RESUMEN
Metronomic chemotherapy is a treatment option for metastatic breast cancer (MBC) patients who require prolonged disease control without cumulative toxicity. Data available on the efficacy and tolerability of prolonged usage of metronomic therapy are limited. We analyzed patients with MBC, enrolled in a clinical trial, who obtained a prolonged clinical benefit for a duration of at least 12 months with vinorelbine 30 or 40 mg orally three times a week, cyclophosphamide 50 mg daily and capecitabine 500 mg three times a day (VEX regimen). The patients were treated at the European Institute of Oncology, Milan. We identified 67 MBC patients. The median age before starting the VEX regimen was 53 years. There were 59 patients (88%) who had hormone-receptors positive and HER2 negative BC. We had 37 patients who received VEX as the first-line treatment for MBC, while 30 patients were pretreated. The objective response rate was 49% (95% CI, 37-62). The median duration of VEX treatment after the first year was 14 months (min-max range 0.3-81.3 months). The progression-free survival at 3 years was 25.4% (95% CI, 15.7-36.2) and at 4 years was 18.5% (95% CI, 10.1-28.8 time 0 corresponds to 1 year after starting VEX). A total of 25 patients required a dose reduction, 7% of patients experienced G3 hand and foot syndrome. Metronomic VEX regimen can induce prolonged clinical benefit in MBC. On the basis of this long-term safety evaluation, there is no evidence of specific cumulative or delayed toxicities with metronomic chemotherapy.
Asunto(s)
Administración Metronómica , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Capecitabina/uso terapéutico , Ciclofosfamida/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Supervivencia sin Progresión , Vinorelbina/uso terapéuticoRESUMEN
BACKGROUND: Chemotherapy-induced alopecia (CIA) is a distressing side effect of cancer therapy. The trial aimed to assess feasibility and effectiveness of scalp-cooling system DigniCap® to prevent CIA in primary breast cancer patients receiving an anthracycline containing adjuvant chemotherapy (CT). METHODS: Hair loss (HL) was evaluated by patient self-assessment and by the physician according to the Dean's scale at baseline and after each cycle of CT. The primary efficacy endpoint was the patient self-assessment HL score evaluated at least 3 weeks after completing CT. A Dean's scale score of 0-2 (i.e. HL ≤50%) was considered a success. RESULTS: From July 2014 to November 2016, 139 consecutive breast cancer patients were enrolled and received at least one treatment with scalp cooling. Fifty-six out of 131 evaluated patients successfully prevented HL (43%, 95% CI: 34-51%). Twenty-four patients (32%) discontinued the scalp cooling because of alopecia or scalp-cooling related AE, three patients had missing information on CIA, and 48 patients (64%) had a HL greater than 50% after CT. No serious AEs were reported. CONCLUSIONS: DigniCap® System resulted as a promising medical device to be safely integrated in supportive care of early breast cancer patients. Longer follow-up is needed to assess long-term safety and feasibility. CLINICAL TRIAL REGISTRATION NUMBER: NCT03712696.
Asunto(s)
Alopecia/prevención & control , Antraciclinas/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Anciano , Alopecia/inducido químicamente , Neoplasias de la Mama/psicología , Frío , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Cuero CabelludoRESUMEN
The purpose of this study was to assess the prognostic and predictive value of tumor-infiltrating lymphocytes (TILs) in the triple-negative breast cancer (TNBC) cohort of the phase III IBCSG trial 22-00, comparing low-dose oral 'metronomic' cyclophosphamide-methotrexate maintenance chemotherapy (CM-maintenance) to no-CM-maintenance in early breast cancer. TILs were evaluated in full-face hematoxylin-and-eosin-stained sections of tumor samples confirmed centrally as TNBC (< 1 % of ER and PgR immunoreactivity and absence of HER2 overexpression or amplification). Mononuclear cells were evaluated in the stromal area within the borders of the invasive tumor. The primary endpoint was breast cancer-free interval (BCFI). Cox proportional hazards regression model assessed the association of BCFI and secondary endpoints with TILs score. In the 647 tumor samples, the median percentage of TILs was 18 % (IQR = 8-40 %), with 18 % having TILs ≥ 50 % (lymphocyte-predominant breast cancer, LPBC). At a median follow-up of 6.9 years, TILs were associated with better prognosis. For every 10 % increase of TILs, BCFI risk reduction was 13 % (HR 0.87, 95 % CI 0.79-0.95,P = 0.003). DFS, DRFI, and OS risk reductions were 11 % (P = 0.005), 16 % (P = 0.003), and 17 % (P < 0.001), respectively. Multivariable analysis confirmed the independent prognostic value of TILs. No significant TILs-by-treatment interaction was observed (P = 0.39) for associations of TILs with BCFI, although patients with LPBC receiving CM-maintenance had a greater breast cancer risk reduction (HR 0.64,95 % CI 0.23-1.78) than those with non-LPBC (TILs < 50 %) (HR 0.96, 95 % CI 0.67-1.40). TILs score is a potent prognostic factor in patients with TNBC. Low-dose chemotherapy confers a greater (not statistically significant) clinical benefit in patients with LPBC.
Asunto(s)
Ciclofosfamida/administración & dosificación , Linfocitos Infiltrantes de Tumor/patología , Metotrexato/administración & dosificación , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Administración Metronómica , Adulto , Anciano , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Humanos , Quimioterapia de Mantención , Metotrexato/uso terapéutico , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
The aim of this study is to evaluate the outcome of occult breast cancer (OBC) in patients with axillary presentation overall and according to the immunohistochemically defined tumour subtypes. We reviewed information on 15,490 consecutive primary breast cancer patients, who underwent surgery at the European institute of oncology between September 1997 and December 2008. Patients with OBC were compared with an equal number of patients with small invasive breast carcinomas (pT1) observed at the same institution during the same period, matched for year of surgery, age, nodal status and biological features. Eighty patients with OBC (study group) and 80 patients with early breast cancer (control group) were identified. There was no significant difference in the disease-free survival (5 years DFS 66 vs. 68% P = 0.91) and the overall survival (5 years OS 80 and 86% P = 0.99) between the OBC and control groups. A statistically significant worse outcome was observed within the group of OBC for patients with more than four involved lymph nodes and with triple negative tumours. The outcome of OBC patients is comparable with that of matched patients with small sized breast cancer. High risk of relapse and death was observed in OBC patients with triple negative tumours and extensive nodal involvement.
Asunto(s)
Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Adenocarcinoma/cirugía , Adulto , Axila , Neoplasias de la Mama/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Persona de Mediana Edad , Análisis Multivariante , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismoRESUMEN
BACKGROUND: Adjuvant chemotherapy for Luminal B-like breast cancers usually includes anthracycline-based regimens. However, some patients are reluctant to receive chemotherapy because of side-effects, especially alopecia, and ask for a "less intensive" or personalized approach. PATIENTS AND METHODS: We conducted a phase II feasibility trial to evaluate pegylated liposomal doxorubicin (PLD, Caelyx®) as adjuvant chemotherapy. Patients who received surgery for pT1-3, any N, and luminal B-like early-stage breast cancer (EBC) candidates for adjuvant chemotherapy were included. PLD was administered intravenously at 20 mg/m2 biweekly for eight courses. Endocrine therapy was given according to menopausal status. Trastuzumab was administered in HER2-positive disease. The primary endpoint was to evaluate the feasibility of this regimen, defined as the ability of a patient to achieve a relative dose intensity (RDI) of at least 85% of the eight cycles of treatment. Secondary endpoints included adverse events (AEs), tolerability, breast cancer-free survival, disease-free survival, and overall survival. RESULTS: From March 2016 to July 2018, 63 patients were included in the trial. Median age was 49 years (range: 33-76), with mostly pre- and peri-menopausal (65%) and stage I-II (94%). Only 5% of patients had HER2-positive EBC. Median RDI was 100% (range: 12.5-100%; interquartile range, IQR: 87.5-100%). The proportion of patients meeting the primary endpoint was 84% (95% confidence interval, CI: 73-92%). Overall, 55 out of 63 enrolled patients completed treatment (87%, 95% CI: 77-94%). Most common AEs were palmar-plantar erythrodysesthesia (12.2%), fatigue (10.4%), and mucositis (8.5%). Only 13% of patients had G3 AEs. None had alopecia. After a median follow-up of 3.9 years (range: 0.3-4.7) two distant events were observed, and all patients were alive at the date of last visit. CONCLUSIONS: The trial successfully met its primary endpoint: the regimen was feasible and well tolerated and could be considered for further evaluation as a treatment option for patients with contraindications to standard anthracyclines or requiring a personalized, less intensive approach.
Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/análogos & derivados , Estudios de Factibilidad , Femenino , Humanos , Persona de Mediana Edad , PolietilenglicolesRESUMEN
In order to evaluate the outcome of patients with breast cancer according to response after primary therapy and according to clinical and biologic baseline features, we identified patients who were treated with preoperative therapy and who underwent surgery at the European Institute of Oncology (IEO), Milan, Italy, between 1995 and 2006. The outcome of patients who achieved pathological complete remission (pCR) and patients with residual disease (RD) at final surgery was analyzed. Of the 687 patients treated with preoperative therapy, we identified 82 patients who achieved pCR (12%) and 605 patients with RD (88%). A statistically significant difference in disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) was observed for patients with pCR compared with those who had RD (5 year DFS 73% vs. 59% P = 0.029; 5 year DDFS 81% vs. 72% P = 0.085; 5 year OS 88% vs. 77% P = 0.033). At the multivariate analysis, for patients achieving pCR, large tumor size (> 5 cm) correlated with worse DFS (HR 3.18; 95% CI 1.34-7.51); clinical nodal involvement was associated with poorer DFS and DDFS (HR 6.94; 95% CI 1.62-29.73 and HR 9.87 95% CI 1.29-75.53, respectively). pCR after preoperative systemic therapy correlated with significant improved outcome. A substantial rate of relapse was observed for patients with large tumors and with clinical nodal involvement at baseline. Further improvement in adjuvant treatment might be warranted.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Mastectomía , Adulto , Biopsia , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Distribución de Chi-Cuadrado , Supervivencia sin Enfermedad , Femenino , Humanos , Italia , Estimación de Kaplan-Meier , Metástasis Linfática , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Neoplasia Residual , Selección de Paciente , Modelos de Riesgos Proporcionales , Radioterapia Adyuvante , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Carga TumoralRESUMEN
BACKGROUND: Triple negative breast cancer encompasses several biological entities with different outcomes and is a priority to identify which patients require more treatment to reduce the risk of recurrence and which patients need less treatment. PATIENTS AND METHODS: Among the 210 women with first primary invasive apocrine non metastatic breast cancer operated on between January 1998 and December 2016 at the European Institute Oncology, Milan, we identified 24 patients with a pT1-pT2, node-negative, triple negative subtype and Ki-67 ≤ 20% who did not receive adjuvant chemotherapy (CT). We compared the outcome of this cohort with a similar group of 24 patients with ductal tumors who received adjuvant chemotherapy, matched by pathological stage and biological features and also with a similar group of 12 patients with apocrine tumors who received adjuvant chemotherapy. RESULTS: The median age was 64 and 61 years in the apocrine (w/o CT) and ductal group, respectively. The median value of Ki-67 expression was 12% in the apocrine group (w/o CT) and 16% in the ductal group (p < 0.001). After a median follow-up of 7.5 years, no patients in the apocrine group (w/o CT) experienced a breast cancer related event compared with 4 events in the ductal carcinoma group (Gray test p-value = 0.11). CONCLUSIONS: The outcome of selected apocrine triple negative breast cancer patients who did not received adjuvant chemotherapy is excellent and supports a treatment de-escalation. Multicenter projects focusing on the possibility of avoiding adjuvant chemotherapy in selected subtypes of triple negative breast cancers with favorable outcome are warranted.
Asunto(s)
Neoplasias de la Mama/mortalidad , Carcinoma Ductal de Mama/mortalidad , Mastectomía/mortalidad , Neoplasias de la Mama Triple Negativas/mortalidad , Glándulas Apocrinas/patología , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/cirugía , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Humanos , Antígeno Ki-67/análisis , Persona de Mediana Edad , Recurrencia Local de Neoplasia/etiología , Pronóstico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/cirugíaRESUMEN
INTRODUCTION: We performed a retrospective analysis of HER2-overexpressing metastatic breast cancer patients to describe clinical outcomes of those who, despite progression of the disease (PD), maintained trastuzumab for multiple chemotherapy lines. We also compared survival of these patients with that of those who halted trastuzumab at first PD. METHODS: We identified 101 patients treated between July 2000 and January 2007. Nineteen were still receiving the first-line trastuzumab-based treatment without evidence of PD and were not included in this analysis. Of the remaining 82 patients, 59 retained trastuzumab for one or more additional lines of chemotherapy after PD, according to our institution policy. Twenty-three patients who changed treating institution and stopped trastuzumab at first progression were used as a control group. RESULTS: For patients retaining trastuzumab, the median follow-up was 39.6 months. Clinical outcomes showed the typical degradation between first and second lines of therapy which we would expect by halting trastuzumab at first progression. Response rates were 35% and 16% and median times to progression were 7.25 and 5.25 months for the first and second lines of trastuzumab therapy, respectively. The median overall survival (OS) rates were 70 months for patients who retained trastuzumab and 56 months for patients who halted the drug (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.51 to 1.18; P = 0.52). If we consider OS from the start of trastuzumab therapy, the figures are 53.9 and 34.8 months, respectively (HR 0.78, 95% CI 0.58 to 1.32; P = 0.2). CONCLUSION: A nonstatistically significant trend of improved survival for patients retaining trastuzumab is observed. This is in line with most retrospective analyses and recent randomized data. Retaining trastuzumab after progression is a reasonable option, but further randomized data are warranted to better define its role in comparison with other available options.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Adulto , Anciano , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales Humanizados , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Hibridación Fluorescente in Situ , Persona de Mediana Edad , Metástasis de la Neoplasia , Estudios Retrospectivos , Trastuzumab , Resultado del TratamientoRESUMEN
INTRODUCTION: Metastatic breast cancer typically involves the lungs, bones, brain, and liver and only occasionally affects the gastrointestinal (GI) tract. The relevant published data have been limited to case reports and small series of patients. PATIENTS AND METHODS: The present study focused on the treatment and outcomes of breast cancer patients with GI involvement diagnosed at the European Institute of Oncology. We analyzed the clinicopathologic features of the GI metastases and compared them with those of the primary tumors according to their histologic type (ductal or lobular carcinoma). RESULTS: From the database of the Department of Pathology, 40 patients who had undergone endoscopy or GI surgery with a final diagnosis of metastatic breast cancer from 2000 to 2014 were identified. The greatest proportion of patients (75%) had had primary invasive lobular carcinoma. Of the 40 patients, 82% had hormone receptor-positive disease in the metastatic lesion; 34 patients were candidates for systemic therapy. The median length of observation after GI metastasis was 18 months (range, 0.6-79 months). The overall survival from the diagnosis of GI involvement was 33 months (95% confidence interval, 16.8-38.3 months). CONCLUSION: Lobular breast carcinoma has a greater propensity to metastasize to the GI tract compared with other breast cancer subtypes. In the presence of GI symptoms, even if nonspecific, the GI tract should be thoroughly studied. Systemic treatment, including hormonal therapy, should be considered.
Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/mortalidad , Carcinoma Lobular/mortalidad , Neoplasias Gastrointestinales/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja Gruesa , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/terapia , Carcinoma Ductal de Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/secundario , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/diagnóstico por imagen , Carcinoma Lobular/secundario , Carcinoma Lobular/terapia , Quimioterapia Adyuvante/métodos , Endoscopía Gastrointestinal , Femenino , Neoplasias Gastrointestinales/diagnóstico por imagen , Neoplasias Gastrointestinales/secundario , Neoplasias Gastrointestinales/terapia , Tracto Gastrointestinal/diagnóstico por imagen , Tracto Gastrointestinal/cirugía , Humanos , Persona de Mediana Edad , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Few data are available on the benefit of metronomic cyclophosphamide, capecitabine, and vinorelbine as first-line therapy in patients with metastatic triple-negative breast cancer. METHODS: This phase II study assessed the safety and efficacy of metronomic oral chemotherapy with vinorelbine 40 mg orally 3 times a week, cyclophosphamide 50 mg daily, and capecitabine 500 mg 3 times a day (VEX regimen) in untreated metastatic triple-negative breast cancer patients. The biopsy of the metastatic site had to be triple-negative, independent of the hormone receptor expression of the primary tumor. The primary endpoint was time to progression (TTP). Secondary endpoints included assessment of safety and clinical benefit (objective response rate plus stable disease rate at ≥24 weeks). RESULTS: 25 patients were included, and 22 were evaluable for both efficacy and toxicities (median age, 66 years). Median TTP was 6.4 months (95% confidence interval 3.6-12.6). The most common grade 1-2 toxicities were nausea, diarrhea, leuko-/neutropenia, and reversible liver enzyme alteration. Grade 3 events included hand and foot syndrome (9%). CONCLUSION: The VEX regimen demonstrated activity and was relatively well tolerated when given as first-line therapy in selected metastatic breast cancer patients with triple-negative disease.
RESUMEN
BACKGROUND: Inflammatory breast cancer (IBC) is a rare and highly aggressive disease. A neoadjuvant regimen with chemotherapy and an antiangiogenic strategy was investigated. PATIENTS AND METHODS: Patients with primary or recurrent IBC who were candidates for neoadjuvant treatment received weekly carboplatin and paclitaxel plus bevacizumab every 3 weeks and oral metronomic cyclophosphamide for 6 months. Trastuzumab was added for patients with HER2+ tumors and endocrine therapy was added for patients with estrogen receptor and/or progesterone receptor ≥ 10% tumors. Oral metronomic capecitabine and cyclophosphamide was continued for 6 months after surgery in those patients with a response. The primary efficacy endpoints were pathologic complete remission (pCR) and the objective response. RESULTS: From July 2010 to December 2013, 34 patients with IBC were included. The surrogate intrinsic tumor subtypes were as follows: luminal B-like (HER2-), 10 (29%); luminal B-like (HER2+), 8 (24%); HER2+ (nonluminal), 6 (18%); and triple negative, 10 (29%). An objective response was obtained in 30 patients (88%; 95% confidence interval, 73%-97%) and a pCR in 10 patients (29%; 95% confidence interval, 15%-48%). The proportion of pCR was significantly greater in the patients with HER2+ tumors (57%) than in patients with triple-negative (20%) or luminal B-like (HER2-) tumors (0%; P = .019). After a median follow-up of 4.4 years, the 5-year disease-free survival and overall survival was 58% and 72%, respectively. The achievement of pCR was associated with longer disease-free (P = .12) and overall (P = .029) survival. CONCLUSION: In patients with IBC, neoadjuvant treatment with the investigated regimen was successful and well tolerated. Further studies evaluating the potential benefit of an antiangiogenic strategy in this setting are awaited.
Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Antineoplásicos Inmunológicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab/administración & dosificación , Neoplasias Inflamatorias de la Mama/tratamiento farmacológico , Terapia Neoadyuvante/métodos , Inhibidores de la Angiogénesis/efectos adversos , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/efectos adversos , Biomarcadores de Tumor/metabolismo , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Inflamatorias de la Mama/mortalidad , Neoplasias Inflamatorias de la Mama/patología , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: High levels of tumor-infiltrating lymphocytes (TILs) in primary triple negative and HER2-positive breast cancer (BC) have been associated with an improved patients' outcome. The role of TILs in Luminal (hormone receptor positive and HER2 negative) tumors remains to be elucidated. Moreover, the association between TILs and prognosis in the metastatic setting is still unknown. PATIENTS AND METHODS: We evaluated the relationship between TILs and time to progression (TTP) in metastatic BC patients enrolled in a prospective phase II trial of metronomic chemotherapy, that used cyclophosphamide 50 mg daily, capecitabine 500 mg thrice daily and vinorelbine 40 mg orally three times a week (VEX combination). RESULTS: Of the 108 ER + BC patients enrolled in the VEX trial, 92 (85%) had sufficient tumor tissue and were assessed for TILs in H&E stained slides. TILs were evaluated in 38 primary BC samples and 54 metastatic sites. High (≥10%) TILs levels were significantly correlated with high Ki-67 labeling index. At multivariable analysis, each 10% increase in TILs strongly predicted a worse TTP (HR: 1.27, p = 0.008). VEX trial patients, categorized by a 3 tiers system (0-4%, 5-9% and >10% TILs) showed significantly different progression free survival curves (p = 0.011). CONCLUSIONS: High TILs levels are significantly associated with a worse TTP in Luminal metastatic BC patients treated by metronomic chemotherapy. Our data confirm the reliability of TILs as a biomarker in the BC metastatic setting. The putative unfavorable prognostic role of TILs in Luminal BC patients might have clinical utility if validated by further studies.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/inmunología , Linfocitos Infiltrantes de Tumor , Administración Metronómica , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Capecitabina/administración & dosificación , Ciclofosfamida/administración & dosificación , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Antígeno Ki-67/metabolismo , Recuento de Linfocitos , Persona de Mediana Edad , Metástasis de la Neoplasia , Estudios Prospectivos , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Factores de Tiempo , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , VinorelbinaRESUMEN
In a phase II study we assessed the safety and efficacy of metronomic oral chemotherapy with vinorelbine, cyclophosphamide capecitabine in patients with metastatic breast cancer, either as first-line (naïve group) or second-line or greater therapy (pre-treated group). Eligible patients had histologically or cytologically proven, hormone-receptor positive metastatic breast cancer. The primary end point was median time to progression (TTP). A total of 43 patients in the naïve group and 65 in the pre-treated group were enrolled. The median TTP was 25.1 months in the naïve group and 11.2 months in the pre-treated group. The most frequently reported grade 2 treatment-related adverse events were leukopenia and hand and foot syndrome. Metronomic combination of cyclophosphamide, capecitabine and vinorelbine showed significant activity and good tolerability in patients hormonal receptor positive, metastatic breast cancer patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Capecitabina/administración & dosificación , Ciclofosfamida/administración & dosificación , Vinblastina/análogos & derivados , Administración Metronómica , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Capecitabina/efectos adversos , Ciclofosfamida/efectos adversos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Análisis Multivariante , Metástasis de la Neoplasia , Modelos de Riesgos Proporcionales , Factores de Tiempo , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , VinorelbinaRESUMEN
PURPOSE: Experimental data suggest a complex cross-talk between HER-2 and estrogen receptor, and it has been hypothesized that HER-2-positive tumors may be less responsive to certain endocrine treatments. Clinical data, however, have been conflicting. We have conducted a meta-analysis on the interaction between the response to endocrine treatment and the overexpression of HER-2 in metastatic breast cancer. EXPERIMENTAL DESIGN: Studies have been identified by searching the Medline, Embase, and American Society of Clinical Oncology abstract databases. Selection criteria were (a) metastatic breast cancer, (b) endocrine therapy (any line of treatment), and (c) evaluation of HER-2 expression (any method). For each study, the relative risk for treatment failure for HER-2-positive over HER-2-negative patients with 95% confidence interval was calculated as an estimate of the predictive effect of HER-2. Pooled estimates of the relative risk were computed by the Mantel-Haenszel method. RESULTS: Twelve studies (n = 2,379 patients) were included in the meta-analysis. The overall relative risk was 1.42 (95% confidence interval, 1.32-1.52; P < 0.00001; test for heterogeneity = 0.380). For studies involving tamoxifen, the pooled relative risk was 1.33 (95% confidence interval, 1.20-1.48; P < 0.00001; test for heterogeneity = 0.97); for studies involving other hormonal drugs, a pooled relative risk of 1.49 (95% confidence interval, 1.36-1.64; P < 0.00001; test for heterogeneity = 0.08) was estimated. A second meta-analysis limited to tumors that were either estrogen receptor positive, estrogen receptor unknown, or estrogen receptor negative/progesterone receptor positive yielded comparable results. CONCLUSIONS: HER-2-positive metastatic breast cancer is less responsive to any type of endocrine treatment. This effect holds in the subgroup of patients with positive or unknown steroid receptors.
Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Receptor ErbB-2/metabolismo , Tamoxifeno/uso terapéutico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Humanos , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Resultado del TratamientoRESUMEN
BACKGROUND: The aggressive biological behavior and the lack of target therapy prompts the search for new therapeutic approaches for triple-negative breast cancers. PATIENTS AND METHODS: We evaluated the efficacy in terms of Ki-67 variation and clinical response but also the toxicity of a neoadjuvant regimen based on metronomic principles including ECF (epidoxorubicin with cisplatin on day 1 with low-dose 5-fluorouracil in continuous infusion every 21 days for 4 courses) followed by paclitaxel (90 mg/m(2)) on day 1, 8, and 15 every 28 days for 3 courses in combination with metronomic oral cyclophosphamide 50 mg/d for 12 weeks in patients with HER2-negative breast cancer (T2-T4a-d, N0-3, M0) with estrogen receptor and progesterone receptor < 10%. RESULTS: We enrolled 34 patients from June 2009 to May 2013. All were considered evaluable on an intention-to treat basis. The mean difference between the percentage of Ki-67 positive cells evaluated in surgical resection specimens and in pretreatment tumor core biopsy was 41% (95% confidence interval [CI], 30-51; P < .0001) for the entire population, and 22% (95% CI, 7-38; P = .0097) in patients who did not achieve pathological complete response (pCR). Responses to the treatment were obtained in 31 patients [91%] of the patients, and 19 patients (56%; 95% CI, 35-70) had a pCR. Stable disease was observed in 3 patients and none had progressive disease. Grade ≥ 3 hematologic adverse events included leukopenia in 9% (3 of 34), neutropenia in 38% (13 of 34), and anemia in 3% (1 of 34) of patients. Nonhematologic Grade ≥ 3 toxicities included only stomatitis in 1 patient. CONCLUSION: A neoadjuvant program with an ECF regimen followed by weekly paclitaxel with metronomic cyclophosphamide proved to be very effective, with high pCR rates, reduction of Ki-67, and it was associated with a low toxicity profile.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante/métodos , Terapia Neoadyuvante/métodos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Adulto , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Epirrubicina/administración & dosificación , Epirrubicina/efectos adversos , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversosRESUMEN
BACKGROUND: Letrozole withdrawal for 3 months might permit estrogenic stimulation in residual resistant breast cancer disease susceptible to letrozole reintroduction. We investigated the impact of a 3-month letrozole-free interval on serum estradiol levels in patients with early stage breast cancer. PATIENTS AND METHODS: Postmenopausal women with estrogen receptor- and/or progesterone receptor-positive (> 10% of immunoreactive cells), node-negative early breast cancer were eligible. Patients received letrozole for 5 years with a 3-month treatment-free interval after the first year of therapy. The primary end point was to evaluate the increase in serum estradiol levels after a 3-month treatment-free interval. The secondary end points were the evaluations of other biologic markers (eg, follicle-stimulating hormone, luteinizing hormone, cholesterol, high-density lipoprotein, triglycerides, osteocalcin). RESULTS: From November 2007 to February 2012, 130 evaluable patients were enrolled. The median age was 61 years. Mean values of estradiol levels at time of discontinuation were 5.6 pg/mL (standard deviation 1.7). Estradiol levels increased after a 3-month treatment-free interval by a mean of 3.3 pg/mL (66%; P < .0001). Follicle-stimulating hormone and luteinizing hormone levels decreased from baseline by a mean of 7.5 mU/mL (P < .0001), and 1.4 mU/mL (P = .0062), respectively. Triglycerides decreased from baseline by a mean of 8.6 mg/dL (P = .036), and osteocalcin increased by a mean of 2.8 ng/mL (P = .013). CONCLUSION: Intermittent letrozole significantly affects estradiol levels.
Asunto(s)
Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Nitrilos/administración & dosificación , Posmenopausia , Triazoles/administración & dosificación , Anciano , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Quimioterapia Adyuvante/métodos , Femenino , Humanos , Letrozol , Persona de Mediana Edad , Receptores de Estrógenos/metabolismoRESUMEN
BACKGROUND: No analyses have investigated the prognostic role of medial presentation in breast cancer patients on disease-free survival (DFS) and overall survival according to immunohistochemically-defined subtypes. PATIENTS AND METHODS: We collected information from the institutional clinical database on consecutive breast cancer patients who underwent conservative surgery at the European Institute of Oncology, Milan, Italy, between 1994 and 2008. We compared the outcomes of patients with medial breast cancer with those of patients with nonmedial tumors observed at the institution during the same period. RESULTS: Among 7369 evaluable patients, 2254 (24%) had their primary tumors in medial quadrants and 7015 (76%) in other areas. Five-year DFS was 84.7% and 86.6% (P = .008) in patients with medial and nonmedial disease, respectively. In multivariate analysis, medial location was correlated with greater risk of recurrence (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.11-1.35; P < .0001) and death (HR, 1.27; 95% CI, 1.09-1.49; P = .0028). CONCLUSION: Medial presentation is an adverse prognostic factor for breast cancer patients.
Asunto(s)
Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Recurrencia Local de Neoplasia/mortalidad , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Italia , Estimación de Kaplan-Meier , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
Metronomic therapy (MT) refers to repetitive, low doses of chemotherapy drugs. MT exerts an effect not only on tumour cells, but also on their microenvironment. In particular, the low-dose schedule compromises the repairing process of endothelial cells, leading to an anti-angiogenic effect. In addition to the anti-angiogenic effect, MT could have an immunological action through the restoration of the anticancer effect of the immune system and induction of tumour dormancy. Consequently the association of targeted therapy with anti-angiogenic properties or specific immunologic drugs could enhance the efficacy of MT. During the past 15 years, several studies have been published evaluating the metronomic strategy in breast cancer. We conducted a systematic review of the results of phase I, II and III studies testing MT in breast cancer patients. The analyses included the efficacy and toxicity data of MT, and the future development of this strategy in breast cancer are also discussed. The systematic review presented here suggests that MT is a treatment option for breast cancer patients, has a low toxicity profile, efficacy in most patients and has potentially significant cost-effective advantages for public health.
Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Administración Metronómica , Femenino , HumanosRESUMEN
Breast cancer diagnosed in young patients has been reported to have a more aggressive biologic behaviour and to be associated with a more unfavorable prognosis compared with the disease in older patients. However controversies exist regarding the optimal treatment and if more aggressive therapies are really crucial in this population. Very young women with this disease are faced with personal, family, professional, and quality-of-life issues that further complicate the phase of treatment decision-making. Moreover it's mandatory in young patients to consider the impact of acute but also late toxicities in relation to long life-expectancy, too. Dose-dense and high-dose chemotherapy are two examples of more aggressive therapies that failed to show a clear beneficial in a feasible way compared to standard regimens also in young patients. The benefit evidenced in patients with ER-positive disease raises the hypothesis that efficacy of dose-intensive chemotherapy might simply be related to its endocrine effects. The study of the biology and of the oncogenic pathways should be a research priority so to aid management of young patients with breast cancer, and more important, to better tailor treatments that could be offered to young women or, simply to use better the modalities available today. For the time being, young age alone should not be a reason to prescribe more aggressive therapies and there are no evidence to recommend a specific chemotherapy regimen for young women.
RESUMEN
Tamoxifen alone or the combination of ovarian function suppression (OFS) and tamoxifen are the mainstay of hormonal therapy in premenopausal women with endocrine-responsive breast cancer. The results of large trials conducted with the third generation of aromatase inhibitors (AIs) in the metastatic, neoadjuvant and adjuvant setting, indicated better outcomes among postmenopausal breast cancer patients with endocrine responsive disease given AIs than among those given tamoxifen. These results supported the investigation of AIs in combination with OFS in premenopausal women with hormone receptor positive breast cancer. In this article we reviewed the efficacy and toxicity data on the use of AIs combined with OFS in premenopausal breast cancer patients in metastatic, neoadjuvant and adjuvant setting. Given the available evidence at the time in metastatic setting for premenopausal patients suitable of endocrine therapy the AI is a viable option, if tamoxifen resistance is proven, although mandates the use of OFS. In neoadjuvant setting the AIs in combination of OFS should not be used outside of a clinical trial. In the adjuvant setting, tamoxifen alone or OFS plus tamoxifen are reasonable options. Despite the lack of conclusive data favoring the combination of tamoxifen plus OFS, this treatment might be a reasonable option for subgroups of patients such as very young patients, OFS alone should nort be considered unless tamoxifen was contraindicated. Similarly, in cases where tamoxifen is contraindicated, AIs as an adjunct to OFS is a treatment option in premenopausal patients. New large randomized studies are required to confirm the role of OFS plus an AI in premenopausal women.