Neoadjuvant endocrine therapy in breast cancer.

The use of endocrine therapy is well established as a primary treatment for locally advanced breast cancer. However, despite the current popularity of neoadjuvant chemotherapy for operable tumours, there is relatively little published evidence for pre-operative endocrine therapy in operable disease, particularly outside of the elderly population. The wider use of aromatase inhibitors (AIs) has encouraged studies that compare the efficacy of AIs with tamoxifen in the neoadjuvant setting, but there remains a lack of comparison of neoadjuvant with adjuvant endocrine therapies. This review discusses the current evidence regarding primary endocrine therapy, along with the factors involved in choosing appropriate patients for neoadjuvant therapy and the current opinions on length of treatment time and measurement of response prior to surgery.

Exemestane after non-steroidal aromatase inhibitors for post-menopausal women with advanced breast cancer.

A retrospective analysis was performed on 31 consecutive locally advanced or metastatic breast cancer patients who commenced exemestane 25mg/d orally following previous treatment with Tamoxifen and a non-steroidal third-generation aromatase inhibitor (AI). Patients were seen 3 monthly until clinical or radiological disease progression. Median age was 64 years (range 34-90 yrs). The average number of recurrences before starting exemestane was three (range 1-6). There were two complete responses (CR), four partial responses (PR), 12 with stable disease (SD) and 12 with progressive disease (PD). Objective response rate (CR+PR) was 19.4% and overall clinical benefit (CR+PR+SD >or= 24 weeks) was 54.8%. The median durations of objective response and overall clinical benefit were 18 and 14 months, respectively. This data support the anti-tumour activity of exemestane 25mg daily in patients with locally advanced and/or metastatic breast cancer who have been previously exposed to non-steroidal AIs and Tamoxifen.

Pre-treatment haemoglobin levels and the prediction of response to neoadjuvant chemotherapy in breast cancer.

AIMS: A low pre-treatment haemoglobin level has been shown to negatively influence outcome in the treatment of tumours of the cervix, bladder and head and neck by radiotherapy. The purpose of this study was to assess the influence of baseline haemoglobin levels on the response to neoadjuvant chemotherapy for breast cancer. MATERIALS AND METHODS: One hundred and thirty-nine women receiving neoadjuvant chemotherapy for operable breast tumours (T2-4, N0-1, M0) were accessed from our prospective database. Women were treated between March 1999 and June 2004. The median age was 47 years (range 25-70). Most women were treated with 5-fluorouracil, epirubicin and cyclophosphamide chemotherapy (122/139 patients). Baseline haemoglobin levels were compared for clinical responders (partial or complete) and non-responders (stable or progressive disease) using Student's t test and logistic regression. The analysis was adjusted for nodal status, tumour size, tumour grade and menopausal status. RESULTS: The overall response rate was 84.9% (118/139), with a complete clinical response in 24.5% (34/139). Mean haemoglobin levels were 13.3 g/dl in responders and 13.4 g/dl in non-responders (range 7.9-15.8). The distributions of haemoglobin levels were not significantly different when comparing either responders with non-responders or 'good' responders with 'poor' responders (P = 0.70 and P = 0.32, respectively). If haemoglobin is treated as a binary variable using 12.0 g/dl as the threshold, there is a non-significant trend towards a reduction in the probability of achieving a good response if baseline haemoglobin is below 12.0 g/dl (odds ratio = 0.26, confidence interval = 0.06-1.21; P = 0.086). The rate of complete pathological response was 4.3% (6/139). The mean haemoglobin level in these patients was 14.2 g/dl (range = 12.8-15.7), but the small numbers precluded further analysis. CONCLUSIONS: There is no evidence for an influence of pre-treatment haemoglobin levels on the clinical response to neoadjuvant chemotherapy in breast cancer. It is unlikely that correction of anaemia above that which is warranted clinically will improve outcomes.

A systematic review of the role of imaging before salvage radiotherapy for post-prostatectomy biochemical recurrence.

A substantial proportion of patients who have undergone a radical prostatectomy for localised prostate cancer will have either persistently detectable prostate-specific antigen (PSA) levels or a delayed rise in PSA. The optimum treatment for these situations is not known. The key question is whether the PSA is reflective of local or distant progression. For salvage radiotherapy to be most effective, treatment should be considered before the PSA level is allowed to rise too high, when disease is more likely to be confined to the prostate bed. However, at low PSA levels, current imaging techniques are poor at detecting disease, making it difficult to differentiate local and distant recurrences and to target the radiotherapy appropriately. We review current and investigational imaging techniques, including bone scan, computed tomography, magnetic resonance imaging, positron emission tomography and Prostascint, assessing their utility in the situation of biochemical recurrence after radical prostatectomy.

The relationship of the neo-angiogenic marker, endoglin, with response to neoadjuvant chemotherapy in breast cancer.

Endoglin (CD105) is upregulated in endothelial cells of tissues undergoing neovascularisation. A greater number of CD105-positive vessels predicts poor survival in breast cancer. We examine whether CD105 expression predicts response to neoadjuvant chemotherapy. Fifty-seven women (median age 50 years, range 29-70) received neoadjuvant chemotherapy for operable breast cancer. Immunohistochemical staining using monoclonal antibodies to CD105 and CD34 was performed on pretreatment biopsies and post-treatment surgical specimens. Individual microvessels were counted in 10 random fields at x 200 magnification. Median counts were correlated with clinical and pathological response using the Mann-Whitney U-test. Forty-five out of fifty-seven patients (79%) responded clinically, 22 (39%) responded pathologically. On pretreatment biopsies, clinical responders had significantly lower median CD105-positive vessel counts than nonresponders (median counts 5 and 9.3/high-power field (hpf), median difference=4.0/hpf, 95% CI 0.5-8.0/hpf, P=0.02). For pathological responders and nonresponders, median counts were 4.8 and 5.5/hpf (median difference -0.5/hpf, 95% CI=-2.5-2.0/hpf, P=0.77). CD34 expression (total microvessel density) did not correlate with response. Pretreatment CD105 expression predicts for clinical response to chemotherapy, with a lower initial count being favourable. Patients with high baseline new vessel counts or increased counts after conventional therapy may benefit from additional antiangiogenic therapy.

Intracerebroventricular angiotensin II-induced thirst and sodium appetite in rat are blocked by the AT1 receptor antagonist, Losartan (DuP 753), but not by the AT2 antagonist, CGP 42112B.

In the rat, intakes of water and 1.8% NaCl induced by I.C.V. angiotensin II were inhibited by prior I.C.V. injection of the angiotensin subtype 1 receptor antagonist, Losartan, but not by the subtype 2 receptor antagonist, CGP 42112B. Drinking induced by I.C.V. carbachol was unaffected by either antagonist.