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Primary neuroendocrine breast carcinomas are rare and little-known tumors. Only a limited number of studies on neuroendocrine breast carcinomas have been reported in the literature, and the vast majority of them are small retrospective series or case reports. According to the World Health Organization (WHO), they account for only 2 % to 5 % of breast cancers. Their diagnosis relies on the presence of a neuroendocrine architecture and the expression of neuroendocrine markers (chromogranin A and/or synaptophysin). The revised 2012 WHO classification subdivides them into three categories: (i) well-differentiated neuroendocrine carcinomas, (ii) poorly differentiated neuroendocrine carcinomas or small-cell carcinomas, and (iii) invasive breast carcinomas with neuroendocrine differentiation. Their clinical features and radiological characteristics are not different from those of other types of breast cancer. Because of discordant results, their clinical outcome is still poorly defined. So far, no standard treatment has been established, and most clinicians draw on their experience of invasive ductal cancer. The role of specific treatments like platinum-based chemotherapy, somatostatin analogues, peptide receptor radionucleide therapy or temozolomide remains unclear. A better knowledge of the molecular pathways involved in their carcinogenesis could help to identify new potential therapeutic targets. The efficacy of targeted therapies has to be studied., (Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Prevalence of brain metastases is increasing in breast cancer. Brain metastases represent a poor-prognosis disease for which local treatments continue to play a major role. In spite of the presence of a physiological blood-brain barrier limiting their activity, some systemic treatments may display a significant antitumor activity at the central nervous system level. In HER2-positive metastatic breast cancer with brain metastases not previously treated with whole brain radiotherapy, capecitabine and lapatinib combination obtains a volumetric reponse in two thirds of patients (LANDSCAPE study). If confirmed, these results could modify in selected patients the layout of therapeutic strategies. Promoting novel targeted approaches and innovative therapeutic combinations is a critical need to improve survival of breast cancer patients with brain metastases.

Background: Chemotherapy for the treatment of early-stage breast cancer (ESBC) patients improves survival outcomes. However, its most common acute toxicity is myelosuppression, which can reduce the delivered dose and compromise the survival benefit. Because FEC100-docetaxel (FEC100-D) is a common protocol for ESBC, we evaluated its febrile neutropenia (FN) incidence and the role of its hematological toxicity on the individual relative dose-intensity (RDI)., Patients and Methods: It is a French single-center, observational, retrospective study. Patients received adjuvant/neoadjuvant FEC100-D treatment, without primary prophylaxis by granulocyte colony-stimulating factors (G-CSF). The neutrophil count the day before the planned chemotherapy cycle had to be over 1,500.mm(-3) for the treatment to be administered. Data collected included: date and dose of chemotherapy cycles, FN and high grade of hematological toxicity occurrence for each course, G-CSF prescription., Results: One thousand, seven hundred and fifty-seven cycles in 284 patients were delivered. FN was observed in 4.9% (n = 14) of the patients, without hospitalizations or deaths after. Grade 3-4 neutropenia occurred in 5.8% of the cycles, during the first cycle in 40% of cases. Seventeen percent of our patients received less than 85% of RDI., Conclusion: The hematotoxicity of this treatment is acceptable. The risk of FN is low. No G-CSF primary prophylaxis is needed without additional risk factor.

Background: An increasing number of patients is treated for breast cancer during their professional life. The aim of this study was to assess factors impacting return to work and time to return to work after treatment., Patients and Methods: One thousand and sixty-seven patients less than 60 years of age, and surgically treated in our institution between January 1st, 2004 and December 31st, 2005 received a questionnaire with medical, sociodemographic and professional items. An answer was obtained in 586 cases. Two hundred and seventy-three patients were evaluable. All the clinical files of these patients were reviewed., Results: Overall, 79.8% of the patients returned to work after a median delay of 11.5 months. In the multivariate analysis, the factors affecting the return to work were: age (P<0.0001), educational level (P<0.001), colleagues' support (P<0.001), chemotherapy (P<0.05), lymphedema (P<0.01), and the physical (P=0.01) and psychological (P<0.01) constraints of the job. The factors affecting the time until return to work were very quite similar. No significant difference was observed according to the type of surgery, radiation therapy or not, hormonotherapy or not., Conclusion: Eighty percent of the patients with a professional activity before treatment returned to work; the factors affecting return to work were medical, demographic and socio-professional.

Fifty-two thousand new breast cancers occur each year in France, 7% in patients less than 40 years. The standard regimens of adjuvant chemotherapy for breast cancer now include anthracyclines and taxanes. These therapeutics advances have significantly improved the prognosis of these young women who may later wish to become mother and have biological offspring. The impact of chemotherapy on reproductive function should be accurately assessed and the ovarian reserve has to be taken into account. The estimated risk of chemo-induced amenorrhea and infertility has to be balanced with the expected results and risks of methods of fertility preservation. The place of different options for fertility preservation depends on patient age, presence or not of a partner and the time available before the initiation of treatment. For these breast cancer patients who will receive chemotherapy, new techniques of in vitro oocyte maturation seem promising. Even if some ethical and technical issues are unresolved, fertility preservation must now be part of the management of these young patients receiving adjuvant chemotherapy for breast cancer. This new approach must be multidisciplinary and complex.

Unlabelled: The intraoperative determination of axillary node micrometastasis according to the Rapid GeneSearch Breast Lymph Node (BLN) is based on RT-PCR (mRNA of mammaglobine and CK19) detects metastases > 0.2 mm., Patients and Methods: Eighty-three pts between November 2007 and June 2008 were included (33 from Centre Jean-Perrin and 50 from Centre Oscar-Lambret). Lymph nodes were cut in 2 mm slices, and 1 out of 2 was examined with BLN; the others were examined by imprints then histological exam with immunohistochemistry., Results: Forteen pts had micro- or macrometastasis. Seven were positive with intraoperative imprints including six macrometastasis and one micrometastasis; seven were positive with BLN and seven at histological exam with two cases of discordance. Sensitivity was 92%, specificity 98%. Positive predictive value 92%, and negative predictive value 98%. The median time for intraoperative determination was 40 minutes for 2 SLN., Discussion: Half each lymph node is study by each method. This explains the discordances observed. Limit of BLN is the absence of CTI detection; however there is no consensus about the necessity of axillary clearance in such a case., Conclusion: In this series BLN reduces axillary clearance and improves comfort patients.

Nausea and emesis are one of the most feared secondary effect of chemotherapy. The development of antiemetic therapies has increased after the introduction of cisplatin, a cytotoxin with the highest emetic potential. Chemotherapy-induced nausea and vomiting (CINV) have been classified into acute, delayed and anticipatory based on the time of onset. According to the percentage of nausea and emesis without any antiemetic treatment, chemotherapy is divised into highly, moderate, low and very low emetic potential. The discovery of emetics stimuli neurotransmitters and their receptors has led to the introduction of new molecules which associated with steroids have prevented nausea and vomiting chemotherapy-induced for 70 to 80% of the patients receiving chemotherapy with high emetic potential. Numerous studies have evaluated the various antiemetics and recommendations were issued by learned societies in US and Europe. This text discusses the physiopathology of nausea and vomiting, the development of anti-emetics and the new discovered antiemetics. Finally, a synthesis of the recommandations from the guidelines developed by the Multinational Association of Supportive Care in Cancer (MASCC), the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) is presented.

Male breast cancer (MBC) is considered as a rare disease comprising about 1% of all breast cancers. As compared to women breast cancer, MBC has some similarities and also some particularities related to age, comorbidities, breast volume, diagnostic delay, prognosis and survival. Modified radical mastectomy (MRM) with axillary dissection is the gold standard. Sentinel lymph node dissection is a promising option for early stages. Adjuvant radiation is proposed because of the high frequency of node involvement and central tumor location. In hormone receptor positive tumors tamoxifen remains the gold standard endocrine therapy because of the lack of data on aromatase inhibitors. Adjuvant chemotherapy can be proposed to high-risk patients while trastuzumab should be an option in breast cancer that overexpresses HER2. In the setting of considerable evolution in the management of women breast cancer, this review aimed to point out on the similarities and particularities of MBC and the future challenges to improve MBC outcome.

The development of molecular targeted therapies requires some specific methodological approaches. Dose-limiting toxicities are rare in phase I studies the maximal tolerated dose is rarely established. On the contrary, the biological active dose is often determined as the dose inducing biological effect on the target without significant clinical toxicity. Several designs of phase II are described (selection phase II, randomized phase II, stratified phase II...). All of them are indicated in specific situations. The discontinuation treatment studies and the validation of biomarkers (as surrogate endpoints or as classifiers) are the two main particularities of phase III studies designed for the assessment of molecular targeted therapies.

We evaluated the contribution of an epirubicin-based adjuvant chemotherapy on disease-free survival (DFS) in poor prognosis, node-negative breast cancer (BC) patients. Poor prognostic factors were defined as: pathologic tumor size >or= 4 cm, estrogen-receptor negative, and progesterone-receptor negative. Scarff-Bloom Richardson grade 2 tumors must have two of these factors, and only one in case of grade 3. Between 1988 and 1994, 328 patients were randomized to receive either no systemic treatment (control, n = 161), or fluorouracil 500 mg/m(2), epirubicin 50 mg/m(2), cyclophosphamide 500 mg/m(2), 6 cycles every 21 days (FEC50, n = 167), without any hormonal treatment. The median follow up was 114 months. The 10-year DFS rates were 64 and 71%, respectively (p = 0.23). In the Cox regression model, independent prognostic factors of relapse were the number of nodes examined < 10 (p = 0.002), BCS (p = 0.01), and premenopausal status (p = 0.04). In this model, the relative risk of relapse was 1.46 (CI95 %: 1.05-1.87) in favor of FEC50. In patients who underwent BCS, 21 % developed a local relapse (24 versus 18 %, respectively). The 10-year local DFS was 70.5 and 79.3 %, respectively (p = 0.27). The 10-year overall survival was not different (74.1 versus 70.7 %, p = 0.82). After 10 years of follow-up, the FEC50 regimen reduced the risk of relapse in poor-prognosis node-negative BC patients. The incidence of local relapse was high, and probably related to inclusion criteria. Epirubicin was probably underdosed in such patients, and ongoing studies using 100 mg/m(2) of epirubicin will give us the answer in a near future.

The risk of thrombosis is particularly high in cancer patients, due to many associated risk factors : surgery, immobilization, central venous access, elderly patients... Furthermore, cancer induces a state of hypercoagulability. Thrombophlebitis in this context carries a poor prognosis partially explained by the link with metastasis. Various treatments further increase the risk of thrombosis. Surgery is the most studied therapeutic modality increasing the incidence. Several medical treatments might synergize increasing the thrombosis rate up to 40% for some combinations. Anti-angiogenic treatments like VEGF inhibitors, thalidomide increase the risk of thrombosis. The curative treatment of thromboses has recently been improved; a treatment by LWMH only for 3 to 6 months gives the best results. LWMH for 4 weeks has been proposed as a preventive measure after surgery only; no preventive treatment can be proposed outside this situation.

Between February 2001 and March 2003, 542 sentinel lymph node procedures were performed for localised breast carcinoma (T0-T1, N0, M0) without any previous treatment. Frozen sections were performed in 515 cases and they did not reveal metastases in 446 cases. Fifty-two micrometastases < 2 mm and 18 macrometastases were reported by definitive histopathological exam. Axillary clearance was performed in 50/70 patients (38 with micrometastases and 12 for macrometastases). Modalities of histopathological procedure are discussed and particularly number and interval of serial slides with or without immunochemistry ; 81.8% (36/44) of micrometastases were detected on the two first serial sections. Decisional value of axillary clearance performed in case of micrometastases is also evaluated.

The objective of this double blind parallel-group multicentre study was to compare the efficacy and safety of the combination ondansetron + methylprednisolone + lorazepam (O + M + L) in the prevention of emesis induced by chemotherapy with cyclophosphamide or adriamycin . This tritherapy was compared to a bitherapy O + M. Patients included were suffering from severe haemopathy or breast cancer. They had to have an incomplete response to a previous antiemetic association of 5HT3 serotoninergic receptor antagonist and corticoid. One hundred and thirty-five adult patients were included and were randomised to receive : O + M + L or O + M for 3 days. The emesis control during the 3 days of treatment (no emetic episode during the complete course) was significantly superior in the group O + M + L than in the group O + M (69% versus 46%, p = 0. 042); nausea control on the worst day of the cure was significantly superior in the group O + M + L than in the group O + M (p = 0.04) with 76% of patients in the group O + M + L having complete or major nausea control compared to 51% in the group O + M. The stability of quality of life during the days following chemotherapy measured by one questionnaire, including two scales, one cancer specific (FLIC) and one emesis specific (FLIE), appeared significantly better in group O + M + L (p = 0.04 and p = 0.019). Safety of both antiemetic regimens was good and similar between the two treatment groups. This trial shows that the adjunction of lorazepam to ondansetron and corticoid in combination increases the antiemetic control for patients with an incomplete response to a previous regimen containing a 5HT3 serotoninergic receptor antagonist and a corticosteroid in the prevention of chemotherapy-induced emesis.

Aromatase inhibitors used in breast cancer, are drugs that inhibit the transformation of androstenedione and testosterone, respectively in estradiol and estrone. Two classes have been described: steroidal inhibitors which act competitively and irreversibly and non steroidal inhibitors which block the P 450 cytochrome. The first one is aminoglutethimide which has an adrenal effect on 11, 18 and 21 hydroxylase. Rogletimide, less powerful and less specific is a aminoglutethimide analogue. The response rates obtained with formestane is not different. The clinical development has been stopped due to a lack of specificity. Letrozole, vorozole, exemestane and anastrozole are more powerful and more specific. Letrozole and vorozole are at least as efficient and better tolerated than aminoglutéthimide. Anastrozole, letrozole and vorozole are at least as efficient as megestrol acetate and better tolerated in advanced breast cancer patients receiving a second line hormone therapy.

In the context of a medicoeconomic study of the adjuvant treatment of breast cancer, we evaluated the cost of the recurrence. This cost was assessed from the medical records of 146 patients having presented either distant metastases, or a local recurrence followed or not by metastases between 1983 and 1990. We checked according to published data that the frequency of the metastatic risk is negligible if beyond 5 years after the local recurrence. Costs are expressed in 1995 French Francs (FF), with the French Social Security point of view. From the medical records, we calculated the mean cost of each type of recurrence using medical costs (visits, drugs and treatments, assessments, tests, hospital care, outpatient services.) and non medical costs (patient transportation). The costs are 175,168 FF (standard deviation or SD: 127,972) for metastatic recurrence, and respectively 287,582 FF (SD: 142,280) and 115,705 FF (SD: 78,677) for local recurrence followed or not by metastases. There is a significant difference between these figures (p < 0.001). The hospitalization costs are around 66% of the total cost of each type of recurrences and they are significantly higher (p < 0.005) when metastatic disease occurs after a local recurrence. The mean cost of isolated local recurrence added to metastatic recurrence, 290,873 FF, is not different from that of local recurrence followed by metastases, 287,582 FF (p = 0.15). These results will be integrated in a model in order to evaluate the long-term economic consequences of an adjuvant strategy in the treatment of breast cancer and presented in other publications.

In this study a cost analysis of therapeutics used in the adjuvant treatment of breast cancer has been performed. Four strategies were considered: chemotherapy (FEC, 6 courses), hormone therapy (tamoxifen, 20 mg/day during 3 years), the association of chemotherapy and hormone therapy, or standard follow-up with neither chemotherapy nor hormone therapy. The costs of these strategies were analysed according to the payer's perspective (social security system). In order to complete the economic data, specific investigations were performed at the Centre Oscar-Lambret (COL), a Cancer Center located in Lille (France). The study shows a high cost for chemotherapy (63,767 FF at 5 years) and a high cost for the association (68,891 FF), in comparison to the cost of hormone therapy alone (45,540 FF) or to the follow-up without adjuvant therapy (38,416 FF). These costs could be confronted to the efficacy data of these different strategies and to the cost of avoided relapses. Cost-effectiveness and cost-benefit ratios of these adjuvant strategies could then be assessed.

It is a randomised cross-over multicenter study comparing the efficacy and the tolerance of granisetron (Gra) 1 mg and ondansetron (Ond) 8 mg, oral, given during two consecutive cycles to 188 naive patients scheduled to receive a moderately emetogenic chemotherapy. The antiemetic treatment is given one day per course, 1 hour before chemotherapy and the second administration from 8 to 12 hours after the beginning, during each of the two cycles; alternatively according to the randomisation. Five criteria are assessed; nausea (ordinal and visual analogic scales), emeric episodes (vomiting orland retching), complete response (minor or no nausea, no emetic episode and no rescue treatment), patient preference and tolerance. The intent to treat analysis showed no significant difference at cycle 1 between Gra and Ond; at cycle 2, there is no significant difference in the number of emetic episodes; for the prevention of nausea, the ordinal scale shows a significant difference (p = 0.028 in favour of Gra at day 1 (D1) but not from D2 to D5. Gra induced more complete response than Ond at D1 (p = 0.028), but not from D2 to D5. The cross-over study did not show any period or order effect, whereas a treatment effect on Ond was significant in favour of Gra (p = 0.01). There is no significant patients preference in favour of Gra or Ond. In conclusion, Gra was more efficient in preventing nausea and obtaining complete response on the first day of treatment, significantly at the second cycle. Both Gra and Ond had a good antiemetic activity for moderately emetogenic chemotherapy with complete response rates always over 50% on day 1; delayed emesis remain less weli controlled.

The quality of life has become an indispensable element in the evaluation of treatments, especially as clinical trials are generally conducted in more than one country. In cancerology, numerous questionnaires have been developed and validated, but most of them are in English. This article presents the stages of translation and validation of the French version of the FLIC (Functional Living Index-Cancer). It applies to a sample of 200 patients, 47% of whom have breast cancer. The acceptability of this questionnaire is good (92.2%). The main psychometric criteria were verified. The Cronbach alpha coefficient, equal to 0.90, shows good reliability. A factor analysis was conducted to examine construct validity; it revealed a 5-factor solution accounting for 62% of the variance. These 5 factors are associated with specific domains; physical, psychological and social functioning, current well-being and disease symptoms. The global scores of the FLIC correlate significantly with those of the different scales of the EORTC QLQ-C30. Moreover, clinical relevance is ensured by its correlation with certain clinical variables (WHO index, location of tumour). The French version of the FLIC can be used to measure the quality of life of patients afflicted with cancer, but further studies are necessary to confirm its reliability.

Hormonotherapy in metastatic breast cancer is actually performed using 3 therapeutic classes: antiestrogen as tamoxifen (TAM), progestins, megestrol acetate (MA) and medroxyprogesterone acetate (MPA), aromatase-inhibitors as aminoglutethimide (AG). We investigated therapeutic efficacy of progestins compared to other hormonotherapies in case of breast cancer with bone metastasis. In a literature review, we found ten randomized trials comparing: MPA versus AG, MPA versus MA, MPA versus TAM, MA versus AG versus TAM. The results show an advantage on the response rate using MPA; the usual dose was 900-2,000 mg daily. MPA mode of action can explain these results since they combine gestagenic, androgenics and glucocorticoid effects.

Despite health public problems arised by metastatic breast cancer, specific studies remain rare, and especially when concerning second line chemotherapy. Today, these studies seem essential to allow the clinician, facing the choice between different treatments, to make the best decision. Two recent treatments, docetaxel and paclitaxel, administered every 3 weeks, were compared to the referenced treatment: vinorelbine administered every week. The study aims at evaluating these 3 therapeutic options on second line treatment of metastatic breast cancer. For each of these 3 strategies, our end points were: (1) the duration of progression free survival; (2) the quality adjusted on progression free survival; (3) the cost including the intrinsic cost of chemotherapy as well as the cost of treatment-related and disease-related complications, due to toxicity. Savings obtained with the treatment by delaying relapse were subtracted from expenditure. We used a Markov model to describe the patient's evolution after the administration of the compared treatments. The evaluation concerns the period from the beginning of second line chemotherapy to death. Only direct medical costs were taken into account. Non medical costs and indirect costs were excluded. For each clinical state, resources utilisation was estimated by a retrospective multicentric analysis of 153 medical records of metastatic breast cancer, treated on second line. Resources valuation of hospital costs were based on a national survey on the cost of medical services per DRGs. Quality of life was estimated by a group of nurses in oncology, using the feeling thermometer and standard gamble technics. Incremental cost utility ratios were calculated. Docetaxel reduces the time spent in progression, decreases the number of complications due to progressive disease and thereby provides better quality of life. It provides a benefit of 57 disease- and discomfort-free days, compared to vinorelbine and 22 days compared to paclitaxel. Docetaxel may be thought of as a self-financing strategy as a result of savings in hospital admissions, providing net saving of French Francs (FF) 6,800 in 1993 prices, compared with expenditure associated with vinorelbine treatment and FF 700 compared with the equivalent figures for paclitaxel. A sensitivity analysis confirms the robustness of those results.

In recent studies, the economic criteria has begun to be integrated to the appraisal in cancerology. The question asked by the economist can be framed as follows: what incremental cost should the collectivity or the health insurance system consent, in order to improve the care of cancer patients? This involves first that the cost of the strategies, foreseen or already implemented, can be appraised, then, that indicators can be defined to capture health improvement, and finally, that this health improvement can be quantified. In this article, we present the process of integrated appraisal (cost/result approach). We specifically analyze costs in cancerology, their source and their evolution. We demonstrate the meaning of the integration of economic costs and medical results. We emphasize on the fact that part of the costs, especially those supported by the patient and his close relations, are most of the time excluded from the analysis. Two main points should be carefully analyzed, when proceeding to an appraisal in cancerology: the measurement of the patient's QoL, which represents an expression of the results of the strategy of care; the financing modalities, for the same type of care, if we consider the specificity of the structures involved and the organization of the care. We conclude by mentioning how difficult this task is and under which conditions it should be developed.

The BRCA1 gene modification is responsible for an autosomal dominant syndrome of inherited early onset breast and/or ovarian cancer. This gene is estimated to account for almost half of inherited breast cancers and three quarters of inherited breast/ovarian cancers. This suggests that about 1 out of 500 women may carry BRCA1 mutation. The BRCA1 gene was isolated by positional cloning in 1994. More than 100 different mutations have been found in the germline of affected individuals. We looked by systematic sequencing at BRCA1 germline mutations in 36 patients treated at the Centre Oscar-Lambret for breast and/or ovarian cancer and that belonged to high risk families. We have found 24 mutations: 9 true mutations inducing modifications of the BRCA1 protein (BRCA1+), 5 mutations with unknown consequences on the BRCA1 protein and 10 mutations corresponding to polymorphisms that had been previously described. All the BRCA1+ cases had a HPG3 tumor. The median age of discovery and the receptor positivity percentage are lower in hereditary breast cancer than in the standard population of the breast cancers treated in our center. Consequently, BRCA1 mutations are associated to parameters thought to be of bad prognosis.

The French Northern Oncology Group carried out a randomised, cross-over study comparing two anti-emetic treatment strategies in 150 chemotherapy-naive patients, receiving their first two courses of moderately-emetogenic drugs. Nausea and vomiting were assessed using a self-administered questionnaire for five days. Anti-emetic treatments consisted of granisetron (G) 3 mg intravenously (iv) before chemotherapy or ondansetron (O) 8 mg intravenously, followed by 8 mg orally every eight hours for the next three days (for a total of 9 tablets). No significant difference was detected between treatment regimens in terms of their ability to control either acute vomiting (no vomiting - G = 72%; O = 77%) or acute nausea (no nausea - G = 54%; O = 47%), nor in terms of the number of total responders, (no emesis and no nausea) on day 1 (G = 52%; O = 45%) or on days 1- 5 ( mean G - 37%; O = 32%). Furthermore, there was also no significant difference between patient preference for the two treatments, either with regard to efficacy (G = 39%; O = 34%) or tolerability (G = 29%; O = 27%). In conclusion, no difference was observed between the two treatments.

Topoisomerase I inhibitors are a new therapeutic class whose clinical evaluation began a few years ago; Irinotecan (CPT-11) gave interesting results in colon cancer; side effects were neutropenia, diarrhea, vomiting and a cholinergic syndrome. Topotecan was useful in lung and ovarian cancer; side effects were mostly hematologic. Undergoing studies concern dose optimization, mode of administration and therapeutic associations.

This study was designed to evaluate the efficiency of the association ondansetron-dexamethasone during successive courses in 22 chemotherapy-naive female patients receiving a chemotherapy regimen including cisplatin at a dose of 100 mg/m2. The antiemetic treatment consisted of dexamethasone 20 mg i.v. and ondansetron 24 mg i.v. the day of chemotherapy, then ondansetron 8 mg per os every 8 hours for 5 days. A complete control of emesis with no or mild nausea was observed in 41% of cases on the first day of the first course, in 9.5% after the 3rd course. No patient experienced a complete response after the sixth. Similar results were obtained when nausea and vomiting were assessed on the worst day of D2 or D3. Our study shows that, as with other antiemetics, ondansetron-dexamethasone efficiency decreases with the number of courses.

One hundred and three patients previously treated with chemotherapy including an anthracycline were entered in a VMMC protocol study: vindesine (Eldisine), mitoxantrone (Novantrone) and mitomycin C (Ametycine). Group A consisted of 41 women who received the protocol published by Belpomme: vindesine (2.5 mg/m2 day 1 and 8) and mitoxantrone (12 mg/m2/day) every 4 weeks, and mitomycin C (8 mg/m2) every 8 weeks. Group B consisted of 62 patients who were treated with a modified protocol: vindesine (2.5 mg/m2) and mitoxantrone (12 mg/m2) every 3 weeks on day 1, and mitomycin C (8 mg/m2) every 6 weeks. Tolerance was acceptable with 79% of patients complaining of weakness. There was a 66% incidence of gastro-intestinal toxicity, a 10.7%-incidence of neurotoxicity (reversible dysethesias), and a 5.8% incidence of cardiotoxicity. There was considerable hematotoxicity of grade 2, 3 and 4: neutropenia 16.6%, thrombocytopenia 7.7%, anemia 21.4%. There was a 19.2% overall objective response rate (CR and PR) (95% confidence interval: 12-30) (CR: 3.2%). The median duration of the response was 39 weeks. There was no significant difference in response rates whether or not the patients (19 cases) were undergoing simultaneous hormonal therapy and no difference according to the protocol used. Similarly, neither menopause nor a previous response to anthracyclines had any effect on the response rate. The 19.2% response in this protocol is similar to other breast cancer salvage chemotherapy protocols for patients who have failed to respond to anthracyclines (< 20%).

The ten-year results of the meta-analysis of the adjuvant systemic treatment of early breast cancer are summarized. The five-year results are confirmed and a few new informations arise: tamoxifen is more efficient when given more than two years; the results of chemotherapy are significant in post-menopausal patients less than 70 years old.

We investigated binding characteristics of bFGF in membranes prepared from 4 human breast cancer cell lines (MCF-7, T-47D, BT-20 and MDA-MB-231) and 38 primary breast cancer biopsies. Results of competitive binding experiments were analysed using the "Ligand" program to determine binding site concentrations and affinities. bFGF mitogenic activity was also measured by [3H]-thymidine incorporation into DNA of breast cancer cell lines. The presence of high-affinity binding sites was demonstrated in each cell type (Kd: 0.5 nM). The presence of these high-affinity binding sites was confirmed by saturation experiments. A second class of low-affinity binding sites was detected in the 2 hormono-independent cells (BT-20: Kd = 2.9 nM; MDA-MB-231: Kd = 2.7 nM). bFGF stimulated the proliferation of MCF-7, 7-47D, BT-20 and not of MDA-MB-231 cell lines. In breast cancer biopsies, binding sites were detectable in 36/38 cases; high-affinity binding sites (Kd < 1 nM) were present in 19/39 cases and low-affinity binding sites (Kd > 2 nM) were present in 29/36 cases (the 2 classes of binding sites were present in 12 biopsies). No relation between FGF binding sites and node involvement nature or grade of tumor was evidenced. Negative correlations (Spearman test) were found between total bFGF binding site concentrations and estradiol receptor concentrations (P = 0.05) or progesterone receptor concentrations (P = 0.009). The demonstrations of 1), bFGF specific binding sites in breast cancer membranes; and 2) bFGF growth stimulation of some breast cancer cell lines, indicate that this factor could be involved in the growth of most breast cancers, and could act (among other factors) directly on the growth of cancer cells.

Most pancreatic cancers cannot be resected at the time of diagnosis. The efficiency of chemotherapy is poor and does not seem to modify the spontaneous evolution of the tumor. 5FU alone, whatever the regimen, is the most active drug leading to a response rate of 20-30%; polychemotherapy protocols--particularly FAM and SMF--are not any more active; survival of patients does not differ when using mono- or polychemotherapy. Patients with pancreatic cancer that cannot be resected should be treated by 5FU monochemotherapy when not entering a clinical trial.

We present a method for automated analysis of urinary trypsin inhibitory capacity. The validity of the method has been established. The mean value of urinary antitryptic activity is higher in patients with disseminated cancers (70 IU/1, n = 243) than in healthy donors (14,4 IU/1, n = 117). However, frequency distribution of urinary trypsin inhibitor values shows a great overlap, so that an increased level of urinary trypsin inhibitor cannot be considered as a marker of neoplastic diseases but seems to be a non specific indicator of inflammatory syndromes.

The binding characteristics of IGF1 on membranes prepared from 5 human breast cancer cell lines were investigated in detail. The presence of one class of high affinity IGF1 binding sites was demonstrated (BT-20: n = 230 fmol/mg protein, Ka = 0.7 nM-1; MCF-7: n = 124 fmol/mg protein, Ka = 1 nM-1; T-47D: n = 61 fmol/mg protein, Ka = 1.1 nM-1; HBL-100: n = 18 fmol/mg protein, Ka = 3.2 nM-1; MDA-MB-231: n = 7 fmol/mg protein, Ka = 2.8 nM-1). Chemical cross-linking of 125I IGF1 to breast cancer cell membranes then sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed one major band of relative molecular weight 130000. The specificity of these receptors was studied: native or recombinant IGF1 had the same potency to inhibit 125I IGF1 binding; IGF2 was able to compete for binding, whereas insulin competed with a potency lower than 1/100 that of IGF1. These characteristics of IGF1 binding sites in breast cancer cell membranes correspond to the previously described binding unit of type I IGF receptors (IGF1-R). Finally we determined that for a routinely used standard assay, it was necessary to incubate for 5 h at 4 degrees C a high amount of membrane protein (400 micrograms) and 200,000 cpm of tracer. Considering the known effect of IGF1 on breast cancer cell multiplication, it is tempting to suggest that this factor might play a major role in the growth of breast cancer: the measurement of IGF1-R, using this standardized method, will give an assessment of these tumors IGF1 sensitivity; it can be performed on the membrane fraction obtained when preparing cytosol for steroid receptor assay.

One hundred-twenty-seven advanced breast cancer patients who had been -for most of them- heavily pretreated with chemo- and/or hormone therapy received 500 mg aminoglutethimide and 30 mg hydrocortisone/day. The response rate was 20% (58% when stabilizations were included); the best responses were observed in skin and node metastases. The response rate in bone metastasis was 16%. The general condition of the patient (according to the Karnofsky index) was improved in 50% of the responders (including stabilizations) and in 23% of the non-responders. The survival of patients who were only stabilized was close to the survival of responders. The tolerability of this treatment was very good.

Aminoglutethimide (AG) is a drug that inhibits several steps of steroidogenesis; it is used in post-menopausal advanced breast cancer. More recently it has been proposed as a hormone therapy in prostatic cancer. Clinical studies involving patients resistant to orchidectomy and estrogens have generally given poor objective results and a frequent subjective response. It is too early to predict the interest of AG in the hormone therapy of prostate cancer since the studies are too few and since it has been used very late in the evolution of cancer.

Plasma levels of cholesterol, HDL cholesterol (HDL chol), LDL cholesterol (LDL chol), triglycerides, Al apoprotein and B apoprotein were studied in 73 patients receiving 500 mg aminoglutethimide (AG)/day and 40 mg hydrocortisone/day for advanced breast cancer. These dosages were done before treatment and then repeated during AG therapy. When all patients were considered together, a significant increase of cholesterol, HDL chol, LDL chol and Al apoprotein was noted. If one considers two groups of patients: group A (where cholesterol and triglycerides plasma levels were normal before treatment) and group B (where cholesterol and/or triglycerides plasma levels were high before treatment), it appears that variations differ in both groups. In group A patients we found an increase in cholesterol, chol LDL, B apoprotein and to a lesser extent Al apoprotein plasma levels. In group B patients there was an increase in cholesterol, HDL chol and Al apoprotein plasma levels.

Aminoglutethimide (AG) is a drug that inhibits steroid synthesis; it is used in advanced breast cancer. After the observation of abnormalities in lipid metabolism in patients, we realized an experimental study to try to look for a pathogenetic hypothesis. Three groups of rats received respectively AG, Hydrocortisone (HC) or both (AG + HC) and were compared to controls. Animals treated with AG (with or without HC) had a greater liver content of triglycerides, cholesterol and phospholipids than controls. Cholesterol plasma level was higher in animals treated with AG + HC. The bile flow was higher in rats receiving AG and AG + HC whereas biliary salt concentrations were lower. These variations could be the consequence of both an enzymatic induction and an inhibition of some cytochrome P450 dependent hydroxylases.