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Purpose@#The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea. @*Materials and Methods@#We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016. @*Results@#The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003). @*Conclusion@#Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.
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Purpose@#This study investigated pathological complete response (pCR) according to androgen receptor (AR) in breast cancer patients undergoing neoadjuvant chemotherapy and estimated the relationship between AR expression and clinicopathological factors. @*Materials and Methods@#We identified 624 breast cancer patients who underwent surgery after neoadjuvant chemotherapy at the National Cancer Center in Goyang, Korea from April 2016 to October 2019. We retrospectively collected the clinicopathologic information and AR expression results and analyzed the data according to cancer stage, hormonal receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, tumor subtype, and pCR. @*Results@#Among the 624 breast cancer patients, 529 (84.8%) were AR-positive (AR+) patients and 95 (15.2%) were AR-negative (AR–) patients. AR+ patients showed more estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, HER2-positivity, and HR-positive and HER2-negative (HR+/HER2–) subtype. The rate of pCR was 31.4% (196/624). AR– patients had a significantly higher rate of pCR than AR+ patients (AR– 43.2% vs. AR+ 29.3%, p=0.007). The tumor factors associated with pCR were early stage, histologic grade 3, ER-negative, PR-negative, AR-negative, HER2-positive, and high Ki-67 values. In univariable analysis, AR+ significantly decreased the state of pCR (odds ratio, 0.546; 95% confidence interval, 0.349 to 0.853; p=0.008). According to tumor subtype, AR– tumor showed higher pCR rate in HR+/HER2– subtype (AR– 28.6% vs. AR+ 7.3%, p=0.022). @*Conclusion@#AR expression is predominant in the HR+/HER2– subtype. AR– is significantly associated with the pCR rate in breast cancer patients, especially within HR+/HER2– subtype. When determining neoadjuvant chemotherapy for the HR+/HER2– subtype, AR expression can be considered as a pCR predictive marker.
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Purpose@#Patient-derived tumor cells can be a powerful resource for studying pathophysiological mechanisms and developing robust strategies for precision medicine. However, establishing organoids from patient-derived cells is challenging because of limited access to tissue specimens. Therefore, we aimed to establish organoids from malignant ascites and pleural effusions. @*Materials and Methods@#Ascitic or pleural fluid from pancreatic, gastric, and breast cancer patients was collected and concentrated to culture tumor cells ex vivo. Organoids were considered to be successfully cultured when maintained for five or more passages. Immunohistochemical staining was performed to compare the molecular features, and drug sensitivity was assayed to analyze the clinical responses of original patients. @*Results@#We collected 70 fluid samples from 58 patients (pancreatic cancer, n=39; gastric cancer, n=21; and breast cancer, n=10). The overall success rate was 40%; however, it differed with types of malignancy, with pancreatic, gastric, and breast cancers showing 48.7%, 33.3%, and 20%, respectively. Cytopathological results significantly differed between successful and failed cases (p=0.014). Immunohistochemical staining of breast cancer organoids showed molecular features identical to those of tumor tissues. In drug sensitivity assays, pancreatic cancer organoids recapitulated the clinical responses of the original patients. @*Conclusion@#Tumor organoids established from malignant ascites or pleural effusion of pancreatic, gastric, and breast cancers reflect the molecular characteristics and drug sensitivity profiles. Our organoid platform could be used as a testbed for patients with pleural and peritoneal metastases to guide precision oncology and drug discovery.
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Purpose@#For liposarcoma (LPS), clinical course and proper treatment strategies have not been well-established. Recently, immune-checkpoint inhibitors have shown potential efficacy in LPS. We aimed to describe the clinical course of LPS and evaluate the clinical impact of programmed death-ligand 1 (PD-L1). @*Materials and Methods@#We reviewed all consecutive patients (n=332) who underwent curative-intent surgery for localized LPS at Asan Medical Center between 1989 and 2017. PD-L1 testing was performed in well-differentiated and dedifferentiated LPS. @*Results@#The median age was 56 years with males comprising 60.8%. Abdomen-pelvis (47.6%) and well-differentiated (37.7%) were the most frequent primary site and histologic subtype, respectively. During a median follow-up of 81.2 months, recurrence was observed in 135 (40.7%), and 86.7% (117/135) were loco-regional. Well-differentiated subtype (hazard ratio [HR], 0.38), abdomen-pelvis origin (HR, 2.43), tumor size larger than 5 cm (HR, 1.83), positive resection margin (HR, 2.58), and postoperative radiotherapy (HR, 0.36) were significantly related with recurrence-free survival as well as visceral involvement (HR, 1.84) and multifocality (HR, 3.79) in abdomen-pelvis LPS. PD-L1 was positive in 31.5% (23/73) and 51.3% (39/76) of well-differentiated and dedifferentiated LPS, respectively, but had no impact on survival outcomes. @*Conclusion@#Clinical course of LPS was heterogeneous according to histology and anatomic location. Clear resection margin was important to lower recurrence and postoperative radiotherapy might have additional benefit. A decent portion of well-differentiated and dedifferentiated LPS were positive for PD-L1, but its prognostic role was unclear. Further research is needed to determine clinical implications of PD-L1, especially for advanced-stage LPS with unmet needs for effective systemic treatment.
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Purpose@#This study aimed to evaluate the survivals of patients with metastatic or recurrent gastric cancer (MRGC) over a period of 16 years and to investigate the recent changes in chemotherapy patterns. @*Materials and Methods@#A total of 5,384 patients who received chemotherapy for MRGC between 2000 and 2015 were analyzed. The analysis focused on a comparison of the first-line chemotherapy between four periods: 2000–2003 (period 1), 2004–2007 (period 2), 2008–2011 (period 3), and 2012–2015 (period 4). @*Results@#There were 880 patients (16%) in period 1, 1,573 (29%) in period 2, 1,435 (27%) in period 3, and 1,496 (28%) in period 4. Cytotoxic doublet-based therapy was the most commonly used (78%) first-line chemotherapy, and the combination of trastuzumab and doublet chemotherapy was provided to 288 patients. The OS rates at 12 and 24 months were steadily improved as follows: 39.2% and 14.6% in period 1, 43.5% and 17.6% in period 2, 50.3% and 20.6% in period 3, and 51.7% and 24.1% in period 4, respectively (p < 0.001). Among the patients who received the doublet-based chemotherapy, the median OS of those who received trastuzumab was 18.0 months (95% CI, 15.5–20.6), while that of those who received other doublet therapies was 11.2 months (95% CI, 10.8–11.6). @*Conclusion@#The OS was improved over time with advancements in chemotherapy, particularly the introduction of the anti-HER2–targeted agent, which contributed to the increase in the number of long-term survivors and established the superiority of OS for the treatment of MRGC.
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Purpose@#This study aimed to evaluate the survivals of patients with metastatic or recurrent gastric cancer (MRGC) over a period of 16 years and to investigate the recent changes in chemotherapy patterns. @*Materials and Methods@#A total of 5,384 patients who received chemotherapy for MRGC between 2000 and 2015 were analyzed. The analysis focused on a comparison of the first-line chemotherapy between four periods: 2000–2003 (period 1), 2004–2007 (period 2), 2008–2011 (period 3), and 2012–2015 (period 4). @*Results@#There were 880 patients (16%) in period 1, 1,573 (29%) in period 2, 1,435 (27%) in period 3, and 1,496 (28%) in period 4. Cytotoxic doublet-based therapy was the most commonly used (78%) first-line chemotherapy, and the combination of trastuzumab and doublet chemotherapy was provided to 288 patients. The OS rates at 12 and 24 months were steadily improved as follows: 39.2% and 14.6% in period 1, 43.5% and 17.6% in period 2, 50.3% and 20.6% in period 3, and 51.7% and 24.1% in period 4, respectively (p < 0.001). Among the patients who received the doublet-based chemotherapy, the median OS of those who received trastuzumab was 18.0 months (95% CI, 15.5–20.6), while that of those who received other doublet therapies was 11.2 months (95% CI, 10.8–11.6). @*Conclusion@#The OS was improved over time with advancements in chemotherapy, particularly the introduction of the anti-HER2–targeted agent, which contributed to the increase in the number of long-term survivors and established the superiority of OS for the treatment of MRGC.
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CD19 chimeric antigen receptor T-cell (CAR-T) therapy, a genetically engineered cell therapy, showed unprecedented efficacy in the treatment of relapsed or refractory diffuse large B-cell lymphoma. Two agents, axicabtagene ciloleucel and tisagenlecleucel, were approved by the Food and Drug Administration in 2017. However, CAR-T therapy is a treatment with complex logistics and high costs, as well as inherent adverse events, including cytokine-release syndrome and neurotoxicity. In addition, predictive biomarkers for efficacy and toxicity are lacking. Industry-academy cooperation is urgently required to develop CAR-T therapy that is effective, safe, and affordable for patients in Korea.
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CD19 chimeric antigen receptor T-cell (CAR-T) therapy, a genetically engineered cell therapy, showed unprecedented efficacy in the treatment of relapsed or refractory diffuse large B-cell lymphoma. Two agents, axicabtagene ciloleucel and tisagenlecleucel, were approved by the Food and Drug Administration in 2017. However, CAR-T therapy is a treatment with complex logistics and high costs, as well as inherent adverse events, including cytokine-release syndrome and neurotoxicity. In addition, predictive biomarkers for efficacy and toxicity are lacking. Industry-academy cooperation is urgently required to develop CAR-T therapy that is effective, safe, and affordable for patients in Korea.
Subject(s)
Humans , B-Lymphocytes , Biomarkers , Cell- and Tissue-Based Therapy , Korea , Lymphoma, B-Cell , Lymphoma, Large B-Cell, Diffuse , Organization and Administration , Receptors, Antigen , T-Lymphocytes , United States Food and Drug AdministrationABSTRACT
PURPOSE: The prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer has markedly improved since the introduction of trastuzumab. We aimed to evaluate the association between stromal tumor-infiltrating lymphocyte (sTIL) or FcrR polymorphisms and survival among patients with metastatic HER2-positive breast cancer who were treated with trastuzumab. METHODS: A total of 56 women with recurrent or metastatic HER2-positive breast cancer who received the trastuzumab-taxane combination as first-line treatment were included in this retrospective analysis. The single-step multiplex allele-specific real-time polymerase chain reaction technique was employed for FcrR3A genotyping. sTILs were identified via immunohistochemical analysis of surgical (n=34, 60.7%) or biopsy specimens of metastatic lesions (n=22, 39.3%). RESULTS: We classified patients based on the sTIL level (≤10% [n=44] or >10% [n=12]); high sTIL counts were more commonly observed in patients with hormone receptor-negative tumors than in those with hormone receptor-positive tumors (34.8% vs. 12.1%, p=0.02). There was a significant association between high sTIL levels and longer progression-free survival in comparison to low sTIL levels (median, 28.4 months vs. 16.8 months; p=0.03). With regard to the FcrR3A-158 genotype, patients were classified into the Phenylalanine/Phenylalanine group (23 patients, 41.1%), Phenylalanine/Valine group (23 patients, 41,1%), or Valine/Valine group (10 patients, 17.9%); these classifications were not associated with clinical outcomes. CONCLUSION: High sTIL expression may be associated with better efficacy of trastuzumab-containing therapy in patients with metastatic HER2-positive breast cancer. However, this finding warrants further evaluation in the larger population.