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1.
Jpn J Clin Oncol ; 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223698

RESUMO

The standard treatment for ductal carcinoma in situ became well established through the results of several valuable clinical trials, and its therapeutic benefits have now come to be taken for granted. Ductal carcinoma in situ has an extremely good prognosis with the current treatment approach, with a 10-year breast cancer-specific survival rate of 97-98%. According to one retrospective cohort study, the breast cancer-specific survival rate of patients with low-grade ductal carcinoma in situ does not differ significantly between patients undergoing and not undergoing surgery. Some patients with ductal carcinoma in situ are not at a risk of progression to invasive cancer, but the predictors of such progression have not yet been clearly identified. Therefore, the same therapeutic strategies have been used to treat ductal carcinoma in situ and under the assumption that they have risks of invasive breast cancer, and a well-balanced risk/benefit ratio in respect of treatment has not yet been achieved. Based on the results of several recent clinical trials aimed at ensuring provision of a well-balanced treatment for patients with ductal carcinoma in situ which carries a good prognosis, de-escalation of postoperative adjuvant therapy has now begun. Currently, not only is the optimization of postoperative adjuvant therapy accelerating, but also clinical trials to de-escalate basic surgical treatments are under way. There is a possibility of achieving individualized treatment for patients with ductal carcinoma in situ of the breast with reduced treatment intervention. In this review, we present an overview of the current treatment approaches and potential future management strategies for ductal carcinoma in situ of the breast.

2.
Breast Cancer ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138789

RESUMO

BACKGROUND: Trastuzumab has improved breast cancer (BC) prognosis and reduced anthracycline use. However, the characteristic changes of anthracycline-related cardiomyopathy (ARCM) in patients with BC remain unclear. We aimed to update our understanding of ARCM in the trastuzumab era. METHODS: This retrospective observational cohort study included 2959 patients with BC treated with anthracyclines at three regional cancer centers in Niigata City between 1990 and 2020. Seventy-five patients (2.5%) developed ARCM and were categorized into two groups: pre- 2007 (early phase) and post-2007 (late phase), corresponding to before and during the trastuzumab era in Japan. RESULTS: ARCM incidence peaked at 6% in the 1990s, then decreased and stabilized at 2% until the 2010s. Survivors of anthracycline-treated BC increased more rapidly in the late phase, with four times as many patients with ARCM compared to the end of the early phase (26 and six, respectively). Although the rate of change in accumulation from the early phase to the late phase was slight in the anthracycline-treated BC group, it was more pronounced in the ARCM group (P < 0.001). Mean anthracycline use in the late phase was significantly lower than in the early phase (307 vs. 525 mg/m2, P < 0.001). Five-year survival rates in the late phase tended to be higher than early phase (45% and 28%, respectively. P = 0.058). Human epidermal growth factor receptor type 2 (HER2) positivity with trastuzumab therapy in the late phase was an independent predictor for mortality within 10 years (hazard ratio = 0.24, 95% confidence interval: 0.10-0.56; P = 0.001). CONCLUSIONS: HER2-positive patients with ARCM receiving trastuzumab therapy had a better prognosis than HER2-positive and HER2-negative patients with ARCM not receiving trastuzumab therapy, and this trend has been increasing in the trastuzumab era. These findings highlight the importance of HER2-targeted treatments in improving prognosis for BC patients with ARCM.

4.
Breast Cancer ; 31(2): 157-164, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37973686

RESUMO

This article provides updates to readers based on the newly published Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer Screening and Diagnosis, 2022 Edition. These guidelines incorporate the latest evaluation of evidence from studies of diagnostic accuracy. For each clinical question, outcomes for benefits and harms were established, and qualitative or quantitative systematic reviews were conducted. Recommendations were determined through voting by a multidisciplinary group, and guidelines were documented to facilitate shared decision-making among patients and medical professionals. The guidelines address screening, surveillance, and pre- and postoperative diagnosis of breast cancer. In an environment that demands an integrated approach, decisions are needed on how to utilize modalities, such as mammography, ultrasound, MRI, and PET/CT. Additionally, it is vital to understand the appropriate use of new technologies, such as tomosynthesis, elastography, and contrast-enhanced ultrasound, and to consider how best to adapt these methods for individual patients.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Japão , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Detecção Precoce de Câncer/métodos , Mamografia/métodos , Programas de Rastreamento
6.
Skin Health Dis ; 3(6): e302, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38047252

RESUMO

We herein report a typical case of alopecia neoplastica secondary to breast cancer. Alopecia neoplastica is a rare form of alopecia resulting from metastasis of a primary tumour to the scalp and is often misdiagnosed as alopecia areata.

7.
Breast Cancer Res Treat ; 202(3): 485-496, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37676450

RESUMO

PURPOSE: The Phase III POTENT trial demonstrated the efficacy of adding S-1 to adjuvant endocrine therapy for estrogen receptor-positive, HER2-negative early breast cancer. We investigated the efficacy of S-1 across different recurrence risk subgroups. METHODS: This was a post-hoc exploratory analysis of the POTENT trial. Patients in the endocrine-therapy-only arm were divided into three groups based on composite risk values calculated from multiple prognostic factors. The effects of S-1 were estimated using the Cox model in each risk group. The treatment effects of S-1 in patients meeting the eligibility criteria of the monarchE trial were also estimated. RESULTS: A total of 1,897 patients were divided into three groups: group 1 (≤ lower quartile of the composite values) (N = 677), group 2 (interquartile range) (N = 767), and group 3 (> upper quartile) (N = 453). The addition of S-1 to endocrine therapy resulted in 49% (HR: 0.51, 95% CI: 0.33-0.78) and 29% (HR: 0.71, 95% CI 0.49-1.02) reductions in invasive disease-free survival (iDFS) events in groups 2 and 3, respectively. We could not identify any benefit from the addition of S-1 in group 1. The addition of S-1 showed an improvement in iDFS in patients with one to three positive nodes meeting the monarchE cohort 1 criteria (N = 290) (HR: 0.47, 95% CI: 0.29-0.74). CONCLUSIONS: The benefit of adding adjuvant S-1 was particularly marked in group 2. Further investigations are warranted to explore the optimal usage of adjuvant S-1.

8.
Breast Cancer Res Treat ; 202(3): 473-483, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37688665

RESUMO

PURPOSE: Mammography screening has increased the detection of subcentimeter breast cancers. The prognosis for estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative T1a/bN0M0 breast cancers is excellent; however, the necessity of adjuvant endocrine therapy (ET) is uncertain. METHODS: We evaluated the effectiveness of adjuvant ET in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer who underwent surgery from 2008 to 2012. Standard ET was administrated after surgery. The primary endpoint was the cumulative incidence of distant metastasis. All statistical tests were 2-sided. RESULTS: Adjuvant ET was administered to 3991 (83%) of the 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%], diseases). The median follow-up period was 9.2 years. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32-0.93). In multivariate analysis, the independent risk factors for distant metastasis were no history of ET, mastectomy, high-grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% with and without ET, respectively (adjusted HR, 0.57; 95% CI, 0.39-0.83). In addition, adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs. 6.9%; sHR, 0.17, and 1.9% vs. 5.2%; sHR, 0.33). CONCLUSIONS: The prognosis was favorable in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, adjuvant ET reduced the incidence of distant metastasis with minimal absolute risk difference. These findings support considering the omission of adjuvant ET, especially for patients with low-grade and no lymphatic invasion disease.

9.
Breast Cancer ; 30(4): 584-595, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36930419

RESUMO

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.


Assuntos
Biomarcadores Tumorais , Variações do Número de Cópias de DNA , Neoplasias de Mama Triplo Negativas , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/genética , Biomarcadores Tumorais/genética , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Intervalo Livre de Doença
10.
Breast Cancer ; 29(1): 1-8, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34665435

RESUMO

PURPOSE: Radiotherapy (RT) and endocrine therapy (ET) are standard treatment options after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). We investigated the national patterns of adjuvant therapy use after BCS for DCIS in Japan. METHODS: We obtained relevant data of patients diagnosed with DCIS undergoing surgery and treated with BCS between 2014 and 2016 from the Japanese Breast Cancer Registry database. The relationship between the clinicopathologic, institutional, and regional factors, and adjuvant treatment was examined using multivariable analyses. RESULTS: We identified 9516 patients who underwent BCS for DCIS. Overall, 23% received no adjuvant treatment, 71% received RT, 32% received ET, and 26% received combination therapy. The percentages of patients who received ET and combination therapy in 2016 were significantly lower [odds ratio (OR): 0.71, 0.77, respectively] than in 2014. The proportion of RT was low among young or elderly patients (OR: 0.75, 0.44, respectively) and in non-certified facilities (OR: 0.56). The proportion of ET was high in non-certified facilities (OR: 1.58) and among patients with positive margins (OR: 1.62). Combination therapy was higher among patients with positive margins (OR: 1.53). CONCLUSIONS: Our study found a distinct adjuvant treatment pattern after BCS for DCIS depending on clinicopathologic factors, year, age, which indicate that physicians provide individualized treatment according to the background of the patients and the biology of DCIS. The facilities and regions remain significant factors of influencing adjuvant treatment pattern.


Assuntos
Neoplasias da Mama/terapia , Carcinoma Intraductal não Infiltrante/terapia , Mastectomia Segmentar , Radioterapia Adjuvante/tendências , Adulto , Fatores Etários , Neoplasias da Mama/epidemiologia , Carcinoma Intraductal não Infiltrante/epidemiologia , Estudos de Coortes , Humanos , Japão/epidemiologia , Margens de Excisão , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Breast Cancer ; 28(4): 896-903, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33599914

RESUMO

BACKGROUND: We conducted a prospective study with the intention to omit surgery for patients with ductal carcinoma in situ (DCIS) of the breast. We aimed to identify clinicopathological predictors of postoperative upstaging to invasive ductal carcinoma (IDC) in patients preoperatively diagnosed with DCIS. PATIENTS AND METHODS: We retrospectively analyzed patients with DCIS diagnosed through biopsy between April 1, 2010 and December 31, 2014, from 16 institutions. Clinical, radiological, and histological variables were collected from medical records. RESULTS: We identified 2,293 patients diagnosed with DCIS through biopsy, including 1,663 DCIS (72.5%) cases and 630 IDC (27.5%) cases. In multivariate analysis, the presence of a palpable mass (odds ratio [OR] 1.8; 95% confidence interval [CI] 1.2-2.6), mammography findings (≥ category 4; OR 1.8; 95% CI 1.2-2.6), mass formations on ultrasonography (OR 1.8; 95% CI 1.2-2.5), and tumor size on MRI (> 20 mm; OR 1.7; 95% CI 1.2-2.4) were independent predictors of IDC. Among patients with a tumor size on MRI of ≤ 20 mm, the possibility of postoperative upstaging to IDC was 22.1%. Among the 258 patients with non-palpable mass, nuclear grade 1/2, and positive for estrogen receptor, the possibility was 18.1%, even if the upper limit of the tumor size on MRI was raised to ≤ 40 mm. CONCLUSION: We identified four independent predictive factors of upstaging to IDC after surgery among patients with DCIS diagnosed by biopsy. The combined use of various predictors of IDC reduces the possibility of postoperative upstaging to IDC, even if the tumor size on MRI is larger than 20 mm.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Intraductal não Infiltrante/diagnóstico , Feminino , Humanos , Mamografia/métodos , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos
12.
Jpn J Clin Oncol ; 51(3): 434-443, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33420502

RESUMO

OBJECTIVE: The Japan Clinical Oncology Group 1505 trial is a single-arm multicentre prospective study that examined the possibility of non-surgical follow-up with endocrine therapy for patients with low-grade ductal carcinoma in situ. In that study, the eligible criteria included histopathological findings comprising low to intermediate nuclear grade and absence of comedo necrosis, and cases were entered according to the local histopathological diagnosis. Nuclear grade is largely based on the Consensus Conference criteria (1997), whereas comedo necrosis is judged according to the Rosen's criteria (2017). The purpose of this study was to standardize and examine the interobserver agreement levels of these histopathological criteria amongst the participating pathologists. METHODS: We held slide conferences, where photomicrographs of haematoxylin-eosin-stained slides from 68 patients with ductal carcinoma in situ were presented using PowerPoint. The nuclear grade and comedo necrosis statuses individually judged by the pathologists were analysed using κ statistics. RESULTS: In the first and second sessions, where 22 cases each were presented, the interobserver agreement levels of nuclear grade whether low/intermediate grade or high grade were moderate amongst 29 and 24 participating pathologists, respectively (κ = 0.595 and 0.519, respectively). In the third session where 24 cases were presented, interobserver agreement levels of comedo necrosis or non-comedo necrosis were substantial amongst 25 participating pathologists (κ = 0.753). CONCLUSION: Although the concordance rates in nuclear grade or comedo necrosis were not high in a few of the cases, we believe that these results could provide a rationale for employing the present criteria of nuclear grade and comedo necrosis in the clinical study of ductal carcinoma in situ.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Núcleo Celular/patologia , Oncologia , Carcinoma in Situ/patologia , Feminino , Humanos , Japão , Necrose , Variações Dependentes do Observador , Estudos Prospectivos , Reprodutibilidade dos Testes
13.
Sci Rep ; 9(1): 13343, 2019 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527824

RESUMO

Our objectives were to determine whether clinic-pathological markers and immune-related gene signatures in breast cancer exhibit any change upon brain metastasis and whether previously reported genes significantly associated with brain metastases and the epithelial-mesenchymal transition (EMT) were reproducible and consistent in our dataset. Sixteen pair-matched samples from primary breast cancers and brain metastases diagnosed were collected from the Japan Clinical Oncology Group Breast Cancer Study Group. Gene expression profiles for immune-, brain metastases-, and EMT-related genes were compared between primary breast cancers and brain metastases. Potential therapeutic target genes of 41 FDA-approved or under-investigation agents for brain metastases were explored. Immune-related signatures exhibited significantly lower gene expression in brain metastases than in primary breast cancers. No significant differences were detected for the majority of genes associated with brain metastases and EMT in the two groups. Among 41 therapeutic target candidates, VEGFA and DNMT3A demonstrated significantly higher gene expression in brain metastases. We found that distinct patterns of gene expression exist between primary breast cancers and brain metastases. Further studies are needed to explore whether these distinct expression profiles derive from or underlie disease status and compare these features between metastases to the brain and other sites.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica/genética , Transcriptoma/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Barreira Hematoencefálica/fisiologia , Neoplasias Encefálicas/secundário , Neoplasias da Mama/patologia , DNA (Citosina-5-)-Metiltransferases/biossíntese , DNA (Citosina-5-)-Metiltransferases/genética , DNA Metiltransferase 3A , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Pessoa de Meia-Idade , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genética
14.
Cancer Med ; 8(12): 5468-5481, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31361400

RESUMO

Our aim was to investigate the efficacy and safety of initial neoadjuvant endocrine therapy with exemestane alone followed by tailored treatment, either continued exemestane monotherapy or exemestane plus docetaxel-cyclophosphamide (TC) combination therapy, in postmenopausal patients with primary invasive estrogen receptor-positive, human epidermal growth factor receptor 2-negative, stage I-IIIA breast cancer and Ki67 labeling index ≤30%. In this open-label phase II study, patients initially received exemestane 25 mg/d for 12 weeks. Responders were defined as patients who achieved complete response (CR), partial response (PR) with Ki67 labeling index ≤5% after treatment, or stable disease with Ki67 labeling index ≤5% both before and after treatment. For the subsequent 12 weeks, exemestane monotherapy was continued for responders (group A), whereas nonresponders received exemestane plus four cycles of TC (docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks) (group B). Clinical response rate (ie the proportion of patients with CR or PR) at 24 weeks was the primary endpoint. Of 64 patients provisionally enrolled between December 2010 and May 2016, 58 (median age 60 years) started the study treatment. Five patients discontinued treatment in the initial exemestane monotherapy period, and 39 completed the study treatment. Clinical response rates at 8-12 and 24 weeks were 71% (10/14, 95% confidence interval [CI] 41.9%-91.6%) and 57% (8/14, 95% CI 28.9%-82.3%), respectively, in group A, and 16% (4/25, 95% CI 4.5%-36.1%) and 56% (14/25, 95% CI 34.9%-75.6%), respectively, in group B. Grade ≥3 adverse events were reported in 8% (1/15) and 53% (20/38) in group A and group B, respectively. The tailored treatment maintained the favorable clinical response to exemestane alone in responders and improved clinical response in nonresponders. TRIAL NUMBER: UMIN000004752 (UMIN Clinical Trials Registry).


Assuntos
Androstadienos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/administração & dosagem , Docetaxel/administração & dosagem , Idoso , Androstadienos/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclofosfamida/farmacologia , Docetaxel/farmacologia , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Receptores de Estrogênio/metabolismo , Análise de Sobrevida , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos
15.
Cancer Med ; 7(7): 3044-3056, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29905023

RESUMO

Patients with estrogen receptor (ER)-positive breast cancer are less likely to achieve a pathological complete response (pCR) with neoadjuvant chemotherapy. Neoadjuvant endocrine therapy may be more appropriate than neoadjuvant chemotherapy in these hormone-sensitive patients. Most patients with ER-positive breast cancer are postmenopausal, and therefore, generally older and less able to tolerate chemotherapy. We aimed to investigate the efficacy and safety of tailored neoadjuvant endocrine and chemoendocrine therapy for postmenopausal breast cancer patients. Untreated patients with primary invasive ER-positive, HER2-negative, stage I-IIIA breast cancer, and Ki67 index ≤30% were enrolled. Patients received exemestane 25 mg/d for 12 weeks. Based on clinical response and change in Ki67 index, assessed at 8-12 weeks, patients with complete response (CR), partial response (PR) with Ki67 index ≤5% after treatment, or stable disease (SD) with Ki67 index ≤5% before and after treatment were defined as responders. For the subsequent 24 weeks, responders continued exemestane monotherapy (group A), and nonresponders received exemestane 25 mg/d plus cyclophosphamide 50 mg/d (group B). The primary endpoint was clinical response at weeks 24 and 36. A total of 59 patients (median age, 69 years) started initial exemestane monotherapy. After exclusion of three patients who discontinued during this period, 56 remained enrolled to receive subsequent treatment. Clinical response rates (CR and PR) and 95% CI at weeks 24 and 36 were 85% (12/14; 57.2%-98.2%) and 71% (10/14; 41.9%-91.6%), respectively, in group A; and 54% (23/42; 38.7%-70.2%) and 71% (30/42; 55.4%-84.3%), respectively, in group B. At week 36, no significant difference was found in median Ki67 index between the groups (3.5% and 4.0%). There were no treatment-related deaths. We found that clinical response comparable to that of responders was achieved in nonresponders after addition of cyclophosphamide to the initial endocrine therapy.

16.
Cancer Chemother Pharmacol ; 81(2): 269-275, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29196963

RESUMO

A prospective randomized phase II trial was conducted to evaluate the time course effects of toremifene (TOR) and letrozole (LET), as adjuvant hormone therapy, on serum lipid profiles and bone metabolism in estrogen receptor (ER)-positive, postmenopausal breast cancer patients.Fifty-four postmenopausal breast cancer patients [ER positive, HER2 negative, T1-2, node metastases (n = 0-3), M0] who had undergone curative resection were enrolled. They were randomized to receive either TOR 40 mg/day or LET 2.5 mg/day as adjuvant hormone therapy. Serum lipids and bone markers were measured prior to, and again at 6, 12, and 24 months after initiation of treatment. Changes in serum lipids and bone markers were compared. Serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were decreased compared with the baseline values at 6 months in 6.5 and 14.0% of patients, respectively, receiving TOR. Lipid levels did not change in patients administered LET. Significant differences were observed in TC and LDL-C between the two groups at 12 and 24 months. In the TOR group, serum bone-specific alkaline phosphatase (BAP) was decreased by 25.0% at 12 months, and serum cross-linked N-telopeptide of type-I collagen (NTx) was decreased by 13.6% at 6 months, and these reductions were maintained for at least 24 months. In contrast, in the LET group, serum BAP did not change and NTx was increased by 16.0% at 6 months and by 18.6% at 24 months, as compared with the baseline.TOR and LET exert different effects on serum lipid profiles and bone metabolism markers. The effects of TOR, as adjuvant hormone therapy, on both lipids and bone metabolism in postmenopausal breast cancer patients are superior to those of LET.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Neoplasias da Mama/tratamento farmacológico , Letrozol/efeitos adversos , Lipídeos/sangue , Toremifeno/efeitos adversos , Idoso , Fosfatase Alcalina/sangue , Antineoplásicos Hormonais/uso terapêutico , Quimioterapia Adjuvante , Colesterol/sangue , LDL-Colesterol/sangue , Colágeno Tipo I/sangue , Feminino , Humanos , Letrozol/uso terapêutico , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Prospectivos , Toremifeno/uso terapêutico
17.
Artigo em Inglês | MEDLINE | ID: mdl-32529167

RESUMO

PURPOSE: It has been suggested that the biological characteristics of breast cancer may differ among different geographic or ethnic populations. Indeed, triple-negative breast cancer (TNBC), the most lethal breast cancer subgroup, has been reported to show a higher incidence in Japan than in the US. However, most genomic studies of these tumors are from Western countries and the genomic landscape of TNBC in an Asian population has not been thoroughly investigated. Here, we sought to elucidate the geographic and ethnic diversity of breast cancer by examining actionable driver alterations in TNBC tumors from Japanese patients and comparing them with The Cancer Genome Atlas (TCGA) database, which gather data primarily from non-Asian patients. MATERIALS AND METHODS: We performed comprehensive genomic profiling, including an analysis of 435 known cancer genes on Japanese TNBC patients (N=53) and compared the results to independent data obtained from TCGA (N=123). RESULTS: Driver alterations were identified in 51 out of 53 Japanese patients (96%). Although the overall alteration spectrum of Japanese patients was similar to that of the TCGA, we found significant differences in the frequencies of alterations in MYC and PTK2. We identified three patients (5.7%) with a high tumor mutation burden, although no microsatellite instability was observed in any of the Japanese patients. Importantly, pathway analysis revealed that 66.0% (35/53) of Japanese patients, as well as 66.7% (82/123) of the TCGA cohort, had alterations in at least one actionable gene targetable by an FDA-approved drug. CONCLUSION: Our study identified actionable driver alterations in Japanese patients with TNBC, revealing new opportunities for targeted therapies in Asian patients.

18.
Oncotarget ; 8(61): 103671-103681, 2017 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-29262592

RESUMO

BACKGROUND: Immune checkpoint inhibitors are reported to be effective in patients with brain metastases. However, detailed characteristics of the brain metastasis immune microenvironment remain unexplored. RESULTS: The median tumor-infiltrating lymphocyte (TIL) category in brain metastases was 5% (1-70%). In 46 pair-matched samples, the percentages of TILs were significantly higher in primary breast tumors than in brain metastases (paired t-test, P < 0.01). The numbers of CD4/CD8/Foxp3-positive cells were significantly higher in primary breast tumors than in brain metastases (paired t-test, P < 0.05 for all antibodies). In patients with triple-negative breast cancer specifically, low TIL numbers were associated with significantly shorter overall survival compared to high TIL numbers (log-rank test, P = 0.04). MATERIALS AND METHODS: We retrospectively identified 107 patients with breast cancer and brain metastases who had undergone surgery between 2001 and 2012 at 8 institutions, and collected 191 samples including brain metastases alone and primary tumors with pair-matched brain metastasis samples. Hematoxylin and eosin-stained slides were evaluated for TILs and categorized according to the extent of staining. Immunohistochemistry for CD4, CD8, Foxp3, PD-L1, PD-L2, and HLA class I was also performed. CONCLUSIONS: There are significantly fewer TILs in brain metastases than in primary breast tumors.

19.
Jpn J Clin Oncol ; 47(8): 671-677, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28486668

RESUMO

Ductal carcinoma in situ (DCIS) has a good prognosis with the current treatment approach, with a 10-year breast cancer-specific survival rate of 97-98%. In ductal carcinoma in situ without micrometastasis, surgery and postoperative adjuvant therapy significantly improve local control, however it has been reported that the selection of the surgical procedure and adjuvant therapy does not influence breast cancer death. On the other hand, owing to widespread mammography screening, the frequency of early breast cancer detection has increased. In early breast cancer, increased incidence of DCIS is remarkable. However, there is not enough reduction of advanced cancer to match it. Problems with overdiagnosis are now being discussed all over the world. It has been reported that surgery for low-grade ductal carcinoma in situ does not contribute to breast cancer-specific survival. However, it is currently impossible to reliably identify a population that does not progress to invasive cancer even without treatment. Recently, a non-surgery clinical trial for low-risk ductal carcinoma in situ was started. There is a possibility of achieving individualized treatment for ductal carcinoma in situ with less treatment intervention, without compromising the good prognosis obtained with the current treatment approach. This review presents an overview of the current treatment approaches, problems with overdiagnosis and potential future management strategies for ductal carcinoma in situ of the breast.


Assuntos
Neoplasias da Mama/terapia , Carcinoma Intraductal não Infiltrante/terapia , Detecção Precoce de Câncer/métodos , Mamografia/métodos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos
20.
World J Surg ; 40(1): 38-44, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26404528

RESUMO

BACKGROUND: Women have accounted for over 30% of new medical students since 1995 in Japan. Establishing support systems for women surgeons to continue their work is a major issue in Japan. Mentorship can be one of the most effective means to help women surgeons to continue their work. The purpose of this study was to clarify the current status of mentorship among Japanese women surgeons and to discuss the role of mentors for women surgeons. METHODS: Invitation letters were sent to all female members of the Japan Association of Women Surgeons in April 2011. An 84-item questionnaire survey was sent to those who agreed to participate in this study via the internet. RESULTS: Fifty-five surgeons participated in this study, a response rate of 48.7%. Sixty-seven percent of respondents found it difficult to continue in their job; 85% thought mentorship was necessary for women surgeons to progress in their careers; and 84% reported that they already had a mentor. Respondents thought that a mentor helped them to advance their clinical career, to stay in their job, and to provide moral support. However, mentors appeared to be less useful in helping them to advance their research career, to network, to increase their status, and to achieve a work-life balance. CONCLUSIONS: This study revealed areas where mentors appeared to be less helpful to women surgeons. The survey gave an indication of how to help improve and develop the career and personal life of women surgeons in Japan.


Assuntos
Mentores , Médicas , Sociedades Médicas , Especialidades Cirúrgicas/educação , Cirurgiões/normas , Inquéritos e Questionários , Adulto , Feminino , Humanos , Internet , Japão , Estudantes de Medicina/estatística & dados numéricos
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