Incorporating paclitaxel into anthracycline-based adjuvant therapy resulted in a significant improvement in RFS and distant RFS. When given as primary systemic therapy, the paclitaxel-containing regimen allowed breast-sparing surgery in a significant percentage of patients.

Purpose: The European Cooperative Trial in Operable breast cancer (ECTO) randomly tested whether efficacy of adjuvant doxorubicin followed by i.v. cyclophosphamide, methotrexate, and fluorouracil (CMF; doxorubicin ! CMF, arm A) could be improved by adding paclitaxel (doxorubicin/paclitaxel ! CMF) as adjuvant (arm B) or primary systemic therapy (PST, arm C). We report here feasibility, tolerability, locoregional antitumor activity, and breast conservation rate. Methods: A total of 1,355 women entered the study. Feasibility and safety were compared in arm A versus arms B plus C. Surgical findings were compared in arms A plus B versus arm C. Results: Grade 3 or 4 National Cancer Institute toxicities were low (<5%) in all arms. Neuropathy was more frequent in the paclitaxel-containing arms (grade 2, 20.5% versus 5.0%; grade 3, 1.3% versus 0.2%). At 31months of follow-up, asymptomatic drop of left ventricular ejection fraction was similar in all arms, whereas symptomatic cardiotoxicity was recorded in three patients (0.5%) in A and in three patients (0.3%) in B plus C. PST induced clinical complete plus partial remissionin 78%, with anin-breast pathologic complete response rate of 23% and anin-breastplus axilla pathologic complete response rate of 20%. In the multivariate analysis, only estrogen receptor (ER) status was significantly associated withpathologic complete response (odds ratio for ERnegative, 5.77; 95% confidence interval, 3.49-9.52; P < 0.0001). PTS induced a significant axillary downstaging (P < 0.001), and breast sparing surgery was feasible in 65% versus 34% (P <0.001).Conclusions: Doxorubicin/paclitaxel ! CMF is feasible, safe, and well tolerated. Given as PST, it is markedly active, allowing for breast-sparing surgery in a large fraction of patients.

Early response to TAC can reliably identify patients with a high chance of achieving a pCR. New effective treatments need to be explored for patients without an early response.

Breast conservation after neoadjuvant chemotherapy is feasible in most patients with operable breast cancer. For surgical planning, tumor characteristics and response to neoadjuvant chemotherapy should be taken into account. Improved breast-imaging modalities are necessary to improve detection of residual disease after neoadjuvant chemotherapy, especially when breast cancer is of lobular invasive histology. Margin assessment by intraoperative frozen-section analysis is helpful to avoid reoperation. To achieve an optimal result, an interdisciplinary surgical approach is important.

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erythrocytes. It is partly explained by acute phase increases in plasma fibrinogen concentration and viscosity. In particular, however, we found that the filterability of both polymorphonuclear and mononuclear leucocytes is reduced in acute cerebral infarction. This may not only explain the reduced filterability of blood but also promote malperfusion of the microcirculation and infarction.Reduced filterability of leucocytes may be part of the acute phase response to injury, as suggested by the correlation with fibrinogen concentration in the patients with stroke and by similar findings in the controls with chest infection. Preceding infection is an important risk factor for cerebral infarction.5 The risk of infarction also increases with age, and we observed decreased filterability of leucocytes in controls aged over 40. We suggest that mechanisms by which increasing age and infections increase the risk of cerebral infarction include increased plasma fibrinogen concentration and viscosity and decreased filterability of leucocytes, each of which tends to reduce capillary flow. Women attending our breast clinic with cyclic breast pain of at least two months' duration were included in the study. Women not menstruating regularly, taking the contraceptive pill, or with breast abnormalities were excluded. The women were asked to record their pain on a linear analogue scale from one to 100 daily from the first day of menstruation.2 The nodularity of the breasts was assessed by palpation on one day of the luteal phase of the cycle each month.Patients who kept full records during a control month were randomised into the six month trial. They were asked to apply 5 g of cream each evening from the tenth day of one menstrual cycle to the first day of the next. Two different preparations in identical containers labelled first or second were used; one contained 1% natural progesterone and the other was without the active hormone. The active and placebo creams were applied for three months, each in random order, and only the statistician knew the order of the treatments. For each patient a mean pain score was calculated from the seven worst daily pain scores during the premenstrual phase each month. The seven worst days were usually consecutive and most often the days before the next period. The pain and nodularity scores for each patient were analysed by non-parametric tests, which compared differences within patients.Thirty two women were entered into the study; 17 were randomised to use the active drug first and 15 the placebo. Seven did not return for their monthly appointments (usually after the first month). Thus complete data were available for 25 of the women, 14 of whom used the active treatment first and 11 the placebo.The data were first analysed for trends in the pain and nodularity scores over time, but no evidence of any such trends was found. To compare the drugs a mean pain score and a total nodularity score were calculated for each patient's three month exposure to each drug. The results (table) showed a small...

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From theoretical considerations and the phantom experiments a significant negative impact of the technical modifications could be excluded. Instead, the method described here showed to be beneficial in measuring tumor oxygenation in breast tumors. The authors strongly advise to consider exclusively intratumoral pO(2) values as proven by ultrasonography for oxygenation profiling, as in 40% of all measurements the origin of single pO(2) values or tracks was questionable.