Biomedical subjects
Publications and source records attributed to M Espié.
Although the adjuvant tamoxifen benefit/risk rate is unquestionable in breast cancer treatment, the increase of endometrial cancer in chemoprevention is about to be a real problem. In the studies currently published metrorragia in the main signal. Levonogestrel intra-uterine device has not proved its efficacy for the decrease of this risk.
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TP53 activation by genotoxic drugs can induce apoptosis or cell-cycle arrest. Thus, whether the gene is mutated or wild type could affect the response of a tumour to chemotherapy. Clinical data are unclear, possibly as a result of heterogeneity of tumours, drugs, methods of assessing response, or TP53 status. We studied 50 non-inflammatory, locally advanced breast cancers that had been treated with high doses of a combination of epirubicin and cyclophosphamide. We noted eight complete responses, which all occurred in the 14 patients with tumours containing mutated TP53 (p<0.0001). In high-grade, advanced breast cancers, inactivation of the TP53 pathway could greatly improve the response to this chemotherapy regimen.
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Amphiregulin (AR) and its receptor, epidermal growth factor receptor (EGFR), were evaluated by dual immunostaining in a series of 84 invasive ductal breast carcinoma specimens, 33 of which were from locally advanced inflammatory (T4d) cancer. Co-expression of AR and EGFR was always found in non-malignant breast tissues adjacent to tumours (24/24). Alternatively, expression of AR and EGFR was found in invasive epithelial tumour cells in 50% and 17.8% of specimens, respectively. In tumour stroma, 59.5% and 30.9% of specimens, respectively, were positively stained. By univariate analysis, AR and EGFR expression in invasive carcinomas was correlated with large tumour size, inflammatory carcinoma, node involvement, Bloom-Richardson (SBR) grade III, and absence of oestrogen receptor. EGFR expression in stromal cells was correlated with non-inflammatory carcinoma. A putative autocrine loop with AR and EGFR expression in invasive carcinoma was detected in 14.3% of cases. Stromal expression of AR and EGFR expression in invasive tumour cells was detected in 11.9% of cases and related to poor prognostic parameters. By multivariate analysis, AR expression in invasive tumour was strongly related to inflammatory carcinoma (p=0.005) and marginally related to SBR grade III (p=0.07). EGFR expression in invasive tumour and stromal cells was correlated with absence of oestrogen receptor and non-inflammatory carcinoma (p=0.002 and p=0.015, respectively).
In oncological medicine, professionals work with patients in very separate areas of specialization. This specialization does not always seem the best approach, however, this kind of specialized care can benefit the patients. We would like, in the following text, to share with you a daily experience of an oncologist and a psychoanalyst treating a patient. First, we will present the oncologist's point of view: his way of understanding the patient's journey, his role which is sometimes difficult to accept and maintain between taking action and speaking, the richness and benefits of multidisciplinary care, the oncologist/patient relationship which unfolds over a long-term and finally, his stance facing what wee call the 'end of life'. Secondly, the psychoanalyst will consider her place in a medical service, working with women facing breast cancer. Through oncological case studies, wee will follow in detail the psychological work which unfolds during regular sessions between patients and the psychoanalyst. We will try to analyse the dynamic in the triad: oncologist/patient/psychoanalyst, and the potential journey from this triad to a triangulation, rich in potential for psychological elaboration and evolution. Both, the oncologist and the psychoanalyst will illustrate their work's pecularities and will try to show how their care and intervention in a case come together in one common goal: to be listening to both the physical and the psychological distress of their patients.
BACKGROUND: This phase II study was designed to assess the efficacy and safety of gemcitabine in patients with metastatic breast cancer (MBC) previously treated with an anthracycline- or anthracenedione-containing regimen as first-line therapy for metastatic disease. PATIENTS AND METHODS: Forty-seven patients with MBC were enrolled in five French centers. Patients were eligible if they had received one prior chemotherapy regimen with an anthracycline or anthracenedione for metastatic disease, if they had responded to that prior regimen, and if they had relapsed at least 6 months after the first response. Fifteen patients received more than one prior anthracycline regimen; thus, gemcitabine was third-line therapy for 30% of patients. Gemcitabine 1,200 mg/m(2) was administered as a 30-min intravenous infusion on days 1, 8, and 15 of a 28-day cycle for a maximum of eight cycles after the best response was obtained. RESULTS: Objective responses were seen in 12 of 41 assessable patients (4 complete responses and 8 partial responses), for an objective response rate of 29% (95% confidence interval, 16-46%). The median response duration was 8.1 months (range: 2.5-27.4 months). Serious hematological toxicity was minimal, with grade 4 neutropenia in 2% of the patients (no neutropenic fever), grade 3 neutropenia in 28% of the patients, and grade 3 thrombocytopenia in 6% of the patients. Among the nonhematological toxicities, asthenia was the most common. CONCLUSIONS: Gemcitabine given at this dose and schedule is a well-tolerated treatment with definitive antitumor activity in pretreated MBC patients. This result warrants future exploration of the use of gemcitabine as a single agent and in combination in patients with MBC.
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PURPOSE: Several studies have demonstrated that systematic breast cancer screening increases overall survival. We report our experience regarding diagnosis of breast lesions detected using mammography. METHODS: Case reports of patients operated on in either 1992 or 1993 were retrospectively reviewed. A multivariate analysis of the clinico-pathological correlation was performed. RESULTS: Four hundred fifty seven patients representing on total 544 procedures, were included in the study. Mean age was 50.5 years (range 19-80 years). Most of the patients had no previous history of mammary lesion. Mammography was performed with prophylactic intent in more than 60% of the cases. Four hundred twelve (75.7%) benign lesions were diagnosed. Main lesions were: adenofibroma (15.7%), fibrocystic mastopathy (66.3%), adenosis (26.2%), ductal hyperplasia (23.9%), lobular hyperplasia (10.7%), and combined ductal and lobular hyperplasia (8.5%). Hyperplasia accompanied by cytonuclear atypia was observed in 49 (11%) cases. One hundred thirty two (24.3%) malignant lesions were reported, including 69 (52.3%) invasive carcinomas and 63 (47.7%) in situ carcinomas. Only nine axillary lymph node dissections were positive and 75 minimal breast cancers were diagnosed. The multivariate analysis showed that only radiological signs are a risk factor for cancer. The relative risk for cancer when focus of irregular and vermicular microcalcifications are diagnosed is 4.2 (2.0-8.5). It is 5.6 (2.5-12.5) in case of spiculated opacity. CONCLUSION: Exeresis following radiological prophylactic screening allows diagnosis of high-risk benign lesions and low-stage breast cancer. Radiological parameters are the most powerful predictive factors for malignancy.
Our purpose was to evaluate the late physical and psychosocial difficulties of premenpausal patients treated for a localized breast cancer and to weigh the impact of chemotherapy on long-term quality of life. Two self-administered questionnaires, the EORTC core QLQ-C30 and the breast module (BR23) were mailed to 179 premenopausal node-negative women continuously disease-free, previously enrolled in a trial testing the efficacy of adjuvant CMF chemotherapy (Espié et al, 1997). The core questionnaire evaluates the physical, role, emotional, cognitive and social functioning and global health status. The breast module includes four functional scales: body image, sexual functioning, sexual enjoyment and future perspective. It also includes symptom scales such as arm or breast symptoms. Some specific professional and social states were added. 119 (68%) patients (mean age 54 years, range 30-69) participated. Mean follow-up time since diagnosis was 9.6 years (4-16). 68% had conservative and 32% radical surgery (with reconstructive surgery in 50%). CMF was given to 77 (65%) patients. Irradiation was administered in 75% of patients irrespective of adjuvant therapy. QLQ-C30 scale scores were similar in patients who had or had not received chemotherapy. Disturbance in body image, sex life and breast symptoms did not differ between patients who had or had not received adjuvant CMF. No major socioprofessional difficulties were reported except problems in borrowing from banks not related to past chemotherapy. With long follow-up, most premenopausal women treated for a localized breast cancer cope with the disease and its treatments. Adjuvant CMF chemotherapy does not appear to impair quality of life nor social and professional life in these patients.
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PURPOSE: To evaluate tolerance and efficiency of a boost dose delivered by high-dose-rate brachytherapy (HDRB) in conservative treatment of breast cancer. To evaluate the feasibility of brachytherapy on an out-patient basis. METHODS: One hundred and six patients with T1-T2, N0-N1 breast cancers (108 breasts) have been treated with lumpectomy, external irradiation (45 Gy in 5 weeks), and a boost dose on the tumor bed with HDR iridium brachytherapy. Two fractions of 5 Gy were delivered 6 or 24 hours apart. Implantation was done during the lumpectomy (group A: 24 cases) or 3 to 4 weeks after the end of external irradiation (group B: 84 cases). For group B, the application was performed on local anesthesia, and did not require hospitalization. Characteristics of the population were as follows: T1: 77 (71.3%); T2: 31 (28.7%); median tumor size: 1.5 cm; histology: intraductal carcinomas (DCIS): 14 (13%); infiltrative ductal carcinomas (IDC): 84 (77.8%); others: 10 (9.2%). For IDC, surgical margins were found positive in 15 cases, and an extensive intraductal component was present in 22 cases. RESULTS: All ambulatory HDR implants were performed as planned. No immediate toxicity was noticed, except 5 local hematomas. With a median follow-up of 45 months, 5 local relapses were observed (5-year local relapse rate: 5.1%). Only histological grade III was significantly correlated with local relapse. The 5-year disease-free survival and overall survival were respectively 93.8% and 93.3%. Cosmetic result was evaluated in 87 cases, and was good or excellent in 48 cases (63.2%), acceptable in 27 cases, and poor in 5 cases. CONCLUSION: HDRB allows the boost dose to be performed on an out-patient basis. It seems to offer the same local control as other boost techniques for localized breast cancer with acceptable cosmetic results.
BACKGROUND: Almost 10% of breast and ovarian cancer are inherited, and the majority are linked to BRCA1 and BRCA2 germline mutations. Despite the uncertainty, consensus guidelines were defined to assist practitioners', and patients' decisions about the health care decisions to be made. METHODOLOGY: The ad hoc committee consisted of 14 experts designated by the French National Institute for Health and Medical Research. They all attended eleven workshops at which a systematic analytical review of more than 3,500 articles was carried out. Five additional experts critically analyzed the first version of the report. PROCESS: Two thresholds were defined on a probability scale giving the risk of developing breast or ovarian cancer, to serve as a means of deciding as whether an intervention is worthwhile. The first threshold is that above which an intervention can be envisaged or recommended; the second is that under which an intervention can be ruled out; between the two, the decision has to be made on a each by case basis. SCREENING AND PREVENTIVE STRATEGIES ANALYZED: About breast cancer: 1) hormonal interventions; 2) primary prevention (diet, family planning and chemoprevention); 3) screening (breast self-examination, clinician breast examination, tumor markers, imaging); 4) prophylactic mastectomy. About ovarian cancer: 1) hormonal stimulation; 2) screening (clinical screening, ultrasound and tumor markers); 3) prophylactic oophorectomy. MAIN CONCLUSIONS: With each strategy the following points were dealt with: the information to be delivered to the consult and, the procedure and the indications. The committee's opinion about BRCA mutation screening is that population-based or even large scale implementation are not justified. The committee feels that specific management is indispensable and advocates the use of defined and evaluated procedures, and involvement in clinical trials.
BACKGROUND: Almost 10% of breast and ovarian cancer are inherited, and the majority are linked to BRCA1 and BRCA2 germline mutations. Despite the uncertainty in the management of women gene carriers, consensus guidelines were defined to assist practitioners', and patients' decisions about the health care decisions to be made. METHODOLOGY: The Ad Hoc Committee consisted of 14 experts designated by the French National Institute for Health and Medical Research. They all attended eleven workshops at which a systematic analytical review of more than 3500 articles was carried out. Five additional experts critically analysed the first version of the report. CRITERIA AND DECISION PROCESS: Two thresholds were defined on a probability scale giving the risk of developing breast or ovarian cancer, to serve as a means of deciding as whether an intervention is worthwhile. The first threshold is that above which an intervention can be envisaged or recommended; the second is that under which an intervention can be ruled out; between the two, the decision has to be made on a each by case basis. STRATEGIES ANALYZED: About breast cancer: 1) hormonal interventions; 2) primary prevention (diet, family planning and chemoprevention); 3) screening (breast self-examination, clinician breast examination, tumor markers, imaging); 4) prophylactic mastectomy. About ovarian cancer: 1) hormonal stimulation; 2) screening (clinical screening, ultrasound and tumor markers); 3) prophylactic oophorectomy. MAIN CONCLUSIONS: With each strategy the following points were dealt with; the information to be delivered to the Consultant, the procedure and the indications. In addition, the Committee's opinion about BRCA1 and BRCA2 mutation screening is that population-based or even large scale implementation are not justified. Although no scientific evidence is available, the Committee feels that specific management is indispensable and advocates the use of defined and evaluated procedures, and involvement in clinical trials.
Screening has led to the earlier detection of non palpable ductal or lobular carcinoma in situ microinvasive carcinoma and invasive breast cancer 1 cm or less in size (minimal breast cancer). Formerly, most of these cancers were cured by mastectomy but the dramatic change in frequency has prompted interest in the role of conservation treatment. Minimal breast cancer is a heterogeneous group of lesions, no single approach will be appropriate for all form of these diseases and methods must be developed to determine the most appropriate treatment for each patient.
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