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Unlabelled: We have compared 2-deoxy-2-[(18)F]-fluoro-D-glucose positron emission tomography (FDG-PET) images of large or locally advanced breast cancers (LABC) acquired during Anthracycline-based chemotherapy. The purpose was to determine whether there is an optimal method for defining tumour volume and an optimal imaging time for predicting pathologic chemotherapy response., Method: PET data were acquired before the first and second cycles, at the midpoint and at the endpoint of neoadjuvant chemotherapy. FDG uptake was quantified using the mean and maximum standardized uptake values (SUV) and the coefficient of variation within a region of interest. Receiver-operator characteristic (ROC) analysis was used to determine the discrimination between tumours demonstrating a high pathological response (i.e. those with greater than 90% reduction in viable tumour cells) and low pathological response., Results: Only tumours with an initial tumour to background ratio (TBR) of greater than five showed a difference between response categories. In terms of response discrimination, there was no statistically significant advantage of any of the methods used for image quantification or any of the time points. The best discrimination was measured for mean SUV at the midpoint of therapy, which identified 77% of low responding tumours whilst correctly identifying 100% of high responding tumours and had an ROC area of 0.93., Conclusion: FDG-PET is efficacious for predicting the pathologic response of most primary breast tumours throughout the duration of a neoadjuvant chemotherapy regimen. However, this technique is ineffective for tumours with low image contrast on pre-therapy PET scans.

This study aimed to evaluate patterns of local and distant disease recurrence in patients having primary chemotherapy and compared patterns of relapse in patients with a complete pathological response with those who had residual breast disease. This is an observational study using a sequential series of patients treated with primary chemotherapy. They were followed up for a minimum of 5 years. All data was collected prospectively. Three hundred forty-one consecutive patients with breast cancer were treated with up to eight cycles of doxorubicin-based chemotherapy. Clinical and pathological response rates were evaluated and patients were followed up for disease recurrence (local and distant) and overall survival. Fifty-two patients (16.5%) had a complete pathological response to chemotherapy. Distant disease recurrence occurred in nine patients (17.3%) but no local recurrence was observed. In patients not having a complete pathological response, 86 patients (32.6%) subsequently developed metastases. Local recurrence of disease occurred in 12 (4.5%). There was a statistically significant difference in overall survival between patients whose tumours had a complete pathological response compared with patients who had residual disease in the breast following chemotherapy (88% versus 70% at 5 years, p = 0.036). Following primary chemotherapy, about 84% of patients had residual disease in the breast. Surgery is necessary to ensure complete removal of residual tumour and excellent rates of local control are achievable. A complete pathological response is associated with fewer local and distant recurrences as well as improved survival although there are no differences in time to development of metastatic relapse.

Primary chemotherapy achieves high clinical response rates and facilitates breast conservation in many patients with large and locally advanced breast cancer. It may also serve to indicate responsiveness to chemotherapeutic agents. A pathological complete response to primary chemotherapy is a primary predictor and surrogate marker of long-term outcome, but occurs in only approximately 15% of patients. Docetaxel is of particular interest in this setting. Primary docetaxel chemotherapy has single-agent activity in both dose-dense and traditional schedules, with acceptable tolerability. Furthermore, concomitant docetaxel-anthracycline schedules have shown promise in Phase II trials, achieving clinical overall response rates (ORRs) of 77-96%, pathological complete responses of up to 24%, and breast conservation in up to 89% of patients. Two Phase III studies have shown that pathological complete response is significantly improved with the addition of docetaxel to anthracycline-based therapy versus the latter alone: the Aberdeen study achieved a rate of 34% versus 16%, respectively (p = 0.04), and the NSABP-B27 study a rate of 26% versus 14%, respectively (p < 0.001). The Aberdeen study has suggested that the addition of docetaxel may yield a survival benefit at 5 years (p = 0.04). The Phase II GEPAR-DUO study hints at a benefit for sequential over concomitant docetaxel-based therapy, with improvements in both clinical response (ORR 87% versus 77%, respectively) and pathological complete response (23% versus 12%, respectively). Non-anthracycline docetaxel-based primary regimens have shown early promise. As we continue to define the optimal regimen, a growing body of evidence supports the use of docetaxel in primary chemotherapeutic regimens for breast cancer.

Purpose: Primary chemotherapy is commonly used in patients with breast cancer to downstage the primary tumour prior to surgery. There is a need to establish, prior to commencement of chemotherapy, predictors of clinical and pathological response, which may then be surrogate markers for patient survival and thus allow identification of patients who are most likely to benefit from such treatment., Patients and Methods: A total of 104 patients with large and locally advanced breast cancers received an anthracycline/docetaxel-based regimen prior to surgery. Immunohistochemistry was carried out on pre-treatment core biopsies of the tumour to detect hormone receptors (oestrogen-ER; progesterone-PR), a proliferation marker (MIB-1), the oncoprotein Bcl-2, an extracellular matrix degradation enzyme (cathepsin D), p53, and an oestrogen associated protein (pS2). Both clinical and pathological response were assessed following completion of chemotherapy., Results: Patients whose tumours did not express oestrogen receptor (p = 0.02) or did not express Bcl-2 (p < 0.01) had a better pathological response in a univariate analysis. However, in a multivariate model, it was only the absence of detectable Bcl-2 protein that predicted a better pathological response (p = 0.001)., Conclusions: This study has identified that patients whose breast cancers are most likely to experience the greatest degree of tumour destruction by primary chemotherapy do not express either oestrogen receptors or Bcl-2. This may have important implications in the selection of patients with breast cancer for primary chemotherapy who are most likely to gain a survival benefit., (Copyright 2004 Kluwer Academic Publishers)

Neoadjuvant chemotherapy produces substantial increases in clinical response rates and rates of breast conserving therapy. Pathologic response rate, though generally low, is an important outcome as it is presumably associated with eradication of micrometastatic disease and may likely result in improved outcomes. Anthracyclines have long been considered the most efficacious chemotherapy agents for neoadjuvant therapy of early breast cancer. Unfortunately, not all patients respond to neoadjuvant anthracycline-based chemotherapy. In an effort to improve primary tumor response, docetaxel, an active agent in breast cancer, has been evaluated in the neoadjuvant setting. Several randomized trials, including the NSABP B-27, GEPAR-duo, and the Aberdeen trial, evaluating docetaxel in sequence with a doxorubicin-based neoadjuvant regimen have been reported, with encouraging findings. We designed the Aberdeen trial with two primary aims: (1) to evaluate primary docetaxel in patients that initially fail a neoadjuvant anthracycline-based polychemotherapy regimen, and (2) to compare a docetaxel-based neoadjuvant regimen with a standard anthracycline-based regimen in patients who do respond to the first four cycles of the anthracycline-based regimen. Eligible patients (n = 162) had previously untreated large (> or = 3 cm) or locally advanced (T3, T4, T x N2) breast cancer. All received four cycles of CVAP, after which clinical response was assessed. Responding patients were then randomized to four additional cycles of CVAP or to docetaxel 100 mg/m2 every 3 weeks for four cycles. Patients failing to respond to CVAP received the docetaxel regimen. After the first four cycles of CVAP, the overall response rate (ORR) was 67%. Ultimately, responses were higher in the group randomized to docetaxel compared with those continuing CVAP (cCR: 94% vs. 66%; p = 0.001; pCR 34% vs. 16%; p = 0.04). The addition of docetaxel improved overall survival and disease-free survival for patients responding to four cycles of CVAP as compared with those receiving eight cycles of CVAP. Relative dose intensity was higher and the incidence of severe leukopenia was lower in the group randomized to docetaxel. These data and data from the NSABP B-27 and GEPAR-duo trials strongly support a combined anthracycline/docetaxel regimen in the neoadjuvant setting.