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Pathological complete response (pCR) is an important predictor of long-term survival in patients with breast cancer receiving neoadjuvant chemotherapy (NAC). At present, the accuracy of traditional radiological assessments during treatment in predicting pCR is poor. Unidimensional and 3D volumetric ultrasound measurements prior to, after 4 cycles (mid-treatment), and at the end of 8 cycles (end-treatment) of chemotherapy were available from a subset of 55 patients enrolled in Neo-tAnGo, a National Cancer Research Network (NCRN) UK neoadjuvant chemotherapy breast cancer trial. Proportional changes in longest diameter (LD) and volume as well as absolute residual size thresholds were examined for their ability to predict pCR or pCR plus minimal residual disease (pCR/MRD). Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) and likelihood ratios (LRs) were calculated. Receiver-operator characteristic (ROC) curves and logistic regression models were also constructed. At mid-treatment, neither complete radiological response, nor proportional LD or volume changes were found predictive of final pCR. A small residual tumour volume (≤ 1 cm³ vs. > 1 cm³) at mid-treatment, however, was associated with pCR/MRD (P = 0.014). Sensitivity, specificity, PPV, NPV, LR+ and LR- values were 61%, 77%, 61%, 77%, 2.62 and 0.51, respectively. The area under the ROC curve was 0.689 (P = 0.03). Volume ≤ 1 cm³ at mid-treatment was found significant in a logistic regression (OR: 0.194, P = 0.011). At end-treatment, no ultrasound measurements were found predictive of pCR or pCR/MRD. In conclusion, proportional tumour size changes (the basis of the RECIST criteria) were not found predictive of good pathological response, although residual volume ≤ 1 cm³ at mid-treatment was found to be predictive of pCR/MRD. However, multiple volume and LD thresholds were examined and uncorrected P values presented, increasing the possibility of type I errors. Replication in an independent dataset is required.

To compare the long-term outcome of women with primary or locally advanced breast cancer randomised to receive either doxorubicin and cyclophosphamide (AC) or doxorubicin and docetaxel (AD) as primary chemotherapy. Eligible patients with histologic-proven breast cancer with primary tumours > or = 3 cm, inflammatory or locally advanced disease, and no evidence of distant metastases, were randomised to receive a maximum of 6 cycles of either doxorubicin (60 mg/m(2)) plus cyclophosphamide (600 mg/m(2)) i/v or doxorubicin (50 mg/m(2)) plus docetaxel (75 mg/m(2)) i/v every 3 weeks, followed by surgery on completion of chemotherapy. Clinical and pathologic responses have previously been reported. Time to relapse, site of relapse, and all-cause mortality were recorded. This updated analysis compares long-term disease-free (DFS) and overall survival (OS) using stratified log rank methods. A total of 363 patients were randomised to AC (n = 181) or AD (n = 182). A complete pathologic response was observed in 16% for AC and 12% for AD (P = 0.43). The number of patients with positive axillary nodes at surgery with AC was 61% and AD 66% (P = 0.36). At a median follow-up of 99 months there is no significant difference between the two groups for DFS (P = 0.20) and OS (P = 0.24). Deaths were due to metastatic breast cancer in 96% of patients. Our data do not support a clinical benefit for simultaneous administration of AD compared with AC. However, the data do not exclude a smaller benefit than the study was powered to detect and are consistent with an increase in both disease-free and overall survival of about 5% for AD compared with AC. Outcome is consistent with the pathologic complete response following surgery.

In 141 postmenopausal node-positive patients with primary breast cancer, routine biochemical markers (alkaline phosphatase, gamma-glutamyl transpeptidase, carcinoembryonic antigen), and chest x-ray, in combination with history and clinical examination, have been performed at 3 monthly intervals for at least 2 years. Sixty one patients relapsed at a median time of 14 months. The recurrence was detected at routine follow-up in 40 (66%) patients. Of these 40 patients, 26 (65%) presented with symptoms, 11 (28%) were asymptomatic but were found to have relapsed on clinical examination, and only 3 (8%) had their relapse diagnosed on the basis of an abnormal chest x-ray. The remaining 21 patients presented early with symptoms. Therefore symptoms and clinical examination accounted for the detection of relapse in 58 of the 61 (95%) patients. Of the patients who had relapsed, 49% (30 of 61) had one or more abnormal markers/chest x-rays prior to relapse, rising to 79% (48 of 61) at the time of relapse. Of 80 patients with no evidence of recurrence, 36% (29) had no marker abnormality recorded, whereas in 64% (51) one or more abnormalities were found. These results suggest that history and examination are the important procedures in follow-up, and that abnormal markers are not always due to metastatic disease and may be misleading.