Results of the GYNECO 02 study, an FNCLCC phase III trial comparing hysterectomy with no hysterectomy in patients with a (clinical and radiological) complete response after chemoradiation therapy for stage IB2 or II cervical cancer.

BACKGROUND: Concomitant chemoradiation (CRT) (including brachytherapy) is considered the standard management for stage IB2 or II cervical cancer in many countries. Nevertheless, some of them discuss completion surgery (hysterectomy [HT]) after CRT. The aim of this study was to investigate the therapeutic impact of such surgery. METHODS: A randomized trial was opened in France in 2003 to evaluate the interest in HT after CRT. Inclusion criteria were: (a) stage IB2 or II cervical cancer without extrapelvic disease on conventional imaging; (b) pelvic external radiation therapy (45 Gy with or without parametrial or nodal boost) with concomitant cisplatin chemotherapy (40 mg/m2 per week) followed by uterovaginal brachytherapy (15 Gy to the intermediate risk clinical target volume); and (c) complete clinical and radiological response 6-8 weeks after brachytherapy. Patients were randomized between HT (arm A) and no HT (arm B). Unfortunately this trial was closed because of poor accrual: 61 patients were enrolled (in 2003-2006) and are reported on here. RESULTS: Thirty one and 30 patients were enrolled, respectively, in arm A and arm B. Twelve patients recurred (five of them died): respectively, eight and four in arm A and arm B. The 3-year event-free survival rates were 72% (standard error [SE], 9%) and 89% (SE, 6%) (not significant [NS]) in arm A and arm B, respectively. The 3-year overall survival rates were 86% (SE, 6%) and 97% (SE, 3%) (NS) in arm A and arm B, respectively. CONCLUSIONS: Results of the current trial seem to suggest that completion HT had no therapeutic impact in patients with clinical and radiological complete response after CRT (but this conclusion is limited by the lack of power).

Validation of the Tenon breast cancer score for predicting non-sentinel lymph node status in breast cancer patients with sentinel lymph node metastasis: a prospective multicenter study.

BACKGROUND: Axillary lymph node dissection (ALND) is the standard treatment for patients with sentinel node (SN) metastasis, but most of these patients have negative non-sentinel nodes (non-SN). We have developed a scoring system (the Tenon score) to help identify a subgroup of patients who have a low risk of having non-SN metastases and who may thus forgo ALND. Here we validated the Tenon score in an independent cohort of SN-positive patients. PATIENTS AND METHODS: We tested the accuracy of the Tenon score for predicting non-SN status in a prospective multicenter study of 226 SN-positive breast cancer patients. We calculated the false-negative rate, sensitivity, specificity, and positive (PPV) and negative predictive values (NPV). Receiver operating characteristics (ROC) curves were constructed and the areas under the curve (AUC) were calculated as a measure of discriminatory capacity. RESULTS: At least one non-SN was positive in 63 patients (27.9%). One hundred and twenty (53.1%) of the 226 patients had a Tenon score of 3.5 or less. Among these 120 patients, five had at least one positive non-SN. With a score cut-off of 3.5, the negative predictive value was 95.8% and the false-negative rate was 4.2%. Overall, the Tenon score accurately predicted non-SN status, with an AUC of 0.82 (95% confidence interval, 0.77-0.88). CONCLUSION: In this multicenter study of an independent patient population, the Tenon score was accurate and reproducible for predicting non-SN status in breast cancer patients. The simplicity and reliability of the variables on which the Tenon score is based may be an advantage over other scoring systems.

Management of lobular neoplasia diagnosed by core needle biopsy: study of 52 biopsies with follow-up surgical excision.

Lobular neoplasia (LN) is a risk factor for bilateral breast cancer without consensus as to its appropriate management. The authors report on a retrospective multi-institutional study concerning 52 patients in whom a diagnosis of LN was made after core needle biopsy (CNB) and who subsequently underwent surgical excision. The excision specimens revealed seven cases of invasive carcinoma and three cases of ductal carcinoma in situ, indicating an underestimation of lesions at CNB in 19% of cases, and in particular in those patients with pleomorphic LN, and when clinical, radiological masses were detected. This lesion is increasingly being diagnosed by CNB due to widespread screening. Follow-up surgical excision should be performed in order to examine the whole lesion in the case of masses or when the histologic specimen reveals a pleomorphic subtype. In other cases, annual mammographic surveillance should be undertaken due to the persistent long-term risk of developing bilateral breast cancer.

[Infiltrating breast cancer in women younger than 25 years: 13 cases]. / Cancer du sein infiltrant chez les femmes de moins de 25 ans. A propos de 13 cas.

OBJECTIVE: To study the prognosis of breast cancer in woman younger than 25 years and to compare it with that of other age groups to identify prognostic and histologic factors specific to this group. METHOD: Retrospective study of all cases of infiltrating ductal carcinoma treated at our hospital from January 1977 through July 2005, examining clinical, histologic, and treatment variables as well as 5-year overall survival and 5-years disease-free survival rates. RESULTS: The study included 13 women younger than 25 years at diagnosis. Their average age at diagnosis was 23.3 years (CI=1 year). Time from initial signs of disease until diagnosis averaged 6.6 months (CI=2.5). Clinically, the average tumor size was 28.78 mm (CI=6.06), with 46% classified as T1, 31% as T2 and 23% as T4d. We found 92.3% to be invasive ductal carcinoma, with 30% including an in-situ component; 53.8% were SBR grade 3 and 23% included axillary node invasion. Hormone receptors were present in 61.5% of tumors. During the follow-up period, we observed two deaths (with a 5-year overall survival rate, however, of 91%) and 6 recurrences (5-year disease-free survival: 66.5%). CONCLUSION: Prognosis appears unfavorable among young women (younger than 40 years) with breast cancer. In our series, neither prognosis nor clinical or histologic characteristics differed in the subgroup of very young women (younger than 26 years).

Fertility after conservative treatment for borderline ovarian tumors: a French multicenter study.

OBJECTIVE: To examine fertility outcomes and determinants of fertility after conservative surgery for women with borderline ovarian tumors. DESIGN: Retrospective multicenter study. SETTING: Thirteen specialized gynecologic units and one cancer center. PATIENT(S): In a study of women with borderline ovarian tumors, 162 of 360 women underwent conservative surgery; from these 162, we compared epidemiologic, surgical, and histological parameters between 21 women who conceived and 44 women who failed to conceive. INTERVENTION(S): Conservative surgery for borderline ovarian tumors. MAIN OUTCOME MEASURE(S): Fertility results and outcome. RESULT(S): Women undergoing conservative treatment were significantly younger and more likely to be nulliparous. Tumor size was significantly smaller in the conservative treatment group. Thirty pregnancies occurred in 21 (32.3%) of the 65 women who wished to conceive after conservative treatment. Twenty-seven pregnancies were spontaneous, whereas three occurred after ovarian stimulation and IUI (one case) or IVF (2 cases). Women who conceived did not differ from women who did not conceive in terms of the tumor recurrence rate or the mean time to recurrence (39.6 +/- 28.2 and 22.9 +/- 14.9 months, respectively). Age at initial treatment was the only determinant of fertility. CONCLUSION(S): Despite a high recurrence rate, our results confirm that conservative surgery for women with borderline ovarian tumors is an acceptable option and that fertility is preserved in nearly one third of cases.

[Standards, Options and Recommendations for the management of invasive cervical cancer patients (non metastastic)]. / Standards, Options and Recommandations Cancers invasifs du col utérin stades non métastatiques, version abrégée.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French cancer centers and specialists from French public university and general hospitals and private clinics. Its main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop, according to the definitions of the Standards, Options and Recommendations, clinical practice guidelines for the management of invasive cervical cancer patients. Methods : Data were identified by searching Medline and the personal reference lists of members of the expert groups, then submitted for review to independent reviewers. RESULTS: This is a synthesis of the Standards, Options and Recommendations elaborated by a working group of experts. Pretherapeutic assessment, classification, diagnosis, therapeutic modalities (surgery, radiotherapy, radiochemotherapy, chemotherapy), therapeutic strategies by disease stage and follow-up are covered. Algorithms for the management of patients are also included.

[Standards, Options and Recommendations 2000: non metastatic endometrial cancer]. / Standards, Options et Recommendations 2000: cancer de l'endomètre, stades non métastatiques (rapport abrégé).

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Cancer Centers, and specialists from French Public Universities, General Hospitals and Private Clinics, and some specialists learned societies. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The SORs are developed using a methodology based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for the management of patients with carcinoma of the endometrium according to the definitions of the Standards, Options and Recommendations project. METHODS: Data were identified by searching Medline , web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 63 independent reviewers. RESULTS: The main recommendations for the management of carcinoma of the endometrium are: 1) The diagnosis of carcinoma of the endometrium is based on biopsy and histological examination. However, as first intention, the first elements for diagnosis can be obtain from a hysterography, or particularly, a endovaginal ultrasound examination. Ultrasound allows locoregional metastases to be detected, the CT scan allows the lymph node involvement to be assessed and magnetic resonance imaging allows the myometrium invasion to be evaluated. 2) For the majority of patients, surgery is the initial treatment, both for localised and advanced-stage carcinomas. The excised sample can be used for pathological analysis and tumour staging, using the FIGO (Fédération internationale de gynécologie obstétrique) classification. Surgery for patients with stage I and II carcinomas involves total extrafascial hysterectomy with bilateral salpingo-oophorectomy., In patients with stage III and IV carcinomas radical surgery should be performed, when possible. If this is not possible, then surgery should be as complete as possible and be associated with a complementary treatment. In patients with the most advanced carcinomas, tumour reduction by surgery should be performed. 3) Complementary treatment includes external-beam radiotherapy and brachytherapy. The decision concerning the extent and type of irradiation should be taken taking into consideration the stage and the prognostic factors present. For patients with stage I and II carcinoma, complementary treatment with brachytherapy can be performed, if the myometrium invasion is not deep, or if the carcinoma is grade 2 or 3. Patients with stage III carcinomas can be treated with pelvic or abdominal-pelvic complementary irradiation. In patients that cannot undergo surgery, exclusive radiotherapy can be performed. 4) In the absence of any symptoms, surveillance should include a general clinical and gynaecological examination. All patients with symptoms should undergo an additional work-up.

[Primary squamous cell carcinoma of the breast: clinical study and review of the literature]. / Carcinomes épidermoïdes primitifs du sein : étude clinique et revue de la littérature.

From the analysis of our series and a review of the literature, we have done a summary of the clinicopathologic patterns and treatment of squamous cell carcinoma of the breast. It usually presents as a large palpable mass in a woman over 50 years old. There are no specific iconographic features, but a relative frequency of presentation as abscess or cyst. The overall and disease-free survivals are worse than other histological types of breast cancer. These neoplasms have a basal-like and triple negative profile and they respond poorly to standard treatment of breast carcinomas. They are usually treated by radical surgery. Optimal chemotherapy regimens is not yet determined and platin based chemotherapy could offer an effective alternative as the developpement of specific targeted therapies (anti Her1) could do.

Comparison of models to predict nonsentinel lymph node status in breast cancer patients with metastatic sentinel lymph nodes: a prospective multicenter study.

PURPOSE: Several models have been developed to predict nonsentinel lymph node (non-SN) status in patients with breast cancer with sentinel lymph node (SN) metastasis. The purpose of our investigation was to compare available models in a prospective, multicenter study. PATIENTS AND METHODS: In a cohort of 561 positive-SN patients who underwent axillary lymph node dissection, we evaluated the areas under the receiver operating characteristic curves (AUCs), calibration, rates of false negatives (FN), and number of patients in the group at low risk for non-SN calculated from nine models. We also evaluated these parameters in the subgroup of patients with micrometastasis or isolated tumor cells (ITC) in the SN. RESULTS: At least one non-SN was metastatic in 147 patients (26.2%). Only two of nine models had an AUC greater than 0.75. Three models were well calibrated. Two models yielded an FN rate less than 5%. Three models were able to assign more than a third of patients in the low-risk group. Overall, the Memorial Sloan-Kettering Cancer Center nomogram and Tenon score outperform other methods for all patients, including the subgroup of patients with only SN micrometastases or ITC. CONCLUSION: Our study suggests that all models do not perform equally, especially for the subgroup of patients with only micrometastasis or ITC in the SN. We point out available evaluation methods to assess their performance and provide guidance for clinical practice.

Prospective multicenter comparison of models to predict four or more involved axillary lymph nodes in patients with breast cancer with one to three metastatic sentinel lymph nodes.

PURPOSE: Three models have been developed to predict four or more involved axillary lymph nodes (ALNs) in patients with breast cancer with one to three involved sentinel lymph nodes (SLNs). Two scores were developed by Chagpar et al (Louisville scores excluding or including method of detection), and a nomogram was developed by Katz et al. The purpose of our investigation was to compare these models in a prospective, multicenter study. PATIENTS AND METHODS: Our study involved a cohort of 536 patients having one to three involved SLNs who underwent ALN dissection. We evaluated the area under the receiver operating characteristic curve (AUC), calibration (for the Katz nomogram only), false-negative (FN) rate, and clinical utility of the three models. Results were compared with the optimal logistic regression (OLR) model that was developed from the validation cohort. RESULTS: Among the 536 patients, 57 patients (10.6%) had > or = four involved ALNs. The AUC for the Katz nomogram was 0.84 (95% CI, 0.81 to 0.86). The Louisville score excluding method of detection was 0.75 (95% CI, 0.72 to 0.78). The Louisville score including method of detection was 0.77 (95% CI, 0.74 to 0.79). The FN rates were 2.5% (eight of 321 patients), 1.8% (two of 109 patients), and 0% (zero of 27 patients) for the Katz nomogram and the Louisville scores excluding and including method of detection, respectively. The Katz nomogram was well calibrated. Optimism-corrected bootstrap estimate AUC of the OLR model was 0.86. Using this result as a reasonable target for an external model, the performance of the Katz nomogram was remarkable. CONCLUSION: We validated the three models for their use in clinical practice. The Katz nomogram outperformed the two other models.

Prospective multicentric randomized study comparing periareolar and peritumoral injection of radiotracer and blue dye for the detection of sentinel lymph node in breast sparing procedures: FRANSENODE trial.

PURPOSE: To determine the optimal injection path for blue dye and radiocolloid for sentinel lymph node (SLN) biopsy in early breast cancer. PATIENTS AND METHODS: A prospective randomized multicentric study was initiated to compare the peritumoral (PT) injection site to the periareolar (PA) site in 449 patients. RESULTS: The detection rate of axillary SLN by lymphoscintigraphy was significantly higher (P = .03) in the PA group (85.2%) than in the PT group (73.2%). Intraoperative detection rate by blue dye and/or gamma probe was similar (99.11%) in both groups. The rate of SLN detection was somewhat higher in the PA group than in the PT group: 95.6% versus 93.8% with blue dye (P = .24) and 98.2% versus 96.0% by probe (P = .16), respectively. The number of SLNs detected by lymphoscintigraphy and by probe was significantly higher in the PA group than in the PT group, 1.5 versus 1.2 (P = .001) and 1.9 versus 1.7 (P = .02). The blue and hot concordance was 95.6% in the PA group and 91.5% in the PT group (P = .08). The mean ex vivo count of the SLN was significantly higher in the PA group than in the PT group (P < .0001). CONCLUSION: This study strongly validates the PA injection technique given the high detection rate (99.1%) of SLN and the high concordance (95.6%) between blue dye and the radiotracer, as well as higher significant ex and in vivo counts, improving SLN probe detection.

[Standards, Options and Recommendations for the management of ductal carcinoma in situ of the breast (DCIS): update 2004]. / Recommandations pour la pratique clinique: Standards, Options et Recommandations 2004 pour la prise en charge des carcinomes canalaires in situ du sein (rapport abrégé).

The " Standards, Options and Recommendations " (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centres (FNCLCC), the 20 French cancer centres, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. Objectives : To update the Standards, Options and Recommendations clinical practice guidelines for the management of ductal carcinoma in situ of the breast (DCIS). Methods : The working group identified the questions requiring up-dating from the previous guideline. Medline(r) and Embase(r) were searched using specific search strategies from year 1996 to year 2003. In addition several Internet sites were searched in October 2002. Results : Clinical guidelines have been defined for the management of diagnosis, treatment, follow-up, and treatment of recurrence of DCIS. The issue of hormone replacement therapy has also been addressed in the context of DCIS.

Breast microcalcifications: multivariate analysis of radiologic and clinical factors for carcinoma.

Screening mammography contributes to the improvement of breast carcinoma survival through early detection and treatment of non-palpable lesions. Microcalcifications are of fundamental importance in this process. The percentage of malignant lesions found in biopsies for microcalcifications varies from 10% to 40%. The purpose of this study was to evaluate the relationship between clinical and radiologic records and the presence of malignant breast diseases. To establish the basis for the study, 211 mammographic files showing clustered microcalcifications from 204 women were prospectively reviewed and clinical records were retrospectively drawn. Definitive pathologic analysis was available for all. The value for cancer of each criterion was investigated by univariate and multivariate analyses. A first analysis was performed on the entire population and a second one was performed with stratification on morphologic subgroups. There were 99 malignant lesions (47%). In the entire group, no clinical criterion was significant. In the univariate analysis, five radiologic variables were significant: morphologic type(p < 0.0001), number of calcifications per cluster(p < 0.0001), linear or triangular distribution(p < 0.0002), diameter of the area (p < 0.01),and number of clusters (p = 0.011). In the multivariate analysis, two criteria remained significant: morphologic type 4 (irregularly punctiform) or 5 (vermicular) microcalcifications(Le Gal's classification) (p < 0.0001) and diameter of the cluster larger than 25 mm (p = 0.032). In subgroups,in the multivariate analysis, the "age > 60 years" criterion was statistically significant in the group of regular punctiform microcalcifications (type 2); for irregularly punctiform microcalcifications (type 4), "number of microcalcifications > 20" was significant. The morphologic features of microcalcifications must be the first criterion evaluated. They permit identification of characteristically benign (annular calcifications) or malignant calcifications (vermicular calcifications). For the remainder of the calcification types, other criteria must be taken into account, and their value vary with (according to) the morphologic aspect. These findings have implications for the management of women with microcalcifications and could help breast specialists make treatment decisions.