RESUMEN
BACKGROUND: Rates and risk factors of local, axillary and supraclavicular recurrences can guide patient selection and target for postmastectomy radiotherapy (PMRT). PATIENTS AND METHODS: Local, axillary and supraclavicular recurrences were evaluated in 8106 patients enrolled in 13 randomized trials. Patients received chemotherapy and/or endocrine therapy and mastectomy without radiotherapy. Median follow-up was 15.2 years. RESULTS: Ten-year cumulative incidence for chest wall recurrence of >15% was seen in patients aged <40 years (16.1%), with ≥4 positive nodes (16.5%) or 0-7 uninvolved nodes (15.1%); for supraclavicular failures >10%: ≥4 positive nodes (10.2%); for axillary failures of >5%: aged <40 years (5.1%), unknown primary tumor size (5.2%), 0-7 uninvolved nodes (5.2%). In patients with 1-3 positive nodes, 10-year cumulative incidence for chest wall recurrence of >15% were age <40, peritumoral vessel invasion or 0-7 uninvolved nodes. Age, number of positive nodes and number of uninvolved nodes were significant parameters for each locoregional relapse site. CONCLUSION: PMRT to the chest wall and supraclavicular fossa is supported in patients with ≥4 positive nodes. With 1-3 positive nodes, chest wall PMRT may be considered in patients aged <40 years, with 0-7 uninvolved nodes or with vascular invasion. The findings do not support PMRT to the dissected axilla.
Asunto(s)
Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Metástasis Linfática , Mastectomía , Recurrencia Local de Neoplasia , Adulto , Axila , Neoplasias de la Mama/patología , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Persona de Mediana Edad , Radioterapia Adyuvante , Receptores de Estrógenos/metabolismo , Factores de Riesgo , Insuficiencia del TratamientoRESUMEN
BACKGROUND: The benefit of adjuvant chemotherapy in postmenopausal patients with estrogen receptor (ER)-positive lymph node-negative breast cancer is being reassessed. PATIENTS AND METHODS: After stratification by ER status, 1669 postmenopausal patients with operable lymph node-negative breast cancer were randomly assigned to three 28-day courses of 'classical' CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy followed by tamoxifen for 57 months (CMFâtamoxifen) or to tamoxifen alone for 5 years. RESULTS: ERs were positive in 81% of tumors. At a median follow-up of 13.1 years, patients with ER-positive breast cancers did not benefit from CMF [13-year disease-free survival (DFS) 64% CMFâtamoxifen, 66% tamoxifen; P = 0.99], whereas CMF substantially improved the prognosis of patients with ER-negative breast cancer (13-year DFS 73% versus 57%, P = 0.001). Similarly, breast cancer-free interval (BCFI) was identical in the ER-positive cohort but significantly improved by chemotherapy in the ER-negative cohort (13-year BCFI 80% versus 63%, P = 0.001). CMF had no influence on second nonbreast malignancies or deaths from other causes. CONCLUSION: CMF is not beneficial in postmenopausal patients with node-negative ER-positive breast cancer but is highly effective within the ER-negative cohort. In the future, other markers of chemotherapy response may define a subset of patients with ER-positive tumors who may benefit from adjuvant chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Receptores de Estrógenos/biosíntesis , Anciano , Neoplasias de la Mama/patología , Ciclofosfamida/administración & dosificación , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Metástasis Linfática , Metotrexato/administración & dosificación , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Tamoxifeno/administración & dosificaciónRESUMEN
BACKGROUND: The International Breast Cancer Study Group Trial VIII compared long-term efficacy of endocrine therapy (goserelin), chemotherapy [cyclophosphamide, methotrexate and fluorouracil (CMF)], and chemoendocrine therapy (CMF followed by goserelin) for pre/perimenopausal women with lymph-node-negative breast cancer. PATIENTS AND METHODS: From 1990 to 1999, 1063 patients were randomized to receive (i) goserelin for 24 months (n = 346), (ii) six courses of 'classical' CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy (n = 360), or (iii) six courses of CMF plus 18 months goserelin (CMFâ goserelin; n = 357). Tumors were classified as estrogen receptor (ER) negative (19%), ER positive (80%), or ER unknown (1%); 19% of patients were younger than 40. Median follow-up was 12.1 years. RESULTS: For the ER-positive cohort, sequential therapy provided a statistically significant benefit in disease-free survival (DFS) (12-year DFS = 77%) compared with CMF alone (69%) and goserelin alone (68%) (P = 0.04 for each comparison), due largely to the effect in younger patients. Patients with ER-negative tumors whose treatment included CMF had similar DFS (12-year DFS CMF = 67%; 12-year DFS CMFâ goserelin = 69%) compared with goserelin alone (12-year DFS = 61%, P= NS). CONCLUSIONS: For pre/perimenopausal women with lymph-node-negative ER-positive breast cancer, CMF followed by goserelin improved DFS in comparison with either modality alone. The improvement was the most pronounced in those aged below 40, suggesting an endocrine effect of prolonged CMF-induced amenorrhea.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Antineoplásicos Hormonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Goserelina/administración & dosificación , Humanos , Ganglios Linfáticos/patología , Metotrexato/administración & dosificación , Persona de Mediana Edad , Estadificación de Neoplasias , Premenopausia , Receptores de Estrógenos/biosíntesisRESUMEN
BACKGROUND: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. PATIENTS AND METHODS: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin-eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). RESULTS: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. CONCLUSION: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy.
Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/patología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/irrigación sanguínea , Neoplasias de la Mama/patología , Quimioterapia Adyuvante/métodos , Ciclofosfamida/uso terapéutico , Progresión de la Enfermedad , Femenino , Fluorouracilo/uso terapéutico , Goserelina/uso terapéutico , Humanos , Menopausia/fisiología , Metotrexato/uso terapéutico , Persona de Mediana Edad , Invasividad Neoplásica , Neovascularización Patológica/diagnóstico , Valor Predictivo de las Pruebas , Pronóstico , Resultado del TratamientoRESUMEN
Selective estrogen receptor modulators (SERMs) and selective estrogen down regulators (SERDs) act as estrogen receptor (ER) agonists or antagonist depending on the targeted tissue and the specific configuration of the used SERM or SERD. Effects on bone, endometrium and breast cancer are of interest. Endocrine treatments have been used in breast cancer since the end of the 19th century. In the second part of the last century different compound of SERMs and SERDs have been developed and we will discuss them mainly as used in the treatment and prevention of breast cancer. Tamoxifen is the widely investigated and most used representative of these drugs and has been introduced in the advanced disease, in the neoadjuvant and adjuvant setting and for prevention of the disease. Its role has been challenged in the last years by the introduction of third generation aromatase inhibitors that have proven a higher activity than tamoxifen and a different toxicity pattern. Several other SERMs have been investigated, but none of them was clearly superior to tamoxifen. The main interest in different SERMs has to be seen in the slightly different safety profile between the different compounds. SERDs act as pure estrogen antagonist. They have been used in the treatment of advanced breast cancers and their role in other settings still needs further investigation. The increased use of aromatase inhibitors as first line endocrine therapy raises new questions on the role that tamoxifen and other SERMs or SERDs may play in breast cancer. The sequencing of endocrine therapies and the combination of endocrine therapies with new targeted therapies in hormone sensitive breast cancer remains a very important research issue. Polymorphisms in genes coding for tamoxifen metabolizing enzymes, as for instance, the CYP2D6 genotype, have the potential of becoming clinically useful predictive marker for tamoxifen response. With this meaningful newer knowledge it is possible that the place of tamoxifen in the treatment of breast cancer will be redefined in the future.
Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Moduladores de los Receptores de Estrógeno/uso terapéutico , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Anastrozol , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/prevención & control , Neoplasias de la Mama/terapia , Quimioterapia Adyuvante , Ensayos Clínicos como Asunto , Terapia Combinada , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Estradiol/análogos & derivados , Estradiol/uso terapéutico , Femenino , Fulvestrant , Genotipo , Humanos , Terapia Neoadyuvante , Nitrilos/uso terapéutico , Receptores de Estrógenos/efectos de los fármacos , Moduladores Selectivos de los Receptores de Estrógeno/farmacocinética , Tamoxifeno/efectos adversos , Tamoxifeno/farmacocinética , Tamoxifeno/uso terapéutico , Triazoles/uso terapéuticoRESUMEN
BACKGROUND: To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial. METHODS: We evaluated 4895 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial who received at least some study medication (median follow-up 60.3 months). Bone fracture information (grade, cause, site) was collected every 6 months during trial treatment. RESULTS: The incidence of bone fractures was higher among patients treated with letrozole [228 of 2448 women (9.3%)] versus tamoxifen [160 of 2447 women (6.5%)]. The wrist was the most common site of fracture in both treatment groups. Statistically significant risk factors for bone fractures during treatment included age, smoking history, osteoporosis at baseline, previous bone fracture, and previous hormone replacement therapy. CONCLUSIONS: Consistent with other trials comparing aromatase inhibitors to tamoxifen, letrozole was associated with an increase in bone fractures. Benefits of superior disease control associated with letrozole and lower incidence of fracture with tamoxifen should be considered with the risk profile for individual patients.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Mama/complicaciones , Fracturas Óseas/epidemiología , Nitrilos/uso terapéutico , Tamoxifeno/uso terapéutico , Triazoles/uso terapéutico , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Método Doble Ciego , Femenino , Fracturas Óseas/etiología , Humanos , Incidencia , Letrozol , Persona de Mediana Edad , Posmenopausia , Factores de RiesgoRESUMEN
BACKGROUND: Extracapsular tumor spread (ECS) has been identified as a possible risk factor for breast cancer recurrence, but controversy exists regarding its role in decision making for regional radiotherapy. This study evaluates ECS as a predictor of local, axillary, and supraclavicular recurrence. PATIENTS AND METHODS: International Breast Cancer Study Group Trial VI accrued 1475 eligible pre- and perimenopausal women with node-positive breast cancer who were randomly assigned to receive three to nine courses of classical combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil. ECS status was determined retrospectively in 933 patients based on review of pathology reports. Cumulative incidence and hazard ratios (HRs) were estimated using methods for competing risks analysis. Adjustment factors included treatment group and baseline patient and tumor characteristics. The median follow-up was 14 years. RESULTS: In univariable analysis, ECS was significantly associated with supraclavicular recurrence (HR = 1.96; 95% confidence interval 1.23-3.13; P = 0.005). HRs for local and axillary recurrence were 1.38 (P = 0.06) and 1.81 (P = 0.11), respectively. Following adjustment for number of lymph node metastases and other baseline prognostic factors, ECS was not significantly associated with any of the three recurrence types studied. CONCLUSIONS: Our results indicate that the decision for additional regional radiotherapy should not be based solely on the presence of ECS.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Recurrencia Local de Neoplasia/patología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/radioterapia , Terapia Combinada , Ciclofosfamida/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Metástasis Linfática , Metotrexato/administración & dosificación , Estadificación de Neoplasias , Premenopausia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: The role of chemotherapy in addition to combined endocrine therapy for premenopausal women with endocrine-responsive early breast cancer remains an open question, yet trials designed to answer it have repeatedly failed to adequately accrue. The International Breast Cancer Study Group initiated two concurrent trials in this population: in Premenopausal Endocrine Responsive Chemotherapy (PERCHE), chemotherapy use is determined by randomization and in Tamoxifen and Exemestane Trial (TEXT) by physician choice. PERCHE closed with inadequate accrual; TEXT accrued rapidly. METHODS: From 2003 to 2006, 1317 patients (890 with baseline data) were randomly assigned to receive ovarian function suppression (OFS) plus tamoxifen or OFS plus exemestane for 5 years in TEXT. We explore patient-related factors according to whether or not chemotherapy was given using descriptive statistics and classification and regression trees. RESULTS: Adjuvant chemotherapy was chosen for 64% of patients. Lymph node status was the predominant determinant of chemotherapy use (88% of node positive treated versus 46% of node negative). Geography, patient age, tumor size and grade were also determinants, but degree of receptor positivity and human epidermal growth factor receptor 2 status were not. CONCLUSIONS: The perceived estimation of increased risk of relapse is the primary determinant for using chemotherapy despite uncertainties regarding the degree of benefit it offers when added to combined endocrine therapy in this population.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Toma de Decisiones , Androstadienos/administración & dosificación , Antineoplásicos/administración & dosificación , Antineoplásicos Hormonales/administración & dosificación , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Femenino , Goserelina/administración & dosificación , Humanos , Premenopausia , Ensayos Clínicos Controlados Aleatorios como Asunto , Tamoxifeno/administración & dosificaciónRESUMEN
BACKGROUND: Low p27 and high Skp2 immunoreactivity are associated with a poor prognosis and other poor prognostic features including resistant phenotypes and antiestrogen drug resistance. We investigated these proteins in two International Breast Cancer Study Group trials studying node-negative early breast cancer. PATIENTS AND METHODS: Trial VIII compared chemotherapy followed by goserelin with either modality alone in premenopausal patients. Trial IX compared chemotherapy followed by tamoxifen with tamoxifen alone in postmenopausal patients. Central Pathology Office assessed p27 and Skp2 expression in the primary tumor by immunohistochemistry among 1631 (60%) trial patients. RESULTS: p27 and Skp2 were inversely related; 13% of tumors expressed low p27 and high Skp2. Low p27 and high Skp2 were associated with unfavorable prognostic factors including larger size and higher grade tumors, absence of estrogen receptor and progesterone receptor, human epidermal growth factor receptor 2 overexpression and high Ki-67 (each P < 0.05). Low p27 and high Skp2 were not associated with disease-free survival (P = 0.42 and P = 0.48, respectively). The relative effects of chemo-endocrine versus endocrine therapy were similar regardless of p27 or Skp2. CONCLUSIONS: We confirm the association of low p27 and high Skp2 with other poor prognostic features, but found no predictive or prognostic value, and therefore do not recommend routine determination of p27 and Skp2 for node-negative breast cancer.
Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/química , Neoplasias de la Mama/tratamiento farmacológico , Antígeno Nuclear de Célula en Proliferación/análisis , Proteínas Quinasas Asociadas a Fase-S/análisis , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/patología , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Goserelina/administración & dosificación , Humanos , Inmunohistoquímica , Metotrexato/administración & dosificación , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Tamoxifeno/administración & dosificación , Resultado del TratamientoRESUMEN
Quality of life (QL) is an important consideration when comparing adjuvant therapies for early breast cancer, especially if they differ substantially in toxicity. We evaluated QL and Q-TWiST among patients randomised to adjuvant dose-intensive epirubicin and cyclophosphamide administered with filgrastim and progenitor cell support (DI-EC) or standard-dose anthracycline-based chemotherapy (SD-CT). We estimated the duration of chemotherapy toxicity (TOX), time without disease symptoms and toxicity (TWiST), and time following relapse (REL). Patients scored QL indicators. Mean durations for the three transition times were weighted with patient reported utilities to obtain mean Q-TWiST. Patients receiving DI-EC reported worse QL during TOX, especially treatment burden (month 3: P<0.01), but a faster recovery 3 months following chemotherapy than patients receiving SD-CT, for example, less coping effort (P<0.01). Average Q-TWiST was 1.8 months longer for patients receiving DI-EC (95% CI, -2.5 to 6.1). Q-TWiST favoured DI-EC for most values of utilities attached to TOX and REL. Despite greater initial toxicity, quality-adjusted survival was similar or better with dose-intensive treatment as compared to standard treatment. Thus, QL considerations should not be prohibitive if future intensive therapies show superior efficacy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Adulto , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Epirrubicina/administración & dosificación , Femenino , Humanos , Estudios Longitudinales , Recurrencia Local de Neoplasia/tratamiento farmacológico , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
BACKGROUND: Aromatase inhibitors are considered standard adjuvant endocrine treatment of postmenopausal women with hormone receptor-positive breast cancer, but it remains uncertain whether aromatase inhibitors should be given upfront or sequentially with tamoxifen. Awaiting results from ongoing randomized trials, we examined prognostic factors of an early relapse among patients in the BIG 1-98 trial to aid in treatment choices. PATIENTS AND METHODS: Analyses included all 7707 eligible patients treated on BIG 1-98. The median follow-up was 2 years, and the primary end point was breast cancer relapse. Cox proportional hazards regression was used to identify prognostic factors. RESULTS: Two hundred and eighty-five patients (3.7%) had an early relapse (3.1% on letrozole, 4.4% on tamoxifen). Predictive factors for early relapse were node positivity (P < 0.001), absence of both receptors being positive (P < 0.001), high tumor grade (P < 0.001), HER-2 overexpression/amplification (P < 0.001), large tumor size (P = 0.001), treatment with tamoxifen (P = 0.002), and vascular invasion (P = 0.02). There were no significant interactions between treatment and the covariates, though letrozole appeared to provide a greater than average reduction in the risk of early relapse in patients with many involved lymph nodes, large tumors, and vascular invasion present. CONCLUSION: Upfront letrozole resulted in significantly fewer early relapses than tamoxifen, even after adjusting for significant prognostic factors.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Posmenopausia , Antineoplásicos Hormonales/administración & dosificación , Inhibidores de la Aromatasa/administración & dosificación , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Letrozol , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Nitrilos/administración & dosificación , Pronóstico , Tamoxifeno/administración & dosificación , Factores de Tiempo , Resultado del Tratamiento , Triazoles/administración & dosificaciónRESUMEN
BACKGROUND: We evaluated the ability of CA15-3 and alkaline phosphatase (ALP) to predict breast cancer recurrence. PATIENTS AND METHODS: Data from seven International Breast Cancer Study Group trials were combined. The primary end point was relapse-free survival (RFS) (time from randomization to first breast cancer recurrence), and analyses included 3953 patients with one or more CA15-3 and ALP measurement during their RFS period. CA15-3 was considered abnormal if >30 U/ml or >50% higher than the first value recorded; ALP was recorded as normal, abnormal, or equivocal. Cox proportional hazards models with a time-varying indicator for abnormal CA15-3 and/or ALP were utilized. RESULTS: Overall, 784 patients (20%) had a recurrence, before which 274 (35%) had one or more abnormal CA15-3 and 35 (4%) had one or more abnormal ALP. Risk of recurrence increased by 30% for patients with abnormal CA15-3 [hazard ratio (HR) = 1.30; P = 0.0005], and by 4% for those with abnormal ALP (HR = 1.04; P = 0.82). Recurrence risk was greatest for patients with either (HR = 2.40; P < 0.0001) and with both (HR = 4.69; P < 0.0001) biomarkers abnormal. ALP better predicted liver recurrence. CONCLUSIONS: CA15-3 was better able to predict breast cancer recurrence than ALP, but use of both biomarkers together provided a better early indicator of recurrence. Whether routine use of these biomarkers improves overall survival remains an open question.
Asunto(s)
Fosfatasa Alcalina/sangre , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/diagnóstico , Mucina-1/sangre , Neoplasias de la Mama/sangre , Femenino , Humanos , Recurrencia Local de Neoplasia , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
BACKGROUND: We sought to determine whether a high-risk group could be defined among patients with operable breast cancer in whom a search of occult central nervous system (CNS) metastases was justified. PATIENTS AND METHODS: We evaluated data from 9524 women with early breast cancer (42% node-negative) who were randomized in International Breast Cancer Study Group clinical trials between 1978 and 1999, and treated without anthracyclines, taxanes, or trastuzumab. We identified patients whose site of first event was CNS and those who had a CNS event at any time. RESULTS: Median follow-up was 13 years. The 10-year incidence (10-yr) of CNS relapse was 5.2% (1.3% as first recurrence). Factors predictive of CNS as first recurrence included: node-positive disease (10-yr = 2.2% for > 3 N+), estrogen receptor-negative (2.3%), tumor size > 2 cm (1.7%), tumor grade 3 (2.0%), < 35 years old (2.2%), HER2-positive (2.7%), and estrogen receptor-negative and node-positive (2.6%). The risk of subsequent CNS recurrence was elevated in patients experiencing lung metastases (10-yr = 16.4%). CONCLUSION: Based on this large cohort we were able to define risk factors for CNS metastases, but could not define a group at sufficient risk to justify routine screening for occult CNS metastases.
Asunto(s)
Neoplasias de la Mama/patología , Neoplasias del Sistema Nervioso Central/secundario , Neoplasias de la Mama/mortalidad , Neoplasias del Sistema Nervioso Central/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Premenopausia , Modelos de Riesgos Proporcionales , Recurrencia , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
BACKGROUND: Controversy persists about whether chemotherapy benefits all breast cancer patients. PATIENTS AND METHODS: In the International Breast Cancer Study Group (IBCSG) trial VII, 1212 postmenopausal patients with node-positive disease were randomized to receive tamoxifen for 5 years or tamoxifen plus three concurrent courses of cyclophosphamide, methotrexate and 5-fluorouracil ('classical' CMF) chemotherapy, either early, delayed or both. In IBCSG trial IX, 1669 postmenopausal patients with node-negative disease were randomized to receive either tamoxifen alone or three courses of adjuvant classical CMF prior to tamoxifen. Results were assessed according to estrogen receptor (ER) content of the primary tumor. RESULTS: For patients with node-positive, ER-positive disease, adding CMF either early, delayed or both reduced the risk of relapse by 21% (P=0.06), 26% (P=0.02) and 25% (P=0.02), respectively, compared with tamoxifen alone. There was no difference in disease-free survival when CMF was given prior to tamoxifen in patients with node-negative, ER-positive tumors. CONCLUSIONS: CMF given concurrently (early, delayed or both) with tamoxifen was more effective than tamoxifen alone for patients with node-positive, endocrine-responsive breast cancer, supporting late administration of chemotherapy even after commencement of tamoxifen. In contrast, sequential CMF and tamoxifen for patients with node-negative, endocrine-responsive disease was ineffective.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Tamoxifeno/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/cirugía , Intervalos de Confianza , Ciclofosfamida/uso terapéutico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Femenino , Fluorouracilo/uso terapéutico , Humanos , Mastectomía Segmentaria , Metotrexato/uso terapéutico , Persona de Mediana Edad , Neoplasias Hormono-Dependientes/mortalidad , Neoplasias Hormono-Dependientes/cirugía , Posmenopausia , Probabilidad , Pronóstico , Valores de Referencia , Medición de Riesgo , Tasa de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
We evaluated quality of life (QL) and quality-adjusted survival in International Breast Cancer Study Group Trial IX, a randomised trial including 1669 eligible patients receiving tamoxifen for 5 years or three prior cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) followed by 57 months tamoxifen. During the time with CMF toxicity (Tox), without symptoms and toxicity (TWiST), and following relapse (Rel), patients scored their QL indicators and a utility indicator for subjective health estimation between 'perfect' and 'worst' health. Scores were averaged within Tox, TWiST and Rel and transformed to utilities. Mean durations for the three transition times were weighted with utilities to obtain mean quality-adjusted TWiST (Q-TWiST). Patients receiving CMF reported significantly worse scores for most QL domains at month 3, but less hot flushes. After completing chemotherapy, there were no differences by treatment groups. Benefits evaluated by Q-TWiST favoured the additional chemotherapy. CMF provided 3 more months of Q-TWiST for patients with ER-negative tumours, but CMF provided no benefit in Q-TWiST for patients with ER-positive tumours. Q-TWiST analysis based on patient ratings is feasible in large-scale cross-cultural clinical trials.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/mortalidad , Ciclofosfamida/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Ganglios Linfáticos/patología , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Estadificación de Neoplasias , Posmenopausia , Receptores de Estrógenos/metabolismo , Tasa de Supervivencia , Tamoxifeno/administración & dosificaciónRESUMEN
BACKGROUND: Few chemotherapy regimens are suitable for the treatment of elderly patients with advanced breast cancer. With the aim of finding a regimen with a low burden of subjective non-overlapping toxic effects, vinorelbine and capecitabine were chosen to be investigated in a phase I dose-finding study. PATIENTS AND METHODS: Thirty-six patients with advanced breast cancer were stratified for the presence of bone and non-bone involvement and treated at four dose levels from capecitabine 800 mg/m2 orally days 1-14 and vinorelbine 20 mg/m2 intravenously days 1 and 8, to capecitabine 1250 mg/m2 orally days 1-14 and vinorelbine 25 mg/m2 intravenously days 1 and 8, for a maximum of six cycles. None of the patients had received prior chemotherapy for metastatic/advanced disease. Fifty-three per cent of patients with bone metastases and 67% of patients without bone metastases had visceral disease. The median age was 70 years for the 15 with bone involvement patients and 73 years for the 21 without bone involvement patients. RESULTS: Twenty-eight patients were fully evaluable for hematological dose-limiting toxicity (DLT), and all patients for other DLTs and for antitumor activity. One DLT with grade 3 venous thrombosis at dose level 2 and two dose-limiting neutropenia events at level 3 occurred in patients without bone involvement. Two dose-limiting neutropenia events were observed at dose level 2 for patients with bone involvement. Thus, the recommended dose was defined at level 1 (capecitabine 1000 mg/m2 days 1-14 and vinorelbine 20 mg/m2 days 1 and 8) for patients with bone involvement. For patients without bone involvement, the recommended dose was at level 2 (capecitabine 1250 mg/m2 days 1-14 and vinorelbine 20 mg/m2 days 1 and 8). For patients without bone involvement the overall response rate was 48% and the time to progression (TTP) was 4.5 months [95% confidence interval (CI) 3.3-6.9]. For patients with bone involvement the overall response rate was 53% and TTP was 5.3 months (95% CI 2.7-7.8). CONCLUSIONS: This regimen of capecitabine and vinorelbine is well tolerated and effective in elderly patients with metastatic breast cancer. Toxicity was mainly hematological and was observed at a lower dose in patients with bone involvement. A phase II study with the two different dose levels for elderly patients with and without bone involvement is currently being conducted.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Vinblastina/análogos & derivados , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Capecitabina , Desoxicitidina/administración & dosificación , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Fluorouracilo/análogos & derivados , Humanos , Metástasis de la Neoplasia , Resultado del Tratamiento , Vinblastina/administración & dosificación , VinorelbinaAsunto(s)
Neoplasias de la Mama/etiología , Neoplasias de la Mama/patología , Terapia de Reemplazo de Hormonas , Recurrencia Local de Neoplasia , Anciano , Neoplasias de la Mama/genética , Femenino , Genes BRCA1 , Genes BRCA2 , Predisposición Genética a la Enfermedad , Humanos , Menopausia , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Breast cancer is extremely rare in children, and consequently no consensus has been reached on the optimal treatment modalities. The medical history and treatment plan for a 7.5-year old male breast cancer patient is described. Radical mastectomy with sentinel node biopsy was performed in October 2002. As no malignant cells were detected in the sentinel node, and no BRCA1-2 mutations were detected, no further radio- or chemotherapy was performed. A "wait-and-see" policy was decided on. Further treatment will be given if this becomes necessary with the development of metastases.
Asunto(s)
Neoplasias de la Mama Masculina/patología , Carcinoma/patología , Neoplasias de la Mama Masculina/genética , Neoplasias de la Mama Masculina/cirugía , Carcinoma/genética , Carcinoma/cirugía , Niño , Predisposición Genética a la Enfermedad , Humanos , MasculinoRESUMEN
BACKGROUND: Current information on the prognostic importance of body mass index (BMI) for patients with early breast cancer is based on a variety of equivocal reports. Few have data on BMI in relationship to systemic treatment. PATIENTS AND METHODS: Patients (6792) were randomized to International Breast Cancer Study Group trials from 1978 to 1993, studying chemotherapy and endocrine therapy. BMI was evaluated with eight other factors: menopausal status, nodal status, estrogen receptor status, progesterone receptor status, tumor size, vessel invasion, tumor grade and treatment. BMI was categorized as normal (< or =24.9), intermediate (25.0-29.9) or obese (> or =30.0). RESULTS: Patients with normal BMI had significantly longer overall survival (OS) and disease-free survival (DFS) than patients with intermediate or obese BMI in pairwise comparisons adjusted for other factors. Subset analyses showed the same effect in pre- and perimenopausal patients and in those receiving chemotherapy alone. When assessed globally and adjusted for other factors, BMI significantly influenced OS (P = 0.03) but not DFS (P = 0.12). CONCLUSIONS: BMI is an independent prognostic factor for OS in patients with breast cancer, especially among pre-/perimenopausal patients treated with chemotherapy without endocrine therapy.