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Introduction: Although neoadjuvant chemotherapy (NAC) for locally advanced breast cancer can improve operability and local disease control, there is a lack of reliable biomarkers that predict response to chemotherapy or long-term survival. Since expression of aldehyde dehydrogenase-1 (ALDH1) is associated with the stem-like properties of self-renewal and innate chemoresistance in breast cancer, we asked whether expression in serial tumor samples treated with NAC could identify women more likely to benefit from this therapy. Method(s): Women with locally advanced breast cancer were randomly assigned to receive four cycles of anthracycline-based chemotherapy, followed by four cycles of taxane therapy (Arm A), or the same regimen in reverse order (Arm B). Tumor specimens were collected at baseline, after four cycles, and then at surgical resection. ALDH1 expression was determined by immunohistochemistry and correlated with tumor response using Fisher's exact test while Kaplan-Meier method was used to calculate survival. Result(s): A hundred and nineteen women were enrolled into the study. Fifty seven (48%) were randomized to Arm A and 62 (52%) to Arm B. Most of the women (90%) had ductal carcinoma and 10% had lobular carcinoma. Of these, 26 (22%) achieved a pathological complete response (pCR) after NAC. There was no correlation between baseline ALDH1 expression and tumor grade, stage, hormone receptor, human epidermal growth factor receptor 2 (HER2) status and Ki67 index. ALDH1 negativity at baseline was significantly associated with pCR (P = 0.004). The presence of ALDH1(+) cells in the residual tumor cells in non-responding women was strongly predictive of worse overall survival (P = 0.024). Moreover, serial analysis of specimens from non-responders showed a marked increase in tumor-specific ALDH1 expression (P = 0.028). Overall, there was no survival difference according to the chemotherapy sequence. However, poorly responding tumours from women receiving docetaxel

Introduction: The aims of this study were to investigate whether drug sequence (docetaxel followed by anthracyclines or the drugs in reverse order) affects changes in the maximal standard uptake volume (SUVmax) on [18F]flourodeoxyglucose positron emission tomography (FDG-PET) during neoadjuvant chemotherapy in women with locally advanced breast cancer. Method(s): Women were randomly assigned to receive either drug sequence, and FDG-PET scans were taken at baseline, after four cycles and after eight cycles of chemotherapy. Tumour response to chemotherapy was evaluated based on histology from a surgical specimen collected upon completion of chemotherapy. Result(s): Sixty women were enrolled into the study. Thirty-one received docetaxel followed by anthracyclines (Arm A) and 29 received drugs in the reverse order (Arm B). Most women (83%) had ductal carcinoma and 10 women (17%) had lobular or lobular/ductal carcinoma. All but one tumour were downstaged during therapy. Overall, there was no significant difference in response between the two drug regimens. However, women in Arm B who achieved complete pathological response had mean FDG-PET SUVmax reduction of 87.7% after four cycles, in contrast to those who had no or minor pathological response. These women recorded mean SUVmax reductions of only 27% (P < 0.01). Women in Arm A showed no significant difference in SUVmax response according to pathological response. Sensitivity, specificity, accuracy and positive and negative predictive values were highest in women in Arm B. Conclusion(s): Our results show that SUVmax uptake by breast tumours during chemotherapy can be dependent on the drugs used. Care must be taken when interpreting FDG-PET in settings where patients receive varied drug protocols. © 2010 Schneider-Kolsky et al.; licensee BioMed Central Ltd.

Background: The aim of this study was to evaluate the correlation between serum VEGF level and response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. Method(s): Following informed consent, 63 patients with locally advanced breast cancer suitable for NCT were recruited. Participants were randomly assigned to receive either sequential FEC100 (x4) and Docetaxel 100/m2 (x4), or the reverse sequence. Serial assessment of response was performed with physical examination, mammography, ultrasound, tumor biopsy and PET scans. Blood samples were collected at baseline and after 4 cycles of chemotherapy. Serum VEGF levels were determined by using enzyme-linked immunosorbent assay (ELISA) and correlated with final pathological response (complete, partial or no response). Result(s): Data from fifty-seven patients were evaluable. Of those, thirteen patients (22.8%) achieved complete pathological response (pCR), 18 (31.5%) had residual node negative disease (pPR) and 26 (45.5%) had less significant response (NR) to NCT. There was no correlation between baseline serum VEGF levels and other base line tumour characteristics of grade, size, cell type, hormone receptor, Her2 status, or tumor PET SUV. There was a weak correlation of tumor micro-vessel density as assessed by CD31 stain and serum VEGF (r=0.3). There was a statistically significant association between lower baseline serum VEGF (<200pg/ml) and better final pathological response (pCR or pPR) (p= 0.030). Serial measurements looking at increase or decrease of serum VEGF during treatment showed no useful predictive trends (p=0.979). Conclusion(s): Our study showed a statistically significant correlation between baseline serum VEGF and final pathological response to NCT in patients with locally advanced breast cancer. Serum VEGF may be potentially used as one of the markers in predicting response to NCT and thereby useful in selecting patients for appropriate treatment. However, this study is limite

The aims of this study were to (i) compare the effect of drug sequence on tumour glucose uptake volumes (SUV) using PET; and (ii) correlate SUV uptake changes with pathological response to chemotherapy in women with locally advanced breast cancer undergoing sequential chemotherapy with Taxotere and Anthracyclines. Women with biopsy confirmed breast cancer were randomised to receive either Taxotere (4 cycles) followed by Anthracyclines (4 cycles) or drugs in reverse order. All underwent FDG- PET before chemotherapy, after 4 cycles and after completion of chemotherapy. Changes in SUV after 4 cycles were compared to baseline and correlated to pathological response after surgery. At that stage, patients were classified into either complete elimination of tumour (cPR), small residual tumour (pPR) or no response (nPR).The two groups were compared using Mann Whitney U test, Kruskal Wallis and Chi Square test. Sixty patients were recruited, 31 receiving Taxotere followed by Anthracyclines and 29 receiving drugs in reverse order. Most patients presented with ductal carcinoma. Overall, 23% of tumours achieved cPR, 30% a pPR and 47% a nPR. There was no significant difference in the pathological response rates between the two drug regimens. Women receiving Anthracyclines followed by Taxotere who achieved cPR had a median SUV reduction of 83% after 4 cycles, while those who had nPR had a median SUV reduction of only 27% (P < 0.01). In contrast, SUV reductions in the other group of women were not statistically different between the 3 pathological response rates. FDG-PET appears to be a useful predictor of tumour response to Anthracycline-based chemotherapy in women with breast cancer.

INTRODUCTION: The aims of this study were to investigate whether drug sequence (docetaxel followed by anthracyclines or the drugs in reverse order) affects changes in the maximal standard uptake volume (SUVmax) on [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) during neoadjuvant chemotherapy in women with locally advanced breast cancer. METHODS: Women were randomly assigned to receive either drug sequence, and FDG-PET scans were taken at baseline, after four cycles and after eight cycles of chemotherapy. Tumour response to chemotherapy was evaluated based on histology from a surgical specimen collected upon completion of chemotherapy. RESULTS: Sixty women were enrolled into the study. Thirty-one received docetaxel followed by anthracyclines (Arm A) and 29 received drugs in the reverse order (Arm B). Most women (83%) had ductal carcinoma and 10 women (17%) had lobular or lobular/ductal carcinoma. All but one tumour were downstaged during therapy. Overall, there was no significant difference in response between the two drug regimens. However, women in Arm B who achieved complete pathological response had mean FDG-PET SUVmax reduction of 87.7% after four cycles, in contrast to those who had no or minor pathological response. These women recorded mean SUVmax reductions of only 27% (P < 0.01). Women in Arm A showed no significant difference in SUVmax response according to pathological response. Sensitivity, specificity, accuracy and positive and negative predictive values were highest in women in Arm B. CONCLUSIONS: Our results show that SUVmax uptake by breast tumours during chemotherapy can be dependent on the drugs used. Care must be taken when interpreting FDG-PET in settings where patients receive varied drug protocols.