A real-world study on the efficacy and safety analysis of paclitaxel liposome in advanced breast cancer / 中华肿瘤杂志

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.

Progestinas y cáncer de mama en terapia de reemplazo hormonal: cómo actúan y qué alternativas son más seguras / Progestins and breast cancer in hormone replacement therapy: how do they work, and what alternatives are safer

En algunos estudios se ha asociado a la terapia de reemplazo hormonal (TRH) con estrógenos y progestinas a un mayor riesgo de cáncer de mama que la terapia con estrógenos solos. Sin embargo, dependiendo de su naturaleza algunas progestinas serían más seguras que otras. Se buscaron y analizaron artículos atingentes al tema en las bases de datos Google Scholar, PubMed, Science, SciELO y Cochrane, introduciendo los siguientes términos: terapia de reemplazo hormonal y cáncer de mama, progestinas y cáncer de mama, receptor de progesterona. Específicamente se ha asociado a las progestinas sintéticas acetato de medroxiprogesterona, noretisterona y levonorgestrel con un mayor riesgo de cáncer de mama, no así a la progesterona natural, a la progesterona oral micronizada ni a la didrogesterona. La progesterona natural, progesterona micronizada y didrogesterona serían más seguras en TRH para evitar el desarrollo de cáncer de mama, lo que estaría dado por la mayor especificidad en su acción.

In some studies, hormone replacement therapy (HRT) with estrogens and progestins has been associated with a higher risk of breast cancer than therapy with estrogens alone. However, depending on their nature, some progestins may be safer than others. This article analyzes the mode of action of progesterone in breast tissue and also the role of some progestins in the development of this pathology. Articles related to the subject were searched for and analyzed in Google Scholar, PubMed, Science, SciELO and Cochrane databases, introducing the following terms: hormone replacement therapy and breast cancer, progestins and breast cancer, progesterone receptor. Specifically, synthetic progestins medroxyprogesterone acetate, norethisterone, and levonorgestrel have been associated with an increased risk of breast cancer, but not natural progesterone, micronized oral progesterone, or dydrogesterone. Natural progesterone, micronized progesterone and dydrogesterone would be safer in HRT to prevent the development of breast cancer, which would be due to the greater specificity of their action.

El organofosforado clorpirifos como disruptor estrogénico y factor de riesgo para el cáncer de mama / The organophosphorus chlorpyrifos as endocrine disruptor and breast cancer factor risk

El clorpirifos (CPF) es un insecticida de amplio espectro que se utiliza en Argentina y en otros países de Latinoamérica. Se emplea para el control de plagas en la producción de frutas, hortalizas, cereales y plantas ornamentales. El principal mecanismo de acción descripto para este insecticida es la inhibición de la acetilcolinesterasa. Sin embargo, reportes más recientes sugieren múltiples efectos del plaguicida independientes de la inhibición de esa enzima. El objetivo de este trabajo es transmitir a la comunidad los resultados de nuestras investigaciones obtenidos utilizando diferentes dosis de CPF en distintos modelos experimentales, tanto in vitro como in vivo. En relación a esto, hemos evidenciado una acción del CPF sobre el sistema redox celular que conduce al incremento de especies reactivas del oxígeno y consecuentemente a la activación de diferentes vías de señalización. Además, hemos determinado que el insecticida CPF puede comportarse como un disruptor endócrino modulando la acción de los estrógenos y alterando la normal estructura del tejido mamario. Nuestros resultados alertan sobre el impacto que este compuesto podría tener sobre la salud, sugiriendo la necesidad de revisar su uso dado que manifiesta acciones a dosis encontradas en el ambiente.

Chlorpyrifos (CPF) is a broad spectrum insecticide used in Argentina and other Latin American countries. It is commonly used for pest control in the production of fruits, vegetables, cereals and ornamental plants. The main mechanism of action described for this insecticide is the inhibition of acetylcholinesterase activity. However, more recent reports suggest multiple effects for this pesticide in an independent way from the inhibition of this enzyme. The objective of this work is to convey to the community the results of our investigations obtained using different doses of CPF in various experimental models, both in vitro and in vivo. In this connection, we have shown a CPF action on the cellular redox system which leads to increased reactive oxygen species and the consequent activation of different signaling pathways. In addition, we have determined that the insecticide CPF acts as an endocrine disruptor modulating the action of estrogen and altering the normal structure of breast tissue. Our findings warn about the impact that this compound might have on health, suggesting the need to review its use since adverse actions were found at environmentally relevant doses.

Folatos y riesgo de cáncer de mama: revisión sistemática / Folate and breast cancer risk: A systematic review

An increased folate intake may be beneficial in deficient populations. However, in women with adequate levels it may not deliver additional benefits while it may increase the risk for some forms of cancer. A systematic literature review of benefits or risks of folate in the development of breast cancer was performed using MEDLINE, systematic review of selected articles and references of the selected articles looking specifically at serum folate levels, dietary folate intake or total folate intake and the risk of developing breast cancer. Fourteen case-control studies, fourteen cohort studies, seven case-control nested studies, two randomized trials and two meta-analyses were selected for analysis based on pre-established criteria. The reviewed evidence does not support the hypothesis that higher intakes of dietary folate reduce the risk for breast cancer. Some studies showed a higher risk of breast cancer in populations exposed to high folate intake post fortification, especially when folic acid is used. The results support the need to be cautious and to limit the exposure of women to high intakes of folic acid, especially in countries with mandatory food fortification.

Progestógenos: farmacologia e uso clínico / Progestagens: pharmacology and clinical use

Os progestógenos são esteroides que podem ser sintéticos ou naturais. A progesterona é o único progestágeno natural. Os progestógenos sintéticos tentam mimetizar o efeito da progesterona, e são chamados de progestinas. Cada progestina apresenta diferentes propriedades farmacológicas, dependendo da molécula da qual foi originada, usualmente testosterona e progesterona. Pequenas mudanças estruturais nas moléculas originais levam a diferenças consideráveis na atividade de cada uma das progestinas. O objetivo deste trabalho é revisar a origem dos progestógenos, as peculiaridades de cada grupo e seu uso clínico mais comum. As informações já levantadas sobre o efeito das progestinas em patologias importantes e prevalentes, como o câncer de mama e eventos tromboembólicos, também será abordado.

Progestagens are natural or synthetic steroids, and progesterone is the only natural one. Synthetic progestagens, called progestins, were created to mimic the effects of natural progesterone. The progestins have different pharmacological properties depending on the parent molecule, usually testosterone or progesterone, from which they are derived. Very small structural changes in the original molecule may induce considerable differences in the activity of the derivative. The aim of this paper is to review the origin of each progestin, the peculiarities of each group and its most common clinical use. The current knowledge about the effect of progestins on important and prevalent diseases, such as breast cancer and thromboembolic events, will also be addressed.

Modelo experimental de carcinoma mamário em ratas induzidas com 7, 12-dimetilbenz(a)antraceno / Induction of experimental mammary carcinogenesis in rats with 7, 12-dimethylbenz(a)anthracene

Objetivo: Testar um modelo experimental de indução de carcinogênese em raras Sprague-Dawley. Métodos: Foram estudadas 30 ratas fêmeas virgens Sprague-Dawley, induzidas ao carcinogênese mamário. Com 50 dias de vida, foi injectado 7,12-dimerilbenz(a)antrace no ventre por gavage. Com 12 semanas, as glândulas mamárias foram examinadas, assim como os tecidos cerebrais, pulmonares, ossos do fêmur e fígado. Resultados: Doze semanas após a injeção de DMBA, 85% das ratas apresentaram pelo menos um tumor mamário visível. Conclusão: O modelo experimental de carcinoma mamário induzido por DMBA mostrou-se efetivo e de fácil reprodução.

Objective: To test an experimental model of chemical mammary carcinogenesis induction in Sprague-Dawley rats. Methods: Thirty virgin Sprague-Dawley female rats, aged 50 days, received 20 mg of 7,12-dimethyLbenz(a)anthracene (DMBA) intragastrically by gavage. At 12 week their mammary glands were examined. Brain, Liver, bone and Lung tissue were also analyzed. Results: Twelve weeks after DMBA injection, 85% rats presented at Least one breast tumor. Conclusion: This experimental animal model of chemical mammary induced carcinogenesis is feasible and can be used in further experiments on the role of tumorigenic biomodulator substances.

[ effect of Dorema aucheri extract on breast tumor induced by DBMA in rats]

Dorema aucheri is from the piaceae family that exists in margins of Zagros mountains in Iran. In this study, the effect of 200 and 400 mg doses of Dorema aucheri extract on DMBA induced breast tumors in rats was investigated. This experimental study, was conducted in Herbal Medicine Research Center of Yasuj University of Medical Sciences. Forty rats were allocated in experimental and control groups. In experimental groups, after receiving DMBA, Dorema aucheri alcoholic extract in doses of 200 and 400 mg/kg of body weight were used orally for 12 weeks. One group of control animals received DMBA only and the other group received 200 mg of Dorema aucheri extract. At the end of 12 weeks, the tumor mass was isolated and evaluated by hematoxylin eosin histology staining. The average tumor size, number of tumors, and histology of tumors in groups were compared. The gathered data were analyzed using SPSS version 18, using ANOVA and Paired T test. Mean of tumor number were significantly different in experimental and control groups. No tumor was seen in control group which received 200 mg of the extract while breast tumor was seen in other groups. Mean of tumor number in animals which received 400 mg of extract was significantly higher that the other groups [p<0.05]. It seems that the dose of 400 mg extract of Dorema aucheri increases the tumor size, causes weight loss, decreases longevity and durability of rats while dose of 200 mg of extract reduces the tumor growth and tumor necrosis in Sprague Dawley female rat's with breast tumor induced by DMBA

Terapia hormonal da pós-menopausa e câncer: [revisão] / Postmenopausal hormone therapy and cancer: [review]

O objetivo desta revisão é analisar as principais evidências clínicas sobre os efeitos da terapia hormonal da pós-menopausa no risco de desenvolver neoplasias mamária, endometrial, ovariana e colorretal. As principais considerações: a) as mulheres devem ser orientadas sobre a associação entre terapia hormonal e risco de câncer de mama, apesar do risco absoluto ainda permanecer relativamente baixo b) mulheres com antecedente de câncer de mama devem considerar terapias alternativas para o tratamento de sintomas de menopausa c) mulheres com útero devem receber terapia combinada com estrogênio e progesterona.

Isoflavone-deprived soy peptide suppresses mammary tumorigenesis by inducing apoptosis

During carcinogenesis, NF-kappaB mediates processes associated with deregulation of the normal control of proliferation, angiogenesis, and metastasis. Thus, suppression of NF-kappaB has been linked with chemoprevention of cancer. Accumulating findings reveal that heat shock protein 90 (HSP90) is a molecular chaperone and a component of the IkappaB kinase (IKK) complex that plays a central role in NF-kappaB activation. HSP90 also stabilizes key proteins involved in cell cycle control and apoptosis signaling. We have determined whether the exogenous administration of isoflavone-deprived soy peptide prevents 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced rat mammary tumorigenesis and investigated the mechanism of action. Dietary administration of soy peptide (3.3 g/rat/day) significantly reduced the incidence of ductal carcinomas (50%), the number of tumors per multiple tumor-bearing rats (49%; P < 0.05), and extended the latency period of tumor development (8.07 +/- 0.92 weeks) compared to control diet animals (10.80 +/- 1.30; P < 0.05). Our results have further demonstrated that soy peptide (1) dramatically inhibits the expression of HSP90, thereby suppressing signaling pathway leading to NF-kappaB activation; (2) induces expression of p21, p53, and caspase-3 proteins; and (3) inhibits expression of VEGF. In agreement with our in vivo data, soy peptide treatment inhibited the growth of human breast MCF-7 tumor cells in a dose-dependent manner and induced apoptosis. Taken together, our in vivo and in vitro results suggest chemopreventive and tumor suppressive functions of isoflavone-deprived soy peptide by inducing growth arrest and apoptosis.

Hormonas femeninas y cáncer de mama: estado de la polémica y evidencias en 2008: ¿qué responder a las pacientes? / Female hormones and breast cancer: controversies and evidences at 2008: what to answer to our patients?

The use of Hormone Replacement Therapy (HRT) has evolved from a massive utilization to a restricted use under very precise medical indications, in the light of the deletereous effects its indiscriminate prescription could entail. It is not beneficial for secondary prevention, but rather implies additional cardiocerebrovascular risks, and therefore it must be preferentially employed during perimenopausic and non-late periods, in the smallest possible dose and only over short periods of time, restricting its prescription to women presenting with severe estrogen deprivation syndrome or to osteoporotic patients intolerant to calcium and bifosfonates therapy. Breast cancer risk -which is low- is related to a estrogen therapy extended for more than seven years or associated with the use of progesterone for a period exceeding five years. Personal medical records of breast cancer imply absolute contraindication. Currently there are no research work supporting the safe use of phytoestrogens as an alternative therapy. It is likely that in upcoming days transdermal estrogen administration associated with natural progesterone could allow an increased use of them, but for the time being there are no massive studies supporting their recommendation.

El uso de terapia de reemplazo hormonal ha evolucionado desde su empleo masivo a un uso restringido bajo indicaciones precisas, a la luz de los efectos deletéreos que pudiera significar su indicación indiscriminada. No es de utilidad en la prevención secundaria y más bien representa riesgos adicionales cardiovasculares y cerebro vasculares, por lo que se debe emplear de preferencia en el periodo peri-menopáusico y no tardío, en la menor dosis posible y por el menor tiempo necesario, restringiendo su indicación a las mujeres con síntomas de deprivación estrogénica severa o a mujeres osteoporóticas que no toleran la terapia de calcio y bifosfonatos. El riesgo de cáncer de mama -que es bajo- está relacionado con una terapia estrogénica prolongada de 7 años o más o en asociación con el empleo de progesterona por más de 5 años. Antecedentes personales de cáncer de mama representan una contraindicación absoluta. No hay trabajos a la fecha que apoyen el empleo sin riesgo de fitoestrógenos como una terapia alternativa al uso de estrógenos. Es posible que en el futuro la administración transdérmica de los estrógenos, asociado a progesteronas naturales permitan su mayor utilización, pero aún no se dispone de estudios masivos que aprueben su recomendación.

Terapia hormonal na menopausa: quando não usar: [revisão] / Hormone therapy in menopause: when not to use: [review]

A menopausa corresponde à cessação permanente da menstruação, conseqüente à perda da função folicular ovariana ou à remoção cirúrgica dos ovários. A idade média para ocorrência da menopausa natural gira em torno de 50 anos. A deficiência estrogênica decorrente da menopausa está associada com sintomas vasomotores, atrofia urogenital, declínio cognitivo, assim como a um aumento no risco de doenças crônico-degenerativas, aterosclerose e doença cardiovascular, osteoporose e doença de Alzheimer. A estrogenioterapia permanece sendo o tratamento mais efetivo para o manejo dos sintomas vasomotores e atrofia urogenital. Em mulheres com útero presente, a progesterona natural ou os progestogênios devem ser associados ao tratamento com estradiol para antagonizar os efeitos proliferativos deste hormônio sobre o endométrio e anular o risco de hiperplasia/carcinoma endometrial. Por outro lado, em determinadas condições clínicas, a terapia hormonal não é recomendada ou é mesmo contra-indicada. Neste artigo, focalizamos criticamente essas situações clínicas em que não se deve indicar a terapia hormonal na menopausa.

Menopause is defined as the permanent cessation of menses, as a result of the loss of ovarian follicular function or of surgical removal of ovaries. The mean age for occurrence of natural menopause is around 50 years. Estrogen deficiency has been associated with vasomotor symptoms, urogenital atrophy, and cognitive impairment, as well as increased risk of chronic degenerative diseases such as osteoporosis and Alzheimer’s disease. Estrogen therapy remains the most effective treatment for the management of vasomotor symptoms and urogenital atrophy. Progesterone or progestins should be added to estrogen treatment in women with uterus, in order to antagonize the estrogen-induced endometrial proliferation. In turn, in specific clinical conditions hormone therapy is not recommended. In the present article, the authors critically focus these clinical conditions in which hormone therapy should not be used.

Múltiplos fibroadenomas bilaterais após transplante renal e imunossupressão com ciclosporina A / Multiple bilateral fibroadenomas after kidney transplantation and immunossuppression with cyclosporine A

O fibroadenoma é a neoplasia benigna mais freqüente da mama feminina e é considerado tumor misto, constituído por quantidades variáveis de tecido conjuntivo e epitelial. A ciclosporina parece ter implicações no desenvolvimento de fibroadenomas mamários em pacientes transplantadas renais em idade reprodutiva. Descrevemos o caso no qual a paciente, em uso terapêutico de ciclosporina A, após transplante renal, apresentou vários nódulos mamários bilaterais na evolução. O exame físico e os achados de imagem sugeriram fibroadenoma, diagnóstico que foi confirmado após biópsias.

Fibroadenoma is the most frequent benign neoplasia in the female breast and it is considered a mixed tumor, constituted by variable amounts of connective and epithelial tissue. Cyclosporine A seems to be related with the development of mamary fibroadenomas in patients who underwent kidney transplantation in reproductive age. We reported the case in which the patient, in therapeutic use of cyclosporine A, after kidney transplantation, presented several bilateral lumps. The imaging and palpable findings suggested fibroadenoma, confirmed after biopsy.