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In the current study, the radio frequency magnetron sputtering technique was used to sputter a thin layer of titanite nitride (TiN) or silicon nitride (SiN) on the surface of AA2024-T4 alloy. To investigate the wear behavior and coefficient of friction between coated aluminum alloy pin and a steel disc (Ck50) contact bodies, different percentages of Copper oxide (CuO) and molybdenum disulfide (MoS2) Nanoparticles were added to the sunflower and engine (HD 50) oils. The results reveal important enhancement in wear rate and coefficient of friction when Nanoparticles powder was added to the oil in comparison with dry and base oils conditions. The optimum results for wear rate and coefficient of friction were obtained at the 1%wt of both Nanoparticles additive. The results also show a significant enhancement in wear and friction conditions when the surface of the aluminum alloy pin was coated with TiN and SiN in comparison with the uncoated surface.

The tribological properties of adding copper oxide (CuO) and molybdenum disulfide (MoS2) nanoparticles powder in both organic (castor oil) and mineral oil (moulding oil) were investigated. These properties include coefficient of friction and wear between two surfaces, CK50 steel alloy and 2024-T4 aluminum alloy. The Nano lubricants were prepared by dispersing CuO and MoS2 nanoparticle powders at variable weight fractions 0.3, 0.5, 0.7, 1.0 and 2.0% in each oil lubricant. The friction and wear tests were carried out using a pin on the disk test principle by the vertical universal friction testing machine (MMW-1A). The instability problem with the lubricant suspension was solved by adding different weight fractions of GUM ARABIC, which leads to 2% of it gives more stable suspensions. The best results from both friction and wear Tribo tests are observed in 1%W of adding both nanoparticles to both oil lubricants. The formation of Tribo film due to the adsorption and adherence of Nano additives on the surfaces was responsible in reducing the wear properties. Hybrid (1%Wt CuO + 1Wt% MoS2) nanoparticles that added to both oils indicates more decreasing in friction and wear compared to the base oil. The coefficient of friction for hybrid Nano-particulate lubricants reduced to 81.7% and 76.03%, while the wear rate reduced to 93.17% and 92.23% compared to castor oil and moulding oil respectively as a base oil. The study provides insights into how Nano-lubricant additives could contribute towards tribological enhancement and improved product quality.

Screening digital mammography: one year result for the Alpes-Maritimes region Purpose. After one year of experience with screening digital mammography, the results of this technique (n=9640) are compared to screen-film mammography (n=240 376) with double reading. Methods. Evaluation for each technique of the rate of call-back, positive results before and after work-up by the first reader and distribution based on the BI-RADS classification by the ACR, rate of complementary US, detected abnormalities (microcalcifications) and detected cancers. Results. The rate of positive mammograms was significantly higher for the digital technique (17.3% versus 15.1%) because of the first reader (16.3% versus 13.9%) whereas it was significantly lower after complementary work-up (3% versus 3.7%). The rate of BI-RADS 0 was significantly higher with digital imaging irrespective of patient age. The rate of US was higher for type 1 and 2 breasts at digital imaging (46% versus 36%, p Conclusion. The increased number of positive results at first reading and increased number of US for digital mammography may relate to a learning curve and difficulties in comparing with prior examinations. These results should continuously be monitored and compared to national averages.

La castration et le tamoxifene ont ete pendant des decennies les principaux traitements antihormonaux des patientes atteintes de cancer du sein en situation metastatique et adjuvante. Depuis la possibilite d'utiliser en clinique de nouveaux agents antihormonaux, la connaissance des mecanismes de resistance a ces traitements suscite de plus en plus d'interet. Dans cette revue breve, nous nous. attacherons a decrire les principaux mecanismes de resistance permettant d'expliquer les nouvelles strategies therapeutiques dans cette population de cancers du sein hormonodependants.

The aim of this study was to reexamine the prognostic role of tumor cell kinetics measured by S-phase fraction (SPF) and to establish its clinically relevant threshold values. SPF was determined by flow cytometry in a group of 920 consecutive breast cancer patients, all followed at our institute for 10 years (1988 to 1998). Mean age was 60.5 years (27–89 years). Median follow-up was 63 months (3–150 months). All patients had initial surgical treatment. SPF quartiles were: Q1=3.08%, median value = 5.98%, Q3=10.22%. A significant difference in overall specific survival was obtained between two populations divided by a cutoff at Q1 (p

Resume Les reactions cutanees reactivees referent a la reactivation de lesions cutanees par un agent cytotoxique apres radiotherapie externe survenant uniquement dans un territoire irradie. Le docetaxel est un membre de la famille des taxanes dont le principal mecanisme d’action consiste a interrompre la division cellulaire par blocage de la polymerisation des microtubules. Aussi bien dans les cancers mammaires que pulmonaires, les taxanes sont de plus en plus utilises et efficaces, en association a la radiotherapie. La plupart des reactions cutanees reactivees qui sont rapportees dans la litterature concernent le paclitaxel et autres drogues. Nous rapportons 2 cas de reactions cutanees reactivees par docetaxel survenues apres irradiation. Meme si les causes restent a determiner, des hypotheses peuvent etre etablies. La connaissance de cet effet secondaire et de son implication dans la therapeutique necessite un depistage precoce afin de ne pas compromettre le bon deroulement du traitement.

Objectives. To investigate tumor response rate and treatment toxicity of a modified combination chemotherapy consisting of bleomycin (B), methotrexate (M), and CCNU (C) for patients with locally advanced, squamous-cell carcinoma of the vulva (not amenable to resection by standard radical vulvectomy) or recurrent disease (after incomplete resection). Tumor resectability was reassessed in patients who had responded to chemotherapy. Methods. The regimen consisted of bleomycin 5 mg intramuscular (im) days 1-5, CCNU 40 mg per os (po) days 5-7, and methotrexate 15 mg po days 1 and 4 during the first week. During weeks 2-6 the patient was administered bleomycin 5 mg im days 1 and 4, and methotrexate 15 mg po on day 1 of the week. This 6-week cycle was repeated at 49-day intervals. Results. Twenty-five eligible patients with a median age of 66 years (range, 39-82 years) were entered in this phase II trial. Twelve patients had primary locally advanced disease, 13 patients had a locoregional recurrence, and all received up to three BMC cycles. Two complete and twelve partial responses were observed (response rate, 56%; 95% confidence limits, 35-76%). The BMC regimen was associated with major hematological side effects and mild signs of bleomycin-related pulmonary toxicity. At a median follow-up of 8 months, 3 patients were alive, 18 had died due to malignant disease, 2 had died due to toxicity, and 2 had died due to intercurrent disease and unknown cause. The median progression-free survival was 4.8 months and the median survival was 7.8 months. The 1-year survival was 32% (95% confidence limits, 13-51%). Conclusion. The present data confirm the therapeutic activity of the BMC regimen in locoregionally advanced or recurrent squamous-cell carcinoma of the vulva. Following neoadjuvant chemotherapy, the overall response rate was 56%. BMC is an outpatient treatment that may play a role in the palliative therapy of advanced or recurrent vulva cancer. (C) 2001 Academic Press.

One hundred and twenty-nine patients with dissiminated breast cancer were selected to study the clinical applicability of changes in CA 15-3, tissue polypeptide specific antigen (TPS) and carcinoembryonic antigen (CEA) during therapy and how these compare with responses as assessed by UICC criteria in a multicentre study. The alterations in tumour marker levels followed the course of disease but indicated changes in the disease state earlier than clinical assessment (UICC criteria). Patients were grouped according to whether they had progressive disease (PD in groups III and IV), stable disease (SD in group II) or partial remission/complete remission (PR/CR in group I) during a treatment period of 6 months. The number of patients with a 50% decrease of the marker level, and the time at which this reduction was reached, was analysed in patient groups I–III. TPS showed this 50% decrease more frequently (69%) and also earlier (1.1 months) than either CA 15-3 (46% and 2.5 months) or CEA (47% and 1.7 months). The number of patients for whom marker levels increased by 25% or more was analysed in patient groups III and IV versus groups I and II. Such rises were seen more often in patients with progressive disease (TPS 82%, CA 15-3 62% and CEA 61%) than in patients with a more favourable prognosis (TPS 43%, CA 15-3 22% and CEA 24%). The dynamics of changes in tumour marker levels were different during treatment in patients with SD, PR or CR. However, the markers showed similar behaviour in patients developing PD during the study period. TPS appeared to indicate outcome somewhat better than did either CA 15-3 or CEA. Combined determination of CA 15-3 and TPS during therapy for metastatic breast cancer is recommended.

PURPOSE To compare the efficacy and toxicity profiles of a combination of fluorouracil (5-FU) with recombinant human interferon alfa-2a (Roferon-A; Hoffman La-Roche AG, Basel, Switzerland) versus the combination of 5-FU with leucovorin (LV) in the treatment of advanced colorectal cancer. PATIENTS AND METHODS A total of 496 previously untreated colorectal cancer patients were randomized to receive either Roferon-A (9 MIU) subcutaneously three times per week, with 5-FU (750 mg/m2/d) by continuous intravenous (i.v.) infusion (CIV) on days 1 to 5, then, after a 9-day hiatus, as a weekly i.v. bolus at the same dose (IFN/5-FU); or LV (200 mg/m2/d) by i.v. infusion plus 5-FU (370 mg/m2/d) by i.v. bolus on days 1 to 5, repeated every 4 weeks (LV/5-FU). RESULTS There were no significant differences between IFN/5-FU and LV/5-FU in the overall response rate (21% v 18%), duration of response (7.3 v 6.2 months), or survival time (median, 11.0 v 11.3 months). Toxicity profiles differed; constitutional symptoms and myelosuppression were more frequent and more severe with IFN/5-FU, and gastrointestinal symptoms with LV/5-FU. More patients interrupted treatment for adverse events (AEs) with IFN/5-FU than with LV/5-FU. Five treatment-related deaths occurred with each regimen. CONCLUSION The combination IFN/5-FU produced response rates, response durations, and survival times similar to those with LV/5-FU. Biochemical modulation of 5-FU by either IFN or LV appears to result in equivalent efficacy; however, fewer patients were able to tolerate the specified IFN/5-FU combination used in this study.

Dans le cancer du sein, de nombreux facteurs pronostiques et predictifs sont accessibles, ces facteurs permettent d’evaluer l’evolution de la maladie mais aussi d’affiner le choix d’une prise en charge therapeutique. Le statut d’envahissement ganglionnaire (positif ou atients) est un des plus importants parametres pronostiques independants [1]. Les patientes montrant un envahissement ganglionnaire negatif presentent une maladie a bas ou moyen risque alors que les malades montrant au moins un ganglion envahi sont d’emblee considerees a moyen ou haut risque [2]. Le statut ganglionnaire doit etre considere comme un facteur pronostique » pur « et non comme un facteur predictif permettant de predire la reponse au traitement

La chimiotherapie neo-adjuvante (CNA) est de plus en plus utilisee dans le traitement du cancer du sein. Elle permet en effet d’evaluer la reponse tumorale, fournit les informations necessaires a l’etablissement d’un pronostic et est susceptible de permettre le recours a un traitement conservateur (TC). Si les effets secondaires du curage axillaire (CA) [1] et les benefices de la biopsie du ganglion sentinelle (GS) sont connus [2], la pertinence de cette derniere, ainsi que le moment le plus opportun pour sa realisation, demeurent controverses dans le contexte d’une CNA

The antiemetic efficacy and safety of granisetron (40 μg/kg), a selective and potent 5-hydroxytryptamine (serotonin) antagonist, was compared with that of metoclopramide (7 mg/kg) plus dexamethasone (12 mg) in patients receiving fractionated chemotherapy. Patients receiving cisplatin at doses of at least 15 mg/m2 or etoposide at least 120 mg/m2 or ifosfamide at least 1.2 g/m2 on each of 5 consecutive days were eligible. A total of 143 patients received granisetron and 141 received the comparator regimen. The 5-day complete response rate (no vomiting, no worse than mild nausea) for granisetron (46.8%) was equivalent to that for metoclopramide plus dexamethasone (43.9%). The overall 5-day response profile was superior for granisetron (P=0.013) because of fewer failures in this group. The overall incidence of adverse experiences was significantly lower in the granisetron group (60.8% versus 77.3%,P=0.003). Headache and constipation, more prevalent in the granisetron group, are recognized side-effects of serotonin antagonists. Extrapyramidal syndrome, not seen in any granisetron patients, occurred in 20.6% of comparator patients (P

Anthracyclines are among the most active drugs for the treatment of advanced breast cancer. Epirubicin has been found to be as effective as doxorubicin at equimolar doses but significantly better tolerated, especially in terms of alopecia, leucopenia, and cardiac toxicity. The role of anthracycline-containing regimens in adjuvant treatment of breast cancer has been studied by only a few clinical trial teams. In 1986, the French Adjuvant Study Group (FASG) began a randomised trial aimed to investigate the concept of dose intensity as well as the optimal duration of treatment in patients with early breast cancer. Between 1986 and 1990, 621 patients were included in the trial, of whom 595 were evaluable. Patients were randomised to 1 of 3 treatment groups: Group A (n = 207) received FEC 50 (fluorouracil 500 mg/m2, epirubicin 50 mg/m2 plus cyclophosphamide 500 mg/m2) every 21 days for 6 cycles; Group B (n = 193) received FEC 50 every 21 days for 3 cycles; Group C (n = 195) received FEC 75 (fluorouracil 500 mg/m2, epirubicin 75 mg/m2 plus cyclophosphamide 500 mg/m2) every 21 days for 3 cycles. Locoregional radiotherapy was administered after the third cycle of chemotherapy in all treatment arms. Clinical prognostic factors were similar between treatment groups. Approximately 62% of all patients had 1 to 3 positive lymph nodes; 50% of patients were hormone receptor positive and 73% were Scarff-Bloom Richardson (SBR) grade 2 to 3. Toxicity was evaluated in 595 patients (207, 193 and 195 patients in Groups A, B and C, respectively), who received a total of 2301 chemotherapy cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

After one year of experience with screening digital mammography, the results of this technique (n=9640) are compared to screen-film mammography (n=240 376) with double reading.Evaluation for each technique of the rate of call-back, positive results before and after work-up by the first reader and distribution based on the BI-RADS classification by the ACR, rate of complementary US, detected abnormalities (microcalcifications) and detected cancers.The rate of positive mammograms was significantly higher for the digital technique (17.3% versus 15.1%) because of the first reader (16.3% versus 13.9%) whereas it was significantly lower after complementary work-up (3% versus 3.7%). The rate of BI-RADS 0 was significantly higher with digital imaging irrespective of patient age. The rate of US was higher for type 1 and 2 breasts at digital imaging (46% versus 36%, p0.0001) while the reverse was true for denser breasts (49% versus 54%; p:0.0005). More microcalcifications were detected on digital imaging (24.4% versus 21.8%) without impact on the rate of DCIS and invasive carcinomas. The rate of cancers detected with both technique were identical.The increased number of positive results at first reading and increased number of US for digital mammography may relate to a learning curve and difficulties in comparing with prior examinations. These results should continuously be monitored and compared to national averages.

Breast cancer (BC) is the first female cancer in France, accounting for 49,240 new cases in 2004. Approximately 80% of those tumors have positive hormone receptors (HR). Tamoxifen was used in four chemoprevention randomized trials, as well as another SERM (Selective Estrogen Receptor Modulation), raloxifen. This review analyses the updated results of these trials. All trials have shown that the risk of developing HR positive BC was reduced by tamoxifen or raloxifen, but without impact on HR negative BC and overall survival. Moreover, several unfavorable side effects (thrombo-embolic accidents and uterine cancers) have been observed. A new assessment of BC risk factors seems necessary, including not only family history and some histopathological abnormalities (e.g. atypical hyperplasia), but also new elements such as high bone and breast density and thoracic irradiation at young age (Hodgkin's disease). Indeed, tamoxifen efficacy seems optimal in very "high-risk" women. Therefore, the creation of a new and most comprehensive "risk model" is necessary as well as a tailored SERM use (maybe with other compounds), in order to optimize results and reduce potential side effects.

38 adults with recurrent supratentorial malignant gliomas, including glioblastoma multiforme (21), anaplastic astrocytomas (9), probably transformed low-grade astrocytomas (6), pinealoblastoma (1) and non-metastatic tumour of unknown histology (1), were treated with fotemustine 100 mg/m2 intravenously every week for 3 consecutive weeks followed by a 5-week rest period. Maintenance treatment consisted of one infusion every 3 weeks. Patients were divided into three groups according to treatment effect. 10 objective responses (26%) with a median time without progression of 32.7 weeks, 18 stabilisations (47%) and 10 failures (26%) were observed. Pathological findings of the initial primary tumour and neurological functional status were unequally distributed in these groups. Haematological and liver toxicities were mild, delayed, transient and reversible. Thrombocytopenia and leukopenia were more frequent (30%) in patients treated with prior chemotherapy. Fotemustine is a well tolerated active drug in recurrent malignant gliomas with an original and short treatment schedule.

A randomized double-blind study with a 3-yr follow-up comparing the two arms “orchiectomy + Anandron ® (300 mg)” vs “orchiectomy + placebo” in 125 patients with stage D prostate cancer has confirmed the beneficial effects of the combined Anandron ® therapy on subjective parameters and on the best objective response (NPCP criteria), although these effects were not statistically significant, but failed to detect any improvement in time-to-disease progression or survival. Comparison with the results of other trials emphasizes the urgent need to establish suitable prognostic factors by further clinical research before evaluating the benefits of individual drugs.

Depuis 25 ans, la prise en charge des cancers du sein en situation adjuvante et metastatique s’est modifiee de maniere importante avec l’apparition de nouvelles therapeutiques en hormonotherapie, en chimiotherapie et en therapeutique ciblee. L’objectif de cette etude est d’evaluer les facteurs pronostiques classiques influencant la decision therapeutique et la survie en situation metastatique. D’autre part, cette etude epidemiologique a pour but d’evaluer l’evolution de la survie des patientes liees aux modifications therapeutiques mises en place depuis 25 ans.

L’indication standard d’un traitement neo–adjuvant repose sur le desir de realiser une chirurgie conservatrice chez une patiente dont la tumeur est trop grosse pour pouvoir esperer lui eviter un geste mutilant. De nombreux essais therapeutiques randomises ont demontre que cette approche provoquait en effet une diminution de la taille de la tumeur et augmentait par consequent le taux d’exerese partielle. Deux methodes therapeutiques neo–adjuvantes sont utilisees : la chimiotherapie et/ou l’hormonotherapie. Si la chimiotherapie neoadjuvante n’a ete concue que pour eviter les mammectomies totales, l’hormonotherapie neo–adjuvante a ete prescrite aussi a des patientes dont l’etat general etait trop precaire ou l’âge trop avance pour accepter ou tolerer un geste chirurgical. Les 1res hormonotherapies neo–adjuvantes ont ete constituees exclusivement par le tamoxifene. Actuellement, les inhibiteurs de l’aromate de 3e generation y prennent une place de plus en plus importante.

The Zoladex Early Breast Cancer Research Association (ZEBRA) trial compared the efficacy and tolerability of goserelin (Zoladex) with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) chemotherapy in pre-/perimenopausal women with node-positive early breast cancer. The results of disease-free survival (DFS) analyses have already been published. Here we present an update including data on overall survival (OS) from the ZEBRA trial at a median follow-up of 7.3 years. In patients with oestrogen receptor (ER)-positive tumours, non-inferiority of goserelin versus CMF for OS was shown; goserelin was again shown to be equivalent to CMF for DFS. This updated analysis has demonstrated that the two treatments are also equivalent for distant disease-free survival (DDFS). In patients with ER-negative disease, goserelin was inferior to CMF for DFS, DDFS and OS. This follow-up analysis confirms the previously reported outcomes from the ZEBRA trial and demonstrates that goserelin offers an effective alternative to CMF chemotherapy for adjuvant therapy of premenopausal patients with ER-positive, node-positive early breast cancer.

30 patients with advanced ovarian cancer, all platinum pretreated, were treated with an induction cycle of fotemustine. Maintenance therapy was given to 6 patients. No objective response was observed among the 21 evaluable patients. The main toxicities were gastrointestinal, with grade 3 nausea and vomiting reported in 40% of the patients, and haematological, with grade 4 leucopenia reported in 2 patients and grade 4 thrombocytopenia in 5 patients. Therefore, no role has been demonstrated in our cohort for the use of fotemustine, a nitrosourea, in pretreated ovarian cancer. (C) 2003 Elsevier Science Ltd. All rights reserved.

Radiation recall refers to a tissue reaction produced by a chemotherapeutic agent in a previously irradiated field that would not occur in a nonirradiated field. Docetaxel is a member of the taxane group of antineoplastic agents that cause disruption of cell division by enhancing microtubule assembly and inhibiting tubulin depolymerisation. As well as in breast cancer and lung cancer treatment, its association in a chemoradiation planned treatment becomes frequent and effective. Most of radiation recall dermatitis (RDD) reported in literature concerned paclitaxel or other drugs. We report two particularly striking cases of RDD with docetaxel and radiotherapy. Even if etiology remains undetermined, a number of hypotheses can be formulated. Familiarity with this phenomenon and potential complications of chemotherapy following tumor irradiation may expedite early diagnosis and appropriate lifesaving treatment.

Radiological interventional procedures on the breast are still work in progress. Initiation of percutaneous macrobiopsy techniques such as stereotactic or ultrasound-guided core biopsy, mammotomy or Abbi Site-Select procedures allows the physician to expect a high accuracy for the diagnosis of non palpable suspected breast abnormalities, thus eliminating the need for at least half of the surgical biopsies done for this indication. Furthermore, the absence of any lasting post-procedural changes on follow-up mammography contrasts with the scarring associated with traditional surgical open biopsy and obviates confusion in subsequent mammographic interpretation. Recently, development of percutaneous radiofrequency or cryotherapy ablation of breast cancer has been related. All these cost-saving procedures lead to medical and potential medical legal pitfalls that will be discussed.

Hormone therapy of breast cancer has been dominated for a very long time by a single class of drugs, the antiestrogens, and especially tamoxifen. Tamoxifen has been the standard treatment in the adjuvant, neoadjuvant, and metastatic contexts. Ten years ago a new generation of aromatase inhibitors became available that was more selective than previous generations. They form two groups that are quite distinct from a pharmacological standpoint: type II non-steroid inhibitors and type I steroid inhibitors or rather steroid "aromatase inactivators". Aromatase inhibitors are prescribed to menopausal women. They are active in patients with tamoxifen-resistant metastatic cancer. They are a potential alternative to tamoxifen in first-line therapy of women with metastatic cancer. They have been proven useful as neoadjuvant therapy. They are under study in several trials in an adjuvant context. Many issues still remain outstanding.

Between March and September 1988, 74 patients with progressive ovarian cancer after prior platinum-based therapy were treated with the luteinizing hormone-releasing hormone (LHRH) agonist Triptorelin (Decapeptyl(R)). Treatment consisted of i.m. injection of 3.75 mg of microencapsulated Triptorelin on days 1, 8 and 28 followed by 4-weekly injections until tumor progression. No objective responses were observed. Eleven out of 68 evaluable patients (16%) had stable disease. The median progression-free survival was 5 months in patients with disease stabilization and 2 months for all evaluable patients. The median survival for patients with disease stabilization was 17 months, whereas for all patients it was 4 months. The treatment was well tolerated; the only reported adverse events were incidental hot flushes. This study showed that the LHRH agonist Triptorelin has only modest efficacy in patients pretreated with platinum-containing chemotherapy. [(C) 2001 Lippincott Williams & Wilkins.].

In 1986, The Fédération Nationale desCentres de Lutte Contre le Cancer Breast Group initiated a multicenter randomized trial to assess the usefulness of long-term adjuvant tamoxifen treatment. Short-term adjuvant tamoxifen treatment was to be compared with life long adjuvant tamoxifen treatment.Patients who were disease-free after 2 to 3 years of adjuvant tamoxifen treatment were eligible for the trial. From September 1986 to May 1995, 3,793 patients were randomized from France, Belgium, and Argentina. A total of 1,882 patients stopped tamoxifen (short-term group), and 1,911 patients were to continue tamoxifen for life (long-term group) at the same dose as previously prescribed. The protocol was modified in February 1997, limiting tamoxifen treatment to 10 years after randomization, thus giving a comparison between a 2- to 3-year treatment and a 12- to 13-year treatment. To date, the median duration of tamoxifen treatment is 30 months in the short-term group, and 70 months in the long-term group.Overall, longer tamoxifen treatment induced a 23% reduction in relapse rates, leading to a 7-year disease-free survival rate of 78%, compared with 72% in the shorter-treatment group. In contrast, overall survival did not differ between the two groups, with a 79% overall survival rate in both groups. This improvement in disease-free survival could be observed in node-positive patients (P: =.001); however, it was not found in node-negative patients. Prolonged tamoxifen treatment corresponded to a significant increase in disease-free survival in estrogen receptor-positive patients (P: =.03) as well as in estrogen receptor-negative patients (P: =.05). Furthermore, longer treatment reduced contralateral breast cancers and did not increase the number of endometrial cancers.Although no survival advantage was noted, patients did benefit from longer tamoxifen treatment over 3 years and had significantly better disease-free survival compared with patients who stopped hormonal treatment. Long-term follow-up is needed to assess these results. Most patients in the long-term group are still receiving treatment. Comparison of results as time passes will enable conclusions to be made on the value of long-term treatment over 5 years compared with 2 to 3 years.

Three treatment modalities have successively dominated adjuvant therapy of breast cancer in non-menopausal women, namely, castration, chemotherapy and tamoxifen administration. The benefits afforded by each of these modalities seem similar when the treatments are compared indirectly by meta-analysis. Once the anti-tumour action of LH-RH analogues and their reversible action on ovarian function had been established, these analogues were used instead of surgical castration in direct comparisons of the three treatment modalities. Most of the patients in these trials had estrogen and/or progesterone receptor positive tumours. According to the current state-of-the-art and whilst awaiting the final results of ongoing trials, we can conclude that: The survival of surgically castrated patients is the same as that of patients who have received CMF-type chemotherapy. The survival of patients on tamoxifen is the same as that of patients who have received CMF-type chemotherapy if tamoxifen is administered for 5 years. It is lower if tamoxifen is given for only 2 years. In 2 out of 3 trials, patients receiving the combined treatment castration plus tamoxifen had improved recurrence-free survival rates compared to patients on chemotherapy (regardless of whether an anthracyclin was included or not. It is too early to comment on overall survival. Combining castration and chemotherapy seems to be advantageous in patients less than forty and in those in whom chemotherapy has not induced amenorrhea. Combining tamoxifen and chemotherapy markedly decreases the risks of disease recurrence and of death but the high standard deviations recorded mean that this statement has to be tempered. Finally, an arrest of ovarian function by LH-RH analogues that is only temporary apparently does not adversely impinge upon results. This has, however, to be proved in an ad hoc trial and the optimum duration of analogue administration has to be established.

The aim of this investigation was to assess retrospectively docetaxel safety and efficacy in advanced breast cancer patients in a French compassionate use programme. Patients had received1 prior chemotherapy regimen for advanced disease, were either anthracycline-resistant (that is progressed within 6 months after anthracycline-based chemotherapy) or had received the maximum cumulative dose. The recommended docetaxel dose was 100 mg/m2/cycle (75 mg/m2 in case of liver function impairment: transaminases1.5 x upper limit of normal (ULN), alkaline phosphatases3 x ULN). Between August 1993 and December 1995, 889 patients were treated in 67 French centres, of whom 870 were evaluable for safety and 825 were evaluable for patient and treatment characteristics and efficacy. 20.5% (of the 825 patients evaluable for baseline characteristics) had poor performance status (PSor = 2), 49.3% liver metastasis and 9.6% biological liver dysfunction. 98.4% had been previously treated by anthracyclines, 50.8% had resistant disease and 37.1% had received2 prior palliative chemotherapy lines. The most frequent severe toxicity, febrile neutropenia (reported in 223/870 (25.6%) patients evaluable for safety), caused 10 deaths, 6 of these being patients with severe liver impairment before inclusion. Fluid retention syndrome and other common non-haematological toxicities were well tolerated. 3.1% (28/889) of all patients and 11.4% of those with liver dysfunction, died from treatment-related causes. The overall response rate in 825 assessable patients was 22.9% (95% confidence interval (CI): 20.2-26.2%). Median time to treatment failure was 4 months (95% CI: 3.6-4.3) and median survival was 9.8 months (95% CI: 8.8-10.7). This report on the largest series of unselected advanced breast cancer patients treated with docetaxel, supports previous phase II studies, confirming docetaxel's utility in patients relapsing after failing anthracycline-containing palliative chemotherapy.

The survival of patients with breast cancer depends on parameters known as prognostic factors. The first generation of prognostic factors are simple, have been validated, and have proved their usefulness. We know the importance of examining axillary lymph nodes. However, because there has been a constant increase in the percentage of patients with no invaded lymph nodes, tumor size has become an important parameter. The 10-year survival rate of patients with tumors less than 1 cm in diameter exceeds 90% suggesting that there might seem to be no need for adjuvant therapy. According to histological grade assessed by the Scarff-Bloom and Richardson method, grade I tumors have a better prognosis than grade II or III tumors. Knowledge of the concentration of estrogen and progesterone receptors in tumors provides not only prognostic information but also indicates whether hormone therapy is justified. All these first generation factors are intimately linked and, taken together, they are the main factors on which the oncologist bases his decision whether or not to prescribe adjuvant therapy. There is still no consensus regarding the assay methods and normal levels of second generation prognostic factors. Amongst these factors, the most promising are those, like S-phase determination by flow cytometry, that evaluate cell proliferation potential and those that investigate tumor invasiveness by assaying urokinase plasminogen activator or its inhibitor.