Biomedical subjects

B Asselain

Publications and source records attributed to B Asselain.

At least 109 records · Page 6Linked to original sources

PubMed1995

[Recurrences after conservative radiosurgical treatment of breast cancer].

From 1960 to 1989, 154 cases of recurrent breast cancer after conservative radiosurgery were treated at the Curie Institute. Relapse was discovered at clinical examination in 88% of the cases and mammography was only useful in 45%. In 18 cases (12%) an unpalpable tumour was discovered at mammography, especially for intragalactophoric tumors. Cytopuncture yielded a precise diagnosis in 83% of the cases. Overall survival rate after recurrence was 72% at 5 years (62% without metastasis). Survival rate was better for late recurrence, and poorer in cases with subclinical axillary invasion. Neither age nor type of treatment had any effect on survival. Indications for general associated treatment are based on: the invasive character of the recurrent tumour, axillary invasion, tumour size and delay to recurrence after initial surgery.

Breast Neoplasms↗

PubMed1995

Discrete strategies of cancer post-treatment surveillance. Estimation and optimization problems.

We consider the cancer post-treatment surveillance to be represented by a discrete observation process with a non-zero false-negative rate. Using a simple stochastic model of cancer recurrence derived within the random minima framework, we obtain parametric estimates of both the time-to-recurrence distribution and the probability of false-negative diagnosis. Then assuming the false-negative rate known, we give a nonparametric maximum likelihood estimator for the tumor latency time distribution. When designing an optimal strategy of post-treatment surveillance, we proceed from the minimum of the expected delay in detecting tumor recurrence as a pertinent criterion of optimality. To solve this problem we give a dynamic programming algorithm. We illustrate the methods by analyzing data on breast cancer recurrence.

Algorithms↗

PubMed1995

[Diagnosis of non-palpable breast lesions: contribution of cytological punctures after stereotaxic localization].

The authors reviewed the accuracy of stereotaxic fine-needle aspiration cytology. Two hundred-twenty-eight lesions were studied: 103 benign lesions, 125 cancers. Inadequate sample was obtained in 26% of cases. None of the cytology reports were false-positive, whereas 77% of the suspect cytologic reports were malignant on histology. In strongly suspicious lesions at mammography, the decision to perform surgical biopsy should not be postponed as false negative cytologic findings (7 cases) are possible. In patients with a low suspicious lesion, cytology found six cancers. The benign-to-malignant ratio of excisional biopsies of non palpables lesions should be reduced by stereotaxic fine-needle aspiration cytology.

Adult↗

PubMed1995

[Prognostic factors in endometrial cancer: apropos of 206 cases treated at the Curie Institute].

From January 1, 1983 to December 31, 1990 two hundred and six patients with an invasive, non metastatic endometrial carcinoma were first treated at Institut Curie. Initial tumoral staging (TNM) was as follows: stage Ia: 48%, stage Ib: 31%, stage II: 15% and stage III-IV: 6%. Total hysterectomy or colpohysterectomy was performed in 186 cases, with a bilateral oophorectomy in 180 cases. Bilateral limited pelvic lymphadenectomy was performed in 116 cases. Brachytherapy was performed in the pre-operative setting in 25 cases, in the post-operative setting in 134 cases. Only five patients had brachytherapy alone, because of poor medical condition. External irradiation was exclusive in 15 cases and added to surgery for 68 patients. Median follow-up is 61 months (8-122 months). Five-year survival rate is 77% (71-83%); 5-year specific survival rate is 81% (75-87%). Independent prognostic factors for survival in multivariate analysis (Cox regression model) are tumoral stage (p < 0.0001), ovarian involvement (p < 0.0001), histologic node involvement (p = 0.005) and grade (p = 0.01). For local relapse, independent risk factors in the same analysis are ovarian involvement (p = 0.0004), tumoral stage (p = 0.01), age (p = 0.02) and histologic involvement of cervix (p = 0.04). For distant failure, independent risk factors are histologic node involvement (p = 0.0001), tumoral stage (p = 0.002) and grade (p = 0.003).

Adenocarcinoma↗

PubMed1995

Randomized trial comparing two different modalities of administration of the same cytotoxic drugs in metastatic breast cancer.

This protocol compare the efficacy of continuous infusion fluorouracil (5-FU) with weekly doxorubicin (DOX) and cyclophosphamide (CPM) to a "classical" monthly regimen of the same drugs, as a first line of treatment in metastatic breast carcinoma. The first arm of this protocol consisted of FAC: 5-FU 600 mg/m2 i.v. over 1 hour, day(d) 1, 2, 3, DOX 50 mg/m2 i.v. bolus, d1, and CPM, 400 mg/m2 i.v. bolus, d 1, 2, 3. The second arm consisted of FULON: 5-FU 250 mg/m2 per day continuously infused from d1 to d22, CPM 300 mg/m2 i.v. bolus, d1, 8, 15, 22, and DOX 15 mg/m2 i.v. bolus, day 1, 8, 15, 22. Between January 1990 and June 1993, 258 women with proven metastatic breast carcinoma were randomly assigned either to receive FAC or FULON chemotherapy regimen. Chemotherapy courses were administrated every 4 weeks for FAC regimen and every 6 weeks for FULON. Response rate (54 versus 53%), response duration (14 versus 12 months) and overall survival duration (23 versus 21 months) were not significantly different in the two regimens (FAC versus FULON). Preorative prognostic value of liver metastasis or high LDH level was slightly attenuated in patients treated by FULON. Efficacy of infusional 5-FU in metastatic breast cancer could have been lowered by weekly infusion of doxorubicin in the FULON regimen compared to monthly infusion. According to the modalities of delivery of the drugs, the two regimens seem equally effective.

Adult↗

PubMed1994

Simultaneous bilateral breast carcinomas: a retrospective review of 149 cases.

PURPOSE: To evaluate clinical and biological characteristics as well as treatment outcome in simultaneous bilateral breast carcinomas. METHODS AND MATERIALS: Between 1981 and 1990, 149 patients were diagnosed to have simultaneous bilateral breast carcinoma, defined as tumor arising in both breasts within a maximum of a 6-month interval, in the absence of distant metastases. The median age was 58. Out of a total of 298 tumors, the clinical tumor size was T0-T1 in 40%, T2 in 45%, and T3-T4 in 15% of tumors. The majority of patients (83%) were clinically node negative. Seventy-eight percent of all tumors were classified ductal invasive; 6% were invasive lobular carcinomas; in situ tumors were present in 9%. More than two-thirds of all tumors were well or moderately well differentiated. Tumors were estrogen positive in 86% and progesterone positive in 69% of 62% of patients for whom this information was available in both tumors. Treatment had been by bilateral mastectomy in 43%, by exclusive irradiation in 16%, and by combined surgery and radiation in 41%. RESULTS: Median follow-up was 68 months (11-141). A number of positive correlations existed between the tumors in both breasts more often than by chance alone: These were the presence of lobular carcinomas in both breasts (p = 0.06), the same histological grade (p = 0.002), similar ER (p = 0.03) and PR (p = 0.01) status. Five-year rates for survival and disease-free interval were 86% (80-92) and 70% (62-78), respectively. For each patient the stage of the largest tumor at diagnosis was defined as maximum stage. When survival figures were compared between each maximum stage and matched stages of a group of unilateral breast cancer patients treated during the same time interval in our institute, bilateral breast cancer fared not worse than unilateral breast tumors. Treatment related complications occurred in eight patients (5%). CONCLUSION: Simultaneous bilateral breast carcinomas have similar biological, but not clinical, features more frequently than would be predicted by chance alone. So far, the number of patients is too small, and the follow-up is too short to determine whether or not the prognosis is equivalent to that of unilateral breast cancer patients of equal stage. Bilateral conservative treatment is feasible with acceptable cosmetic results and toxicity by using carefully designed radiotherapy techniques.

Adult↗

PubMed1994

Prognostic factors in inflammatory breast cancer and therapeutic implications.

223 inflammatory breast cancer patients were diagnosed at the Institut Curie between 1977 and 1987. Patients received chemotherapy and radiation treatment according to three consecutive randomised trials. Five- and 10- year survival rates were 41 and 32%, respectively. Disease-free interval rates were 25.5% at 5 years and 19% at 10 years. Parameters significantly linked with a pejorative prognosis in a multivariate analysis were: diffuse erythema, lymph node involvement, chest wall adherence, and age above 50 years. When therapeutic response parameters were included in the multivariate analysis, the five most important prognostic factors in order of significance were complete tumour regression after completion of induction treatment (at 8 months), complete regression of inflammatory symptoms after 3 months of neoadjuvant chemotherapy, limited erythema at presentation and, less significantly, complete regression of inflammatory symptoms at 8 months and tumour regression at 3 months. In conclusion, patients who achieved a rapid and complete remission had a better prognosis than patients who had an incomplete response to chemotherapy. High-dose chemotherapy and reversal or prevention of drug resistance will be evaluated in future trials. Detailed information on the biology of this disease should allow the design of new strategies aiming to improve patient management.

Adenocarcinoma↗

PubMed1994

Neoadjuvant versus adjuvant chemotherapy in premenopausal patients with tumours considered too large for breast conserving surgery: preliminary results of a randomised trial: S6.

The aim of this study was to assess a potential advantage in survival by neoadjuvant as compared to adjuvant chemotherapy. 414 premenopausal patients with T2-T3 N0-N1 M0 breast cancer were randomised to receive either four cycles of neoadjuvant chemotherapy (cyclophosphamide, doxorubicin, 5-fluorouracil), followed by local-regional treatment (group I) or four cycles of adjuvant chemotherapy after primary irradiation +/- surgery (group II). Surgery was limited to those patients with a persisting mass after irradiation, and aimed to be as conservative as possible. 390 patients were evaluable. With a median follow-up of 54 months, we observed a statistically significant difference (P = 0.039) in survival in favour of the neoadjuvant chemotherapy group. A similar trend was seen when the time to metastatic recurrence was evaluated (P = 0.09). At this stage, no difference in disease-free interval or local recurrence between these two groups could be observed. The mean total dose of chemotherapy administered was similar in both groups. On average, group I had more intensive chemotherapy regimes (doxorubicin P = 0.02) but fewer treatment courses (P = 0.008) as compared to the treated patients in group II. Haematological tolerance was reduced when chemotherapy succeeded to exclusive irradiation. Breast conservation was identical for both groups at the end of primary treatment (82 and 77% for groups I and II, respectively). Of the 191 evaluable patients in the neoadjuvant treatment arm, 65% had an objective response (> 50% regression) following four cycles of chemotherapy. The objective response rate to primary irradiation (55 Gy) was 85%. Improved survival figures in the neoadjuvant treatment arm could be the result of the early initiation of chemotherapy, but we cannot exclude that this difference might be attributable to a slightly more aggressive treatment. So far, the trend in favour of decreased metastases was not statistically significant. The local control appeared similar in both subgroups.

Adult↗

PubMed1994

Association of p53 mutations with short survival in colorectal cancer.

BACKGROUND/AIMS: Mutations in p53, a tumor suppressor gene located on chromosome 17p, are the most frequent genetic alterations found in human cancers. Increased intracellular concentration of p53, which is frequently but not systematically related to p53 mutation, has been proposed to be associated with poor prognosis in some tumor types. In colorectal cancer, this significance is still a matter of debate. To directly investigate the relationship between prognosis and p53 mutation, this study screened a series of 85 colorectal carcinomas for mutations in exons 5-8 of this gene. METHODS: Polymerase chain reaction-amplified products from tumor DNA were analyzed by denaturing gradient gel electrophoresis and direct DNA sequencing. RESULTS: Forty-four tumors were found to be mutated (52%). A strong correlation between the presence of a mutation and short survival was observed (P = 0.003). When tumors were classified according to their histological stage, a multivariate Cox model analysis showed that p53 mutation, rather than 17p allelic loss (previously proposed to convey prognostic information), was retained as the only independent prognostic factor (relative risk, 2.25; 95% confidence interval, 1.06-4.80; P < 0.029). CONCLUSIONS: Combined with staging, direct monitoring of p53 mutation improves prognostic accuracy for colorectal cancer.

Aged↗

PubMed1993

Age as prognostic factor in premenopausal breast carcinoma.

Whether or not young age at diagnosis is an adverse prognostic factor in breast cancer has long been controversial, in part because much previous work has not taken due account of menopausal status and confounding factors. We have analysed the influence of age on prognosis in a consecutive series of 1703 patients with stage I-III breast cancer. All were premenopausal and all were treated in one centre (Institut Curie, Paris) between 1981 and 1985. Mean age was 44 years (range 23-55) and median follow-up was 82 months. Younger patients had significantly lower survival rates and higher local and distant relapse rates than older patients. The hazard rate of relapse decreased over time in the youngest age group (< or = 33) to reach that of older patients after 5 years. The relation between the hazard of recurrence and age was a continuous one, best fitted by a log-linear function and indicating a 4% decrease in recurrence for every year of age. Multivariate analysis of both survival and disease-free interval demonstrated that the worse prognosis of young age was independent of other factors such as clinical tumour size, clinical node status, histological grade, hormone receptor status, locoregional treatment procedure, and adjuvant systemic therapy. This difference in outlook has yet to be explained biologically but it does suggest the need for a closer look at the natural history of breast cancer in young women.

Adult↗

PubMed1993

Is reseeding from the primary a plausible cause of node failure?

In a previous analysis of node failures in 1251 consecutive patients with node positive oropharyngeal and pharyngolaryngeal squamous cell carcinomas treated by external radiotherapy alone at the Institut Curie, the main reasons for patient exclusion were node recurrence associated with primary failure (N+T failures) and doses less than 55 Gy. These exclusions reduced the number of node failures from 399/1251 (32%) to 77/798 (10%). Multivariate analysis of node recurrence indicated that node size and fixity, treatment duration, and T stage of primary were significant (higher probability of isolated node failure for the T1-T2 primaries). In the present analysis, it is noted that 60% of the N+T failures were observed less than 1 month after the completion of the irradiation and, therefore, were not likely the result of reseeding from the primary tumor. When all 1251 patients were included in the analysis, the probability of nodal failure increased for larger nodes, T4 primaries, lower nodal doses, presence of contralateral node metastases, and nodal fixation to the surrounding structures. No influence of the primary site was found. Treatment duration was closely associated with total dose to the nodes. The best description of the data was obtained with a model including total dose and not treatment time. However, as in the previous analysis, the exclusion of low-dose (less than 55 Gy) treatments resulted in the loss of a significant dose-control relationship. We conclude that the majority of node failures is unlikely to result from reseeding from the primary tumor, and therefore should not be excluded from local-control analyses. From a more radiobiological point of view, the exclusion of palliative treatments is questionable when studying the effect of dose on local control.

Adult↗

PubMed1993

Tumor recurrence versus fibrosis in the irradiated breast: differentiation with dynamic gadolinium-enhanced MR imaging.

To assess the value of magnetic resonance (MR) imaging of the breast in the differentiation of late postirradiation fibrosis from recurrent carcinoma, 35 women with a history of breast carcinoma treated conservatively with radiation therapy underwent MR imaging. Nine patients had recurrent tumors confirmed at biopsy and surgery. Twenty-six patients had a localized fibrotic mass confirmed at biopsy and/or during long-term clinical and radiologic follow-up. In all cases, a localized hypointense area was present on plain spin-echo T1-weighted images. In all recurrent tumors, dynamic gadolinium-enhanced T1-weighted images demonstrated early increased signal intensity of the lesion within 3 minutes after bolus injection. The signal intensity over time in localized fibrosis differed from that in tumor recurrence, with no substantial enhancement on post-contrast T1-weighted images. Short inversion time inversion recovery and spin-echo T2-weighted images were not useful in the differential diagnosis of recurrent tumor versus radiation fibrosis.

Adult↗

PubMed1992

Value of axillary dissection in addition to lumpectomy and radiotherapy in early breast cancer. The Breast Carcinoma Collaborative Group of the Institut Curie.

Axillary dissection in early breast cancer remains controversial because of its substantial side-effects and because its value with respect to recurrence or survival has not been unequivocally proven. Between 1982 and 1987, 658 patients were included in a prospective randomised comparison of lumpectomy alone with lumpectomy plus axillary dissection. All patients had a unilateral breast tumour not exceeding 3 cm in diameter and lymph-node involvement or metastases. Radiation therapy was given to both groups. The two groups of patients were similar with respect to mean age, TNM stage, and presence of hormonal receptors. Median follow-up was 54 months. 5-year survival of the patients was 94.2% (95% Cl: 92.1-96.4). There was a significant advantage in survival in the axillary dissection group (p = 0.014). Recurrence of tumour in the breast was similar in the two groups but visceral metastases, supraclavicular metastases, and lymph-node recurrences were less frequent in the axillary dissection group. Survival was related to the age of the patients (p = 0.005), the presence of positive nodes (p = 0.006), the histological grading (p less than 0.0001), and the presence of hormonal receptors (progesterone p = 0.0008, oestrogen p less than 0.0001). Treatment-adjusted relative risk was 2.4 (95% Cl: 1.3-4.2). The findings show that axillary dissection is justified for treatment of small breast cancers, although whether the better survival is due to axillary clearance itself or to adjuvant treatment for lymph-node involvement is unclear.

Adult↗

PubMed1992

Cyclical mastalgia as a marker of breast cancer susceptibility: results of a case-control study among French women.

A matched case-control study in a population of urban, non-menopaused women living in Paris was performed between 1983 and 1985 to investigate the risk of breast cancer (BC) in relation to various factors with a particular interest in the effect of the use of oral contraceptive (OC) and the existence of cyclical mastalgia (CM). Two hundred and ten non-menopaused women, less than 45 years old, with newly diagnosed BC were compared to 210 controls from the same geographic area matched on year of birth, age, education level and age at first full term pregnancy (FFTP), when justified. The adjusted Relative Risk of BC (RRa) was significantly increased for a total duration of OC use longer than 72 months (RRa 2.80; 95% CI 1.56-5.01), as well as the RRa for OC use above 48 months before FFTP (3.26 95% CI 1.37-7.76) and, to a lesser extent, the RRa for OC use above 48 months after FFTP (2.02 95% CI 1.07-3.84) respectively. Adjustment was performed on familial history of BC, personal history of Benign Breast Disease (BBD), age at menarche. A previous history of cyclical mastalgia was found to be associated with an increased risk of BC. The significant increase remained after adjustment on the previously mentioned confounding factors and OC use: RRa 2.12; 95% CI (1.31-3.43). Under a precise definition related to the hormonal environment, mastalgia appear to be an interesting marker of breast cell susceptibility, the importance of which can only be validated by prospective studies.

Age Factors↗

PubMed1992

Increased levels of soluble low-affinity Fc gamma receptors (IgG-binding factors) in the sera of tumour-bearing mice.

Soluble forms of low affinity Fc gamma receptors (Fc gamma R), also called IgG-binding factors (IgG-BF), have been shown to play a regulatory role in immune responses. By using an immunodot assay with the anti-mouse Fc gamma R MoAb, 2.4G2, the levels of IgG-BF have been measured in the sera of mice bearing syngeneic tumours of lymphoid or non-lymphoid origin or in mice injected with high doses of murine IgG. These sera contained large amounts of IgG-BF as compared with controls. In the case of mice bearing IgG2a- or IgG2b-secreting hybridomas or lymphomas, serum IgG-BF increased progressively with tumour size and serum monoclonal IgG concentration, reaching 4-12 times the normal levels. A less than three-fold increase was found in mice bearing an IgG1-secreting hybridoma or tumours which do not secrete IgG (IgA-secreting hybridoma, non-immunoglobulin-secreting lymphoid tumours or melanoma) or in mice injected with 9 mg of monoclonal IgG2a. The enhancement of serum IgG-BF levels was independent of the expression of Fc gamma R by the tumour cells, suggesting that the majority of IgG-BF secreted in response to tumours was produced by the host rather than by the tumour. The increased production of IgG-BF may participate in the control of tumour growth and in the modulation of the host immune responses in tumour-bearing animals.

Animals↗

PubMed1992

Mammographic features of 455 invasive lobular carcinomas.

Of 6,009 cases of breast cancer studied, 455 (7.6%) were invasive lobular carcinoma (ILC); 341 of these (75%) were pure ILC and 114 (25%) were ILC mixed with ductal forms. The mammographic features were compared with those of the 5,554 other breast carcinomas. Pure ILCs were less frequently round (1% vs 11%) and more frequently spicular (28% vs 23%) or with architectural distortion (18% vs 6%) than the other breast carcinomas. Microcalcifications were less common (24% vs 41%) and retraction of the skin (25% vs 21%) and nipple (26% vs 17%) was more common in pure ILC than in the other breast carcinomas. When complementary magnification views were obtained, only 50% were helpful in diagnosis of ILC while 75% were helpful in diagnosis of other breast carcinomas. Malignancy was less frequently diagnosed in ILC (57%) than in the other breast carcinomas (64%). The results were intermediate in the mixed ILC group.

Adult↗

PubMed1992

[Role of neoadjuvant chemotherapy in the treatment of advanced head and neck tumors. Results of two randomized therapeutical trials conducted at the Institut Curie on 208 patients].

From March 1983 to December 1989, 208 patients with locally advanced squamous cell carcinoma of the head and neck were successively included into two trials randomizing induction chemotherapy versus no pre-irradiation treatment. The chemotherapy regimen of the first trial, which included 100 patients, consisted of two cycles of a combination of cisplatin, bleomycin, vindesine, mitomycin C; while that of the second trial, which included 108 patients, consisted of three cycles of a combination cisplatin, 5-fluorouracil (continuous infusion) and vindesine. Local treatment was the same in two trials: 'primary' radiotherapy in all patients. The response was then evaluated at 55 Gy; in the case of poor response, surgery was performed, otherwise radiotherapy was continued to full doses (possibly followed by salvage surgery). The tumor and lymph node responses to chemotherapy (complete and partial response) were higher in the second trial and in the first one: 70% versus 50% for primary lesions, 47% versus 25% for lymph nodes. The toxicity of the two chemotherapy regimens was minimal. In the two trials, an initial major response to chemotherapy predicted subsequent efficacy of irradiation in 80% of the patients. Complete response rate at the end of irradiation correlates with the previous response to the chemotherapy. With a median follow-up of 60 months with the first chemotherapy regimen and 30 months with the second, overall survival and disease-free interval did not significantly differ in the two groups of patients, with or without chemotherapy. The incidence of distant metastasis was significantly reduced (P < 0.03) in the chemotherapy arms. This negative trial encourages the design of new chemotherapy protocols according to new schemes of treatment. For advanced stages of head and neck cancers (T3, T4, N2, N3), we recently launched a pilot study combining platinum and irradiation, but according to a concomitant schedule.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Survival and acquired genetic alterations in colorectal cancer.

To set the basis for a precise assessment of new therapeutic approaches, the prognosis of patients with colorectal cancer should be evaluated with the highest precision. The recent discovery, in tumor cells, of somatically acquired genetic alterations believed to be instrumental in tumor behavior may provide new independent prognostic factors. In the present study, the usual prognostic factors and a set of genetic alterations, i.e., Ki-ras mutations, DNA content, and allelic losses on chromosome 17p, 18q, 5q, and 1p, were investigated in 109 colorectal carcinomas. Univariate analysis for correlation with 5-year survival showed the following significant associations: histological staging (P less than 0.00001), preoperative serum carcinoembryonic antigen concentration (P less than 0.002), DNA content (P less than 0.009), and allelic loss on the short arm of chromosome 17 (P less than 0.002) and 1 (P less than 0.03). In multivariate analysis, only histological staging and allelic loss on the short arm of chromosome 17 were found to be independently associated with shorter survival (P less than 0.0001 and P less than 0.004, respectively). Loss of 17p alleles in colorectal carcinoma thus appears to be a marker of tumor aggressiveness. Its monitoring may lead to an improved classification of patients when adjuvant chemotherapy is considered.

Aged↗