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Anastrozole ('Arimidex') blocks oestrogen synthesis both peripherally and within the breast in postmenopausal women with large operable breast cancer.

ABSTRACT: The effect of anastrozole on peripheral and tumour aromatase activity and oestrogen levels in postmenopausal patients with oestrogen receptor-rich breast tumours was investigated. Twenty-six patients were randomly allocated to treatment with anastrozole 1 mg (n=13) or 10 mg (n=13), once daily. Before and after 12 weeks' treatment, patients were infused with 3H-Delta4 androstenedione (20 MBq) and 14C-oestrone (E1) (1 MBq) for 18 h. Oestrogens were purified from excised tumours and plasma samples taken after each infusion. Peripheral and tumour aromatase activity and tumour E1 uptake were calculated from levels of 3H and 14C in purified E1 fractions from tumour and plasma. Endogenous tumour oestrogens were measured by radioimmunoassay. Twenty-three patients were available for analysis (1 mg group, n=12; 10 mg group, n=11). Following treatment, anastrozole (1 and 10 mg) markedly inhibited peripheral aromatase in all patients (the difference between pre- and on-treatment values being highly significant P<0.0001). In situ aromatase activity was also profoundly decreased by anastrozole treatment in 16 of 19 tumours (the difference with treatment also being highly significant P=0.0009). Most tumours were able to concentrate E1 beyond levels in the circulation; anastrozole treatment had no consistent effect on uptake of E1. Endogenous tumour levels of both E1 and oestradiol (E2) were significantly reduced with therapy (P=0.028 for E1 and P=0.0019 for E2). Anastrozole (1 and 10 mg daily) effectively suppresses aromatase activity, and subsequently oestrogen levels, within the breast tissue of postmenopausal women with large or locally advanced, operable, oestrogen receptor-rich breast cancers.

SUBMITTER: Miller WR

PROVIDER: S-EPMC2364315 | biostudies-other | 2002 Oct

REPOSITORIES: biostudies-other

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Project description:PurposeAromatase inhibitors (AIs) prolong survival for postmenopausal women with hormone receptor-positive breast cancer (HR + BC) but also burden patients with symptoms, a major reason for suboptimal AI adherence. This study characterizes inter-relationships among symptom measures; describes neuropsychological symptom burden trajectories; and identifies trajectory group membership predictors for postmenopausal women prescribed anastrozole for HR + BC.MethodsThis study utilized prospectively collected data from a cohort study. Relationships among various self-reported symptom measures were examined followed by a factor analysis to reduce data redundancy before trajectory analysis. Four neuropsychological scales/subscales were rescaled (range 0-100) and averaged into a neuropsychological symptom burden (NSB) score, where higher scores indicated greater symptom burden. Group-based trajectory modeling characterized NSB trajectories. Trajectory group membership predictors were identified using multinomial logistic regression.ResultsWomen (N = 360) averaged 61 years old, were mostly White, and diagnosed with stage I HR + BC. Several measures were correlated temporally but four neuropsychological measures had strong correlations and dimensional loadings. These four measures, combined for the composite NSB, averaged (mean ± standard deviation) 17.4 ± 12.9, 18.0 ± 12.7, 19.5 ± 12.8, and 19.8 ± 13.0 at pre-anastrozole, 6, 12, and 18 months post-initiation, respectively. However, the analysis revealed five NSB trajectories-low-stable, low-increasing, moderate-stable, high-stable, and high-increasing. Younger age and baseline medication categories (pre-anastrozole), including anti-depressants, analgesics, anti-anxiety, and no calcium/vitamin D, predicted the higher NSB trajectories.ConclusionThis study found relationships among neuropsychological symptom measures and distinct trajectories of self-reported NSB with pre-anastrozole predictors. Identifying symptom trajectories and their predictors at pre-anastrozole may inform supportive care strategies via symptom management interventions to optimize adherence for women with HR + BC.

Project description:BackgroundOlder women are at the greatest risk of breast cancer development and a considerable number present with comorbidities. Although the majority of breast cancers in this age group express oestrogen receptor (ER), which makes endocrine therapy (primary or adjuvant) feasible, given the huge size of the elderly population, there remains a significant number of patients, in absolute term, whose tumours do not express ER and their management is challenging.MethodsOf a consecutive series of 1,758 older (≥70 years) women with early operable primary breast cancer managed in a dedicated service from 1973-2010, 252(14.3%) had ER-negative (histochemical (H) score ≤50) tumours. Their clinical outcome was retrospectively reviewed and tumour samples collected from diagnostic core biopsies were analysed for progesterone receptor (PgR), HER2 and Ki67 using immunohistochemistry.ResultsThe commonest primary treatment was surgery (N = 194, 77%) followed by primary endocrine therapy (14.3%), primary radiotherapy (5.6%) and supportive treatment only (3.1%). Among the patients undergoing surgery, most of them had grade 3 (78.1%) and node-negative disease (62.2%). Some of them (21.1%) received postoperative radiotherapy. At a median follow-up of 37.5 months, 117 patients had died, out of which 48.6% were due to breast cancer. For those who underwent surgery, the regional and local recurrence rates were 2% and 1.1% per annum respectively. For those who received primary endocrine therapy, 38% progressed at 6 months, however all patients who had primary radiotherapy achieved clinical benefit at 6 months. Regardless of treatment given, the 5-year breast cancer specific and overall survival rates were 70% and 50% respectively. Biological analysis based on good quality needle core biopsy specimensfrom181 patients showed that 26.8% (N = 49), 16.9% (N = 31) and 70.7% (N = 70)expressed positivity for PgR, HER2 and Ki67 respectively. No correlation between these biomarkers and breast cancer specific survival was demonstrated.ConclusionOestrogen receptor negative early operable primary breast cancer in older women is associated with poor prognostic features in terms of biology and clinical outcome. Surgery appears to produce the best outcome as a primary treatment, however for those where neither surgery nor chemotherapy is appropriate, primary radiotherapy can be beneficial.

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Anastrozole ('Arimidex') blocks oestrogen synthesis both peripherally and within the breast in postmenopausal women with large operable breast cancer.

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