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BACKGROUND: A pathologic complete response (pCR) and minimal residual disease (pMRD) after preoperative chemotherapy (PCT) for early stage or locally advanced breast cancer (BC) correlates with a good prognosis. METHODS: Patients who received from 6 to 8 cycles of PCT for BC were monitored by 18F‐2‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography (18F‐FDG‐PET), and the maximal standardized uptake value (SUVmax) was calculated at baseline, after 2 cycles, after 4 cycles, and at the end of PCT. SUVmax percentage changes (Δ‐SUV) were compared with the pathologic response rate. Patients who had a pCR or pMRD in the tumor and an absence of cancer cells in ipsilateral axillary lymph nodes were defined as having obtained an optimal pathologic response (pR), whereas all the other conditions were classified as a pathologic nonresponse (pNR). RESULTS: Of 34 patients, 7 (21%) achieved a pR (3 patients had a pCR, and 4 patients had pMRD). After the second cycle, the Δ‐SUV threshold with optimal negative predictive value to predict a pR was 50%. Twenty‐six patients (76%) had a Δ‐SUV >50%, including all 7 patients who had a pR and 19 patients who had a pNR. Conversely, all 8 patients who had a Δ‐SUV ≤50% had a pNR. All 8 of those patients had estrogen recepetor‐positive tumors. CONCLUSIONS: Early evaluation of metabolic response by 18F‐FDG‐PET during PCT was able to identify 30% of patients, all with estrogen receptor‐positive tumors, who would not obtain pR after completion of chemotherapy program. Cancer 2010. © 2010 American Cancer Society.

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Oestrogen receptors (ESRs) regulate the growth and differentiation of normal ovarian epithelia. However, to date their role as biomarkers in the clinical setting of ovarian cancer remains unclear. In view of potential endocrine treatment options, we tested the role of ESR1 mRNA expression in ovarian cancer in the context of a neo-adjuvant chemotherapy trial. Study participants had epithelial ovarian or peritoneal carcinoma unsuitable for optimal upfront surgery and were treated with neo-adjuvant platinum-based chemotherapy before surgery. RNA was isolated from frozen tumour biopsies before treatment. RNA expression of ESR1 was determined by microarray and reverse transcriptase kinetic PCR technologies. The prognostic value of ESR1 was tested using univariate and multivariate Cox proportional hazards models, Kaplan-Meier survival statistics and the log-rank test. ESR1 positively correlates with proliferation markers and histopathological grading. ESR1 was a significant predictor of survival as a continuous variable in the univariate Cox regression analysis. In multivariate analysis, elevated baseline ESR1 mRNA levels predicted prolonged progression-free survival (PZ0.041) and overall survival (PZ0.01) after neo-adjuvant chemotherapy, independently of pathological grade and age. We conclude that pretreatment ESR1 mRNA is associated with tumour growth and is a strong prognostic factor in ovarian cancer, independent of the strongest clinical parameters used in clinical routine. We suggest that ESR1 mRNA status should be considered in order to minimize possible confounding effects in ovarian cancer clinical trials, and that early treatment with anti-hormonal agents based on reliable hormone receptor status determination is worth investigating.

The combination of paclitaxel 135 mg/m2 (24-hour infusion) and cisplatin 75 mg/m2 is now considered the standard treatment in first-line chemotherapy for stage III suboptimally debulked and stage IV ovarian cancer. Interest is focused on the possibility of evaluating the combination of paclitaxel with carboplatin, because it was found to be less nefrotoxic and less neurotoxic than cisplatin. This study seeks to determine the maximum tolerated dose and to assess the antitumor activity of the combination of a 3-hour paclitaxel infusion followed by carboplatin. Thirty-three chemotherapy-naive patients with stage III-IV epithelial ovarian cancer entered this open, nonrandomized dose-finding study. The first dose level investigated was paclitaxel 125 mg/m2 and carboplatin 250 mg/m2: the dose level progression was performed by alternatively increasing paclitaxel 25 mg/m2 and carboplatin 50 mg/m2. Cycles were repeated every 28 days. At least three patients were treated at each dose level. Overall, 233 and 224 cycles, respectively, are evaluable for nonhematologic and hematologic toxicity. Dose-limiting toxicities (febrile neutropenia and severe fatigue) were observed in two of six patients at level VIII (paclitaxel 225 mg/m2 and carboplatin 400 mg/m2) and therefore the previous dose-level (paclitaxel 200 mg/m2 and carboplatin 400 mg/m2) was considered as the maximum tolerated dose. Neutropenia (grade 3-4 in 63% of cycles), neurotoxicity (grade 2 in 37.5% and grade 3 in 9% of patients), arthromyalgias (grade 2 in 53% of patients and grade 3 in 3% of patients), and grade 3 alopecia were the most common toxicities observed. The incidence of thrombocytopenia was low (grade 3 in 4% of cycles) and no renal toxicity was observed. An objective remission was documented in 74% of 31 evaluated patients, including eight complete remissions (26%) confirmed by second-look surgery. The combination of paclitaxel 200 mg/m2 3-hour infusion followed by carboplatin 400 mg/m2 (30-minute infusion) is a safe and active regimen as first-line chemotherapy for advanced ovarian cancer.