Loss of heterozygosity, allele silencing and decreased expression of p73 gene in breast cancers: prevalence of alterations in inflammatory breast cancers.

The p73 gene is a p53 homologue located at 1p36-33, a region submitted to deletions in breast cancer (BC) and putatively imprinted. To study whether p73 was associated with breast carcinogenesis, loss of heterozygosity (LOH), allele expression and transcript levels were assessed in 59 BC, including 39 BC presenting no inflammatory symptoms (NBC) and 20 inflammatory BC (IBC). IBC is a rare but aggressive form of cancer with a very poor prognosis. Normal breast epithelium (BE) and lymphocytes from patients were used as controls. StyI polymorphism generating GC and/or AT alleles was used to select 22 heterozygous patients. p73 LOH was significantly higher in IBC than in NBC [five of eight cases (62%) versus two of 14 cases (14%); Fisher's exact test, P=0.05]. p73 was biallelically expressed in all BE. In contrast, 12 of 16 (75%) BC were monoallelically expressed, showing that allele silencing was significantly associated with breast carcinogenesis (P=0.012), AT being the preferential silent allele (10 out of 12 tumours). p73 mRNA levels in NBC and IBC were two- and threefold lower than in BE, respectively, suggesting that decreased expression could be related to tumour aggressiveness. In conclusion, LOH, allele silencing and decreased expression of the p73 gene may play a role in breast carcinogenesis.

Conservative treatment versus mastectomy in early breast cancer: patterns of failure with 15 years of follow-up data. Institut Gustave-Roussy Breast Cancer Group.

PURPOSES: A randomized trial was conducted to compare tumorectomy and breast irradiation with modified radical mastectomy. We have analyzed the patterns of failure in each arm of the trial and the prognostic factors that have an independent effect on treatment failures and overall survival. PATIENTS AND METHODS: The trial included 179 patients with breast cancer of up to 20 mm in diameter at macroscopic examination. Eighty-eight patients had conservative management and 91 a mastectomy. All patients had axillary dissection with frozen-section examination. For patients with positive axillary nodes (N+), a second randomization was performed: lymph node irradiation versus no further regional treatment. Patterns of failure were determined by a competing-risk approach and multivariate analysis. A prognostic-score was determined by multivariate analysis. RESULTS: Overall survival, distant metastasis, contralateral breast cancer, new primary malignancy, and locoregional recurrence rates were not significantly different between the two surgical groups, or between lymph node irradiation groups. Most recurrences appeared during the first 10 years. Three distinct prognostic groups were determined taking into account age, tumor size, histologic grading, and number of positive axillary nodes. CONCLUSION: Long-term results support conservative treatment with limited surgery and systematic breast irradiation as a safe procedure for the management of small breast cancers. Four easily obtainable clinical and histologic factors may be combined in a prognostic score that is highly predictive of overall and event-free survival.

Prognostic factors in primary breast sarcomas: a series of patients with long-term follow-up.

PURPOSE: To describe the pathologic characteristics and prognostic factors of primary breast sarcomas (PBSs). PATIENTS AND METHODS: We reviewed the clinical records and pathologic slides of 83 women with PBS treated in our institution between 1954 and 1991, with a median follow-up of 7.8 years. The majority of patients had undergone surgical treatment. RESULTS: The main histologic type was malignant fibrohistiocytoma (n = 57). For the whole population, the 10-year overall survival (OS) and disease-free survival (DFS) rates were 62% and 50%, respectively. For Fédération Nationale des Centres de Lutte Contre le Cancer grade 1, 2, and 3 tumors, the 10-year OS and DFS rates were 82% and 61%, 62% and 51%, and 36% and 25%, respectively (P =.00007 and.004, respectively). For tumors measuring less than 5 cm, 5 to 10 cm, and more than 10 cm, the 10-year OS and DFS rates were 76% and 66%, 68% and 55%, and 28% and 15%, respectively (P =.002 and.009, respectively). In the multivariate analysis, the tumor size and histologic grade were correlated with the 10-year DFS rate (P =.04 and.01, respectively), but only the histologic grade was correlated with OS (P =.01). Angiosarcoma was the only histologic type significantly associated with a poorer outcome in the multivariate analysis. CONCLUSION: PBSs have the same clinical history and prognostic factors as sarcomas arising at other sites. Therefore, it is legitimate to use a similar treatment strategy for PBS as for other sarcomas.

Long-term effect of internal mammary chain treatment. Results of a multivariate analysis of 1195 patients with operable breast cancer and positive axillary nodes.

A multivariate analysis on 1195 patients with operable breast cancer and histologically positive axillary nodes treated by mastectomy and complete axillary dissection at the Institut Gustave-Roussy between 1958 and 1978 suggests a beneficial effect of treatment of the internal mammary chain (IMC) on the risks of death and distant metastasis for the patients with medial tumors. For these patients, surgical IMC dissection and post-operative irradiation have similar effects on both the risk of death and of distant metastasis. For the patients with lateral tumors, no beneficial effect of the treatment of the IMC on these two risks was observed. Postoperative irradiation to the IMC, axilla, chest wall and supraclavicular nodes significantly decreases the risk of locoregional recurrences independent of the tumor site and surgical management of the lymph nodes.

Ten-year results of a randomized trial comparing a conservative treatment to mastectomy in early breast cancer.

A randomized trial was conducted at the Institut Gustave-Roussy (IGR) between 1972 and 1980 comparing tumorectomy and breast irradiation with modified radical mastectomy. One hundred and seventy-nine patients with an infiltrating breast carcinoma up to 20 mm in diameter at macroscopic examination were included: 88 had conservative management, and 91 a mastectomy. All patients had a low-axillary dissection with immediate histological examination. For the patients with positive axillary nodes, a complete axillary dissection was undertaken. Overall survival, distant metastasis, contralateral breast cancer and locoregional recurrence rates were not significantly different between the two treatment groups.

Sentinel lymphadenectomy without systematic axillary dissection in breast cancer patients: predictors of non-sentinel lymph node metastasis.

AIMS: To identify factors predicting metastatic involvement of non sentinel axillary lymph nodes in breast cancer patients who underwent sentinel lymph node (SLN) biopsy followed by complete axillary dissection only in case of metastatic sentinel lymph node. METHODS: A prospective database including 165 breast cancer patients who underwent SLN biopsy without further complete axillary dissection in case of non-metastatic SLN was reviewed. Primary tumor size, pathologic grade, lymphatic invasion in the primary tumor, estrogen receptor status, tumor size in the SLN and number of metastatic SLNs were tested as possible predictors of metastatic involvement of non-SLN. RESULTS: The sentinel lymph node detection rate was 97% (160/165 patients). The mean number of SLNs per patient was 1.8 (range: 1-5). Fifty patients (31.3%) had a metastatic axillary SLN: 10 of the 42 patients with T1a or T1b breast tumors and 40 of the 118 patients with T1c< or = 15mm tumors. Fifteen of the 50 patients with metastatic SLN had metastatic non-SLN. Primary tumor size, tumor size in the SLN, pathologic grade, estrogen receptor status and age were not significantly associated with metastatic involvement of non-SLN. Number of metastatic SLNs fell short of reaching statistical significance (P: NS). Lymphatic invasion in the primary tumor was the only factor significantly associated with the presence of tumor in the non SLN (P<0.01). CONCLUSION: In our series, only lymphatic invasion in the primary tumor was correlated with metastases detection in the non-SLN. We could not identify a subset of patients without metastatic non-SLN in patients with metastatic SLN.

Quality of life after sentinel lymph node biopsy in early breast cancer.

AIM: This study assessed the effects of multiple therapeutic factors on quality of life (QOL) in the treatment of breast cancer. METHODS: We surveyed 179 recurrence-free women with early breast cancer who had undergone a sentinel lymph node procedure, between January 1999 and June 2001. Age, tumour size, breast and axillary procedure, nodal status, chemotherapy, supra-clavicular fossa radiotherapy, and hormone therapy were tested as possible factors associated with poor QOL. RESULTS: Information on QOL was obtained for 148 out of 179 patients. Age less than 55 years and chemotherapy were factors associated with impairment of physical well-being. Tumour size was associated with poor socio-familial well-being. Factors associated with altered arm subscale scores were age <55, axillary procedure, nodal status, chemotherapy and supra-clavicular fossa radiotherapy. Unexpectedly, sentinel lymph node (SLN) procedure delayed the onset of chemotherapy if the metastatic status of SLN was not diagnosed intra-operatively. CONCLUSION: Efforts are needed to improve the QOL of young patients. Axillary procedure affects only QOL related to arm morbidity.

[Surgical treatment of carcinomas of the cervix stage III (author's transl)]. / Place de la chirurgie dans les cancers du col utérin stade III.

This study is devoted to the analysis of the surgical treatment of cancer of the uterine cervix, stage III. Three circumstances are evaluated: - Stage III with urinary disease the purpose of the surgical treatment is most often to save the renal function;--Recurrences after radiotherapy where surgery is the only possible treatment;--Stage III - Three attitudes are pointed out: Radical operation primary. Systematic surgery after preoperative radiotherapy. In the Institut Gustave-Roussy (IGR), Villejuif, exploaratory caeliotomy was performed after a preoperative irradiation of twenty Grays. The post-operative irradiation was then adapted according to the surgical evaluation.

[Contribution of expert systems in clinical practice: apropos of the Penelope experience, an expert system in assisted diagnosis and therapy of ovarian adenocarcinoma]. / Apport des systèmes experts dans la pratique clinique: à propos de l'expérience Pénélope, système expert d'aide au diagnostic et à la thérapeutique des adénocarcinomes de l'ovaire.

An expert system (ES) for Diagnosis and Therapy of ovarian adenocarcinoma has been developed at the Institut Gustave-Roussy. From surgical and histological results, clinical examination and additional investigative reports, the system presents a synthesis and then determines the stage of the disease. The system than proposes therapeutic indications adapted to the characteristics of the illness and of the patient, and edits a report at the end of the ES consultation. This experience allowed us to specify the field of ES applications in oncology. As tools for diagnosis and therapy, they cannot act as a substitute for the know-how of the physician, as too many medical decisions remain difficult to formalize in the ES. On the other hand the use of artificial intelligence techniques appears to be useful for establishing coherent data bases, which are necessary pre-requisites for clinical research in oncology. The integration of the system in the Hospital Information System is the guarantee of its use in current clinical practice.

[Negative second-look laparatomy in ovarian cancers. Survival analysis and prognostic factors from 64 cases treated at the Gustave Roussy Institute]. / Seconde laparotomie négative dans les cancers de l'ovaire. Analyse de la survie et des facteurs pronostiques à partir de 64 cas traités a l'Institut Gustave-Roussy.

This study describes 64 cases of ovarian adenocarcinoma seen in the Gustave-Roussy Institut between 1978 and 1988 and who had a negative second-look laparotomy. The median age was 51 years (30-74). FIGO stages were: I: 7 (11%); II: 3 (5%); III: 39 (61%); IV: 3 (5%); and undetermined: 12 (19%). There were 53% of serous type, 14% of endometrioid type, 13% of undifferencied type, 8% of clear cells type, 3% of mucinous type, and 9% of mixed type tumors. There were 50% of grade 3 tumors. Initial debulking surgery was as complete as possible in 59 patients, with a residual tumor after surgery superior or equal to 2 cm in 25 patients. Post second-look surgery treatment (n = 57) consisted of chemotherapy (CT) alone in 22 patients (34%), radiotherapy (RT) alone in 31 patients (49%), and CT associated with RT in 4 patients (6%). Median follow-up is 100 months. The overall survival rates at 3 and 5 years were respectively 86 and 81%, and disease free survival rates 70 and 61%. Among the 64 patients, 26 relapsed (39%). Median time to relapse was 96 months. There is a statistical difference in the survival between patients who had no or inferior to 2 cm residual tumor and others. Residual tumor was the only factor to be significant in univariate and multivariate analysis of survival.

[Sentinel node biopsy in breast cancer. Will this lead to the end of lymphadenectomy for small tumors without suspected axillary adenopathy?]. / Le ganglion sentinelle dans le cancer du sein. Est-ce la fin du curage pour les petites tumeurs NO?

Sentinel node (SN) biopsy in breast cancer is still in a crucial stage of evaluation. Many teams have obtained excellent results using this method, with a detection rate always higher than 90% and a false negative rate between 0 and 8%, in prospective series. The main question is to know if lymphadenectomy can now be avoided when the SN is negative. The answer will come from the results of the two ongoing trials comparing sentinel node biopsy to axillary lymphadenectomy. But their results will be available only in two or three years. However, many teams, as at Institute Gustave Roussy, are now applying the technique routinely, because of the excellent results obtained during their learning curve. But there are some methodological differences between teams, which can influence the detection and false negative rates. Thus, several methodological standards remain to be defined. This review enable us to clarify a certain number of questions. Today, SN biopsy can only be performed by trained teams, with prospective evaluation of their results or participation in phase III trials.

[Value of x-ray computed tomography in the monitoring of cancer of the ovary. Apropos of 69 cases]. / Intérêt de l'examen tomodensitométrique dans la surveillance des cancers de l'ovaire. A propos de 69 observations.

The authors have studied retrospectively, a group of 69 patients with primitive carcinoma of the ovary who underwent at most one CT examination following the first surgical treatment. In 26 out of these, CT was done within the three months following a second surgical operation. Peritoneal metastases were inconsistently seen (5 true positive, 9 true negative, 0 false positive, 9 false negative). The sensitivity is 36%, the specificity 100% and the accuracy 65%. The score is better in the detection of lymphatic, hepatic and intestinal metastases.

[Diagnosis of local breast cancer recurrences by magnetic resonance imaging]. / Diagnostic des récidives locales du cancer du sein par imagerie par résonance magnétique.

The aim of this study is to determine the diagnostic value of magnetic resonance imaging in the diagnosis of local recurrence of breast cancer. From 1991 to 1994, 61 women were studied prospectively using magnetic resonance imaging. All examinations were made on a 1.5 Testa machine with T1 weighted images and after gadolium-dota injection and dynamic images (T1 weighted sequences every 47 seconds during injection of a gadolinium-dota bolus). All the pre-injection, images in the dynamic series were subtracted from the images after injection. A surgical biopsy was obtained in 39 patients yielding a diagnosis of local recurrence (n = 28) or a benign lesion (n = 11). Among the 28 local recurrences, pathology examination reported invasive cancer in 22 and intra-ductal carcinoma in 6. In 22 patients with normal magnetic resonance imaging, follow-up examinations were performed every 6 months. There were no local recurrences within a delay of 6 to 36 months. Twenty-six of the 28 patients with a local recurrence, cystosteatonecrosis and surgery scar tissue less than 6 months old showed contrast uptake 1 min and 34 s after gadolinium injection during the dynamic sequence. This product uptake yielded nodular images within the invasive carcinomas and linear images in the intraductal cancers. In all cases, it is easier to visualize this contrast uptake in subtraction images. In conclusion, magnetic resonance imaging is a simple reliable method for the diagnosis of local recurrence of breast cancer.

[Treatment of epithelial tumors of the ovary. Value of 2-stage surgery]. / Traitement des tumeurs épithéliales de l'ovaire. Intérêt de la chirurgie en deux temps.

A strategy for the treatment of epithelial tumours of the ovary including two surgical operations is presented. The purpose of the first laparotomy is twofold: the extent of the lesions is accurately determined, and the tumour is excised as widely as possible. Another systematic ("second look") laparotomy enables the surgeon to evaluate the effectiveness of chemotherapy and to complete the tumoral excision if needed. Depending on the findings, supplementary total pelvic-abdominal radiotherapy (20 Gy) may be undertaken.

[Basal cell carcinoma of the vulva: 21 cases]. / Carcinome basocellulaire de la vulve: 21 cas.

INTRODUCTION: Basal cell carcinoma (BCC) accounts for 2 to 3 p. 100 of all vulvar malignancies. PATIENTS AND METHODS: We report a retrospective study of 21 cases treated from 1937 to 1999. RESULTS: Vulvar BCC's occurred in elderly patients (average age: 66 years), with mean delay to diagnosis of 5.5 years. Five patients were referred for recurrence. Lesions were located on the external hairy side of the labia majus, except one located on the internal side. In 4 cases a preexisting risk factor was identified: 2 patients had previously received radiation therapy and 2 other patients had multiple disseminated BCC. Mean BCC diameter was 2 cm. Pathological data were similar to skin BCC, with one case of mixed tumor (BCC and squamous cell carcinoma). The treatment was surgical excision for 19 BCCs. Local recurrence risk was high. Only one patient died of visceral dissemination of the disease. DISCUSSION: More than 250 cases of vulvar BCC have been reported in the literature. Clinical, pathological and follow up data are similar to results in the present series. Treatment of choice consists of surgical excision with tumor-free margins. Because of local recurrence risk and possible association with other primary cancers in this age group, long term follow-up is necessary.

[Conservative treatment in cancer of the breast]. / Traitement conservateur dans le cancer du sein.

Conservative treatment combining breast saving surgical procedures and radiotherapy, is considered as the best treatment for small breast cancers. The purpose of the study is to define the most appropriate surgical technique in order to reach both the complete resection of the primary and the best cosmetic result. Terms corresponding to the type of resection will be define in order to facilitate the comparison between the different studies on tumorectomies for breast cancer. Technical problems will be analyzed in the light of our experience of the conservative treatment especially in what concerns the cosmetic results.