RESUMEN
Background: Male breast cancer (BC) is rare, managed by extrapolation from female BC. The International Male BC Program aims to better characterize and manage this disease. We report the results of part I, a retrospective joint analysis of cases diagnosed during a 20-year period. Methods: Patients with follow-up and tumor samples, treated between 1990 and 2010, in 93 centers/9 countries. Samples were centrally analyzed in three laboratories (the United Kingdom, the Netherlands and the United States). Results: Of 1822 patients enrolled, 1483 were analyzed; 63.5% were diagnosed between 2001 and 2010, 57 (5.1%) had metastatic disease (M1). Median age at diagnosis: 68.4 years. Of 1054 M0 cases, 56.2% were node-negative (N0) and 48.5% had T1 tumors; 4% had breast conserving surgery (BCS), 18% sentinel lymph-node biopsy; half received adjuvant radiotherapy; 29.8% (neo)adjuvant chemotherapy and 76.8% adjuvant endocrine therapy (ET), mostly tamoxifen (88.4%). Per central pathology, for M0 tumors: 84.8% ductal invasive carcinomas, 51.5% grade 2; 99.3% estrogen receptor (ER)-positive; 81.9% progesterone receptor (PR)-positive; 96.9% androgen receptor (AR)-positive [ER, PR or AR Allred score ≥3]; 61.1% Ki67 expression low (<14% positive cells); using immunohistochemistry (IHC) surrogates, 41.9% were Luminal-A-like, 48.6% Luminal-B-like/HER-2-negative, 8.7% HER-2-positive, 0.3% triple negative. Median follow-up: 8.2 years (0.0-23.8) for all, 7.2 years (0.0-23.2), for M0, 2.6 years (0.0-12.7) for M1 patients. A significant improvement over time was observed in age-corrected BC mortality. BC-specific-mortality was higher for men younger than 50 years. Better overall (OS) and recurrence-free survival (RFS) were observed for highly ER+ (P = 0.001), highly PR+ (P = 0.002), highly AR+ disease (P = 0.019). There was no association between OS/RFS and HER-2 status, Ki67, IHC subtypes nor grade. Conclusions: Male BC is usually ER, PR and AR-positive, Luminal B-like/HER2-negative. Of note, 56% patients had T1 tumors but only 4% had BCS. ER was highly positive in >90% of cases but only 77% received adjuvant ET. ER, PR and AR were associated with OS and RFS, whereas grade, Ki67 and IHC surrogates were not. Significant improvement in survival over time was observed.
Asunto(s)
Neoplasias de la Mama Masculina , Adulto , Anciano , Biomarcadores de Tumor/análisis , Neoplasias de la Mama Masculina/mortalidad , Neoplasias de la Mama Masculina/patología , Neoplasias de la Mama Masculina/cirugía , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
BACKGROUND: Everolimus synergistically enhances taxane-induced cytotoxicity in breast cancer cells in vitro and in vivo in addition to demonstrating a direct antiproliferative activity. We aim to determine pharmacodynamics changes and response of adding everolimus to standard neoadjuvant chemotherapy in triple-negative breast cancer (TNBC). PATIENTS AND METHODS: Phase II study in patients with primary TNBC randomized to T-FEC (paclitaxel 80 mg/m(2) i.v. weekly for 12 weeks, followed by 5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), and cyclophosphamide 500 mg/m(2) every 3 weeks for four cycles) versus TR-FEC (paclitaxel 80 mg/m(2) i.v. and everolimus 30 mg PO weekly for 12 weeks, followed by FEC). Tumor samples were collected to assess molecular changes in the PI3K/AKT/mTOR pathway, at baseline, 48 h, 12 weeks, and at surgery by reverse phase protein arrays (RPPA). Clinical end points included 12-week clinical response rate (12-week RR), pathological complete response (pCR), and toxicity. RESULTS: Sixty-two patients were registered, and 50 were randomized, 27 received T-FEC, and 23 received TR-FEC. Median age was 48 (range 31-75). There was downregulation of the mTOR pathway at 48 h in the TR-FEC arm. Twelve-week RR by ultrasound were 29.6% versus 47.8%, (P = 0.075), and pCR were 25.9% versus 30.4% (P = 0.76) for T-FEC and TR-FEC, respectively. mTOR downregulation at 48 h did not correlate with 12-week RR in the TR-FEC group (P = 0.58). Main NCI grade 3/4 toxicities included anemia, neutropenia, rash/desquamation, and vomiting in both arms. There was one case of grade 3 pneumonitis in the TR-FEC arm. No grade 3/4 stomatitis occurred. CONCLUSION: The addition of everolimus to paclitaxel was well tolerated. Everolimus downregulated mTOR signaling but downregulation of mTOR at 48 h did not correlate with 12-week RR in the TR-FEC group. CLINICAL TRIAL NUMBER: NCT00499603.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Neoadyuvante/métodos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Epirrubicina/administración & dosificación , Epirrubicina/efectos adversos , Everolimus , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Transducción de Señal/efectos de los fármacos , Sirolimus/administración & dosificación , Sirolimus/efectos adversos , Sirolimus/análogos & derivados , Serina-Treonina Quinasas TOR/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
BACKGROUND: To determine the relationship between obesity, diabetes, and survival in a large cohort of breast cancer patients receiving modern chemotherapy and endocrine therapy. PATIENTS AND METHODS: We identified 6342 patients with stage I-III breast cancer treated between 1996 and 2005. Patients were evaluated according to body mass index (BMI) category and diabetes status. RESULTS: In a multivariate model adjusted for body mass index, diabetes, medical comorbidities, patient- and tumor-related variables, and adjuvant therapies, relative to the normal weight, hazard ratios (HRs) for recurrence-free survival (RFS), overall survival (OS), and breast cancer-specific survival (BCSS) for the overweight were 1.18 [95% confidence interval (CI) 1.02-1.36], 1.20 (95% CI 1.00-1.42), and 1.21 (95% CI 0.98-1.48), respectively. HRs for RFS, OS, and BCSS for the obese were 1.13 (95% CI 0.98-1.31), 1.24 (95% CI 1.04-1.48), and 1.23 (95% CI 1.00-1.52), respectively. Subset analyses showed these differences were significant for the ER-positive, but not ER-negative or HER2-positive, groups. Relative to nondiabetics, HRs for diabetics for RFS, OS, and BCSS were 1.21 (95% CI 0.98-1.49), 1.39 (95% CI 1.10-1.77), and 1.04 (95% CI 0.75-1.45), respectively. CONCLUSIONS: In patients receiving modern adjuvant therapies, obesity has a negative impact on RFS, OS, and BCSS; and diabetes has a negative impact on RFS and OS. Control of both may be important to improving survival in obese and diabetic breast cancer patients.
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Neoplasias de la Mama/mortalidad , Diabetes Mellitus/epidemiología , Obesidad/epidemiología , Antraciclinas/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Inhibidores de la Aromatasa/uso terapéutico , Composición Corporal , Índice de Masa Corporal , Neoplasias de la Mama/tratamiento farmacológico , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Paclitaxel/uso terapéutico , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Sobrevida , Tamoxifeno/uso terapéutico , Taxoides/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Approximately 2000 American men are diagnosed with breast cancer every year. Limited data are available evaluating toxicity of antihormonal treatments in male breast cancer patients. PATIENTS AND METHODS: We reviewed male breast cancer patients evaluated at our institution (1999-2009). Of 126 patients, 64 met the following inclusion criteria: stage I-III, treated with tamoxifen, at least one follow-up visit after starting tamoxifen. A descriptive analysis of toxic effects was carried out on these 64 patients. RESULTS: Median follow-up from start of tamoxifen therapy was 3.9 years (range 0.3-19.4 years). Median age at diagnosis was 61 years (range 30-79 years). Breakdown by stage: 29.7% (n = 19) stage I, 54.7% (n = 35) stage II, and 15.6% (n = 10) stage III. Thirty-four (53%) patients experienced one or more toxicity while taking tamoxifen. Most common toxic effects are weight gain (14 patients, 22%) and sexual dysfunction (14 patients, 22%). Thirteen (20.3%) patients discontinued tamoxifen due to toxicity: one ocular, one leg cramps, two neurocognitive deficits, two bone pain, three sexual dysfunction, and four thromboembolic events. CONCLUSIONS: To our knowledge, this is the largest study examining tamoxifen-related toxic effects among male breast cancer patients. Among male patients, there is a high rate of discontinuation of tamoxifen. Prospective studies of antihormonal agents in male breast cancer are warranted.
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Antineoplásicos Hormonales/efectos adversos , Neoplasias de la Mama Masculina/tratamiento farmacológico , Tamoxifeno/efectos adversos , Antineoplásicos Hormonales/uso terapéutico , Humanos , Masculino , Estudios Retrospectivos , Disfunciones Sexuales Fisiológicas/inducido químicamente , Tamoxifeno/uso terapéutico , Negativa del Paciente al Tratamiento , Aumento de Peso/efectos de los fármacosRESUMEN
BACKGROUND: The purpose of this study is to evaluate the risk factors and the prevalence of thromboembolic events (TEEs) in breast cancer patients. PATIENTS AND METHODS: This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results-Medicare database. Breast cancer patients diagnosed from 1992 to 2005 ≥66 years old were identified. International Classification of Diseases, Ninth Revision, and Healthcare Common Procedure Coding System codes were used to identify TEEs within 1 year of the breast cancer diagnosis. Analyses were conducted using descriptive statistics and logistic regression. RESULTS: A total of 89 841 patients were included, of them 2658 (2.96%) developed a TEE. In the multivariable analysis, males had higher risk of a TEE than women [odd ratio (OR) = 1.57; confidence interval (CI) 1.10-2.25] and blacks had higher risk than whites (OR = 1.20; CI 1.04-1.40). Compared with stage I patients, patients with stage II, III and IV had 22%, 39% and 98% increase, respectively, in risk. Placement of central catheters (OR = 2.71; CI 2.43-3.02), chemotherapy treatment (OR = 1.66; CI 1.48-1.86) or treatment with erythropoiesis-stimulating agents (ESAs) (OR = 1.33; CI 1.33-1.52) increase the risk. Other significant predictors included comorbidities, age, receptor status, marital status and year of diagnosis. Similar estimates were seen for pulmonary embolism, deep vein thromboembolism and other TEEs. CONCLUSIONS: In total, 2.96% of patients in this cohort developed a TEE within 1 year from breast cancer diagnosis. Stage, gender, race, use of chemotherapy and ESAs, comorbidities, receptor status and catheter placement were associated with the development of TEEs.
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Neoplasias de la Mama Masculina/epidemiología , Neoplasias de la Mama/epidemiología , Tromboembolia/epidemiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Neoplasias de la Mama Masculina/sangre , Neoplasias de la Mama Masculina/patología , Femenino , Humanos , Masculino , Estadificación de Neoplasias , Prevalencia , Factores de Riesgo , Programa de VERF , Tromboembolia/etiología , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: The objective of this retrospective study was to determine whether differences in survival exist between women with de novo stage IV and relapsed breast cancer. PATIENTS AND METHODS: Three thousand five hundred and twenty-four women with de novo stage IV or relapsed breast cancer diagnosed from 1992 to 2007 were identified. Disease-free interval (DFI) was defined as the time from the diagnosis of primary nonmetastatic breast cancer to the date of the first distant metastases. Kaplan-Meier product limit method was used to estimate overall survival (OS). Cox proportional hazards model was fitted to determine the association between metastatic disease (relapsed versus de novo) and OS after controlling for other patient/tumor characteristics. RESULTS: Six hundred and forty-three (18.2%) women had de novo stage IV disease and 2881 (81.8%) had relapsed disease. Median follow-up was 19 months. Median OS among patients with de novo stage IV and relapsed disease was 39.2 and 27.2 months, respectively (P < 0.0001). In the multivariable model, women with relapsed disease had an increased risk of death compared with patients with de novo disease (HR = 1.75, 95% confidence interval 1.47-2.08, P < 0.0001). When the multivariable model was stratified by DFI, women with relapsed disease with DFI <6 months, ≥6 months to <2 years, or ≥2 to <5 years each had a significantly higher risk of death compared with women with de novo stage IV disease. The risk of death was not statistically different among patients with relapsed disease with DFI >5 years compared with those with de novo disease. CONCLUSIONS: This large cohort study provides further insight into the natural history of relapsed and de novo stage IV breast cancer. DFI plays an important role in the prognosis for patients with relapsed breast cancer.