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BACKGROUND: Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its prognostic impact on prognosis of young patients harboring a pathogenic variant (PV) in the BRCA1 and/or BRCA2 genes. PATIENTS AND METHODS: This international, multicenter, retrospective cohort study included young patients (aged ≤40 years) diagnosed with invasive breast cancer and harboring germline PVs in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest [disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS)] were first investigated according to hormone receptor expression (positive versus negative), and then according to breast cancer subtype [luminal A-like versus luminal B-like versus triple-negative versus human epidermal growth factor receptor 2 (HER2)-positive breast cancer]. RESULTS: From 78 centers worldwide, 4709 BRCA carriers were included, of whom 2143 (45.5%) had hormone receptor-positive and 2566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% versus 9.6%, P < 0.001), while the rate of second primary breast cancer was lower (9.1% versus 14.7%, P < 0.001) compared to patients with hormone receptor-negative disease. The 8-year DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive versus negative disease changed over time for DFS, BCSS, and OS (P < 0.05 for interaction of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-year DFS: 60.8% in luminal A-like versus 63.5% in triple-negative versus 65.5% in HER2-positive and 69.7% in luminal B-like subtype). CONCLUSIONS: In young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor-positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.
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An all-plastic one dimensional photonic crystal microcavity incorporating a porphyrin based defect, with enhanced nonlinear optical properties is demonstrated. The results suggest that our system can be a potential candidate towards the realization of flexible and thus reconfigurable low power photonic devices suitable for low cost-scale integrated photonics technology.
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PURPOSE: The everolimus and exemestane combination represents a treatment option for the endocrine sensitive metastatic breast cancer (MBC) patients. The toxicity profile reported in the Bolero 2 trial showed the feasibility in the selected patients. Few data are available for the unselected population. METHODS: In order to evaluate the safety in the unselected population of the clinical practice and to evaluate a possible association of toxicities with previous treatments, clinical data from 181 consecutive patients were retrospectively collected. RESULTS: Due to toxic events, everolimus dosage was reduced to 5 mg in 27% of patients. No association was found in the analysis between toxicity and number of prior therapies, neither between toxicity and response. In the multivariate analysis the previous exposure to anthracyclines for advanced disease represents the only predictive factor of developing grade ≥2 toxicity (OR = 2.85 CI 95% 1.07-7.59, p = 0.036). CONCLUSIONS: The association of everolimus and exemestane has confirmed to be a safe and effective treatment for endocrine sensitive MBC patients even in routine clinical practice. The rate of treatment discontinuation due to toxicity is low and none association between previous number of treatments and response or between toxicity and response was found.
Assuntos
Androstadienos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Everolimo/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Androstadienos/administração & dosagem , Antraciclinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Everolimo/administração & dosagem , Feminino , Humanos , Itália , Pessoa de Meia-Idade , Metástase Neoplásica , Modelos de Riscos Proporcionais , Receptor ErbB-2/análise , Análise de Regressão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Obesity is an independent adverse prognostic factor in early breast cancer patients, but it is still controversial whether obesity may affect adjuvant endocrine therapy efficacy. The aim of our study (ancillary to the two clinical trials Gruppo Italiano Mammella (GIM)4 and GIM5) was to investigate whether the circulating oestrogen levels during treatment with the aromatase inhibitor letrozole are related to body mass index (BMI) in postmenopausal women with breast cancer. METHODS: Plasma concentration of oestrone sulphate (ES) was evaluated by radioimmunoassay in 370 patients. Plasma samples were obtained after at least 6 weeks of letrozole therapy (steady-state time). Patients were divided into four groups according to BMI. Differences among the geometric means (by ANOVA and ANCOVA) and correlation (by Spearman's rho) between the ES levels and BMI were assessed. RESULTS: Picomolar geometric mean values (95% confidence interval, n=patients) of circulating ES during letrozole were 58.6 (51.0-67.2, n=150) when BMI was <25.0 kg m(-2); 65.6 (57.8-74.6, n=154) when 25.0-29.9 kg m(-2); 59.3 (47.1-74.6, n=50) when 30.0-34.9 kg m(-2); and 43.3 (23.0-81.7, n=16) when ≥35.0 kg m(-2). No statistically significant difference in terms of ES levels among groups and no correlation with BMI were observed. CONCLUSIONS: Body mass index does not seem to affect circulating oestrogen levels in letrozole-treated patients.
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Antineoplásicos/uso terapêutico , Índice de Massa Corporal , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Estrona/análogos & derivados , Nitrilas/uso terapêutico , Triazóis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Estrona/sangue , Feminino , Humanos , Letrozol , Pessoa de Meia-Idade , Pós-Menopausa/sangueRESUMO
BACKGROUND: Homocysteinemia has been associated with oncogenic risk. This study was designed to investigate the homocysteine (Hcy) genotype/phenotype interactions together with the inflammatory and nutritional status of cancer patients. PATIENTS AND METHODS: The Hcy levels were analyzed in 47 cancer patients in association with methylenetetrahydrofolate reductase (MTHFR) polymorphisms, folate and inflammatory markers. RESULTS: The MTHFR C677T and A1298C genotype distributions did not differ from those predicted by the Hardy-Weinberg distribution. Conversely, the Hcy levels were higher in the cancer patients (p=0.04), who were also characterized by low-grade inflammation. The Hcy levels correlated with the interleukin-6 (IL-6) (p=0.001), tumor necrosis factor-alpha (TNF-alpha) (p=0.042) and folate (p<0.0001) levels of the patients. Multivariate analysis showed that TNF-alpha (p=0.014) and folate (p=0.019) were independent predictors of elevated Hcy levels in the cancer patients. CONCLUSION: The MTHFR polymorphisms do not significantly contribute to tHcy (total Hcy) levels in cancer patients, and cancer-related inflammation may be associated with elevated tHcy levels, possibly involving a TNF-alpha mediated pathway.
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Neoplasias da Mama/sangue , Neoplasias Colorretais/sangue , Homocisteína/sangue , Adulto , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Estudos de Casos e Controles , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/genética , Feminino , Ácido Fólico/sangue , Humanos , Mediadores da Inflamação/sangue , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Estado Nutricional , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Fotemustine is a cytotoxic alkylating agent, belonging to the group of nitrosourea family. Its mechanism of action is similar to that of other nitrosoureas, characterized by a mono-functional/bi-functional alkylating activity. Worth of consideration is the finding that the presence of high levels of the DNA repair enzyme O6-methylguanine-DNA-methyltransferase (MGMT) in cancer cells confers drug resistance. In different clinical trials Fotemustine showed a remarkable antitumor activity as single agent, and in association with other antineoplastic compounds or treatment modalities. Moreover, its toxicity is generally considered acceptable. The drug has been employed in the treatment of metastatic melanoma, and, on the basis of its pharmacokinetic properties, in brain tumors, either primitive or metastatic. Moreover, Fotemustine shows pharmacodynamic properties similar to those of mono-functional alkylating compounds (e.g. DNA methylating drugs, such as Temozolomide), that have been recently considered for the management of acute refractory leukaemia. Therefore, it is reasonable to assume that this agent could be a good candidate to play a potential role in haematological malignancies.
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Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Compostos de Nitrosoureia/uso terapêutico , Compostos Organofosforados/uso terapêutico , Animais , Antineoplásicos/farmacocinética , Reparo do DNA , Resistencia a Medicamentos Antineoplásicos , Humanos , Modelos Animais , Neoplasias/enzimologia , Neoplasias/genética , Compostos de Nitrosoureia/farmacocinética , Compostos Organofosforados/farmacocinéticaRESUMO
The impact of neurocysticercosis in Africa is not well known, and its role in the occurrence of epilepsy is not well defined. The concomitant high prevalence of both diseases in this region suggests a causal association of cysticercosis and epilepsy. The few attempts to find such a link in Africa have yielded discordant data. In order to answer this question, we conducted a case-control study between June and August 1998 in the Bilomo village in Central Cameroon, where a recent study had demonstrated very high epilepsy prevalence of 58/1000. Ninety-three epilepsy patients and eighty-one age matched controls were included. All subjects were examined by a neurologist and serology for cysticercosis was performed using an ELISA method. Serologies for cysticercosis were positive in twenty-nine out of one hundred and seventy four patients (16.7%; 95% CI: 11.6-23.2). Seventeen cases (18.3%) and twelve controls (14.8%) had a positive serology The odd ratio was 1.3 (95% CI: 0.6-3.0). This study was not in favour of an epidemiological relationship between cysticercosis infection and epileptic disorders.