Evaluation of FLT-PET-CT as an imaging biomarker of proliferation in primary breast cancer.

BACKGROUND: [(18)F]fluorothymidine (FLT) has been proposed as a positron emission tomography (PET)-imaging biomarker of proliferation for breast cancer. The aim of this prospective study was to assess the feasibility of FLT-PET-CT as a technique for predicting the response to neoadjuvant chemotherapy (NAC) in primary breast cancer and to compare baseline FLT with Ki-67. METHODS: Twenty women with primary breast cancer had a baseline FLT-PET-CT scan that was repeated before the second cycle of chemotherapy. Expression of Ki-67 in the diagnostic biopsy was quantified. From the FLT-PET-CT scans lesion maximum and mean standardised uptake values (SUVmax, SUVmean) were calculated. RESULTS: Mean baseline SUVmax was 7.3, and 4.62 post one cycle of NAC, representing a drop of 2.68 (36.3%). There was no significant association between baseline, post chemotherapy, or change in SUVmax and pathological response to NAC. There was a significant correlation between pre-chemotherapy Ki-67 and SUVmax of 0.604 (P=0.006). CONCLUSIONS: Baseline SUVmax measurements of FLT-PET-CT were significantly related to Ki-67 suggesting that it is a proliferation biomarker. However, in this series neither the baseline value nor the change in SUVmax after one cycle of NAC were able to predict response as most patients had a sizeable SUVmax reduction.

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.

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.

Evaluation and management of the complications of lung cancer treatment.

The principal treatment-related complications encountered in the management of lung cancer are presented with particular reference to surgery, radiotherapy, and chemotherapy. The clinical features, risk factors, and management of the complications are discussed.