[Oligometastatic breast cancer : therapeutic implications of a new paradigm]. / Cancer du sein oligométastatique : implications thérapeutiques d'un nouveau paradigme.

INTRODUCTION: Oligometastatic breast cancer incidence is recently increasing thanks to screening and imaging improvements. Unlike patients with metastatic disease, a small number of oligometastatic patients may expect a definitive remission, in case of aggressive management performed with intent to cure. We report the atypical evolution of an oligometastatic breast cancer patient, who lately relapsed with a different Her2 status. RESULTS: A 46 year old women was treated for an infiltrating duct breast carcinoma, initially diagnosed with oligometastases and an Her2- negative status. Treatments were performed in intent to cure but the patient relapsed 5 years later with a solitary Her2-positive liver metastasis. The aggressive local and systemic (using an anti- Her2 targeted therapy) management induced a still complete remission at last follow-up. CONCLUSION: Prognosis of breast oligometastatic cancer is unpredictable, but an aggressive with intent-to-cure management may bring benefits to patients. However very rare, the switch of Her2 status between initial diagnosis and relapse highlights tumor heterogeneity, and the fact that a cell population featuring targetable characteristics may appear due to anticancer drug induced-cell selection.

INTRODUCTION: L'incidence des cancers du sein oligométastatiques est en augmentation, grâce aux progrès du dépistage et de l'imagerie. Au contraire de la maladie métastatique, un faible pourcentage de ces patientes peut espérer une guérison définitive en cas de prise en charge menée en intention curative sur toutes les cibles. Nous rapportons le cas de l'évolution atypique d'une patiente oligométastatique, avec une récidive tardive d'un cancer du sein, aux caractéristiques génétiques transformées. Résultats : Une patiente de 46 ans a été prise en charge initialement pour un adénocarcinome mammaire d'emblée oligo-métastatique ne surexprimant pas Her2. Après un traitement à visée curative, la patiente a rechuté 5 ans plus tard avec une métastase hépatique unique, surexprimant Her2. La prise en charge locale curative et systémique avec une thérapie ciblant Her2 a permis la rémission complète persistante après 3 ans de suivi. CONCLUSION: Le pronostic de la maladie oligométastatique du sein doit être abordé avec prudence, mais un traitement réalisé en intention curative peut apporter un bénéfice aux patientes. Le changement de statut Her2 entre le diagnostic primitif et la récidive -fait très rare- souligne l'hétérogénéité de la population tumorale, dont une fraction présentant des caractéristiques génétiques particulières peut émerger, sous la pression de sélection des drogues anticancéreuses.

Multicentric neoadjuvant pilot Phase II study of cetuximab combined with docetaxel in operable triple negative breast cancer.

Systemic therapy for triple negative breast cancer (TNBC) is mostly based upon chemotherapy. Epithelial Growth Factor Receptor (EGFR) is overexpressed in around 50% of TNBC and may play a role in its pathogenesis. Consequently, we performed a multicentric pilot Phase II neoadjuvant trial of cetuximab (anti-EGFR antibody) combined with docetaxel for patients with operable, Stage II-III TNBC. Therapy consisted of weekly cetuximab (first infusion: 400 mg/m(2), then 250 mg/m(2)) combined with six cycles of docetaxel (T: 100 mg/m(2)) q.3 weeks. Subsequently, all patients underwent surgery. The primary endpoint was pathological complete response (pCR) while clinical response, toxicity and ancillary studies were secondary endpoints. Paraffin-embedded and frozen tumor samples were systematically collected in order to identify predictive biomarkers of efficacy and resistance. From a total of 35 accrued patients, 25 were assessable for pathologic response. The pCR rate was 24% [95% CI: 7.3-40.7]. Complete clinical response rate (cCR) was observed in 22% of cases. Conservative surgery was performed in 75% of patients. Toxicity, mostly cutaneous and hematologic, was manageable. The pre-therapy ratio between CD8+ and FOXP3+ tumor-infiltrating lymphocytes equal or higher than 2.75 was predictive of pCR: 43% versus 0%, p = 0.047. Cetuximab in combination with docetaxel displays a modest activity, but acceptable toxicity as neoadjuvant therapy of operable TNBC. Similarly to previous observations using panitumumab, another anti-EGFR antibody, the immune component of the tumor microenvironment may play an important role in predicting TNBC response to the neoadjuvant therapy.

Impact of geriatric risk factors on pegylated liposomal doxorubicin tolerance and efficacy in elderly metastatic breast cancer patients: final results of the DOGMES multicentre GINECO trial.

BACKGROUND: Metastatic breast cancer chemotherapy in the elderly is considered effective in carefully selected patients, but there is little data regarding its effect in vulnerable patients. METHODS: We evaluated tumour response (primary endpoint), feasibility and outcomes after six courses of an adapted dose of pegylated liposomal doxorubicin (PLD) (40 mg/m(2) every 28 days) as first-line chemotherapy for hormone-resistant MBC. RESULTS: Of 60 patients >70 years (median 77 years), 15% had performance status ≥2 and 73% had visceral metastases. Geriatric assessment included: ≥2 comorbidities, 42%; ≥1 deficiency in Activities of Daily Living (ADL), 10% and Instrumental ADL (IADL), 82%; living in residential homes, 12%; albumin <35 g/L, 17%; body mass index (BMI) <21, 20%; depression, 17%; and lymphocytes ≤1 × 10(3)/mm(3), 27%. Complete response, partial response and stable disease were observed in 5%, 15% and 60%, respectively, but only 48% completed six cycles. Treatment discontinuations were mostly due to disease progression (18%) and non-haematological (NH) toxicities (22%). Eight patients died during treatment (three possibly related to PLD), and 15 had unplanned hospital admissions. Exploratory analyses to identify geriatric covariates associated with treatment outcomes revealed severe haematological toxicities significantly correlated with lymphocytes ≤1 × 10(3)/mm(3). NH toxicities correlated with age ≥80 years and living in residential homes. Progression-free survival (median 6.1 months) decreased with age, deficiency in IADL, cardiac dysfunction and living in residential homes. Overall survival (median 15.7 months) also decreased with living in residential homes. CONCLUSION: Despite manageable haematological toxicities and expected response rates, PLD feasibility was poor in unselected elderly patients.

[Exclusive radiotherapy and concurrent endocrine therapy for the management of elderly breast cancer patients: case study and review of hypofractionated schemes]. / Hormonoradiothérapie exclusive dans la prise en charge du cancer du sein de la personne âgée : cas clinique et revue de la littérature des schémas hypofractionnés.

Normofractionated radiotherapy is standard for adjuvant management of patients treated with breast conservative surgery for breast cancer. However, many elderly patients are not eligible to such strategy, either because of concurrent diseases, or because the tumor is inoperable. Several protocols of exclusive radiotherapy have been reported in the literature, frequently using hypofractionated radiotherapy and endocrine therapy. We report a case of a patient treated with exclusive endocrine and radiotherapy and address the state of the art on hypofractionated schemes for the management of elderly breast cancer patients. While hypofractionated radiotherapy does not compromise the oncologic or cosmetic outcome, there is no prospective data that assesses the place of radiotherapy for the exclusive treatment of elderly patients. This strategy should be further assessed in clinical randomized trial.

Adherence with oral chemotherapy: results from a qualitative study of the behaviour and representations of patients and oncologists.

Oral chemotherapy is increasingly used in oncology. Poor adherence, that is, non-respect of medical advice about taking the therapy and surveillance of adverse effects, is the main risk associated with this administration route. Poor adherence may be explained by non-adherence by the patient to the treatment, misunderstanding the advice or it could also reflect the poor adaptation of the healthcare team to a new administration route. Here we report the results from a qualitative study that aimed to describe and understand existing practice for capecitabine, an oral chemotherapy, which is used for the treatment of metastatic breast and colon cancer. We interviewed 42 patients who were receiving oral capecitabine in groups and individually as well as 10 prescribers. This study was carried out in two specialist cancer centres. The results showed a wide diversity in the prescribers' practices, who make decisions based on their experience of practice guidelines for intravenous chemotherapies. Although the results for the patients do not suggest deliberate non-adherence, they show poor observance of the dose schedule. The most important result of this study is the patient's inability to identify and to report important signs of harmful toxicity.

[Impact of the chemotherapy protocols for metastatic breast cancer on the treatment cost and the survival time of 371 patients treated in three hospitals of the Rhone-Alpes region]. / Impact des protocoles de chimiothérapie administrés pour cancer du sein métastatique sur le coût du traitement et la survie de 371 patientes traitées dans trois établissements de la région Rhône-Alpes.

The chemotherapy of the metastatic breast cancer is characterized by the diversity of the treatment protocols and the utilisation of new expensive molecules posing the double problem of outcomes for the patients and financial effects for the hospitals. This survey describes the different chemotherapy treatments prescribed in the metastatic breast cancer and the direct costs supported by the hospitals according to the patient survival time. A cohort of 371 patients treated for a metastatic breast cancer was followed in three hospitals of the Rhone-Alpes region between 2001 and 2006. The detail of their different antineoplasic treatments, as well as the purchase cost of the drugs and their cost of hospital administration, the cost of the other hospital stays are presented in relation with the survival. The median survival time (35,8 months; CI 95%: [31.7-39.1]) since the first metastasis does not differ significantly according to the hospital. Ninety-three different chemotherapy protocols are observed combining from one to five molecules. Thirty-two different molecules are identified. In first line treatment, there is a significant difference in the use of the new molecules according to hospital (Chi(2) test; P < 10(-3)). The average cost of a chemotherapy treatment is 3,919 euro (+/- 8,069 euro), the higher cost is observed for trastuzumab (23,443 euro). The average time period before the beginning of a new chemotherapy line is 212 days (+/- 237 days) and the mean cost of hospital stay during this period is 3,903 euro (+/- 4,097 euro). If no impact of the chemotherapy treatment strategy is observed on the survival time of the patient, it is the opposite for the hospital treatment cost. These results are asking for a better control system of the authorization procedure of new molecules marketing and the harmonization of the practices.

[Influence of social and cultural patterns on decision-making in oncology]. / Influence des facteurs socioculturels dans la prise de décision médicale en cancérologie.

Shared decision-making is based on the idea of an enlightened participation of the patient to the therapeutic decision process, especially when the ratio between risks and benefits of treatment options is uncertain. The physician owes to ponder the advantages and the inconveniences of chemotherapy, which can be enlightened by a discussion with the patient. Thus, neither shared decision-making nor decision tools are currently used in France. Our aim is to evaluate the variables that step in the therapeutic choice of French physicians concerning the adjuvant chemotherapy prescription in breast cancer. We focus on the impact of different medical cultures on decision processes and shared decision-making conceptions. A socio-anthropological study is carried out with the participation of six French medical centre. First results show the influence of local specificities, professional groups and individual sociocultural background of physicians.

Relationship between nutritional status and quality of life in patients with cancer.

Patients with cancer frequently suffer a deteriorated quality of life and this is an important factor in the therapeutic decision. The correlation between quality of life and malnutrition seems obvious and bidirectional. The aim of our study was to describe the global quality of life and its various dimensions in patients with cancer, as a function of the nutritional status. A transversal observational study was performed in wards in hospitals in Clermont-Ferrand and Saint Etienne on 907 patients. The EORTC questionnaire, QLQ-C30, was used to assess the quality of life. The mean global quality of life score was 48.8 for patients who had a weight loss of more than 10% since the beginning of their illness, compared with 62.8 for the other patients (p<0.001). A significant association with weight was observed for the main dimensions of the quality of life: physical, functional, cognitive, social, fatigue, nausea, pain, loss of appetite, constipation and diarrhoea. This strong relation between quality of life and weight loss shows the importance of dietary management in patients with cancer.

Estimation of the risk for nutritional state degradation in patients with cancer: development of a screening tool based on results from a cross-sectional survey.

BACKGROUND: In routine practice, the evaluation of the nutritional status of patients with cancer is not always performed although there is frequent modification as disease progresses. The validated screening and evaluation tools currently available are time-consuming and costly. In this study we analysed factors that could be used to identify patients likely to need nutritional surveillance or intervention. PATIENTS AND METHODS: A cross-sectional survey was carried out for 2 weeks in June 2006 on 477 patients with cancer. RESULTS: 30.2% of the patients had lost more than 10% of their body weight since the start of the illness. After adjustment, the factors significantly associated with weight loss were: depressive state (OR = 3.49; P = 0.002), digestive or ENT tumours (OR = 3.20; P = <0.001), chemotherapy (OR = 2.66; P = 0.011), male gender (OR = 2.30; P = 0.001) and professional status (OR = 2.08; P = 0.02). Using a logistic model, we calculated the risk of weight loss as a function of the presence of the identified predictive factors. CONCLUSION: We report a simple screening tool, which will not replace the available evaluation methods but will enable targeting of the patients most likely, after a specific evaluation, to benefit from nutritional intervention. This remains to be validated in further prospective studies.

Comprehensive geriatric assessment predicts tolerance to chemotherapy and survival in elderly patients with advanced ovarian carcinoma: a GINECO study.

BACKGROUND: Data from prospective clinical trials are needed to better define standards of care in elderly patients with advanced ovarian carcinoma and to demonstrate the interest of Comprehensive Geriatric Assessment (CGA) in this fragile and heterogeneous population. PATIENTS AND METHODS: From July 1998 to October 2000, 83 advanced ovarian carcinoma patients >70 years old received carboplatin AUC 5 and cyclophosphamide 600 mg/m2, on day 1 of six 28-day cycles. The clinical and biological geriatric covariates prospectively studied were: comorbidities, comedications, cognitive functions (Mini-Mental test), nutritional status and autonomy. RESULTS: Patient characteristics were: median age 76 years, serous histology (73%), FIGO stage III (75%), optimal initial surgery (21%) and performance status (PS) > or =2 (44%). Sixty patients (72%) received six chemotherapy cycles without severe toxicity (STox) or tumor progression. Multivariate analysis retained three factors as independent predictors of STox: symptoms of depression at baseline (P = 0.006), dependence (P = 0.048) and PS > or =2 (P = 0.026). Independent prognostic factors identified for overall survival (Cox model) were depression (P = 0.003), FIGO stage IV (P = 0.007) and more than six different comedications per day (P = 0.043). CONCLUSION: CGA could predict STox and overall survival of elderly advanced ovarian carcinoma patients.

[Intra-abdominal desmoplastic small round-cell tumors. An entity among peritoneal carcinomatoses in young adults]. / Tumeurs desmoplastiques intra-abdominales à petites cellules rondes. Une entité parmi les carcinoses péritonéales de l'adulte jeune.

Desmoplastic small round-cell tumors in young adults were first described in 1989. They may be revealed by an abdominal mass or a peritoneal carcinomatosis. The diagnosis and the initial treatment are based on debulking surgery. Chemotherapy using doxorubicin, ifosfamide, etoposide and cisplatin can then be proposed. Despite some initial chemosensitivity, prognosis remains poor.

Efficacy and safety of the paclitaxel and carboplatin combination in patients with previously treated advanced ovarian carcinoma. A multicenter GINECO (Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens) phase II study.

BACKGROUND: Platinum compounds are the most active drugs in ovarian cancer treatment; cisplatin and carboplatin demonstrated similar efficacies but different toxicity profiles. Paclitaxel combined with cisplatin as first-line treatment improved overall survival when compared to a cisplatin-cyclophosphamide combination, but generated higher rates of neutropenia, febrile neutropenia and neurotoxicity. The paclitaxel-carboplatin combination may be better tolerated than cisplatin-paclitaxel. DESIGN: The objective of the present study was to assess the efficacy and safety of the combination of paclitaxel and carboplatin in previously treated advanced ovarian cancer patients. PATIENTS AND METHODS: During or after platinum-based chemotherapy, 73 patients with progressive advanced epithelial ovarian carcinoma were enrolled to receive every four weeks a three-hour infusion of paclitaxel 175 mg/m2 followed by a 30-minute carboplatin infusion. The carboplatin dose was calculated to obtain the recommended area concentration-versus-time under the curve of 5 mg x ml-1 x min. RESULTS: Toxicity and response could be evaluated for 72 and 62 patients, respectively. Eleven complete and 15 partial responses gave an overall response rate of 42% (95% CI: 30%-54%). Response rates for platinum-refractory patients and those with early (> or = 3 and < 12 months) and late (> 12 months) relapses were 24%, 33% and 70%, respectively. The respective median response duration, the median progression-free survival and median overall survival were 8, 6 and 14 months. Myelosuppression was the most frequent and severe toxicity. Grade 3 and 4 neutropenia occurred, respectively in 30% and 23% of the cycles; 6% of the cycles benefited from medullary growth factors. Only one episode of febrile neutropenia was observed. Grade 3 and 4 thrombocytopenia occurred, respectively during 3% and 1% of the cycles. Alopecia was frequent. Transient peripheral neuropathy developed in 47% of patients but was severe in only one patient. One early death was attributed to progressive disease and possibly to therapy. CONCLUSION: This combined paclitaxel-carboplatin therapy is effective and can be safely administered to ovarian cancer patients who relapse after one or two regimens of platinum-based chemotherapy.

Efficacy and safety of the combination paclitaxel/carboplatin in patients with previously treated advanced ovarian carcinoma: a multicenter French Groupe des Investigateurs Nationaux pour l'Etude des Cancers Ovariens phase II study.

The French Groupe des Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) conducted a multicenter phase II study of carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to evaluate the efficacy and side effects of this combination in pretreated advanced ovarian cancer. Patients with progressive ovarian carcinoma during or after platinum-based chemotherapy received paclitaxel 175 mg/m2 intravenously over 3 hours followed by intravenous carboplatin over 30 minutes every 4 weeks. The dose of carboplatin was calculated using a projected area under the concentration-time curve of 5 mg/mL x min. Of the 50 patients entered, 50 were evaluable for toxicity and 42 for response. There were eight complete and 10 partial responses, for an overall response rate of 43% (95% confidence interval, 28% to 56%). Overall response rates in platinum refractory patients and in those with early (> or = 3 and < 12 months) and late (> or = 12 months) relapse was 28%, 33%, and 71%, respectively. Median response duration, progression-free survival, and overall survivals were 8, 6, and 14 months, respectively. The most frequent and severe toxicity was myelosuppression. Grades 3 and 4 neutropenia occurred in 30% and 23% of cycles, and granulocyte colony-stimulating factor was administered in 6%. Only one case of neutropenic fever was observed. Grades 3 and 4 thrombocytopenia occurred in 3% and 1% of cycles, respectively. Alopecia and moderate nausea or vomiting were frequent. Transitory peripheral neuropathy was present in 45% of patients but was severe in only one patient. One early death was observed due to progressive disease and possibly to therapy. The combination of paclitaxel 175 mg/m2 as a 3-hour infusion and carboplatin dosed to an area under the concentration-time curve of 5 is an effective therapy in patients previously treated with platinum-based chemotherapy and may be administered safely to outpatients who relapse after one or two lines of chemotherapy.

Postmenopausal patients with node-positive resectable breast cancer. Tamoxifen vs FEC 50 (6 cycles) vs FEC 50 (6 cycles) plus tamoxifen vs control--preliminary results of a 4-arm randomised trial. The French Adjuvant Study Group.

In 1986 the true benefit of adjuvant medical treatment in postmenopausal patients with pathological node-positive breast adenocarcinoma was still controversial. The French Adjuvant Study Group (FASG) initiated a randomised trial to elucidate the respective roles of adjuvant chemo-and/or hormonotherapy in this group of patients. Of the 776 patients who have been included between 1986 and 1990, 741 were fully eligible for evaluation. Inclusion criteria were postmenopausal patients aged between 50 and 70 years with adenocarcinoma of the breast, positive pathological nodes and no distant metastasis. Patients were randomised to 1 of 4 treatment arms: Group A (n = 192) received tamoxifen 30 mg/day orally for 3 years; Group B (n = 183) received FEC 50 (fluorouracil 500 mg/m2, epirubicin 50 mg/m2 plus cyclophosphamide 500 mg/m2) for 6 cycles; Group C (n = 182) received tamoxifen 30 mg/day orally for 3 years plus FEC 50 for 6 cycles; Group D (n = 184) received no medical adjuvant treatment. Surgery was either modified radical mastectomy (n = 363) or tumorectomy (n = 378), and postoperative irradiation was given to all patients. All major prognostic factors were well balanced between the 4 patient groups. Toxicity was evaluated in 348 patients in Groups B and C who received a total of 1983 chemotherapy cycles. Median epirubicin dose intensity (mg/m2/week) was 15.8 in Group B and 15.7 in Group C. Grade 3 to 4 neutropenia was observed in 4.7% of cycles for Group B and 3.7% for Group C. Grade 3 to 4 nausea/vomiting were seen in 18% of treatment cycles in Group B and 15% in Group C.(ABSTRACT TRUNCATED AT 250 WORDS)

[Prognostic factors in the response of a first line chemotherapy in advanced breast cancer]. / Etude des facteurs pronostiques de la réponse à une chimiothérapie de première ligne dans le cancer du sein en phase avancée. Groupe ERASME.

Anthracyclines containing regimen are widely used in advanced breast cancer. The response to first line chemotherapy varies according to many individual factors and the theoretical response to a given protocol cannot predict the response of a patient. A randomized clinical trial (ERASME) was initiated in order to evaluate the more appropriate first line chemotherapy scheme in advanced breast cancer. Prognostic factors were included in a multiple logistic regression to explain the response after the first 3 chemotherapy courses (monthly FEC). Three factors were found to be statistically significant: adjuvant hormonotherapy, loco-regional metastases, adjuvant adriamycin containing regimen (pejorative prognostic factor). By combining these factors, this statistical model enables us to predict a response rate to a first line chemotherapy from 27 to 87%. Such a model can be taken into account in a decision-making procedure of first line chemotherapy in advanced breast cancer.