RESUMO
BACKGROUND: The role of endocrine therapy in the treatment of patients in a postmenopausal hormonal state and with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic breast cancer (AMBC) is unclear. METHODS: We analyzed the data from 94 patients with ER-positive HER2-positive AMBC enrolled in the Safari study (UMIN000015168), a retrospective cohort study of 1072 ER-positive AMBC patients in a postmenopausal hormonal state who received fulvestrant 500 mg (F500): (1) to compare time to treatment failure (TTF) and overall survival (OS) by treatment group, and TTF by treatment line; (2) in patients who received endocrine therapy (including F500) or anti-HER2 therapy as initial systemic therapy before chemotherapy, to investigate relations between TTF for the first-line therapy or time to chemotherapy (TTC) and OS; (3) to investigate factors associated with OS. RESULTS: The TTF was longer in the patients treated with F500 as first- or second-line therapy (n = 20) than in those who received later-line F500 therapy (n = 74) (6.6 vs. 3.7 months; HR, 1.98; p = 0.014). In the 59 patients who received endocrine therapy or anti-HER2 therapy as initial systemic therapy before chemotherapy, those with TTC ≥3 years had longer median OS than those with TTC <3 years (10.5 vs. 5.9 years; HR, 0.32; p = 0.001). Longer TTC was associated with prolonged OS. CONCLUSIONS: In patients with ER-positive HER2-positive AMBC enrolled in the Safari study, TTF was longer in patients who received F500 as first- or second-line therapy. In patients who received chemotherapy-free initial systemic therapy, the prolonged OS in those with TTC ≥3 years suggests that this value may be a helpful cut-off for indicating clinical outcomes.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Fulvestranto/uso terapêutico , Neoplasias da Mama/patologia , Pós-Menopausa , Estudos Retrospectivos , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
PURPOSE: Metastatic breast cancer (MBC) is usually incurable; treatment aims to maximize patients' function and quality of life (QOL). Eribulin is a standard treatment in patients with MBC pretreated with anthracycline and taxane; however, the best administration schedule is unknown. METHODS: In this prospective phase II trial of patients with luminal MBC, we administered biweekly eribulin to patients who completed a three-cycle induction treatment. RESULTS: Sixty patients with hormone-receptor-positive and HER2-negative MBC were enrolled; 40 obtained stable disease (SD) or better efficacy after induction therapy, after which they were switched to biweekly maintenance administration. The median progression-free survival (PFS) in patients who switched to maintenance therapy was 15.21 weeks (95% CI 9.71-22.14), starting on the first day of maintenance therapy. Overall survival (OS) in patients who switched to maintenance therapy was 21.39 months (95% CI 18.89-32.89). PFS and OS in the whole population starting from the registration date were 19.00 weeks (95% CI 17.00-25.00) and 21.52 months (95% CI 16.23-24.25), respectively. PFS from the enrollment date for patients who received maintenance therapy was 25.29 weeks (95% CI 19.14-32.14). Patients who achieved complete response or partial response during induction therapy had significantly longer PFS compared to patients with SD. CONCLUSION: The efficacy of biweekly administration of eribulin at maintenance was nonsignificant. However, less frequent visits are convenient, and reduced dose intensity improves safety. Biweekly administration, besides dose reduction, could be an acceptable option for patients who are unable to maintain a standard regimen.
Assuntos
Neoplasias da Mama , Qualidade de Vida , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Quimioterapia de Indução , Estudos ProspectivosRESUMO
BACKGROUND: Only old evidence exists to back up the use of medroxyprogesterone acetate. Therefore, this study aimed to explore the factors that influence the time to treatment failure of medroxyprogesterone acetate in real-world settings as late-line treatment. METHODS: This was a cohort study that used the database of the Safari study on oestrogen receptor-positive post-menopausal advanced breast cancer (UMIN000015168). We created Kaplan-Meier curves for time to treatment failure with medroxyprogesterone acetate. Further, univariate and multivariate analyses were performed using a Cox hazard model of the clinicopathological factors involved in the time to treatment failure of medroxyprogesterone acetate. RESULTS: From the 1031 patients in the Safari study, 279 patients were selected as the population for the analysis of effectiveness of medroxyprogesterone acetate monotherapy. In the analysis of medroxyprogesterone acetate by treatment line, the median time to treatment failure was 3.0 months for third-line treatment and 4.1 months for fourth and subsequent treatment lines. In cases where medroxyprogesterone acetate was used as a third-line or later endocrine treatment, multivariate analysis showed that the length of the disease-free interval was correlated with the length of time to treatment failure of medroxyprogesterone acetate (P = 0.004). With medroxyprogesterone acetate monotherapy as the fourth-line or later treatment, 20% of the patients achieved a time to treatment failure of 12 months or longer. CONCLUSION: In actual clinical practice, patients treated with medroxyprogesterone acetate alone as the fourth or subsequent treatment lines showed a time to treatment failure of 4 months, suggesting that there is merit in using medroxyprogesterone acetate even in late treatment lines, especially in patients with long disease-free interval and those who are difficult to treat using other antineoplastic agents.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Acetato de Medroxiprogesterona/uso terapêutico , Estudos Retrospectivos , Medroxiprogesterona/uso terapêutico , Pós-Menopausa , Estudos de CoortesRESUMO
BACKGROUND: The Safari study (UMIN000015168) was a retrospective, multicenter study in which 1072 consecutive cases of estrogen receptor-positive advanced breast cancer treated using 500 mg fulvestrant were registered. We previously reported the relationship between the patient factors and overall survival after the diagnosis using the same cases and the same factors for the analysis of time to treatment failure in patients with estrogen receptor-positive advanced breast cancer. The current study is an ad hoc analysis that focused on the relationship between the patient factors and overall survival after recurrence by adding factors generally associated with overall survival after recurrence. METHODS: The overall survival after recurrence in patients with estrogen receptor-positive human epidermal growth factor receptor 2 negative recurrent breast cancer was analyzed via univariate and multivariate analyses with a Cox proportional hazards model. RESULTS: A total of 598 cases were used for the analysis of overall survival after recurrence. Multivariate analysis revealed that favorable overall survival (median, 6.4 years) was significantly correlated with long time from recurrence to fulvestrant use (≥3 years), low nuclear or histological grade (G3 vs. G1), long time to treatment failure of initial palliative endocrine therapy (≥12 months) and long time to initial palliative chemotherapy (≥2 years). CONCLUSION: The results of this study indicate that sequential endocrine monotherapy may be a useful treatment option for patients with estrogen receptor-positive/human epidermal growth factor receptor 2 negative recurrent breast cancer who have been successfully treated with initial long-term palliative endocrine therapy.
Assuntos
Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Feminino , Fulvestranto/uso terapêutico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Pós-Menopausa , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos RetrospectivosRESUMO
BACKGROUND: Anthracycline (A) or taxane T-based regimens are the standard early-line chemotherapy for metastatic breast cancer (BC). A previous study has shown a survival benefit of eribulin in heavily pretreated advanced/recurrent BC patients. The present study aimed to compare the benefit of eribulin with treatment of physician's choice (TPC) as first- or second-line chemotherapy for recurrent HER2-negative BC. METHODS: Patients with recurrent HER2-negative BC previously receiving anthracycline and taxane AT-based chemotherapy in the adjuvant or first-line setting were eligible for this open-label, randomized, parallel-group study. Patients were randomized 1:1 by the minimization method to receive either eribulin (1.4 mg/m2 on day one and eight of each 21-day cycle) or TPC (paclitaxel, docetaxel, nab-paclitaxel or vinorelbine) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included time to treatment failure (TTF), overall response rate (ORR), duration of response, and safety (UMIN000009886). RESULTS: Between May 2013 and January 2017, 58 patients were randomized, 57 of whom (26 eribulin and 31 TPC) were analyzed for efficacy. The median PFS was 6.6 months with eribulin versus 4.2 months with TPC (hazard ratio: 0.72 [95% confidence interval (CI), 0.40-1.30], p = 0.276). Median TTF was 6.0 months with eribulin versus 3.6 months with TPC (hazard ratio: 0.66 [95% CI, 0.39-1.14], p = 0.136). Other endpoints were also similar between groups. The most common grade ≥ 3 adverse event was neutropenia (22.2% with eribulin versus 16.1% with TPC). CONCLUSIONS: Eribulin seemed to improve PFS or TTF compared with TPC without statistical significance. Further validation studies are needed.
Assuntos
Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Feminino , Furanos/uso terapêutico , Humanos , Cetonas/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Receptor ErbB-2RESUMO
Purpose To date, it is not clear which anticancer agent is useful in combination with trastuzumab and pertuzumab As the first and second selective regimens for advanced or metastatic breast cancer (AMBC), this multicenter, open-label, phase II trial (JBCRG-M03: UMIN000012232) presents a prespecified analysis of eribulin in combination with pertuzumab and trastuzumab. Methods We enrolled 50 patients with no or single prior chemotherapy for HER2-positive AMBC during November 2013-April 2016. All patients received adjuvant or first-line chemotherapy with trastuzumab and a taxane. The treatment comprised eribulin on days 1 and 8 of a 21-day cycle and trastuzumabplus pertuzumab once every 3 weeks, all administered intravenously. While the primary endpoint was the progression-free survival (PFS), secondary endpoints were the response rate and safety. Results Of 50 patients, 49 were eligible for safety analysis, and the full analysis set (FAS) included 46 patients. We treated 8 (16%) and 41 (84%) patients in first- and second-line settings, respectively. While 11 patients (23.9%) had advanced disease, 35 (76.1%) had metastatic disease. The median PFS was 9.2 months for all patients [95% confidence interval (CI): 7.0-11.4]. In the FAS, 44 patients had the measurable lesions and the complete response rate (CR) was 17.4%, and partial response rate (PR) was 43.5%. The grade 3/4 adverse events were neutropenia (5 patients, 10.2%), including febrile neutropenia (2 patients, 4.1%), hypertension (3 patients, 6.1%), and other (1 patient). The average of the left ventricular ejection fraction did not decline markedly. No symptomatic left ventricular systolic dysfunction was observed. Conclusions In patients with HER2-positive AMBC, eribulin, pertuzumab, and trastuzumab combination therapy exhibited substantial antitumor activity with an acceptable safety profile. Hence, we have started a randomized phase III study comparing eribulin and a taxane in combination with pertuzumab and trastuzumab for the treatment of HER2-positive AMBC. Trial registration ID: UMIN-CTR: UMIN000012232.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/biossíntese , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Feminino , Furanos/uso terapêutico , Humanos , Cetonas/uso terapêutico , Pessoa de Meia-Idade , Compostos de Nitrosoureia , Trastuzumab/uso terapêuticoRESUMO
PURPOSE: To investigate the effectiveness and safety of bevacizumab-paclitaxel combination therapy as first- or second-line chemotherapy for HER2-negative locally advanced or metastatic breast cancer in daily clinical practice. METHODS: In this prospective multicenter observational study, bevacizumab-paclitaxel was administered at the discretion of attending physicians. Cohorts A and B had hormone receptor-positive and triple-negative breast cancer (TNBC), respectively. Primary endpoint was overall survival (OS). Multivariate analyses were conducted to identify prognostic factors. RESULTS: Between November 2012 and October 2014, 767 patients were enrolled from 155 institutions across Japan. Effectiveness was analyzed in 754 eligible patients (cohort A, 539; cohort B, 215) and safety in 750 treated patients (median observation period, 19.7 months). Median OS (95% CI) was 21.7 (19.8-23.6) months in eligible patients; 25.2 (22.4-27.4) months and 13.2 (11.3-16.6) months in cohorts A and B, respectively; and 24.4 (21.9-27.2) months and 17.6 (15.2-20.0) months in patients receiving first- and second-line therapy, respectively. Factors affecting OS (hazard ratio 95% CI) were TNBC (1.75, 1.44-2.14), second-line therapy (1.35, 1.13-1.63), ECOG performance status ≥ 1 (1.28, 1.04-1.57), taxane-based chemotherapy (0.65, 0.49-0.86), cancer-related symptoms (0.56, 0.46-0.68), and visceral metastasis (0.52, 0.40-0.66). Incidences of grade ≥ 3 AEs hypertension, neutropenia, peripheral neuropathy, proteinuria, and bleeding were 35.7%, 27.2%, 7.2%, 3.7%, and 0.3%, respectively. CONCLUSIONS: In Japanese clinical practice, combined bevacizumab-paclitaxel was as effective as in previous studies. Factors that independently predicted poor prognosis in the present study are consistent with those identified previously. TRIAL REGISTRATION: Trial no. UMIN000009086.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/epidemiologia , Paclitaxel/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Paclitaxel/efeitos adversos , Prognóstico , Intervalo Livre de Progressão , Estudos Prospectivos , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismoRESUMO
AIM: To assess the utility of the perioperative use of direct oral anticoagulants for patients with hepatocellular carcinoma (HCC) with cancer-associated thrombosis. CASE REPORT: An 83-year-old woman was admitted with a solitary HCC (10-cm diameter), as well as with multiple sites of venous thromboembolism and macroscopic portal vein tumor thrombosis. She had appropriate liver function without viral hepatitis, triple-positive tumor markers, and secondary polycythemia. Edoxaban at 30 mg was initiated 10 days before surgery to remove HCC. Complete remission of the pulmonary embolism and stability of the deep vein thrombosis and massive superior mesenteric vein thrombosis were recognized preoperatively. An extended left hepatectomy was successfully performed. To avoid hemorrhage complications, we used intravenous administration of nafamostat mesylate for 2 days, thereafter we restarted edoxaban. Superior mesenteric vein thrombosis resolved 5 months after surgery. CONCLUSION: Perioperative oral administration of edoxaban was useful in multidisciplinary treatment for a patient with advanced HCC with cancer-associated thrombosis.
Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Fígado/cirurgia , Trombose/tratamento farmacológico , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Trombose/complicações , Trombose/patologia , Trombose/cirurgiaRESUMO
BACKGROUND: Assessing survival risk is important for discussing treatment options with estrogen receptor-positive (ER+) advanced breast cancer (ABC) patients. However, there are few reports from large-scale databases on the survival risk factors in ER+ ABC. The Safari study (UMIN000015168) was a retrospective, multicenter cohort study involving 1072 Japanese patients receiving fulvestrant 500 mg mostly as a second- or later-line endocrine therapy for ER+ ABC. The follow-up data after the Safari study were examined, focusing on any relationship between clinicopathological factors and overall survival (OS) in ER+ ABC patients. METHODS: OS in patients with ER+ ABC was analyzed by univariate and multivariate analyses with a Cox proportional hazards model in this study. RESULTS: A total of 1031 cases were evaluable for OS analysis. Multivariate analysis showed that younger age (< 60 years), longer time from ABC diagnosis to fulvestrant use (≥ 3 years), no prior palliative chemotherapy before fulvestrant use, and progesterone receptor (PgR) negativity (PgR-) were significantly correlated with prolonged OS (median 7.0 years). For cases with histological or nuclear grade data, lower histological or nuclear grades were also correlated with longer OS. In recurrent metastatic cases, long disease-free interval (DFI) was not correlated with longer OS. CONCLUSIONS: In ER+ ABC patients whose treatment history included fulvestrant, younger age, longer time from ABC diagnosis to fulvestrant use, no prior palliative chemotherapy use, PgR-, and lower histological or nuclear grade correlated positively with prolonged OS.
Assuntos
Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Lobular/mortalidade , Fulvestranto/uso terapêutico , Recidiva Local de Neoplasia/mortalidade , Pós-Menopausa , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: This study aimed to investigate whether schedule modification is safe and effective in patients intolerant to the standard eribulin dose and schedule. METHODS: Patients with metastatic breast cancer (MBC) treated with both anthracycline and taxane and ≤ 3 prior regimens of chemotherapy for MBC received eribulin at the standard dose and schedule (1.4 mg/m2 on days 1 and 8 of a 21-day cycle) in the first cycle; change of dosing schedule (1.4 mg/m2 on days 1 and 15 of a 28-day cycle) was determined by change in neutrophil count, platelet count, aspartate aminotransferase, alanine aminotransferase, total bilirubin, serum creatinine, and non-hematological toxicity on day 8 of the first cycle or day 1 of the second cycle. Clinical benefit rate (CBR; primary endpoint), time to treatment failure (TTF), overall survival (OS), and safety were evaluated. RESULTS: Of the 88 patients who were enrolled and received standard eribulin therapy in the first cycle, 42 patients were moved to the bi-weekly therapy group and 40 continued standard therapy. In the bi-weekly and standard therapy groups, mean relative dose intensity was 62.7 and 90.9%, CBR was 31.0 and 25.0%, median TTF was 81.5 and 75 days, and OS was 523 and 412 days, respectively. Neither group reported severe adverse events. CONCLUSION: This is the first study to show that a bi-weekly eribulin schedule is tolerable and has comparable efficacy in patients intolerant to the standard eribulin schedule. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Center (ID: UMIN 000008491).
Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Furanos/administração & dosagem , Cetonas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Esquema de Medicação , Feminino , Furanos/efeitos adversos , Furanos/uso terapêutico , Humanos , Cetonas/efeitos adversos , Cetonas/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: The JBCRG-C06 Safari study showed that earlier fulvestrant 500 mg (F500) use, a longer time from diagnosis to F500 use, and no prior palliative chemotherapy were associated with significantly longer time to treatment failure (TTF) among Japanese patients with estrogen receptor-positive (ER+) advanced breast cancer (ABC). The objective of this sub-group analysis was to further examine data from the Safari study, focusing on ER + and human epidermal growth factor receptor-negative (HER2-) cases. METHODS: The Safari study (UMIN000015168) was a retrospective, multi-center cohort study, conducted in 1,072 patients in Japan taking F500 for ER + ABC. The sub-analysis included only patients administered F500 as second-line or later therapy (n = 960). Of these, 828 patients were HER2-. Results Multivariate analysis showed that advanced age (≥65 years; p = .035), longer time (≥3 years) from ABC diagnosis to F500 use (p < .001), no prior chemotherapy (p < .001), and F500 treatment line (p < .001) were correlated with prolonged TTF (median = 5.39 months). CONCLUSIONS: In ER+/HER2- patients receiving F500 as a second-line or later therapy, treatment line, advanced age, no prior palliative chemotherapy use, and a longer period from ABC diagnosis to F500 use were associated with longer TTF.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Estradiol/análogos & derivados , Receptores de Estrogênio/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/química , Estradiol/uso terapêutico , Feminino , Fulvestranto , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Retrospectivos , Tempo para o Tratamento , Falha de TratamentoRESUMO
Drug cost is considered an important factor in treatment compliance for cancer patients. However, it is difficult to calculate individual drug costs. We were previously unable to provide sufficient information on costs to cancer patients starting drug therapy. Therefore, we developed a tool, in the form of a spreadsheet, which calculates drug costs for breast cancer treatment. This software tool runs on every terminal for electronic medical charts in our hospital. To evaluate the tool, we created 10 fictional breast cancer patient sets. Five pharmacists calculated the drug costs for a single regimen using method A (without software) and method B (with software). The pharmacists then calculated the drug costs for 3 regimens in the same way. We compared the time taken to calculate costs using method A and method B. For the single regimen, the mean time for method B (22.6±6.9 s) was 6.4-times shorter than that for method A (145.2±28.3 s, p<0.0001). For the 3 regimens, the mean time for method B (35.5±5.0 s) was 8.9-times shorter than that for method A (315.8±43.1 s, p<0.0001). The differences observed were statistically significant. By using the software, we were able to shorten the calculation time for drug costs, and therefore, alleviate the burden on medical staff.
Assuntos
Antineoplásicos/economia , Neoplasias da Mama/economia , Custos de Medicamentos , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Análise Custo-Benefício , Custos de Medicamentos/estatística & dados numéricos , Humanos , Farmacêuticos , SoftwareRESUMO
AIMS: Personalised breast cancer therapy requires pathological characterisation of tumours. The proliferative index, based on Ki67, is pivotal, but a standard method has not been established. Here we look for an easy and practical way to evaluate Ki67. METHODS: Immunohistochemical staining of estrogen receptors, progesterone receptors, HER2 and Ki67 (MIB-1) was performed on resected specimens from 406 primary invasive ductal carcinomas. Ki67 labelling index (LI) from manual counting was compared with visual assessment using a 5-grade scale (Eye-5). Next, 10 pathologists evaluated 100 samples with marked hot spots by using Eye-5. Another 100 samples without marking were also assessed by eight pathologists. One year later, two pathologists reviewed 222 cases with Eye-5. Prognosis was analysed among estrogen receptor-positive cases with postoperative endocrine therapy. RESULTS: Eye-5 showed good correlation to LI. All 136 cases of score 4-5 had LI >20% and all 56 cases of score 1 had LI<20%, which means that manual counting was not necessary for about half of the cases. Interobserver and intraobserver variability was low even when a hot spot was not fixed. Eye-5 also correlated with histological grade and lymph node metastasis. Combining Eye-5 and histological grade created a new algorism to predict LI, which allows 80% of all cases (74% of luminal cases) without manual counting. Cases of Eye-5 score 1-2 had significantly better survival than score 3-5. CONCLUSIONS: Visual assessment of Ki67 by a 5-grade scale (Eye-5) is fast, easy, and reliable with acceptably low interobserver and intraobserver variability. Eye-5 can replace LI in many luminal tumours, and is a strong candidate as a standard method of evaluating Ki67.
Assuntos
Neoplasias da Mama/química , Carcinoma Ductal de Mama/química , Imuno-Histoquímica , Antígeno Ki-67/análise , Percepção Visual , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Biópsia , Neoplasias da Mama/classificação , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/classificação , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The Ki67 labeling index (LI) reflects the proliferative activity of breast cancers and defines luminal A and B tumors; however, no detailed method to measure Ki67 has been standardized. Here, we propose a fast and easy way to evaluate Ki67. METHODS: Immunohistochemical staining of estrogen receptor (ER), progesterone receptor (PgR), HER2 and Ki67 (MIB-1) was performed on 235 primary invasive ductal carcinomas. For each sample, a hot spot with many Ki67+ cells was identified using a low-power field (40×, 4× objective). Three independent areas in high-power field (400×) were selected at the hot spot, and all cancer cells in the 3 areas were manually counted to calculate LI (% Ki67+ cells). Alternatively, micrographs taken at 100× and 200× fields including the hot spot were shown to 2 pathologists, who visually assessed percentages of Ki67+ cells in 10 % intervals at a glance (Eye-10). RESULTS: Eye-10 and LI were strongly correlated (r = 0.9412, P < 0.0001). All cases of Eye-10 ≥ 30 % had LI > 14 %; most of those <10 % had LI < 14 %. Of 170 ER+/HER2- tumors, Eye-10-based subtypes matched 87 % of LI-driven subtypes, and interobserver agreement was good (κ = 0.705). CONCLUSION: Eye-10 is far easier than counting many cancer cells and useful for classifying breast cancers. Eye-10 can exclude obviously high and low Ki67 cases, leaving a "gray zone" around a cutoff point. Combining Eye-10 and manual counting is a good candidate for a standard method to evaluate Ki67.
Assuntos
Neoplasias da Mama/patologia , Imuno-Histoquímica/métodos , Antígeno Ki-67/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
Granulomatous mastitis (GM) is a rare chronic inflammatory breast disease that can be mistaken for a variety of inflammatory and neoplastic disorders of the breast. Erythema nodosum (EN) is a common panniculitis, and is often associated with a variety of diseases, yet coexistence of EN and GM is very rare. In this paper, we present a young Japanese woman with EN associated with GM probably due to Corynebacterium infection. Both lesions of EN and GM were successfully treated with oral minocycline and surgical drainage. To the best of our knowledge, this is the first case of EN associated with GM due to Corynebacterium infection in the English-language published work.
Assuntos
Infecções por Corynebacterium/complicações , Eritema Nodoso/etiologia , Mastite Granulomatosa/complicações , Adulto , Feminino , Mastite Granulomatosa/microbiologia , HumanosRESUMO
BACKGROUND: Oral mucositis is a frequent complication, but is poorly studied among patients with solid tumors. The purpose of this study is to clarify the incidence rate of oral mucositis in Japanese breast cancer patients receiving anthracycline-based chemotherapy(FEC100). METHODS: From June 2007 to July 2008, 61 breast cancer patients eligible for this study received anthracycline-based chemotherapy(FEC100: 5-FU 500mg/m / / 2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2)at National Kyushu Cancer Center and Iwate Medical University Hospital. The incidence rate and grade of oral mucositis were evaluated in these patients. RESULTS: The cumulative incidence of oral mucositis was about 50%. Episodes of oral mucositis were more common during courses with febrile neutropenia than during courses without it(75. 0% vs 44. 9%, p=0. 12). The reduction of oral mucositis was only 13. 6% after administering the steroidal ointment and/or mouthwash, including sodium azulene sulfonate. CONCLUSIONS: New methods are needed to prevent and treat oral mucositis in patients receiving anthracycline- based chemotherapy(FEC100).
Assuntos
Antraciclinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Estomatite/induzido quimicamente , Adulto , Idoso , Antraciclinas/administração & dosagem , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Epirubicina/efeitos adversos , Epirubicina/uso terapêutico , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Pessoa de Meia-Idade , Antissépticos Bucais/uso terapêutico , Esteroides/uso terapêutico , Estomatite/prevenção & controleRESUMO
Unlike early stage breast cancer, metastatic breast cancer (MBC) is generally considered incurable except for a small number of patients with oligometastatic disease. The goal of treatment of MBC should be the prolongation of life and improvement of symptoms and quality of life. The prognoses of patients with MBC, however, have been improved with the introduction of newer, more effective agents. Therefore, the clinical question arises whether MBC patients can be cured with these new therapeutic agents. However, there are a couple of problems in tackling this question, including the duration of follow-up and the presence of strong adjuvant therapy. Firstly, most trials in MBC have a relatively short follow-up; long-term surveillance (>3-5 years) is exceptional, so little is known about the definitive outcome and the exact proportion of long-term survivors. Secondly, most of the patients have received pre- or postoperative adjuvant therapy. The cancer cells at metastatic sites are considered to be relatively resistant to the agents used in metastatic settings. Promisingly, a number of novel therapeutic agents including antibody-drug conjugates, irreversible small molecule HER2-tyrosine inhibitors, and HER2 dimerization inhibitors show promise in the treatment of HER2-overexpressing MBC, as well as PARP-1 [poly(ADP-ribose) polymerase-1] inhibitors for triple-negative breast cancer.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/farmacologia , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante , Docetaxel , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Lapatinib , Poli(ADP-Ribose) Polimerase-1 , Inibidores de Poli(ADP-Ribose) Polimerases , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Receptor ErbB-2/antagonistas & inibidores , Taxa de Sobrevida , Sobreviventes , Taxoides/administração & dosagem , Taxoides/uso terapêutico , Trastuzumab , Resultado do TratamentoRESUMO
BACKGROUND: It is unclear whether individualized treatments based on biological factors have improved the prognosis of recurrent breast cancer. The purpose of this study is to evaluate the survival improvement of patients with recurrent breast cancer after the introduction of third generation aromatase inhibitors (AIs) and trastuzumab. METHODS: A total of 407 patients who received first diagnosis of recurrent breast cancer and treatment at National Kyushu Cancer Center between 1992 and 2008 were retrospectively evaluated. As AIs and trastuzumab were approved for clinical use in Japan in 2001, the patients were divided into two time cohorts depending on whether the cancer recurred before or after 2001. Cohort A: 170 patients who were diagnosed between 1992 and 2000. Cohort B: 237 patients who were diagnosed between 2001 and 2008. Tumor characteristics, treatments, and outcome were compared. RESULTS: Fourteen percent of cohort A and 76% of cohort B received AIs and/or trastuzumab (P < 0.001). The median overall survival (OS) times after breast cancer recurrence were 1.7 years and 4.2 years for these respective cohorts (P < 0.001). Both the time period and treatment of AIs and/or trastuzumab for recurrent disease were significant prognostic factors in multivariate analysis (cohort B vs. cohort A: HR = 0.70, P = 0.01; AIs and/or trastuzumab for recurrent disease: yes vs. no: HR = 0.46, P < 0.001). When patients were categorized into 4 subgroups by the expression of hormone receptor (HR) and HER-2 status, the median OS times of the HR-positive/HER-2-negative, HR-positive/HER-2-positive, HR-negative/HER-2-positive, and HR-negative/HER-2-negative subtypes were 2.2, 2.4, 1.6, and 1.0 years in cohort A and 4.5, 5.1, 5.0, and 1.4 years in cohort B. CONCLUSIONS: The prognosis of patients with recurrent breast cancer was improved over time following the introduction of AIs and trastuzumab and the survival improvement was apparent in HR- and/or HER-2-positive tumors.