goserelin and Fibrosis

A minority of early invasive breast cancers show a pattern of central necrosis and fibrosis (CNF). Previous studies have documented an adverse prognostic impact and association with other adverse pathological features, but its predictive importance for therapy selection is unknown. We examined the prognostic and predictive value of CNF in two randomized clinical trials comparing chemoendocrine therapy with endocrine therapy alone in patients with node-negative breast cancer. A total of 1,850 patients randomly assigned to treatment groups comparing endocrine with chemoendocrine therapy, and with centrally-assessed CNF, ER, PgR and HER2 were included in the analytic cohort. The median follow up was 10 years. CNF was present in 84 of 1,850 trial patients (4.5%). It was associated with tumor characteristics suggesting poor outcome, but was an independent adverse factor for disease-free survival. In the presence of CNF outcome was worse regardless of tumor grade, whereas in the absence of CNF, patients with grade 3 tumors had poorer outcome than those with grade 1-2 tumors. Among patients with estrogen receptor-absent tumors chemoendocrine therapy was superior to endocrine therapy alone only in the absence of CNF [HR (chemoendocrine:endocrine) = 0.46 in CNF-absent, 0.90 in CNF-present], while among those with receptor-positive disease chemoendocrine therapy was beneficial only in the presence of CNF [HR = 0.34 CNF-present, 0.96 CNF-absent]. The results suggest that the presence of CNF reflects a biological difference in early breast cancer that is important in modulating the efficacy of standard therapies. Accordingly we believe that its presence should be routinely reported.

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Disease-Free Survival; Female; Fibrosis; Fluorouracil; Goserelin; Humans; Methotrexate; Necrosis; Prognosis; Proportional Hazards Models; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen; Treatment Outcome

Topics: Adenocarcinoma; Aged, 80 and over; Alopecia; Anilides; Antineoplastic Combined Chemotherapy Protocols; Atrophy; Fibrosis; Goserelin; Humans; Male; Nitriles; Prostatic Neoplasms; Scalp; Skin; Tosyl Compounds

Immunohistochemical and morphometric analysis of the microcirculatory bed in the tumor and non-tumor parenchyma of the prostate was carried out with the use of endothelial cell marker CD34 in patients treated by high-intensity focused ultrasound (HIFU). The numerical density of microvessels in the adenocarcinoma focus did not correlate with the degree of its differentiation, while high values of this parameter were associated with lower incidence of local progression after HIFU. Effective HIFU ablation led to progressive fibrosis and significant reduction of the microcirculatory bed in zones of intact non-tumor glands in control samples; an inverse relationship between the degree of reduction of the microcirculatory bed and the probability of relapse was revealed. The use of HIFU in combination with androgen deprivation was associated with a decrease in numerical density of microvessels in zones of tumor and non-tumor parenchyma in patients with relapses.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Antigens, CD34; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Fibrosis; Flutamide; Follow-Up Studies; Goserelin; High-Intensity Focused Ultrasound Ablation; Humans; Male; Microcirculation; Middle Aged; Prognosis; Prostate; Prostatic Neoplasms; Treatment Outcome; Tumor Microenvironment

Six premenopausal women with uterine fibroids were treated with a combination of tamoxifen, 20 mg/d, and goserelin, 3.6 mg every 28 days, for a total of 24 weeks. Results were compared with those from six women, matched for pretreatment uterine volume, who had been treated with goserelin alone. During combined therapy, plasma and urinary estrogen concentrations were significantly lower than during goserelin alone, whereas sex hormone binding globulin concentrations were significantly higher. Plasma luteinizing hormone and follicle stimulating hormone (FSH) concentrations were both suppressed, in contrast with results during goserelin alone when FSH levels remained within the pretreatment range. None of the women on combined therapy bled in response to the endocrine changes of the initial treatment cycle. Despite this profound pituitary-ovarian suppression, there was no significant change in uterine volume during combined therapy. These results suggest that tamoxifen is acting as an estrogen agonist in women rendered hypoestrogenic with luteinizing hormone-releasing hormone agonists.

Topics: Amenorrhea; Buserelin; Creatinine; Drug Therapy, Combination; Estradiol; Estrogens; Female; Fibrosis; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Progesterone; Tamoxifen; Uterine Diseases