients achieved complete pathological response in the axilla (ypN0). At a median follow up of 65 months, ARR was 3.2% in the SLNB only group and 1.8% in the ALND group (p = 0.398). DFS and OS were significantly worse in patients with ALND as compared to patients with SLNB only (p = 0.011 and 0.047, respectively). We noted more patients in the ALND group had T3-4 tumor. In the subgroup analysis, we showed that in the T1-2 subgroup (n = 377), there was no statistically significant difference in DFS and OS (p = 0.242 and 0.671, respectively) between SLNB only and ALND group. CONCLUSION: Our findings suggest that cN1 patients who were converted to ypN0 following NAC may be safely treated with SLNB only.
Subject(s)
Breast Neoplasms , Sentinel Lymph Node , Humans , Female , Sentinel Lymph Node Biopsy/methods , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Neoadjuvant Therapy/methods , Retrospective Studies , Lymph Node Excision , Axilla/pathology , Lymph Nodes/pathology , Sentinel Lymph Node/pathologyABSTRACT
Importance: Young patients with breast cancer have higher risk for developing contralateral breast cancer (CBC) and have epidemiologic characteristics different from those of older patients. Objective: To examine the incidence and peak occurrence of CBC according to age at primary breast cancer (PBC) surgery. Design, Setting, and Participants: This cohort study included patients who were diagnosed with and underwent surgery for unilateral nonmetastatic breast cancer at Asan Medical Center, Korea, between January 1, 1999, and December 31, 2013, with follow-up through December 31, 2018. Data were analyzed from December 1, 2021, through April 30, 2023. Patients were divided into 2 groups according to their age at surgery for PBC: younger (≤35 years) vs older (>35 years). Main Outcomes and Measures: The main outcomes were cumulative incidence and hazard rate of CBC in the entire study population and in subgroups divided by cancer subtype, categorized according to hormone receptor (HR) and ERBB2 status. Results: A total of 16â¯251 female patients with stage 0 to III breast cancer were analyzed; all patients were Korean. The mean (SD) age was 48.61 (10.06) years; 1318 patients (8.11%) were in the younger group, and 14â¯933 (91.89%) were in the older group. Median follow-up was 107 months (IQR, 79-145 months). Compared with the older group, the younger group had significantly higher incidence of CBC (10-year cumulative incidence, 7.1% vs 2.9%; P < .001) and higher risk (hazard ratio, 2.10; 95% CI, 1.62-2.74) of developing CBC. The hazard rate, which indicates risk for developing CBC at a certain time frame, differed according to the subtype of primary cancer. In patients with the HR+/ERBB2- subtype, the risk increased continuously in both age groups. In patients with the triple negative subtype, the risk increased until approximately 10 years and then decreased in both age groups. Meanwhile, in the HR-/ERBB2+ subtype, risk peaked earlier, especially in the younger group (1.7 years since first surgery in the younger group and 4.8 years in the older group). Conclusions and Relevance: In this cohort study, patients aged 35 years or younger with breast cancer had a higher risk of developing CBC than older patients. Moreover, young patients with the HR-/ERBB2+ subtype tended to have a shorter interval for developing CBC. These findings might be useful in guiding treatment decisions, such as contralateral prophylactic mastectomy.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/epidemiology , Breast Neoplasms/surgery , Incidence , Mastectomy , Cohort Studies , BreastABSTRACT
Importance: The disparate prognostic implications between invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have been demonstrated. However, information on premenopausal patients remains insufficient. Objective: To examine long-term survival outcomes of ILC and IDC in premenopausal patients using national databases. Design, Setting, and Participants: This cohort study used the Surveillance, Epidemiology, and End Results (SEER), Korean Breast Cancer Registry (KBCR), and Asan Medical Center Research (AMCR) databases to identify premenopausal patients with stage I to III ILC or IDC between January 1, 1990, and December 31, 2015. The median follow-up time was 90 (IQR, 40-151) months in the SEER database, 94 (IQR, 65-131) months in the KBCR database, and 120 (IQR, 86-164) months in the AMCR database. Data were analyzed from January 1 to May 31, 2023. Main Outcomes and Measures: The primary outcome was breast cancer-specific survival (BCSS), which was analyzed according to histological type, and the annual hazard rate was evaluated. Survival rates were analyzed using a log-rank test and a Cox proportional hazards regression model with time-varying coefficients. Multivariable analysis was performed by adjusting for tumor characteristics and treatment factors. Results: A total of 225â¯938 women diagnosed with IDC or ILC and younger than 50 years were identified. Mean (SD) age at diagnosis was 42.7 (5.3) years in the SEER database, 41.8 (5.5) years in the KBCR database, and 41.8 (5.5) years in the AMCR database. In terms of race (available for the SEER database only), 12.4% of patients were Black, 76.1% were White, 11.0% were of other race (including American Indian or Alaska Native, Asian, and Native Hawaiian or Other Pacific Islander), and 0.5% were of unknown race). Patients with ILC had better BCSS in the first 10 years after diagnosis than those with IDC (hazard ratios [HRs], 0.73 [95% CI, 0.68-0.78] in the SEER database, 1.20 [95% CI, 0.91-1.58] in the KBCR database, and 0.50 [95% CI, 0.29-0.86] in the AMCR database), although BCSS was worse after year 10 (HRs, 1.80 [95% CI, 1.59-2.02] in the SEER database, 2.79 [95% CI, 1.32-5.88] in the KBCR database, and 2.23 [95% CI, 1.04-4.79] in the AMCR database). Similar trends were observed for hormone receptor-positive tumors (HRs, 1.55 [95% CI, 1.37-1.75] in the SEER database, 2.27 [95% CI, 1.01-5.10] in the KBCR database, and 2.12 [95% CI, 0.98-4.60] in the AMCR database). Considering the annual hazard model of BCSS, IDC events tended to decline steadily after peaking 5 years before diagnosis. However, the annual peak event of BCSS was observed 5 years after diagnosis for ILC, which subsequently remained constant. Conclusions and Relevance: These findings suggest that premenopausal women with ILC have worse BCSS estimates than those with IDC, which can be attributed to a higher late recurrence rate of ILC than that of IDC. Histological subtypes should be considered when determining the type and duration of endocrine therapy in premenopausal women.
Subject(s)
Breast Neoplasms , Carcinoma, Ductal, Breast , Carcinoma, Lobular , Humans , Female , Carcinoma, Lobular/therapy , Carcinoma, Ductal, Breast/therapy , Cohort Studies , Breast Neoplasms/epidemiology , PrognosisABSTRACT
Importance: The number of patients with breast cancer who have children is substantial. However, the emotional burden of this disease and its implication for childhood development remain largely unknown. Objective: To investigate the clinical factors in parenting stress in mothers with breast cancer and the association of maternal depression and parenting stress with their children's emotional development. Design, Setting, and Participants: This cross-sectional study involved a survey of females with stage 0 to 3 breast cancer and was conducted from June 2020 to April 2021 in Seoul, South Korea. Participants were aged 20 to 45 years and completed the Center for Epidemiologic Studies Depression-Revised scale and basic questionnaires on demographic and clinical characteristics. Participants with children completed the Korean Parenting Stress Index Short Form (K-PSI-SF), Child Behavior Checklist, Junior Temperament and Character Inventory, and Children's Sleep Habits Questionnaire. Exposure: Having children in patients with breast cancer. Main Outcomes and Measures: Multivariable logistic and linear regression analyses were performed to investigate the association between maternal depression and parenting stress. Results: A total of 699 females (mean [SD] age, 39.6 [4.6] years) were included, of whom 499 had children (mean [SD] age of children, 8.0 [2.7] years). Depression was more common in patients with children (odds ratio [OR], 2.25; 95% CI, 1.01-5.05) and patients who had gonadotropin-releasing hormone treatment (OR, 1.68; 95% CI, 1.15-2.44). Disease duration was inversely associated with depression (OR, 0.85; 95% CI, 0.76-0.96). Cancer-related factors were not associated with the K-PSI-SF score. Having children aged 6 years or older (ß = 3.09; 95% CI, 0.19-5.99); being the sole primary caregiver (ß = -3.43; 95% CI, -5.87 to -0.99); and reporting certain temperament (eg, novelty seeking: ß = 0.58; 95% CI, 0.46-0.71), emotional problems (eg, anxious/depressed: ß = 8.09; 95% CI, 3.34-12.83), and sleeping pattern (eg, bedtime resistance: ß = 0.57; 95% CI, 0.15-0.99) subscale scores in their children were associated with parenting stress. Depression and parenting stress were correlated (ß = 0.56; 95% CI, 0.45-0.66; P < .001). The emotional challenges encountered by children of mothers with breast cancer were not significantly different from reference values. Conclusions and Relevance: This study found that in patients with breast cancer, child-related factors and depression were significantly associated with parenting stress, but breast cancer-related factors were not correlated. The findings suggest that mothers with breast cancer are susceptible to both depression and parenting stress and that tailored counseling and support are needed.
Subject(s)
Breast Neoplasms , Female , Humans , Child , Adult , Breast Neoplasms/epidemiology , Parenting , Cross-Sectional Studies , Emotions , AnxietyABSTRACT
BACKGROUND: Recently, increased attention has been given on exosomes as ideal nanocarriers of drugs owing to their intrinsic properties that facilitate the transport of biomolecular cargos. However, large-scale exosome production remains a major challenge in the clinical application of exosome-based drug delivery systems. Considering its biocompatibility and stability, bovine milk is a suitable natural source for large-scale and stable exosome production. Because the active-targeting ability of drug carriers is essential to maximize therapeutic efficacy and minimize side effects, precise membrane functionalization strategies are required to enable tissue-specific delivery of milk exosomes with difficulty in post-isolation modification. METHODS: In this study, the membrane functionalization of a milk exosome platform modified using a simple post-insertion method was examined comprehensively. Exosomes were engineered from bovine milk (mExo) with surface-tunable modifications for the delivery of tumor-targeting doxorubicin (Dox). The surface modification of mExo was achieved through the hydrophobic insertion of folate (FA)-conjugated lipids. RESULTS: We have confirmed the stable integration of functionalized PE-lipid chains into the mExo membrane through an optimized post-insertion technique, thereby effectively enhancing the surface functionality of mExo. Indeed, the results revealed that FA-modified mExo (mExo-FA) improved cellular uptake in cancer cells via FA receptor (FR)-mediated endocytosis. The designed mExo-FA selectively delivered Dox to FR-positive tumor cells and triggered notable tumor cell death, as confirmed by in vitro and in vivo analyses. CONCLUSIONS: This simple and easy method for post-isolation modification of the exosomal surface may be used to develop milk-exosome-based drug delivery systems.