Targeting Sphingosine-1-Phosphate Signaling in Breast Cancer.

In recent years, newly emerging therapies, such as immune checkpoint inhibitors and antibody-drug conjugates, have further improved outcomes for breast cancer patients. However, recurrent and metastatic breast cancer often eventually develops resistance to these drugs, and cure is still rare. As such, the development of new therapies for refractory breast cancer that differ from conventional mechanisms of action is necessary. Sphingosine-1-phosphate (S1P) is a key molecule with a variety of bioactive activities, including involvement in cancer cell proliferation, invasion, and metastasis. S1P also contributes to the formation of the cancer microenvironment by inducing surrounding vascular- and lymph-angiogenesis and regulating the immune system. In this article, we outline the basic mechanism of action of S1P, summarize previous findings on the function of S1P in cancer cells and the cancer microenvironment, and discuss the clinical significance of S1P in breast cancer and the therapeutic potential of targeting S1P signaling.

Survival trends and patient characteristics between 2004 and 2016 for breast cancer in Japan based on the National Clinical Database-Breast Cancer Registry.

This is a prognostic report by the Japanese Breast Cancer Society on breast cancer extracted from the National Clinical Database-Breast Cancer Registry of Japan. Here, we present a summary of 457,878 breast cancer cases registered between 2004 and 2016. The median follow-up duration was 5.6 years. The median age at the start of treatment was 59 years (5-95%: 38-82 years) and increased from 57 years between 2004 and 2008 to 60 years between 2013 and 2016. The proportion of patients with Stage 0-II disease increased from 74.5% to 78.3%. The number of cases with estrogen and progesterone receptor positivity increased from 74.8% to 77.9% and 60.5% to 68.1%, respectively. Regarding (neo-)adjuvant chemotherapy, the taxane (T) or taxane-cyclophosphamide (C) regimen increased by 2.4% to 8.2%, but the (fluorouracil (F)) adriamycin (A)-C-T/(F) epirubicin (E)C-T and (F)AC/(F)EC regimens decreased by 18.6% to 15.2% and 13.5% to 5.0%, respectively. Regarding (neo-)adjuvant anti-human epidermal growth factor-2 (HER2)-targeted therapy, the use of trastuzumab increased from 4.6% to 10.5%. The rate of sentinel lymph node biopsy increased from 37.1% to 60.7%, while that of axillary dissection decreased from 54.5% to 22.6%. Improvements in disease-free and overall survival were observed in patients with HER2-positive breast cancer, but there was no apparent trend in patients with hormone receptor-positive, HER2-negative, or triple-negative breast cancers.

2020 Annual Report of National Clinical Database-Breast Cancer Registry: 10-year mortality of elderly breast cancer patients in Japan.

The Japanese Breast Cancer Society initiated the breast cancer registry in 1975, which transitioned to the National Clinical Database-Breast Cancer Registry in 2012. This annual report presents data from 2020 and analyzes the ten-year mortality rates for those aged 65 and older. We analyzed data from 93,784 breast cancer (BC) cases registered in 2020 and assessed 10-year mortality rates for 36,279 elderly patients diagnosed between 2008 and 2012. In 2020, 99.4% of BC cases were females with a median age of 61. Most (65%) were diagnosed at early stages (Stage 0 or I). Breast-conserving surgery rates varied with stages: 58.5% at cStage I, 30.8% at cStage II, and 13.1% at cStage III. Sentinel lymph node biopsy was done in 73.6% of cases, followed by radiotherapy in 70% of those post-conserving surgery and chemotherapy in 21.1% post-surgery. Pathology showed that 63.4% had tumors under 2.0 cm, 11.7% had pTis tumors, and 77.3% had no axillary lymph node metastasis. ER positivity was seen in 75.1%, HER2 in 14.3%, and 30% had a Ki67 positivity rate above 30%. Across all stages and subtypes, there was a trend where the 10-year mortality rates increased for individuals older than 65 years. In Stage I, many deaths were not directly linked to BC and, for those with HER2-type and triple-negative BC, breast cancer-related deaths increased with age. Within Stage II, patients older than 70 years with luminal-type BC often experienced deaths not directly linked to BC, whereas patients below 80 years with HER2-type and triple-negative BC, likely had breast cancer-related deaths. In Stage III, breast cancer-related deaths were more common, particularly in HER2 and triple-negative BC. Our prognostic analysis underscores distinct mortality patterns by stage, subtype, and age in elderly BC patients. It highlights the importance of personalized treatment strategies, considering subtype-specific aggressiveness, age-related factors, and comorbidities.

Annual report of the Japanese Breast Cancer Registry for 2019.

This is an annual report by the Japanese Breast Cancer Society regarding the clinical data on breast cancer extracted from the National Clinical Database-Breast Cancer Registry (NCD-BCR) of Japan. Here, we present an updated summary of 98,300 breast cancer cases registered in 2019. The median age at cancer diagnosis was 61 years (interquartile range 49-72 years), and 30.6% of the breast cancer patients were premenopausal. Of the 93,840 patients without distant metastases, 14,118 (15.0%) and 42,047 (44.8%) were diagnosed with stage 0 and I disease, respectively. Breast-conserving surgery was performed in 42,080 (44.8%) patients. Regarding axillary procedures, 62,677 (66.8%) and 7371 (7.9%) patients underwent sentinel node biopsy and axillary node dissection after biopsy, respectively. Whole breast irradiation was administered to 29,795 (70.8%) of the 42,080 patients undergoing breast-conserving surgery. Chest wall irradiation was administered to 5524 (11.1%) of the 49,637 patients who underwent mastectomy. Of the 6912 clinically lymph node-negative patients who received preoperative therapy, 5250 (76.0%) and 427 (6.2%) underwent sentinel node biopsy and axillary node dissection after biopsy, respectively; however, 602 (8.7%) patients initially underwent axillary node dissection without biopsy.

Baseline interleukin-6 is a prognostic factor for patients with metastatic breast cancer treated with eribulin.

PURPOSE: Eribulin is a unique anti-cancer drug which can improve overall survival (OS) of patients with metastatic breast cancer (MBC), probably by modulating the tumor immune microenvironment. The aim of this study was to investigate the clinical significance of serum levels of immune-related and inflammatory cytokines in patients treated with eribulin. Furthermore, we investigated the association between cytokines and immune cells, such as myeloid-derived suppressor cells (MDSCs) and cytotoxic and regulatory T cells, to explore how these cytokines might affect the immune microenvironment. METHODS: Sixty-eight patients with MBC treated with eribulin were recruited for this retrospective study. The relationship of cytokines, including interleukin (IL)-6, to progression-free survival and OS was examined. CD4+ and CD8+ lymphocyte, MDSCs and regulatory T cell levels were determined in the blood by flow cytometry analysis. RESULTS: In our cohort, patients with high IL-6 at baseline had shorter progression-free survival and OS compared with those with low IL-6 (p = 0.0017 and p = 0.0012, respectively). Univariable and multivariable analyses revealed that baseline IL-6 was an independent prognostic factor for OS (p = 0.0058). Importantly, CD8+ lymphocytes were significantly lower and MDSCs were significantly higher in patients with high IL-6, compared to those with low IL-6. CONCLUSION: Baseline IL-6 is an important prognostic factor in patients with MBC treated with eribulin. Our results show that high IL-6 is associated with higher levels of MDSCs which suppress anti-tumor immunity, such as CD8+ cells. It appears that eribulin is not particularly effective in patients with high IL-6 due to a poor tumor immune microenvironment.

Clinical Significance of Phosphorylated Sphingosine Kinase 1 Expression in Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIM: Sphingosine-1-phosphate (S1P) is a pleiotropic, bioactive, lipid mediator, produced by sphingosine kinase 1 (SphK1). In this study, we evaluated the expression of phosphorylated SphK1 (pSphK1) in patients with pancreatic ductal adenocarcinoma (PDAC) and investigated its clinical significance. MATERIALS AND METHODS: A total of 111 patients who underwent curative-intent resection for PDAC were enrolled. We investigated pSphK1 (Ser-225) expression in surgically resected specimens of PDAC using immunohistochemistry. The patients were divided into two groups according to pSphK1 immunoreactive expression: a pSphK1-high group (n=63) and a pSphK1-low group (n=48). RESULTS: Logistic regression analyses revealed that lymphatic invasion (p=0.007) was a significantly independent factor associated with high pSphK1 immunoreactive expression. The pSphK1-high group showed significantly worse disease-specific survival (DSS) than the pSphK1-low group (5-year DSS rate, 19.6% vs. 58.7%; p=0.001). High pSphK1 immunoreactive expression (hazard ratio=2.547; 95% confidence interval= 1.434-4.527; p=0.001) was an independent prognostic factor for DSS. CONCLUSION: High pSphK1 expression is independently associated with lymphatic invasion and unfavorable prognosis in PDAC patients. Thus, the SphK1-S1P axis may be important in mechanisms of tumor progression, such as lymphatic invasion, in PDAC patients.

Intratumoral Tumor Infiltrating Lymphocytes (TILs) are Associated With Cell Proliferation and Better Survival But Not Always With Chemotherapy Response in Breast Cancer.

OBJECTIVE: To investigate the clinical relevance of intratumoral tumor infiltrating lymphocytes (TILs) in breast cancer as measured by computational deconvolution of bulk tumor transcriptomes. SUMMARY BACKGROUND DATA: Commonly assessed TILs, located in tumor stroma without direct contact with cancer cells (stromal TILs), correlate with breast cancer treatment response and survival. The clinical relevance of intratumoral TILs has been less studied partly due to their rarity; however, they may have nonnegligible effects given their direct contact with cancer cells. METHODS: In all, 5870 breast cancer patients from TCGA, METABRIC, GSE96058, GSE25066, GSE163882, GSE123845, and GSE20271 cohorts were analyzed and validated. RESULTS: The intratumoral TIL score was established by the sum of all types of lymphocytes using the xCell algorithm. This score was the highest in triple-negative breast cancer (TNBC) and the lowest in the ER-positive/HER2-negative subtype. It correlated with cytolytic activity and infiltrations of dendritic cells, macrophages, and monocytes, and uniformly enriched immune-related gene sets regardless of subtype. Intratumoral TIL-high tumors correlated with higher mutation rates and significant cell proliferation on biological, pathological, and molecular analyses only in the ER-positive/HER2-negative subtype. It was significantly associated with pathological complete response after anthracycline- and taxane-based neoadjuvant chemotherapy in about half of the cohorts, regardless of the subtype. Intratumoral TIL-high tumors correlated with better overall survival in HER2-positive and TNBC subtypes consistently in 3 cohorts. CONCLUSIONS: Intratumoral TILs estimated by transcriptome computation were associated with increased immune response and cell proliferation in ER-positive/HER2-negative and better survival in HER2-positive and TNBC subtypes, but not always with pathological complete response after neoadjuvant chemotherapy.

An increase in tumor-infiltrating lymphocytes after treatment is significantly associated with a poor response to neoadjuvant endocrine therapy for estrogen receptor-positive/HER2-negative breast cancers.

BACKGROUND: The reason for the poor prognosis of estrogen receptor (ER) + /human epidermal growth factor receptor 2 (HER2)- breast cancer patients with high levels of tumor-infiltrating lymphocytes (TILs) is poorly understood. The association between TILs and response to neoadjuvant endocrine therapy (NET) was examined. METHODS: We recruited 170 patients with ER + /HER2- breast cancer who were treated with preoperative endocrine monotherapy. TILs were evaluated before and after NET, and their changes were noted. Furthermore, T cell subtypes were examined using CD8 and FOXP3 immunohistochemical analyses. Neutrophil and lymphocyte counts in the peripheral blood were analyzed with reference to TIL levels or changes. Responders were defined as Ki67 expression levels ≤ 2.7% after treatment. RESULTS: Post-treatment (p = 0.016), but not pre-treatment (p = 0.464), TIL levels were significantly associated with the response to NET. TIL levels increased significantly after treatment among non-responders (p = 0.001). FOXP3 + T cell counts increased significantly after treatment in patients with increased TILs (p = 0.035), but not in those without increased TILs (p = 0.281). Neutrophil counts decreased significantly after treatment in patients without increased TILs (p = 0.026), but not in patients with increased TILs (p = 0.312). CONCLUSION: An increase in TILs after NET was significantly associated with a poor response to NET. Given that FOXP3 + T-cell counts increased, and neutrophil counts did not decrease in patients with increased TILs after NET, the induction of an immunosuppressive microenvironment was speculated to play a role in the inferior efficacy. These data might partially indicate the involvement of the immune response in the efficacy of endocrine therapy.

Comprehensive Genomic Profiling Detects Hereditary Cancers and Confers Survival Advantage in Patients With Gynaecological Cancers.

BACKGROUND/AIM: The clinical benefits of comprehensive genomic profiling (CGP) of tumours in patients with gynaecological cancers remain unknown. We investigated the utility of CGP in assessing patient survival and its efficacy in detecting hereditary cancers in gynaecological patients. PATIENTS AND METHODS: We retrospectively analysed the medical records of 104 gynaecological patients who underwent CGP between August 2018 and December 2022. The detection of actionable and accessible genomic alterations and administration of targeted therapy, as recommended by the molecular tumour board (MTB), were assessed. The overall survival (after second-line treatment in cervical and endometrial carcinomas and after platinum-resistant recurrence in ovarian carcinoma) was compared between patients with or without administration of MTB-recommended genotype-matched therapy. Germline findings were assessed using a variant allele frequency-tumour content graph. RESULTS: Among 104 patients, actionable and accessible genomic alterations were observed in 53 patients. Matched therapy was applied in 21 patients, comprising administration of repurposing itraconazole (n=7), immune checkpoint inhibitors (n=7), poly (ADP-ribose) polymerase inhibitors (n=5), and others (n=2). The median overall survival of patients receiving and not receiving matched therapy were 19.3 months and 11.2 months, respectively (p=0.036, hazard ratio=0.48). Among 12 patients with hereditary cancers, 11 patients were previously undiagnosed. Seven patients had hereditary breast and ovarian cancer, and five had other cancer. CONCLUSION: The implementation of CGP testing prolonged overall survival in gynaecological cancer as well as provided an opportunity for genetic counselling for newly-diagnosed patients with hereditary cancers and their families.

Copy number alteration is an independent prognostic biomarker in triple-negative breast cancer patients.

BACKGROUND: Next-generation sequencing (NGS) has enabled comprehensive genomic profiling to identify gene alterations that play important roles in cancer biology. However, the clinical significance of these genomic alterations in triple-negative breast cancer (TNBC) patients has not yet been fully elucidated. The aim of this study was to clarify the clinical significance of genomic profiling data, including copy number alterations (CNA) and tumor mutation burden (TMB), in TNBC patients. METHODS: A total of 47 patients with Stage I-III TNBC with genomic profiling of 435 known cancer genes by NGS were enrolled in this study. Disease-free survival (DFS) and overall survival (OS) were evaluated for their association to gene profiling data. RESULTS: CNA-high patients showed significantly worse DFS and OS than CNA-low patients (p = 0.0009, p = 0.0041, respectively). TMB was not associated with DFS or OS in TNBC patients. Patients with TP53 alterations showed a tendency of worse DFS (p = 0.0953) and significantly worse OS (p = 0.0338) compared with patients without TP53 alterations. Multivariable analysis including CNA and other clinicopathological parameters revealed that CNA was an independent prognostic factor for DFS (p = 0.0104) and OS (p = 0.0306). Finally, multivariable analysis also revealed the combination of CNA-high and TP53 alterations is an independent prognostic factor for DFS (p = 0.0005) and OS (p = 0.0023). CONCLUSIONS: We revealed that CNA, but not TMB, is significantly associated with DFS and OS in TNBC patients. The combination of CNA-high and TP53 alterations may be a promising biomarker that can inform beyond standard clinicopathologic factors to identify a subgroup of TNBC patients with significantly worse prognosis.

Characteristics of female breast cancer in japan: annual report of the National Clinical Database in 2018.

Information regarding patients who were treated for breast cancer in 2018 was extracted from the National Clinical Database (NCD), which is run by Japanese physicians. This database continues from 1975, created by the Japanese Breast Cancer Society (JBCS). A total of 95,620 breast cancer cases were registered. The demographics, clinical characteristics, pathology, surgical treatment, adjuvant chemotherapy, adjuvant endocrine therapy, and radiation therapy of Japanese breast cancer patients were summarized. We made comparisons with other reports to reveal the characteristics of our database. We also described some features in Japanese breast cancer that changed over time. The unique characteristics of breast cancer patients in Japan may provide guidance for future research and improvement in healthcare services.

Total Lesion Glycolysis Levels as Predictive Indicators in Patients With Metastatic and Recurrent Breast Cancer Undergoing Endocrine Therapy With or Without CDK4/6 Inhibitor.

BACKGROUND/AIM: Endocrine therapy (ET) with or without CDK4/6 inhibitors is the primary treatment choice for patients with estrogen receptor (ER)-positive and HER2-negative subtype of metastatic breast cancer (MBC). We examined the metabolic parameters identified using 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in terms of sensitivity, since no predictive factors exist. PATIENTS AND METHODS: We included 136 patients with MBC treated with ET alone (n=107) or combined with CDK4/6 inhibitor (n=29) and examined using FDG-PET before treatment began. The highest maximum value of the standard uptake value (SUVmax), whole-body metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated. RESULTS: Progression-free survival (PFS) was significantly longer in patients with low levels of MTV, TLG, and SUVmax than those with higher levels (median PFS 49.5 vs. 20.7 months, p=0.001 for MTV, 49.5 vs. 20.7 months, p=0.0016 for TLG, 37.0 vs. 20.7 months, p=0.012 for SUVmax). Multivariable analysis revealed that TLG (hazard ratio=6.383, 95% confidence interval=1.167-34.913, p=0.033) was independently and significantly associated with PFS. The relationship between TLG levels and PFS was significant in patients treated with ET with (p=0.0054) and without (p=0.0188) CDK4/6 inhibitor. CONCLUSION: TLG at baseline was a significant predictor for sensitivity to ET alone or combined with CDK4/6 inhibitor. These data may be useful to identify patients that would benefit from ET.

Absolute Lymphocyte Count Is an Independent Prognostic Factor for ER-positive HER2-negative Advanced Breast Cancer Patients Treated With CDK4/6 Inhibitors.

BACKGROUND/AIM: The aim of this study was to elucidate the clinical significance of peripheral blood biomarkers, including absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and C-reactive protein (CRP) in patients with estrogen receptor-positive human epidermal growth factor receptor 2-negative advanced breast cancer treated with the CDK4/6 inhibitors, abemaciclib and palbociclib. PATIENTS AND METHODS: A total of 83 patients treated with fulvestrant plus abemaciclib or palbociclib were included in this study. Progression-free survival (PFS) and overall survival (OS) were compared in relation to baseline levels of ALC, NLR, PLR and CRP. RESULTS: The cut-off values of ALC, NLR, PLR, and CRP for PFS were determined from the receiver operating characteristic curve using the Youden index for area under the curve and set at 1,212/µl, 1.964, 170 and 0.220 mg/dl, respectively. In the abemaciclib-treated group, ALC-high patients showed significantly better PFS than ALC-low patients (p=0.0151) and multivariate analysis revealed that ALC was an independent prognostic factor for PFS (p=0.0085). In the palbociclib-treated group, there was no significant relationship between any peripheral blood biomarkers and PFS. In both treatment groups, ALC-high patients showed significantly better OS than ALC-low patients (p=0.0169 and 0.0290, respectively). Multivariate analysis revealed ALC was an independent prognostic factor for OS in both abemaciclib- and palbociclib-treated groups (p=0.0112 and 0.0202, respectively). CONCLUSION: ALC is an independent prognostic factor for estrogen receptor-positive human epidermal growth factor receptor 2-negative advanced breast cancer patients treated with the CDK4/6 inhibitors abemaciclib and palbociclib.

Prognosis and effectiveness of chemotherapy for medullary breast carcinoma.

PURPOSE: We aimed to determine the prognosis and potential benefit of postoperative chemotherapy according to subtype of medullary breast carcinoma (MedBC), a very rare invasive breast cancer. METHODS: A cohort of 1518 female patients with unilateral MedBC and 284,544 invasive ductal carcinoma (IDC) cases were enrolled from the Japanese Breast Cancer Registry. Prognosis of MedBC was compared to IDC among patients with estrogen receptor (ER)-negative and HER2-negative subtype (553 exact-matched patients) and ER-positive and HER2-negative subtype (163 MedBC and 489 IDC patients via Cox regression). Disease free-survival (DFS) and overall survival (OS) were compared between propensity score-matched adjuvant chemotherapy users and non-users with ER-negative and HER2-negative MedBC. RESULTS: Among ER-negative and HER2-negative subtype patients, DFS (hazard ratio (HR) 0.45; 95% confidence interval (95% CI), 0.30-0.68; log-rank P < 0.001) and OS (HR 0.51; 95% CI 0.32-0.83; log-rank P = 0.004) were significantly better in MedBC than IDC. Patients treated with postoperative chemotherapy showed better DFS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) and OS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) compared to those without. For the ER-positive and HER2-negative subtype, the point estimate for HR for DFS was 0.60 (95% CI 0.24-1.22) while that for OS was 0.98 (95% CI 0.46-1.84) for MedBC. CONCLUSION: In ER-negative and HER2-negative MedBC, the risk of recurrence and death was significantly lower than that of IDC, about half. Postoperative chemotherapy reduced recurrence and mortality. ER-positive and HER2-negative MedBC may have a lower risk of recurrence compared to IDC.

Higher intra-tumoral expression of pro-coagulation genes is a predictor of angiogenesis, epithelial mesenchymal transition and worse patient survival in gastric cancer.

Coagulation regulates angiogenesis in cancer, and is associated with tumor development and metastasis. To date, there have been no studies quantifying the state of intra-tumoral coagulation. We measured intra-tumoral coagulation gene expression using the "Hallmark-COAGULATION" gene set in the MSigDB, performing gene set variation analysis and then assigning a "coagulation score" to quantify gene expression. Clinical, histologic, and genetic data were analyzed in 807 gastric cancer patients from the TCGA_STAD and GSE84437 databases. Tumors with increased expression of pro-coagulation genes were consistently associated with higher AJCC T-categories (p = 0.018), lymph node metastasis (p = 0.036), and stage (p = 0.006) in both cohorts. Patients with high coagulation scores were found to have worse disease-specific survival and overall survival (OS) (p = 0.019 and 0.011, respectively) in TCGA, and worse OS in GSE84437 cohort (p = 0.012). Higher expression of pro-coagulation genes correlated with increased intra-tumoral angiogenesis, as well as increased proportions of lymphatic and microvascular endothelial cells, endothelial cells, and pericytes, calculated by xCell algorithm. High coagulation scores were significantly associated with low tumor mutation burden, but not with intratumor heterogeneity and homologous recombination deficiency. Gastric cancers with high coagulation scores contained higher amounts of M1 macrophages and dendritic cells, and low numbers of Th1 cells (all P<0.001). Genes for epithelial mesenchymal transition (EMT), myogenesis, apical junction, transforming growth factor (TGF)-ß signaling, and angiogenesis were enriched in high coagulation score-gastric cancers (all false discovery rate <0.25). In conclusion, gastric cancers expressing higher levels of pro-coagulation genes demonstrate increased angiogenesis, EMT, TGF-ß signaling and worse patient prognosis.

Prognostic impact of postoperative radiotherapy in patients with breast cancer and with pT1-2 and 1-3 lymph node metastases: A retrospective cohort study based on the Japanese Breast Cancer Registry.

AIM: Postmastectomy radiotherapy (PMRT) is the standard treatment for locally advanced breast cancer. However, the effectiveness of PMRT in patients with pT1-2 and N1 tumours remains controversial. Therefore, this study aimed to determine the prognostic impact of PMRT in patients with breast cancer and with pT1-2 and 1-3 lymph node metastases. METHODS: Using data from the Japanese National Clinical Database from 2004 to 2012, we evaluated the association of PMRT with locoregional recurrence (LRR), any recurrence, and mortality. We enrolled patients who had undergone mastectomy and axillary node dissection and were diagnosed with pT1-2 and N1. We compared clinicopathological factors and prognosis between patients who received (PMRT group) and those who did not receive (No-PMRT group) PMRT. RESULTS: Among 8914 patients enrolled, 492 patients belonged to the PMRT group and 8422 to the No-PMRT group. The median observation time was 6.3 years. There was no significant difference in the incidences of LRR (4.0% versus 5.0%, P = 0.61), recurrence (13.8% versus 11.8%, P = 0.23) and breast cancer death (6.0% versus 4.3%, P = 0.08) at 5 years between the groups. Multivariable analysis revealed that LRR was significantly associated with tumour size, number of node metastases and triple-negative subtype but not with PMRT. CONCLUSIONS: The LRR rate in the No-PMRT group was 5.0% at 5 years among patients with T1-2 and N1. PMRT did not significantly influence LRR in patients with T1-2 and N1. However, PMRT administration should be tailored considering the individual risks of tumour size, 3 node metastases and triple-negative subtype.

Clinicopathological features of male patients with breast cancer based on a nationwide registry database in Japan.

BACKGROUND: Male breast cancer (MBC) is rare; however, its incidence is increasing. There have been no large-scale reports on the clinicopathological characteristics of MBC in Japan. METHODS: We investigated patients diagnosed with breast cancer in the Japanese National Clinical Database (NCD) between January 2012 and December 2018. RESULTS: A total of 594,316 cases of breast cancer, including 3780 MBC (0.6%) and 590,536 female breast cancer (FBC) (99.4%), were evaluated. The median age at MBC and FBC diagnosis was 71 (45-86, 5-95%) and 60 years (39-83) (p < 0.001), respectively. MBC cases had a higher clinical stage than FBC cases: 7.4 vs. 13.3% stage 0, 37.2 vs. 44.3% stage I, 25.6 vs. 23.9% stage IIA, 8.8 vs. 8.4% stage IIB, 1.9 vs. 2.4% stage IIIA, 10.1 vs. 3.3% stage IIIB, and 1.1 vs. 1.3% stage IIIC (p < 0.001). Breast-conserving surgery was more frequent in FBC (14.6 vs. 46.7%, p = 0.02). Axillary lymph node dissection was more frequent in MBC cases (32.9 vs. 25.2%, p < 0.001). Estrogen receptor(ER)-positive disease was observed in 95.6% of MBC and 85.3% of FBC cases (p < 0.001). The HER2-positive disease rates were 9.5% and 15.7%, respectively (p < 0.001). Comorbidities were more frequent in MBC (57.3 vs. 32.8%) (p < 0.001). Chemotherapy was less common in MBC, while endocrine therapy use was similar in ER-positive MBC and FBC. Perioperative radiation therapy was performed in 14.3% and 44.3% of cases. CONCLUSION: Japanese MBC had an older age of onset, were more likely to be hormone receptor-positive disease, and received less perioperative chemotherapy than FBC.

Surgical treatment trends and identification of primary breast tumors after surgery in occult breast cancer: a study based on the Japanese National Clinical Database-Breast Cancer Registry.

BACKGROUND: Occult breast cancer (OBC) is classified as carcinoma of an unknown primary site, and the adequate therapy for OBC remains controversial. This retrospective study aimed to reveal the transition in breast cancer therapy and the frequency of primary breast tumors after resection in clinical OBC (cT0N+) patients using the Japanese Breast Cancer Registry database. METHODS: We enrolled OBC patients with cT0N+ from the registry between 2010 and 2018. On the basis of the period of diagnosis, OBC patients were divided into the following two groups: 2010-2014 and 2015-2018. We described the transition in treatments and tumor characteristics. After breast resection, the frequency of pathological identification of primary tumors and tumor sizes was assessed. RESULTS: Of the 687,468 patients registered, we identified 148 cT0N+ patients with a median age of 61 years. Of these patients, 64.2% (n = 95) received breast surgery (2010-2014: 79.1%, 2015-2018: 50.0%). Axillary lymph node dissection was performed in 92.6% (n = 137, 2010-2014: 91.6%, 2015-2018: 93.4%). The breast tumor size in the resected breast was 0-7.0 cm (median: 0 cm, 2010-2014: 0-7.0 cm [median: 0 cm], 2015-2018: 0-6.2 cm [median: 0 cm]). The pathological identification rate of the primary tumor was 41.1% (n = 39, 2010-2014: 40.4%, 2015-2018: 42.1%). CONCLUSIONS: Breast surgery for cT0N+ decreased between 2010 and 2018. Despite the high identification rate of primary tumors, most tumors were small, and there was no significant change in the identification rate or invasive diameter of the identified tumors after 2010.