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1.
J Bone Miner Metab ; 42(2): 223-232, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38493435

RESUMO

INTRODUCTION: Androgen deprivation therapy (ADT) is widely used for the treatment of prostate cancer. ADT is associated with reduced bone density leading to an increased risk of osteoporotic fracture. The objective of this retrospective cohort study was to quantify fracture risk in men treated with ADT for prostate cancer in real-world practice in Japan. MATERIALS AND METHODS: Data were extracted from the Japanese Medical Data Vision (MDV) database. Men initiating ADT for treatment of prostate cancer between April 2010 and March 2021 were identified and matched to a cohort of prostate cancer patients not taking ADT using a propensity score. Fracture rates were estimated by a cumulative incidence function and compared between cohorts using a Cox cause-specific hazard model. Information was extracted on demographics, comorbidities and bone densitometry. RESULTS: 30,561 men with PC starting ADT were matched to 30,561 men with prostate cancer not treated with ADT. Following ADT initiation, <5% of men underwent bone densitometry. Prescription of ADT was associated with an increased fracture risk compared to not taking ADT (adjusted hazard ratio: 1.63 [95% CI 1.52-1.75]). CONCLUSION: ADT is associated with a 1.6-fold increase in the risk of osteoporotic fracture in men with prostate cancer. Densitometry in this population is infrequent and monitoring urgently needs to be improved in order to implement effective fracture prevention.


Assuntos
Seguro , Fraturas por Osteoporose , Neoplasias da Próstata , Masculino , Humanos , Fraturas por Osteoporose/induzido quimicamente , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/complicações , Antagonistas de Androgênios/efeitos adversos , Androgênios , Japão/epidemiologia , Estudos Retrospectivos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/complicações
2.
Oncology ; 101(7): 407-414, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37075722

RESUMO

INTRODUCTION: This retrospective study was conducted to identify risk factors for developing hand-foot syndrome (HFS) and to determine new strategies for improving quality of life (QoL) in patients undergoing chemotherapy. METHODS: Between April 2014 and August 2018, we enrolled 165 cancer patients at our outpatient chemotherapy center who were undergoing capecitabine chemotherapy. Variables related to the development of HFS were extracted from the clinical records of patients for use in regression analysis. HFS severity was assessed at the time of completing capecitabine chemotherapy. The degree of HFS was classified in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. Multivariate ordered logistic regression analysis was performed to identify risk factors for the development of HFS. RESULTS: Risk factors for the development of HFS included concomitant use of a renin-angiotensin system (RAS) inhibitor (odds ratio [OR] = 2.85, 95% confidence interval [CI] = 1.20-6.79; p = 0.018), body surface area (BSA) (high) (OR = 12.7, 95% CI = 2.29-70.94; p = 0.004), and albumin (low) (OR = 0.44, 95% CI = 0.20-0.96; p = 0.040). DISCUSSION/CONCLUSION: Concomitant use of RAS inhibitor, high BSA, and low albumin were identified as risk factors for the development of HFS. The identification of potential risk factors of HFS may assist in the development of strategies that can be used to improve QoL in patients receiving chemotherapy regimens that include capecitabine.


Assuntos
Síndrome Mão-Pé , Qualidade de Vida , Humanos , Capecitabina/efeitos adversos , Estudos Retrospectivos , Síndrome Mão-Pé/etiologia , Fatores de Risco
3.
J Bone Miner Metab ; 40(6): 998-1006, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36042056

RESUMO

INTRODUCTION: ß-ray strontium-89 (Sr-89) intra-irradiation therapy has been approved and clinically used to reduce bone metastasis pain not alleviated by bone-modifying agents, external radiation, and analgesic agents. We examined the efficacy of zoledronic acid (ZOL) and Sr-89 combination therapy compared with ZOL alone in breast cancer patients with bone metastases. MATERIALS AND METHODS: A randomized controlled trial was conducted on breast cancer patients with bone metastasis to compare the efficacy between ZOL monotherapy and ZOL plus Sr-89 combination therapy. The primary endpoints were changes in urinary NTX levels at 13 weeks and brief pain inventory scores. The secondary endpoints were analgesic drug usages, response rates, changes in bone metabolism markers, quality of life, and adverse event rates. RESULTS: Thirty of the planned 60 cases were randomly assigned to ZOL alone or ZOL + Sr-89. There were no significant differences in the changes in urinary NTX levels between the 2 groups (P = 0.365). There was no consistent difference in the pain score changes between the 2 groups. Sr-89 addition to ZOL slightly reduced the white blood cell and platelet counts. However, all adverse events were Grade 1. Safety and analgesic drug dose reduction were more evident in ZOL + Sr-89. CONCLUSION: This trial showed the lack of benefits from Sr-89 addition to ZOL for breast cancer patients with painful bone metastases. However, safety and analgesic drug dose reduction were more evident in ZOL + Sr-89, indicating its potential for pain control. Sr-89 therapy is safe, thus more effective radiopharmaceuticals are anticipated.


Assuntos
Conservadores da Densidade Óssea , Neoplasias Ósseas , Neoplasias da Mama , Humanos , Feminino , Ácido Zoledrônico/uso terapêutico , Difosfonatos/efeitos adversos , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Qualidade de Vida , Imidazóis/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Dor/tratamento farmacológico , Dor/etiologia , Conservadores da Densidade Óssea/efeitos adversos
4.
Ann Plast Surg ; 88(5): 490-495, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35443265

RESUMO

BACKGROUND: After breast surgery with or without immediate reconstruction, chronic pain can be a major problem for patients. However, few studies have examined the details of the sites of long-lasting postoperative pain. In this study, we specified the postoperative pain location after breast surgery, including reconstruction, to find ways to improve surgical procedures or provide effective pain relief. METHODS: The subjects were 205 Japanese women undergoing mastectomy or breast reconstruction with a tissue expander (TE)/implant or a deep inferior epigastric perforator (DIEP) flap. Patients were asked whether they had pain in different parts of the body at 1 year after surgery. Differences were assessed by cross-tabulation and χ2 statistics. RESULTS: Surveys were completed by 157 subjects. Deep inferior epigastric perforator flap cases had significantly more pain and TE/Imp cases had significantly less pain in the medial breast, upper breast, breast upper medial quadrant, and abdomen (P = 0.006, P = 0.006, P < 0.001, P < 0.001, respectively). In the neck area, pain in TE/Imp cases was significantly worse than that in all other patients (P = 0.025). There was no significant difference in chronic pain in any other body regions among the mastectomy only, TE/Imp, and DIEP flap groups. CONCLUSIONS: The results of the present study revealed that the localization of prolonged postoperative pain after breast surgery differs depending on the surgical procedure. In DIEP flap reconstruction, there was a marked tendency for pain in the inner and upper chest and in the abdomen, whereas TE/IMP surgery resulted in pain around the neck of the affected side. These findings may help improve surgical methods and establish effective pain relief that focuses on the identified pain areas.


Assuntos
Neoplasias da Mama , Dor Crônica , Mamoplastia , Retalho Perfurante , Feminino , Humanos , Neoplasias da Mama/cirurgia , Dor Crônica/etiologia , Dor Crônica/cirurgia , Artérias Epigástricas/cirurgia , Mamoplastia/métodos , Mastectomia/efeitos adversos , Mastectomia/métodos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/cirurgia , Retalho Perfurante/cirurgia , Estudos Prospectivos , Estudos Retrospectivos
5.
Gan To Kagaku Ryoho ; 49(5): 573-576, 2022 May.
Artigo em Japonês | MEDLINE | ID: mdl-35578937

RESUMO

Granulocyte colony-stimulating factor(G-CSF)is useful for preventing febrile neutropenia induced by chemotherapy. Recently, some cases of aortitis have been reported following administration of G-CSF. Here, we present a case of aortitis induced by pegfilgrastim(peg-G)use during neoadjuvant chemotherapy for treating breast cancer. A 61-year-old woman with breast cancer(cT2N1M0, stage ⅡB, triple negative)started neoadjuvant chemotherapy FEC(100). Eleven days after the third course of peg-G administration, the patient developed a fever and general malaise. Blood test results showed an increase in inflammatory markers and severe anemia. The symptoms were not controlled with antibiotics. Blood and urine culture test results were negative. Computed tomography revealed remarkable wall thickening of the aorta. Therefore, we suspected aortitis induced by peg-G. The symptoms rapidly improved with prednisolone therapy. The possibility of aortitis should be considered for those with fever or raised inflammatory markers following the use of G-CSF. Steroids can be used for the treatment of G-CSF-induced aortitis.


Assuntos
Aortite , Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Aortite/induzido quimicamente , Aortite/tratamento farmacológico , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Feminino , Febre , Filgrastim/uso terapêutico , Fator Estimulador de Colônias de Granulócitos , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/uso terapêutico
6.
J Bone Miner Metab ; 39(2): 224-229, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32889575

RESUMO

INTRODUCTION: Aromatase inhibitor (AI)-associated bone loss increases the risk of bone fracture and reduces patients' quality of life, making it a critical issue worldwide. We conducted a prospective non-randomized clinical trial (UMIN-CTR, UMIN 000016173) to assess the effect of denosumab on bone loss in patients treated with adjuvant AI and have previously reported the results at 12 and 24 months. This study aimed to present the results at 36 months of treatment with denosumab for osteopenia in breast cancer patients who were undergoing treatment with adjuvant AI; 36 months is the longest denosumab treatment period reported so far. MATERIALS AND METHODS: Patients received 60-mg denosumab subcutaneously every 6 months. Daily supplements containing 500-mg elemental calcium and at least 400 international units of vitamin D were highly recommended throughout the study period. The levels of bone mineral density (BMD) and bone turnover markers, serum tartrate-resistant acid phosphatase isoform 5b, and bone alkaline phosphatase were determined at baseline and 6, 12, 18, 24, and 36 months. RESULTS: At 36 months, the bone mineral density of the lumbar spine, right femoral neck, and left femoral neck were found to increase by 8.8% (95% confidence interval CI 7.6-10.1), 4.3% (95% CI 3.0-5.5), and 3.1% (95% CI 2.1-4.1), respectively. No non-traumatic clinical fractures occurred in patients receiving AI and denosumab. CONCLUSION: Twice-yearly administration of denosumab to the breast cancer patients treated with adjuvant AI, regardless of the skeletal site, resulted in consistent increases in BMD without severe adverse events at 36 months.


Assuntos
Adjuvantes Farmacêuticos/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Denosumab/uso terapêutico , Adjuvantes Farmacêuticos/farmacologia , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/sangue , Inibidores da Aromatase/farmacologia , Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Neoplasias da Mama/sangue , Denosumab/efeitos adversos , Denosumab/farmacologia , Feminino , Fraturas Ósseas/sangue , Fraturas Ósseas/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fosfatase Ácida Resistente a Tartarato/sangue
7.
Gan To Kagaku Ryoho ; 48(12): 1440-1446, 2021 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-34911907

RESUMO

Since estrogen is essential for the development of breast cancer, hormonal agents are used for breast cancer prevention. Clinical trials with selective estrogen receptor modifiers and aromatase inhibitors(AI)have shown that tamoxifen is the most promising breast cancer chemopreventive agent, but the use of raloxifene must be considered due to adverse events. AI has also proven to be a chemopreventive agent for postmenopausal women. Because chemical prevention carries the risk of adverse events and target's healthy women, it is essential to assess the onset risk to confirm the need for prophylactic administration. However, all current evidence was born in clinical trials for Western's but not for Japanese. Also, the risk assessment tools of breast cancer used was all based on Western data. Therefore, the recommended chemoprevention in the Western countries is still difficult to say as the standard therapy for Japanese women. Today, breast cancer in Japanese women is explosively increasing. Under these circumstances, establishment of assessment tools for onset risk and chemoprevention methods for Japanese women is a pressing issue.


Assuntos
Neoplasias da Mama , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/prevenção & controle , Quimioprevenção , Feminino , Humanos , Comportamento de Redução do Risco , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Tamoxifeno/uso terapêutico
8.
J Bone Miner Metab ; 38(2): 141-144, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32020289

RESUMO

Androgen deprivation therapy and aromatase inhibitors are known to cause a decrease in bone mineral density and an increase in fractures. Patients receiving these treatments have been shown to have a fracture risk equal to or greater than that of patients with osteoporosis with prevalent fractures. This manual was created to prevent fractures in patients with cancer treatment-induced bone loss with high fracture risks who cannot be treated under the current Japanese guideline for the prevention and treatment of osteoporosis. This manual recommends drug treatment for patients with BMD - 2.0 ≤ T score < - 1.5 with the family history of hip fracture or 15% or more 10-year probability of major osteoporotic fractures by FRAX®; or in patients with BMD T score < - 2.0. It is important to verify whether the use of this manual can reduce fractures and improve the quality of life of patients with cancer treatment-induced bone loss by prospective studies.


Assuntos
Reabsorção Óssea/etiologia , Neoplasias/complicações , Sociedades Médicas , Antagonistas de Androgênios/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Densidade Óssea , Diretrizes para o Planejamento em Saúde , Humanos , Estudos Prospectivos , Qualidade de Vida , Fatores de Risco
9.
Gan To Kagaku Ryoho ; 47(6): 973-976, 2020 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-32541177

RESUMO

A 71-year-old man with right and left mammary tumor came to our hospital. Using needle biopsy, we diagnosed both tumors as ER-positive, PgR-positive, and HER2(1+)invasive ductalcarcinoma. We performed radicalmastectomy and axillary dissection. After surgery, the patient received postoperative chemotherapy, radiotherapy, and hormone therapy. The incidence of male breast cancer has been reported to be<1% of all breast cancer cases; only a few cases of simultaneous bilateral male breast cancer has been reported. Here, we report a rare case of synchronous bilateral male breast cancer.


Assuntos
Neoplasias da Mama Masculina , Idoso , Humanos , Excisão de Linfonodo , Masculino
10.
J Bone Miner Metab ; 37(2): 301-306, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29520506

RESUMO

Adjuvant aromatase inhibitor (AI) therapy, for hormone receptor-positive breast cancer, in postmenopausal women is associated with bone loss, leading to an increased risk of fractures. Denosumab, an antibody raised against the receptor activator of nuclear factor-κB ligand, has been proven to protect against AI-induced bone loss. Hence, we aimed to determine whether denosumab is effective in postmenopausal Japanese women with osteoporosis, treated with AI. We prospectively evaluated the bone mineral density (BMD) in the lumbar spine and the bilateral femoral neck in 102 postmenopausal women with clinical hormone receptor-positive breast cancer, stages I-IIIA, during a postoperative period of 12 months. The other inclusion criteria for this study were: women that should receive AIs as adjuvant therapy and those with evidence of osteoporosis (lumbar spine or bilateral femoral neck BMD, equivalent to T-score classification of ≤ - 2.5) upon enrollment. The patients received supplemental calcium, vitamin D, and 60 mg of subcutaneous denosumab every 6 months. The BMD of the lumber spine increased by 4.9 and 6.6% at 6 and 12 months, respectively. An increase in BMD was observed at the femoral neck, bilaterally. Hypocalcemia ≥ grade 2, osteonecrosis of the jaw, and non-traumatic clinical fracture were not observed in this study. Our findings revealed that biannual treatment with denosumab is associated with a great increase of BMD in Japanese women receiving adjuvant AI therapy, irrespective of their previous history of AI therapy.


Assuntos
Inibidores da Aromatase/uso terapêutico , Povo Asiático , Densidade Óssea/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Denosumab/uso terapêutico , Osteoporose/tratamento farmacológico , Osteoporose/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/metabolismo , Inibidores da Aromatase/farmacologia , Biomarcadores/sangue , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Neoplasias da Mama/sangue , Neoplasias da Mama/complicações , Denosumab/efeitos adversos , Denosumab/farmacologia , Feminino , Fraturas Ósseas/patologia , Humanos , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/complicações , Fosfatase Ácida Resistente a Tartarato/metabolismo
11.
J Bone Miner Metab ; 37(5): 864-870, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30868270

RESUMO

Aromatase inhibitors (AIs) are the gold standard therapy for breast cancer in postmenopausal women. AI suppresses the conversion of androgens to estrogens; however, this results in osteopenia, osteoporosis, and bone fracture, thus reducing the patient's quality of life. The use of adjuvant denosumab reduces the risk of clinical fractures in postmenopausal patients with breast cancer receiving AI. However, the efficacy of denosumab in the treatment of AI-associated bone loss has not been prospectively evaluated in Japan. In this study, we aimed to investigate the predictive factors for the efficacy of denosumab in postmenopausal patients with breast cancer treated with AI by analyzing the results of two prospective trials. The patients received 60 mg denosumab subcutaneously every 6 months. The primary endpoint was percentage change in lumbar spine bone mineral density (BMD) from baseline to month 12 in lumbar spine. Post hoc analysis and T tests were performed. A total of 205 patients were enrolled. At 12 and 24 months, the lumbar spine BMD increased by 5.6% [95% confidence interval (CI) 4.9-6.3] and 8.3% (95% CI 7.5-9.1), respectively. Subgroup analysis was conducted according to the time of AI therapy initiation, type of AI therapy, age, time since menopause, baseline body mass index, and BMD. The results showed that baseline lumbar and left femoral BMD was significantly associated with a percentage change in these sites, respectively. In addition, baseline left femoral BMD was also associated with a change in lumbar BMD. In conclusion, the baseline BMD in the lumbar spine was a predictive indicator for the efficacy of denosumab in this site and the baseline BMD in left femoral neck was a predictive indicator in lumbar spine and left femur.


Assuntos
Inibidores da Aromatase/uso terapêutico , Povo Asiático , Neoplasias da Mama/tratamento farmacológico , Denosumab/uso terapêutico , Pós-Menopausa , Idoso , Inibidores da Aromatase/efeitos adversos , Inibidores da Aromatase/farmacologia , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias da Mama/fisiopatologia , Quimioterapia Adjuvante , Denosumab/efeitos adversos , Denosumab/farmacologia , Feminino , Colo do Fêmur/efeitos dos fármacos , Colo do Fêmur/fisiopatologia , Fraturas Ósseas/induzido quimicamente , Fraturas Ósseas/tratamento farmacológico , Humanos , Japão , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Análise Multivariada , Pós-Menopausa/efeitos dos fármacos , Estudos Prospectivos , Resultado do Tratamento
12.
Support Care Cancer ; 27(7): 2673-2677, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30478672

RESUMO

This retrospective study was undertaken to identify predictive factors for developing taxane acute pain syndrome (TAPS) and to determine new strategies for improving QoL in patients undergoing chemotherapy. Between November 2010 and May 2018, we enrolled 121 breast cancer patients at our outpatient chemotherapy center who were undergoing chemotherapy with nanoparticle albumin-bound paclitaxel (nab-PTX) every 3 weeks. Variables related to the development of TAPS were extracted from the patients' clinical records and used for regression analysis. The degree of TAPS was classified as grade 0 = not developed; grade 1 = developed but did not require analgesics; grade 2 = developed but alleviated by analgesics such as acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs); or grade 3 = syndrome developed, causing sleep problems or interfering with daily living activities, but not alleviated by analgesics such as acetaminophen or NSAIDs thus requiring opioids. Multivariate ordered logistic regression analysis was performed to identify predictive factors for the development of TAPS. Significant factors identified for the development of TAPS included dose of nab-PTX (odds ratio (OR) = 11.717, 95% confidence interval (CI) = 11.6161-11.8182; P = 0.0421) and the administration of dexamethasone for up to 3 days (OR = 0.133, 95% CI = 0.0235-0.7450; P = 0.0223). In conclusion, a high dose of nab-PTX and the lack of dexamethasone administration for up to 3 days were identified as significant predictors of the development of TAPS.


Assuntos
Dor Aguda/induzido quimicamente , Albuminas/efeitos adversos , Paclitaxel/efeitos adversos , Dor Aguda/tratamento farmacológico , Adulto , Idoso , Albuminas/administração & dosagem , Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Valor Preditivo dos Testes , Qualidade de Vida , Estudos Retrospectivos , Fatores de Risco , Síndrome
13.
Gan To Kagaku Ryoho ; 46(12): 1891-1893, 2019 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-31879410

RESUMO

A 67-year-old woman with a mass in the right breast was admitted to our hospital. The tumor measured 35mm in diameter in the right breast, and the lymph node measured 30mm in diameter in the right axilla. The mass was diagnosed as malignant based on core needle biopsy. Immunohistochemistry staining for synaptophysin, chromogranin A, and CD56 was positive, suggesting that the tumor was small cell carcinoma. Positron emission tomography-computed tomography imaging excluded any other primary disease. Thus, the patient was diagnosed as having primary small cell carcinoma of the breast. Modified radical mastectomy with axillary lymph node dissection was performed. The pathological diagnosis of the surgical material confirmed small cell carcinoma. The expression of estrogen, progesterone, and human epidermal growth factor receptors was negative. After surgery, chemotherapy- and radiotherapy-based breast cancer treatment were performed. The patient was relapse free 9 months after surgery.


Assuntos
Neoplasias da Mama , Carcinoma de Células Pequenas , Idoso , Axila , Feminino , Humanos , Excisão de Linfonodo , Mastectomia , Recidiva Local de Neoplasia
14.
Breast Cancer Res Treat ; 171(1): 43-52, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29752686

RESUMO

PURPOSE: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Eribulin was approved for the treatment of metastatic breast cancer through the EMBRACE trial, and a subgroup analysis in this clinical trial indicated the efficacy of eribulin in patients with TNBC. However, the prognosis of patients with TNBC is still poor due to various molecular characteristics. Therefore, there is an urgent need for a more effective treatment for the management of TNBC. METHODS: We investigated the synergistic effect of a novel histone deacetylase (HDAC) inhibitor, OBP-801, and eribulin in TNBC cell lines because OBP-801 has been known to enhance the anti-tumor activities of other chemotherapeutic agents. The cell growth was analyzed, and the flow cytometry analysis was conducted to evaluate the effects on cell cycle and the induction of apoptosis. The mechanism underlying the enhancement of inhibition of TNBC cell growth was investigated through Western blot analyses. RESULTS: The combination treatment of OBP-801 with eribulin showed the synergistic inhibition of the growth in TNBC cells, involved with the enhancement of apoptosis. We, for the first time, found that eribulin upregulated survivin and also that OBP-801 could remarkably suppress the upregulation of survivin by eribulin. Moreover, this combination potently suppressed Bcl-xL and the MAPK pathway compared with either agent alone. CONCLUSION: We found that the combination of OBP-801 and eribulin synergistically inhibited the growth with apoptosis in TNBC cells, suggesting that this combination might be a promising novel strategy for treating TNBC patients.


Assuntos
Furanos/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Cetonas/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Peptídeos Cíclicos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Survivina/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Proteína bcl-X/metabolismo , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Humanos , Proteínas Quinases Ativadas por Mitógeno/genética , Survivina/genética , Neoplasias de Mama Triplo Negativas/genética , Proteína bcl-X/genética
15.
J Bone Miner Metab ; 36(6): 716-722, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29116414

RESUMO

Although adjuvant aromatase inhibitor (AI) therapy is widely used in postmenopausal women with hormone receptor-positive breast cancer, it is known to be associated with bone loss and increased fracture risk. Denosumab, a fully human monoclonal antibody against the receptor activator of nuclear factor-κB ligand, has been shown to protect against AI-induced bone loss. However, the efficacy of denosumab in the treatment of AI-associated bone loss has not been prospectively evaluated in Japan. We prospectively monitored bone mineral density (BMD) of the lumbar spine and bilateral femoral necks in 100 postmenopausal women with hormone receptor-positive postoperative breast cancer of clinical stage I-IIIA in whom treatment with AI as adjuvant endocrine therapy was planned or had been ongoing. Study participants received supplemental calcium and vitamin D every day and denosumab (60 mg) subcutaneously every 6 months. At enrollment, patients were required to have evidence of low bone mass without meeting the criteria for osteoporosis. The primary endpoint was percentage change from baseline in lumbar spine BMD at month 12. At 6 and 12 months, lumbar spine BMD increased by 3.3 and 4.7%, respectively. BMD of the femoral necks also increased. Hypocalcemia of grade ≥2, osteonecrosis of the jaw, and non-traumatic clinical fracture did not occur. In conclusion, semi-annual treatment with denosumab was associated with increased BMD in Japanese women receiving adjuvant AI therapy, regardless of prior AI treatment.


Assuntos
Adjuvantes Farmacêuticos/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Povo Asiático , Densidade Óssea , Neoplasias da Mama/tratamento farmacológico , Denosumab/administração & dosagem , Denosumab/uso terapêutico , Pós-Menopausa/efeitos dos fármacos , Adjuvantes Farmacêuticos/farmacologia , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/metabolismo , Biomarcadores/metabolismo , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Denosumab/efeitos adversos , Feminino , Humanos , Japão , Pessoa de Meia-Idade , Fraturas por Osteoporose/tratamento farmacológico , Fosfatase Ácida Resistente a Tartarato/metabolismo
16.
Clin Calcium ; 28(11): 1515-1517, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30374009

RESUMO

Breast cancer is a typical hormone-dependent tumor and at the time of diagnosis more than 60% of breast cancers are positive for estrogen receptors and estrogen(E)is required for proliferation. Since breast cancer is a tumor easily to cause micrometastasis, adjuvant hormonal therapy(HT)for 5 to 10 years after surgery that suppresses the action of estrogen actively prevents recurrence is very popular. However, HT with aromatase inhibitor(AI)for postoperative postmenopausal breast cancer markedly reduces the E concentration in the body, leading to significant bone loss and fracture as known as aromatase inhibitor-induced bone loss(AIBL), a typical example of CTIBL. Under these circumstances, the usefulness of bone modifying agents as a supportive therapy to increase bone density and decrease fracture rate without interrupting the treatment of breast cancer became clear, mainly in Europe and the United States. And recently, our study revealed even in Japanese breast cancer patients denosumab injection every 6 months showed significant increase in bone density. The number of women suffering from breast cancer in Japan reaches approximately 90,000 per year, a considerable number is estimated as a preliminary group of CTIBL, so early appropriate measures are desired.


Assuntos
Densidade Óssea , Neoplasias da Mama/complicações , Osteoporose/etiologia , Inibidores da Aromatase/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Cálcio , Feminino , Humanos , Japão , Recidiva Local de Neoplasia/prevenção & controle
17.
Gan To Kagaku Ryoho ; 45(9): 1381-1384, 2018 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-30237387

RESUMO

A 63-year-old woman experienced left cervical lymph node swelling since May 2012. Based on PET-CT findings, metastases of a malignant tumor to the mediastinal, axillary, and left cervical lymph nodes were suspected. Her left cervical lymph node biopsy revealed metastatic carcinoma of occult cancer, because no primary tumor could be identified despite the specific examinations. She rejected further therapeutic intervention. In July 2013, she was admitted because of anemia, cardiac failure, and fever. She was diagnosed with bone marrow carcinomatosis from occult cancer based on her bone marrow biopsy. Metastatic breast cancer was mostly considered because she tested positive for estrogen and progesterone receptors, CA15-3 levels were increased, and her axillary lymph nodes were swollen. Fulvestrant and zoledronic acid were administered and continued for 20 months, with improvement in anemia and tumor marker levels, and also maintenance of partial response.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Medula Óssea/diagnóstico , Neoplasias da Medula Óssea/tratamento farmacológico , Neoplasias da Mama/diagnóstico , Diagnóstico Diferencial , Fulvestranto/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento
18.
Gan To Kagaku Ryoho ; 45(6): 949-954, 2018 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-30026420

RESUMO

Several cases of hormone receptor-positive HER2-negative advanced and recurrent breast cancer treated with fulvestrant (FUL)were retrospectively investigated to assess the efficacy and safety of the treatment. FUL was administered to a total of 41 patients-33 with recurrent and 8 with Stage IV cancer-from January 2012 to September 2016. The median number of lines that used FUL was 3, the median time to treatment failure(TTF)was 7 months, the overall response rate(RR)was 19.5%, and the clinical benefit rate(CBR)was 53.6%. Our result was similar to those of the FIRST and the FALCON studies, which showed a decrease in RR after the fourth-line. With regard to RR, FUL seemed to provide better results at Cthird-lines of treatment. While a shorter TTF was seen in the cases with liver metastases, a longer TTF was seen in the cases with soft tissue metastases. Therefore, it may be helpful to consider the site of metastasis when predicting the effects of FUL.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Estradiol/análogos & derivados , Adulto , Idoso , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/diagnóstico , Estradiol/efeitos adversos , Estradiol/uso terapêutico , Feminino , Fulvestranto , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Receptor ErbB-2/análise , Estudos Retrospectivos , Resultado do Tratamento
19.
Ann Surg Oncol ; 23(1): 44-50, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26275781

RESUMO

PURPOSE: This study compared the clinical utility of indocyanine green (ICG) fluorescence and radioisotope (RI) for sentinel lymph node (SLN) detection in breast cancer. METHODS: Women with node-negative breast cancer underwent SLN biopsy using ICG fluorescence and RI. The primary end point was the sensitivity of ICG fluorescence compared with RI in the patients with tumor-positive SLNs. Secondary end points included detection rates for SLN, the additive effect of ICG fluorescence to RI, signature of positive SLNs according to tier, and adverse events related to ICG administration. RESULTS: A total of 847 women with clinical node-negative breast cancer underwent SLN biopsy, and 821 patients were included in the per-protocol analysis. SLN mapping was performed using ICG fluorescence and RI. The overall detection of SLNs using ICG fluorescence was identical to RI (97.2 vs. 97.0 %, P = 0.88), and the combination of both methods achieved a significant improvement compared with RI alone (99.8 vs. 97.0 %, P < 0.001). The detection rate for tumor-positive SLN was 93.3 % for ICG fluorescence and 90.0 % for RI, and the sensitivity of the ICG fluorescence method was 95.7 % (95 % CI 91.3-98.3, P = 0.11). The additional use of ICG significantly improved positive SLN detection for RI (97.2 vs. 90.0 %, P < 0.001). There were no serious adverse events related to hypersensitivity to ICG. CONCLUSIONS: The ICG fluorescence method may be an acceptable alternative to SLN detection using RI in breast cancer.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Corantes , Verde de Indocianina , Compostos Radiofarmacêuticos , Biópsia de Linfonodo Sentinela , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Feminino , Fluorescência , Seguimentos , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/cirurgia , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Compostos de Organotecnécio , Prognóstico , Estudos Prospectivos , Cintilografia , Adulto Jovem
20.
Int Heart J ; 57(4): 503-6, 2016 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-27357438

RESUMO

In recent years, the use of a retrograde approach has become a common practice in the treatment of chronic total occlusion (CTO) of the coronary ostium and artery with an anomalous origin. Use of this approach has increased the chances of a successful percutaneous coronary intervention (PCI). However, the approach requires capturing the retrograde guidewire within the aorta, which can often pose a problem. Therefore, we developed a technique in which the retrograde guidewire is passed through the CTO and inserted directly into the antegrade guiding catheter in the ascending aorta. This technique enabled the successful treatment of the ostial CTO of the right coronary artery using retrograde PCI.


Assuntos
Aorta , Oclusão Coronária/terapia , Intervenção Coronária Percutânea , Idoso de 80 Anos ou mais , Angiografia Coronária/métodos , Oclusão Coronária/diagnóstico por imagem , Humanos , Masculino , Intervenção Coronária Percutânea/métodos , Fatores de Risco , Resultado do Tratamento
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