G. Body

N‐3 and N‐6 fatty acids in breast adipose tissue and relative risk of breast cancer in a case‐control study in Tours, France

Experimental studies have indicated that n‐3 fatty acids, including alpha‐linolenic acid (18:3 n‐3) and long‐chain n‐3 polyunsaturated fatty acids inhibit mammary tumor growth and metastasis. Earlier epidemiological studies have given inconclusive results about a potential protective effect of dietary n‐3 polyunsaturated fatty acids on breast cancer risk, possibly because of methodological issues inherent to nutritional epidemiology. To evaluate the hypothesis that n‐3 fatty acids protect against breast cancer, we examined the fatty acid composition in adipose tissue from 241 patients with invasive, nonmetastatic breast carcinoma and from 88 patients with benign breast disease, in a case‐control study in Tours, central France. Fatty acid composition in breast adipose tissue was used as a qualitative biomarker of past dietary intake of fatty acids. Biopsies of adipose tissue were obtained at the time of surgery. Individual fatty acids were measured as a percentage of total fatty acids, using capillary gas chromatography. Unconditional logistic regression modeling was used to obtain odds ratio estimates while adjusting for age, height, menopausal status and body mass index. We found inverse associations between breast cancer‐risk and n‐3 fatty acid levels in breast adipose tissue. Women in the highest tertile of alpha‐linolenic acid (18:3 n‐3) had an odds ratio of 0.39 (95% confidence intervals [CI] = 0.19–0.78) compared to women in the lowest tertile (trend p = 0.01). In a similar way, women in the highest tertile of docosahexaenoic acid (22:6 n‐3) had an odds ratio of 0.31 (95% CI = 0.13‐0.75) compared to women in the lowest tertile (trend p = 0.016). Women in the highest tertile of the long‐chain n‐3/total n‐6 ratio had an odds ratio of 0.33 (95% confidence interval = 0.17–0.66) compared to women in the lowest tertile (trend p = 0.0002). In conclusion, our data based on fatty acids levels in breast adipose tissue suggest a protective effect of n‐3 fatty acids on breast cancer risk and support the hypothesis that the balance between n‐3 and n‐6 fatty acids plays a role in breast cancer.

Cytotoxic drugs efficacy correlates with adipose tissue docosahexaenoic acid level in locally advanced breast carcinoma

SummaryExperimental studies indicated that long-chain polyunsaturated fatty acids may increase sensitivity of mammary tumours to several cytotoxic drugs. To evaluate this hypothesis in breast cancer, we have prospectively studied the association between levels of fatty acids stored in breast adipose tissue and the response of the tumour to chemotherapy in 56 patients with an initially localized breast carcinoma. Adipose breast tissue was obtained at the time of biopsy, and individual fatty acids were measured as a percentage of total fatty acids using capillary gas chromatography. Patients then received primary chemotherapy, combining mitoxantrone, vindesine, cyclophosphamide and 5-fluorouracil every 4 weeks. Tumour size was reassessed after three cycles of chemotherapy. Tumour response was evaluated according to World Health Organization criteria. Complete or partial response to chemotherapy was achieved in 26 patients (47%). Level of n-3 polyunsaturated fatty acids in adipose tissue was higher in the group of patients with complete or partial response to chemotherapy than in patients with no response or with tumour progression (P < 0.004). Among n-3 polyunsaturated, only docosahexaenoic acid (22:6n-3) was significantly associated with tumour response (P < 0.005). In a logistic regression analysis taking into account age, body mass index and tumour size, 22:6 n-3 level proved to be an independent predictor for chemosensitivity (P = 0.03). These results suggest that, in breast cancer, 22:6 n-3 may increase the response of the tumour to the cytotoxic agents used.

73 Post-operative radiotherapy and concomitant adjuvant chemotherapy for breast carcinoma

Between May 1992 and December 1993, 72 patients operated for breast carcinoma underwent radiotherapy (RT) and concomitant adjuvant chemotherapy (CT). There were 2 T0, 23 T1, 47 T2 and 1 T4b. Lymph node status was 59 N0, 10 N1 and 4 unknown. Surgical treatment was lumpectomy (59) or mastectomy (13) and axillary dissection for all. Radiation therapy delivered 50 Gy in 5 weeks to the breast or chest wall. A 10 Gy boost was added to the tumor site after lympectomy. The internal mammary chain was irradiated in 64 patients, the subclavicular area in 53 and the axilla in I patient. The CT regimen was a combination of Mitoxantrone (12xa0mg/m2), 5-FU (500 mg/m2) and Cyclophosphamide (500 mg/m2), 6 cycles were delivered with 21 days interval. Compliance to RT evaluated on dose and treatment length was good for 88%. On the 65 patients analysed for CT: 98% received all 6 cycles at the prescribed dose, but 69% strictly respected intercycle intervals. Mild digestive and cutaneous toxicity (grade 1 and 2) was observed in 50%. Major toxicity was neutropenia (grade 2 or 3) in 18 patients and 1 severe infection. The 3 year actuarial survival rate was 87%. No local relapse was observed Metastases occurred in 6 patients. These preliminary results show that this concomitant association is safe although compliance to chemotherapy should be improved.

Impact on the cosmetic outcome of concurrent administration of adjuvant chemotherapy and radiotherapy after breast-conservative surgery: Differences between patient's and doctor's view

8554 Purpose: A multicenter randomized study comparing after breast-conservative surgery, sequential versus concurrent adjuvant chemotherapy (CT) with radiation therapy (RT) was initiated (ARCOSEI). After a median follow-up of 6.7 (4.3-9) years, we assessed prospectively late effects and cosmesis satisfaction of these two strategies.nnnMETHODS AND MATERIALnAfter breast-conserving surgery, patients were treated either with sequential treatment with CT first followed by RT (arm A) or CT administered concurrently with the same normofractinnated breast RT (arm B).With structured questions, 214 patients (107 in each arm) rated their satisfaction considering cosmesis, the difference in overall appearance, and specific changes of the breast. Late toxicity (LENT/SOMA scale) and cosmesis were blinded to treatment and assessed by a radiation oncologist by a qualitative scale and another semi-qualitative and semi-quantitative evaluation.nnnRESULTSnSubcutaneous fibrosis (SF), telangectasia (T), skin pigmentation (SP), and breast atrophy (BA) were significantly increased in arm B. Patients cosmesis satisfaction was not statistically different between the two arms with 92.6% of good results in arm A and 86% in arm B (p=0.72); although patients have found more important differences in the treated breast in arm B than in arm A, with 28.8% vs 14.3% of bad results, respectively. Physicians prospective assessment found less favorable cosmesis results with concomitant treatment than with sequential one, with 40% and 15% of unsatisfaction, respectively (p=0.0014) using a semi-quantitative and qualitative scale; The use of a subjective 5-point scale found also a worse physicians cosmesis satisfaction in arm B than in arm A (p=0.0013) Conclusion: The concurrent use of CT with RT is significantly associated with an increase incidence of grade 2 or greater late side effects. Rating of cosmesis is also subjective. Patients satisfaction with cosmesis is greater than the doctors for concomitant radiochemotherapy in breast cancer, and is not only determined by radiation late effects. With two methods, physician found a worse cosmesis outcome for concomitant radiochemotherapeutic arm. No significant financial relationships to disclose.

26 Évolution périnatale des kystes ovariens fœtaux : à propos d’une étude multicentrique rétrospective

Objectifs Preciser l’evolution perinatale des kystes ovariens fœtaux en fonction de leur apparence echographique, leur taille et le terme du diagnostic et evaluer la contribution de la ponction in utero sur l’histoire naturelle des kystes ovariens anechogenes. Materiel et methodes A partir d’une etude retrospective multicentrique, 126 kystes de l’ovaire fœtaux ont ete diagnostiques en periode prenatale par echographie et suivis dans dix centres de medecine fœtale francais entre le 1 er janvier 1993 et le 31 decembre 2000. Seuls les cas avec un suivi complet postnatal ont ete retenus. Resultats Le diagnostic a ete fait en moyenne a 33 semaines d’amenorrhee [95 % CI ; 32-34], le diametre moyen du kyste, lors du diagnostic, etait de 40 mm [95 % CI ; 38-42]. Au moment du diagnostic 27 % des kystes avaient des signes echographiques de complications (niveau liquide, sediments, cloison, echogene). Sur les 92 kystes non compliques (anechogene a paroi fine), 70 ont ete suivis par echographie (groupe I) et dans 22 cas (groupe II) une aspiration prenatale du kyste a ete pratiquee. Pour le groupe I, 42,8 % des kystes ont eu une torsion pendant la periode perinatale (16 en periode prenatale et 14 en periode neonatale). L’analyse multivariee par regression logistique a retrouve que l’âge gestationnel du diagnostic et le diametre maximal prenatal sont les deux seuls parametres statistiquement associes avec la torsion perinatale de l’annexe. Pour les kystes du groupe II, 2 n’ont pas ete completement aspires a cause de mouvements fœtaux et dans 4 cas, le kyste a recidive. Seuls 2 nouveaux nes (2 de ceux qui ont recidives) ont une chirurgie postnatale (kystectomie) sans signes evidents de torsion de l’annexe. L’analyse anatomopathologique de tous les cas operes confirme le caractere benin et l’origine folliculaire ou folliculoluteinique des kystes. Conclusion Notre etude confirme le haut risque de complications mecaniques des kystes ovariens fœtaux anechogenes. La ponction prenatale de ces kystes doit etre evoque des le diagnostic, surtout pour ceux diagnostiques tot dans le troisieme trimestre. L’efficacite de cette approche dans notre etude semble prometteuse. Mais des etudes randomisees prospectives sont necessaires pour conclure.

1 Diagnostic prénatal des uropathies obstructives sous-vésicales : à propos D’UNE analyse multivariée

Objectifs Evaluer la pertinence de l’echographie obstetricale dans le diagnostic des uropathies obstructives basses (UOB) chez le fœtus presentant une dilatation urinaire. Preciser la valeur diagnostique de chaque signe echographique et mettre en evidence la meilleure combinaison de signes permettant d’acceder au diagnostic. Methode Notre etude retrospective porte sur 247 fœtus presentant une dilatation urinaire, pris en charge par notre unite de medecine fœtale entre le 1 er janvier 1991 et le 31 decembre 2000. Seuls les cas pour lesquels les donnees prenatales, le suivi post natal ou l’examen fœtopathologique etaient complets, ont ete retenus. L’analyse statistique a ete menee en deux etapes : recherche en analyse univariee des variables associees au diagnostic d’UOB et analyse multivariee au moyen d’une regression logistique afin de mettre en evidence les variables independantes de ce diagnostic. Resultats Dans notre etude 28 fœtus (11 %) presentaient un obstacle urinaire sous-vesical confirme soit par les explorations post natales (n = 10), soit par un examen fœtopathologique lorsque l’issue de la grossesse a ete une interruption medicale (n = 17) ou une mort fœtale in utero (n = 1). Les valves de l’uretre posterieur representaient 75 % de nos cas, les autres diagnostics comportaient des valves de l’uretre anterieur (n = 2), des mega uretre congenitaux (n = 2) et des dysgenesies cloacales (n = 3). En analyse univariee, les variables associees au diagnostic d’obstruction urinaire sous-vesicale etaient le sexe fœtal masculin, (p Conclusion Chez les fœtus presentant une dilatation urinaire, la mise en evidence d’un oligoamnios, d’une mega vessie et ou d’un epaississement de la paroi vesicale est fortement predictif du diagnostic d’obstruction urinaire sous-vesicale.

8 Facteurs de risque d’hémorragie de la délivrance (≥ 1 000 millilitres) par atonie utérine : étude cas/témoins sur 300 dossiers au chu de tours

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 33 - N° 4 - p. 346-347

1177 Prognostic value of histological tumor regression after irradiation for uterine cervix carcinoma

Radio-surgical combination is an effective treatment for centro pelvic cervix carcinoma. Using preoperative radiotherapy, 80% of the patients have no residual disease at the time of surgery. The purpose of this study was to determine the prognostic value of the cervix sterilization after initial irradiation. Patients and methods Between 1976 and 1993, 200 patients with histologically proven cervix carcinoma (91 patients with clinical stage Ib tumor, 91 with stage IIA, and 18 with stage IIB) have been treated by irradiation followed by radical hysterectomy 6 weeks later. The mean age was 48 years. Median follow up was 86 months. One hundred and five patients underwent an utero-vaginal application of caesium 137. A dose of 60xa0Gy was delivered in the reference volume followed by radical hysterectomy and lymphadenectomy. Ninety five patients with bulky centro pelvic tumors received an external pelvic irradiation, a brachytherapy and surgery. The mean dose to whole pelvis was 40xa0Gy (18–50). Result Uncorrected five-year overall survival rate was 96% for stage Ib, 61% for stage IIA and 48% for stage IIB. Sterilization rate after irradiation was 82% for stage Ib, and 61% for stage IIA or IIB. Probability of survival was significantly better in case of tumor sterilization with a 5-year survival rate of 78% versus 65% and 61% for patients with microscopic residual disease and macroscopic persistent tumors, respectively. In univariate analysis, stage and node status according to the lymphography were prognostic factors. A multivariate analysis should be presented. Conclusion Histological sterilization after irradiation appeared as a favorable prognostic factor.

Is lymphadenectomy useful in the treatment of endometrial carcinoma

Newdspletheekddeiacaabiaatiaawitb~(ACR)witb highreapoerateill gynedogieaI adeaecmillomas Chen J-T; Hirai Y; Shimizu Y; Hasumi K, Masubuchi K Department of Gynecology, CMcer Institute Hospital, Tokyo, JPN GYNECOL ONCOL 1990,38/l (l-5) Fourteen patients with recurrent gynecological adenocarcinemas (nine with endometrial cancer and six with ovarian cancer) were treated with cisplatin given by 14-day continuous infusion at a daily dose of 10 mg/m2 in combination with aclarubicin (ACR) at a dose of 20 mg/body on alternate days during each M-day course. The daily dose of cisplatin was given with 1 liter of fluids; no diuretics were administered. The overall response rate was 71.4% (50% in endometrial cancer and 100% in ovarian cancer). It was especially interesting that a 100% response rate was obtained in five patients previously treated with cisplatin; i.e., the present cisplatin dosing schedule was highly effective as second-line therapy in these patients. No renal or gastrointestinal toxicity was observed. These results were pharmacokineticahy explained by the plasma concentration of tilterable platinum. A low-level, plateau-like curve with a great area under fdterable [Pt]-time curve (AUC) seemed to ensure exposure of cancer cells to filterable platinum for sufficiently long periods and freedom from gastrointestinal and renal side effects.