Long-term clinical outcomes of preoperative brachytherapy in early-stage cervical cancer.

OBJECTIVE: The treatment of early-stage cervical cancer (CC) is primarily based on surgery. Adjuvant (chemo)radiotherapy can be necessary in presence of risk factors for relapse (tumor size, deep stromal invasion, lymphovascular space invasion (LVSI), positive margins, parametrial or lymph node involvement), increasing the risk of treatment toxicity. Preoperative brachytherapy can reduce tumor extension before surgery, potentially limiting the need for adjuvant radiotherapy. This study reports long-term clinical outcomes on efficacy and toxicity of preoperative pulse-dose-rate (PDR) brachytherapy in early-stage CC. METHODS: All patients treated at Institut Curie between 2007 and 2022 for early-stage CC by preoperative brachytherapy were included. A PDR technique was used. Patients underwent hysterectomy associated with nodal staging following brachytherapy. RESULTS: 73 patients were included. The median time from brachytherapy to surgery was 45 days [range: 25-78 days]. With a median follow-up of 51 months [range: 4-185], we reported 3 local (4 %), 1 locoregional (1 %) and 8 metastatic (11 %) relapses. At 10 years, OS was 84.1 % [95 % CI: 70.0-100], DFS 84.3 % [95 % CI:74.6-95.3] and LRFS 92.8 % [95 % CI:84.8-100]. Persistence of a tumor residue, observed in 32 patients (44 %), was a significant risk factor for metastatic relapse (p = 0.02) and was associated with the largest tumor size before brachytherapy (p = 0.04). Five patients (7 %) experienced grade 3 toxicity. One patient (1 %) developed grade 4 toxicity. Ten patients (14 %) received adjuvant radiotherapy, increasing the risk of lymphedema (HR 1.31, 95 % CI [1.11-1.54]; p = 0.002). CONCLUSIONS: PDR preoperative brachytherapy for early-stage cervical cancer provides high long-term tumor control rates with low toxicity.

Outcome in early cervical cancer following pre-operative low dose rate brachytherapy: a ten-year follow up of 257 patients treated at a single institution.

OBJECTIVE: To report the outcome of preoperative low dose rate uterovaginal brachytherapy (LDR-UVBT) followed by radical surgery in the treatment of early cervical carcinoma. METHODS: 257 patients treated at Institut Curie from 1985 to 2008 for cervical carcinoma less than 4cm (FIGO stages Ib1, IIA and IIB) were studied. Patients received preoperative LDR-UVBT followed by hysterectomy Piver II type, with pelvic lymph nodes dissection (PLND). Predictive factors for pathological response to brachytherapy were analyzed with logistic regression, as well as survival rates. RESULTS: 44% of patients had residual tumor, 4.3% of patients had parametrial invasion and 17.9% of patients had lymph node involvement. Predictive factors for an incomplete pathological response were: initial clinical tumor size 20mm (OR 2.1), pN1 (OR 2.77), glandular carcinoma (OR 2.51) and lymphovascular invasion (OR 4.35). 7.4% and 2.7% of patients had respectively grade 2 and grade 3 post-therapeutic late complications. Median follow up was 122 months [1-282]. Five-year actuarial overall survival and disease free survival were respectively 83% CI [78.3-87.5] and 80.9% CI [76.3-85.7]. In multivariate analysis, factors affecting significantly the overall survival and disease free survival rates were: lymph node involvement (RR 4.53 and 8.96 respectively), parametrial involvement (RR 5.69 and 5.62 respectively), smoking (RR 3.07 and 2.63 respectively). CONCLUSIONS: Preoperative LDR-UVBT results in good disease control with a low complications rate. Its accuracy could be improved by a better selection of patients. Lymph nodes and parametrial evaluation remains a challenging issue that should be achieved with imaging and minimal invasive surgery.

Abdominoperineal resection for anal cancer.

PURPOSE: Following initial radiotherapy or chemoradiotherapy for the treatment of anal cancer, patients who present with either persistent or locally recurrent disease are treated by abdominoperineal resection. The aim of this retrospective study was to review the long-term survival and prognostic factors after such surgery in a single institution. METHODS: Over a 34-year period (1969-2003), 422 patients with nonmetastatic anal cancer were treated with a curative intent. Of these, 83 (median age 61 years; 74 women) underwent abdominoperineal resection. RESULTS: Forty-one patients underwent abdominoperineal resection for persistent disease and 42 for locally recurrent disease. Postoperative mortality was 4.8 percent and morbidity was 35 percent with 18 percent having perineal wound infections. Median follow-up was 104 months (range, 3-299). The 3-year and 5-year actuarial survival was 62.8 and 56.5 percent respectively. Using univariate analysis, patients below 55 years, females, T1-2 tumors, N0-N1 lymphadenopathy and the absence of locally advanced tumor were associated with significantly improved survival. Surgery, whether for persistent or locally recurrent disease, did not affect the 5-year survival rate. CONCLUSIONS: Abdominoperineal resection for nonmetastatic anal cancer is associated with a high morbidity rate but may result in long-term survival regardless of the indication.

What is the impact of neoadjuvant chemoradiation on outcomes in gastro-intestinal cancer?

Multimodal therapeutic strategies combining chemotherapy, radiation therapy and surgery have been shown to be feasible and to have a positive impact on outcomes by decreasing the risk of locoregional recurrence and often by increasing overall survival. The advantages of neoadjuvant chemo(radio)therapy include optimal tumor control combined with better tolerance and compliance to treatment while also increasing the number of candidates for surgery. Whereas indications for neoadjuvant therapy are increasing, its impact on surgical treatment and postoperative outcomes are not well-known. Surgeons frequently believe that chemo(radio)therapy may amplify intraoperative difficulties, thereby increasing postoperative morbidity and mortality. The aim of this review was to report the state of the art regarding: (i) the role of chemo(radio)therapy; (ii) its impact on surgical indications and modalities; and (iii) its impact on postoperative outcomes for the most frequently encountered gastro-intestinal cancers, i.e. esophageal, rectal, pancreatic, and anal canal cancer.

Toxicity and early clinical outcomes in cervical cancer following extended field helical tomotherapy to para-aortic lymph nodes.

PURPOSE: To evaluate toxicity and early disease outcome among patients treated for cervical cancer with extended-field helical tomotherapy to the para-aortic nodes. PATIENTS AND METHODS: Thirty-eight patients (International Federation of Gynecology and Obstetrics [FIGO] stage IB2-IVA) from four institutions received extended-field helical tomotherapy and were retrospectively evaluated. All had nodal disease. Para-aortic lymph nodes were involved in 31 patients. Patients were assessed for toxicity using version 4 of the National Cancer Institute's common terminology criteria for adverse events. Survival curves were plotted using Kaplan-Meier estimates. RESULTS: All patients underwent radiation to the tumor region (median dose: 45Gy; range: 44-66Gy), pelvic lymph nodes and para-aortic lymph nodes (median dose: 45Gy; range: 44-60Gy). The median dose to positive lymph nodes was 55Gy (range: 45-65Gy). All received platinum-based chemotherapy (31 concurrently). The median follow-up was 15months. Acute toxicity events observed included one patient with grade 5 febrile neutropenia, 11 patients (29%) with grade 3 hematologic complications. Grades 3-4 gastrointestinal and genitourinary toxicities occurred in six (16%) and four (11%) patients, respectively. Three patients had grade 3 pelvic pain (8%). The 6- and 18-month overall survival rates were 94.7 and 63.9%, respectively. The 18-month locoregional control, disease-free survival, and late grade 3 toxicity rates were 60.2, 43.3 and 7.3%, respectively. CONCLUSION: Extended-field helical tomotherapy was associated with low rates of acute gastrointestinal and genitourinary toxicities with early survival and locoregional control similar to other published series.

Human papillomavirus genotype as a major determinant of the course of cervical cancer.

PURPOSE: To determine whether the prognosis of invasive cancers of the uterine cervix is related to the type of human papillomavirus (HPV) associated with the tumor. PATIENTS AND METHODS: Two hundred ninety-seven patients with invasive cervical cancer were prospectively registered from 1986 to 1994. HPV typing was performed on DNA extracted from frozen tumor specimens by means of Southern blot hybridization (SBH) and polymerase chain reaction (PCR) techniques. The median follow-up was 38 months. RESULTS: HPV sequences were detected in 246 patients (83%): 150 patients had HPV16, 31 patients had HPV18, and 14 patients had one of the intermediate-oncogenic-risk HPV types (HPV31, 33, 35, 52, 58). In 51 patients, HPV type remained undetermined, and in 51 patients, no viral sequences were found. No significant associations were observed between virologic data and tumor stage or node status. The 5-year disease-free survival (DFS) rate was 100% for patients with intermediate-risk HPV-associated tumors, 58% for patients with HPV16-positive tumors, and 38% for patients with HPV18-positive tumors (P = .02). In multivariate analysis, patients with HPV18-associated tumors had a relative risk (RR) of death 2.4 times greater (95% confidence interval [CI], 1.29-4.59) than that for patients with HPV16, and 4.4 times greater (95% CI, 3.48-5.32) than that for patients with a tumor associated with a viral type different from HPV16/18. CONCLUSION: The prognosis for invasive cancers of the uterine cervix is dependent on the oncogenic potential of the associated HPV type. HPV typing may provide a prognostic indicator for individual patients and is of potential use in defining specific therapies against HPV-harboring tumor cells.

Contralateral breast cancer: annual incidence and risk parameters.

PURPOSE: To screen for factors that might predict the risk of developing metachronous contralateral breast cancer (CBC), taking into account the influence of local or distant recurrence, and to assess the annual incidence of CBC. PATIENTS AND METHODS: Of 4,748 women with invasive unilateral breast cancer, clinical stage I to IIIa, treated between 1981 and 1987, 282 metachronous CBCs were diagnosed. Due to competing risks between the occurrence of CBC and other events, several options for multivariate analysis were considered. RESULTS: The median follow-up time was 80 months (range, 1 to 158). The cumulative rate of CBC was 4.1% +/- 0.3% at 5 years, and the annual incidence rate of CBC increased slowly, while the risk of local recurrence and metastases decreased after the fourth year. Whichever model we chose, age less than 55 years (relative risk [RR] = 1.40) at the time of diagnosis of the first breast cancer, as well as the presence of lobular type carcinoma (RR = 1.50), was associated with an increased risk of developing a tumor in the contralateral breast. Adjuvant chemotherapy significantly decreased (RR = 0.54) the risk of CBC. CONCLUSION: Lobular histology and age less than 55 years are found to increase the risk of CBC, while adjuvant chemotherapy significantly decreased the risk of CBC. The progressive rise in the annual incidence rates of CBC, together with the absence of a link between clinical prognostic factors of the first cancer and CBC, suggested that CBC can be considered as a second primary breast cancer.

Phytoestrogens after breast cancer.

The current extension of the indications for adjuvant chemotherapy, which predisposes to early menopause, and the media coverage of the benefits of hormone replacement therapy (HRT) have led patients with a history of breast cancer to seek treatments for estrogen deprivation. In breast cancer survivors, most physicians avoid HRT because of concern regarding the potential promotion of growth of occult malignant cells by estrogens, due to the estrogen dependence of breast cancer. Soy phytoestrogens are being promoted as the 'natural alternative' to HRT and have been available without restrictions for several years as nutritional supplements. In this paper, data on the complex mammary effects of phytoestrogens in epidemiological studies, in in vitro studies, as well as in in vivo studies on animal carcinogenesis are reviewed. The potential benefits and risks of phytoestrogens are analyzed, and the prescription of phytoestrogens to postmenopausal women after breast cancer and the coprescription with the anti-estrogen tamoxifen are discussed. The absence of controlled trials and technical checking of extraction and titration in these preparations on 'free sale' raise a new problem in terms of public health and justify close reasoning and a cautious attitude of physicians, as well as straight information given to women, especially after breast cancer.

Neoadjuvant chemotherapy in young breast cancer patients: correlation between response and relapse?

The aim of this analysis was to assess how the clinical response to chemotherapy corresponded to long-term prognosis in patients of less than 35 years of age. A retrospective analysis was made of response and survival data of 609 premenopausal patients who had been treated by four cycles of neoadjuvant chemotherapy followed by surgery and/or radiotherapy. Patients were stratified into three age groups (group 1, < or = 35 years; group 2, 35-40 years; group 3, > or = 41 years). Objective and complete clinical response rates were significantly higher in the youngest patients (below 35 yrs: P = 0.005 and P = 0.001, respectively) in stark contrast to a particularly poor outcome of this subpopulation. Five-year local recurrence rates were 31% in the youngest patients, compared with 26% and 16% in groups 2 and 3, respectively (P = 0.0007). Group 1 patients also had significantly higher 5-year metastatic relapse rates (41% versus 35% and 28%; P = 0.007) and 5-year survival figures were 70%, 82% and 84% for groups 1, 2 and 3 respectively (P = 0.002). Finally, stratification by age and by response revealed that, whilst the outcome of the youngest patients was highly dependent on their response to primary chemotherapy, complete responders showed disease-free survival rates at 5 years that were lower than these of older patients, whatever their response. Despite a seemingly better control of the primary tumour by chemotherapy, the patients in the youngest age group remained at a high risk for local and metastatic relapse. This apparent paradox may be in part attributable to rapid disease progression of micrometastatic tumour subpopulations that are refractory to chemotherapy.

Are cosmetic results following conservative surgery and radiation therapy for early breast cancer dependent on technique?

To assess the cosmetic results in relation to treatment technique, we retrospectively reviewed the results for 1159 Stage I-II breast cancer patients treated with conservative surgery and radiotherapy between 1970-1985. All patients underwent gross excision followed by radiation therapy including an implant or electron beam boost. The total dose to the primary site was greater than or equal to 60 Gy. Because of technical modifications introduced over time after 1981, the population was divided arbitrarily into two cohorts: 504 patients treated through 1981 and 655 treated between 1982-1985. Median follow-up time for surviving patients in the two cohorts were 107 months and 67 months, respectively. Cosmetic outcome was evaluated by the examining physician and scored as excellent, good, fair or poor. Excellent results at 5 years were scored in 59% of early cohort patients and 74% of the latter cohort (p = 0.002). Acceptable results (either good or excellent) were seen in 84% and 94%, respectively (p = 0.02). In the latter cohort, the likelihood of achieving an excellent result, but not an acceptable result, was significantly related to the volume of resected breast tissue and the use of chemotherapy. The number of fields (three-field technique, provided that fields are precisely matched, compared to tangents only) and boost type (implant vs electrons) did not influence the cosmetic outcome. We conclude that our current technique using breast RT to 45-46 Gy and a boost to the primary site of 16-18 Gy is associated with a high likelihood of acceptable cosmetic results and that this likelihood is not diminished by the use of adjuvant chemotherapy, a large breast resection, the use of a third field, or boost type.

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.

Metachronous contralateral breast cancer as first event of relapse.

PURPOSE: To determine which clinical, biological, or treatment-related factors of the first and second primary breast cancers influenced the outcome following contralateral breast carcinoma (CBC). METHODS AND MATERIALS: By August 1994, 319 of 6406 patients with clinical Stage 0 to III breast carcinoma treated between 1981 and 1987 at Institut Curie had developed a second breast cancer that was diagnosed more than 6 months following ipsilateral breast cancer. Of these 319 patients, 235 had a CBC as the first recurrent event and constitute the study population. Comparisons of first and second breast tumor characteristics were done using Fisher's exact test. Survival distributions from the date of CBC were compared by the log-rank test. Prognostic factors for local relapses, distant relapses, and survival after CBC were assessed by univariate and multivariate analysis using the Cox proportional hazards model. RESULTS: The diagnosis of CBC was more frequently guided by mammographies than for ipsilateral tumors (p < 0.0001). The proportion of early stage tumors < or = T1 was significantly higher in the opposite breast as compared to the the first primary tumor (p < 0.0001). A greater rate of noninvasive tumors was observed in CBCs (p = 0.0003). Median follow-up time from the diagnosis of CBC was 54 months (1-137). Five-year survival following CBC was 79% (+/- 6). Five-year local (CBC breast or chest wall) and distant failure rates were 15 and 24%, respectively. Time interval to the occurrence of CBC (< 2 years, 2-5 years, > 5 years) had no influence on survival. Cox model analysis showed that the risk factors for distant metastases were stage and progesterone receptor levels of the contralateral tumor. The risk of distant failure in CBC was not influenced by the extent of surgery. CONCLUSIONS: In this selected population of CBCs as first recurrent events, a follow-up policy based on clinical examination and annual mammography enabled the detection of CBCs at an earlier stage than the primary ipsilateral cancer. The outcome after CBC was determined only by the characteristics of the contralateral tumor. Breast-conserving treatment should be recommended when it is feasible. Adjuvant chemotherapy should be delivered according to the same criteria as the primary tumor.

Mammographically detected ductal carcinoma in situ of the breast treated with breast-conserving surgery and definitive breast irradiation: long-term outcome and prognostic significance of patient age and margin status.

PURPOSE: This study was performed to determine the long-term outcome for women with mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast treated with breast-conserving surgery followed by definitive breast irradiation. METHODS AND MATERIALS: An analysis was performed of 422 mammographically detected intraductal breast carcinomas in 418 women from 11 institutions in North America and Europe. All patients were treated with breast-conserving surgery followed by definitive breast irradiation. The median follow-up time was 9.4 years (mean, 9.4 years; range, 0.1-19.8 years). RESULTS: The 15-year overall survival rate was 92%, and the 15-year cause-specific survival rate was 98%. The 15-year rate of freedom from distant metastases was 94%. There were 48 local failures in the treated breast, and the 15-year rate of any local failure was 16%. The median time to local failure was 5.0 years (mean, 5.7 years; range, 1.0-15.2 years). Patient age at the time of treatment and final pathology margin status from the primary tumor excision were both significantly associated with local failure. The 10-year rate of local failure was 31% for patient age < or = 39 years, 13% for age 40-49 years, 8% for age 50-59 years, and 6% for age > or = 60 years (p = 0.0001). The 10-year rate of local failure was 24% when the margins of resection were positive, 9% when the margins of resection were negative, 7% when the margins of resection were close, and 12% when the margins of resection were unknown (p = 0.030). Patient age < or = 39 years and positive margins of resection were both independently associated with an increased risk of local failure (p = 0.0006 and p = 0.023, respectively) in the multivariable Cox regression model. CONCLUSIONS: The 15-year results from the present study demonstrated high rates of overall survival, cause-specific survival, and freedom from distant metastases following the treatment of mammographically detected ductal carcinoma in situ of the breast using breast-conserving surgery and definitive breast irradiation. Younger age and positive margins of resection were both independently associated with an increased risk of local failure. The 15-year results in the present study serve as an important benchmark for comparison with other treatment modalities. These results support the use of breast-conserving surgery and definitive breast irradiation for the treatment of appropriately selected patients with mammographically detected ductal carcinoma in situ of the breast.

Breast cancer occurred after treatment for Hodgkin's disease: analysis of 133 cases.

PURPOSE: To assess the clinical and histological characteristics of breast cancer (BC) occurring after Hodgkin's disease (HD) and give possible therapies and prevention methods. MATERIALS AND METHODS: In a retrospective multicentric analysis, 117 women and two men treated for HD subsequently developed 133 BCs. The median age at diagnosis of HD was 24 years. The HD stages were stage I in 25 cases (21%), stage II in 70 cases (59%), stage III in 13 cases (11%), stage IV in six cases (5%) and not specified in five cases (4%). Radiotherapy (RT) was used alone in 74 patients (63%) and combined modalities with chemotherapy (CT) was used in 43 patients (37%). RESULTS: BC occurred after a median interval of 16 years. TNM classification (UICC, 1978) showed 15 T0 (11.3%), 44 T1 (33.1%), 36 T2 (27.1%), nine T3 (6.7%), 15 T4 (11.3%) and 14 Tx (10.5%). Ductal infiltrating carcinoma and ductal carcinoma in situ (DCIS) represented 81.2 and 11.3% of the cases, respectively. Among the infiltrating carcinoma, the axillary involvement rate was 50%. Seventy-four tumours were treated by mastectomy without (67) or with (ten) RT. Forty-four tumours had lumpectomy without (12) or with (32) RT. Another four received RT alone, and one CT alone. Sixteen patients (12%) developed isolated local recurrence. Thirty-nine patients (31.7%) developed metastases and 34 died; 38 are in complete remission whereas five died of intercurrent disease. The 5-year disease-specific survival rate was 65.1%. The 5-year disease-specific survival rates for the pN0, pN1-3 and pN>3 groups were 91, 66 and 15%, respectively (P<0.0001), and 100, 88, and 64% for the TIS, T1 and T2. For the T3 and T4, the survival rates decreased sharply to 32 and 23%, respectively. These secondary BC are of two types: a large number of aggressive tumours with a very unfavourable prognosis (especially in the case of pN>3 and/or T3T4), and many tumours with a 'slow spreading' such as DCIS and microinvasive lesions. These lesions developed especially in patients treated exclusively by RT. CONCLUSIONS: The young women and girls treated for HD should be carefully monitored in the long-term by clinical examination, mammography and ultrasonography. We suggest that a baseline mammography is performed 5-8 years after supradiaphragmatic irradiation (complete mantle or involved field) in patients who were treated before 30 years of age. Subsequent mammographies should be performed every 2 years or each year, depending on the characteristics of the breast tissue (e.g. density) and especially in the case of an association with other BC risk factors. This screening seems of importance due to excellent prognosis in our T(1S)T(1) groups, and the possibility of offering these young women a conservative treatment.

Squamous cell carcinoma of the pyriform sinus: retrospective study of 351 cases treated at the Institut Gustave-Roussy.

The first part of the study was devoted to 199 tumors treated by surgery, either conservative for the smallest tumors (18 cases) or radical (181 cases), with systematic postoperative radiotherapy. The 3-year survival rate was 48% and the 5-year, 33%, with a 12% local recurrence rate, a 7.5% neck recurrence rate, and 27.6% rate distant metastases. Histologic correlations were developed. The second part of the study reported 152 cases treated by external radiotherapy alone either as a variant of our treatment protocol for the small-sized tumors (31 cases) or, for the major part (121 cases), as a result of surgical inoperability or patient refusal. The former subgroup had a variable survival rate (65% at 3 years and 40% at 5 years) equivalent to similarly staged patients treated with conservation laryngeal surgery, whereas the prognosis of the latter subgroup was poor. The two main causes of failure were the inability to apply the curative treatment protocol in 35% of patients ineligible for a surgery and the high risk of distant metastases in the 65% of patients able to undergo the usual management.

Medullary breast carcinoma: prognostic implications of p53 expression.

Medullary breast carcinoma (MBC) is a rare pathological type of breast cancer. The rate of p53 protein accumulation is higher in MBC than in common invasive ductal carcinoma. Whether this particular feature of MBC influences the outcome after treatment is unknown. We retrospectively analyzed the characteristics, treatment and outcome of 71 patients with MBC treated between 1981 and 1996. The median age was 51 years (range 27-81) and the median clinical tumor size was 25 mm (range 0-70 mm). Breast-conserving treatment was offered when possible: 55 patients had undergone a tumorectomy and radiotherapy while 16 patients had undergone a mastectomy. p53 protein accumulation was determined by immunohistochemistry on paraffin-embedded tumor specimens from 58/71 samples available for this study. The median follow-up for the 56 survivors was 113 months (range 30-241). The 10-year survival and metastasis-free survival rates were 81% and 81.4%, respectively. The local recurrence rate was 16.4%. The two factors predicting outcome were pathological axillary node involvement in the 60 patients who underwent axillary dissection and adjuvant chemotherapy. p53 accumulation was found in 33/58 patients (57%). p53 status was not predictive of survival nor of distant or local recurrences. We confirm that medullary breast carcinoma has a favorable prognosis despite its aggressive pathological features. p53 protein accumulation, found in the majority of MBCs, was not related to outcome.

[Invasive cancer of the uterine cervix in young women: retrospective study of 236 cases]. / Le cancer invasif du col utérin de la femme jeune: étude rétrospective de 236 cas.

The study of cases treated between 1970 and 1984 at the Institut Curie, in women aged 40 years and under, was undertaken in order to determine the influence of age on prognosis. The incidence of these cases was stable throughout the 15 years study period as was the very high incidence of earlier cases: 84.5%. Earlier cases were treated with combined radiotherapy and surgery and advanced cases with radiotherapy alone. Overall survival rate was 75% at 5 years, 60% at 10 and 15 years: but 85% for the 36-40 years of age group, 74% for the 30-35 years of age group and 67% for women aged 29 and less. Five year survival rate for operated cases is the same for the 36-40 age group as for all age patients, according to the lymph node status. In contrast, it was 85% in the N-younger group, and 30% for those patients with lymph node involvement. In conclusion, from our study it appears that the overall survival rate for women of 36 years and less, and mainly 29 years and less, is significantly lower than that for older women, and that their prognosis is especially poor in the case of lymph node involvement.

[Pelvic lymph node invasion in cancer of the uterine cervix]. / L'envahissement ganglionnaire pelvien dans les cancers du col utérin.

Pelvic lymph node invasion is an important prognostic factor for cervical cancer. It is generally accepted that iliac lymph nodes must be treated systematically, but the extent of lymph node dissections is open to discussion. One hundred and eighty two cases of cervical cancer with lymph node invasion were treated at the Institut Curie between 1960 and 1988, by colpohysterectomy with lymph node dissection (168 cases) combined with preoperative brachytherapy and, in some cases, pre- and/or postoperative radiotherapy; in 14 cases, only an exploratory operation was performed. External iliac lymph node invasion was found in 95% of cases, situated in the middle and internal chains. Common iliac lymph node invasion was found in 24% of cases, but was only exceptionally isolated (3%). It is therefore possible, by means of well defined, localized external iliac dissection, with frozen section histological examination, to determine the exact lymph node status. Lumboaortic lymph node invasion was found in 8.2% of cases. The overall survival rate was 49% at 5 years and 40.5% at 10 years. Factors which influence survival are: the cervical volume (p = 0.015), the unilateral or bilateral nature of invasion (p = 0.0015), the number of lymph nodes invaded (two or more than two) (p = 0.0001), capsular rupture (p = 0.0008), lymph node adhesions other than venous (p = 0.0002), common iliac invasion (p = 0.0001). On Cox's model, the principal factors were the number of lymph nodes invaded, adhesion other than venous, common iliac invasion; on the other hand, venous adhesion does not modify the prognosis. The five-year survival rates following external iliac dissections and complete pelvic dissections were not significantly different. Finally, postoperative radiotherapy ensured a higher five-year survival rate than preoperative radiotherapy, but the cervical volume was greater and primary invasion was more frequent in these cases. Postoperative radiotherapy of 15 grays after preoperative radiotherapy did not appear to modify the survival and therefore appears to be useless.

[Contralateral breast cancer: metastasis or second primary cancer?]. / Cancer controlatéral du sein: métastase ou second cancer primitif?

Metachronous contralateral breast cancer (CBC) is defined as a tumour in the opposite breast which was diagnosed more than 6 months following the detection of the first cancer. We screened, for factors that might predict the risk of developing CBC, a cohort series of 4748 women who had invasive unilateral breast cancer, clinical stage I-IIIa and had been treated at Institut Curie (Paris) between 1981 and 1987. Two hundred and eighty two CBC had been diagnosed with a median follow-up of 80 months. The cumulative rate of CBC was 4.1% at 5 years. We studied relationships between CBC and family history of breast cancer, age at diagnosis of first cancer, menopausal status, tumour size, node involvement, histological type, Scarff Bloom Richardson grade, estrogen and progesterone receptor measurements, as well as the type of primary treatment. Due to competing risks between the occurrence of CBC, local recurrence and metastasis, several options for multivariate analysis were considered. In model I, we focused on the occurrence of CBC, and ignored others events. In model II, only CBC, if first site of failure was taken into account, and in model III we considered others events as time-dependant covariates. Whichever the model we chose, age less than 55 years (RR = 1.40) as well as the presence of lobular type carcinoma (RR = 1.50), were associated with an increased risk of developing a tumour in the contralateral breast. In contrast, the risk of CBC was significantly decreased by adjuvant chemotherapy (RR = 0.54). Neither tumor stage or lymph node involvement influence the risk of CBC. These results suggested that CBC is a second primary breast cancer.

[CSF-1 (colony stimulating factors 1) and CSF-1 receptor. General review and expression in invasive breast tumors]. / CSF-1 (colony stimulating factor 1) et récepteur du CSF-1. Revue générale et expression dans les tumeurs mammaires invasives.

CSF-1 (colony stimulating factor-1), initially considered to be a monocyte specific growth and differentiation factor [4], has recently been shown to be produced in human endometrium [16], placenta [7], as well as in numerous solid tumors [19-23, 26, 27]. The CSF-1 receptor (a protein product of c-fms) [24] is a member of the tyrosine kinase receptor family and an autocrine or paracrine mechanism of activation has been suggested. Overactivation of this receptor can lead to a malignant phenotype in various cell systems [20, 21]. We review the biology of CSF-1 and fms expression in normal as well as in malignant tissues with particular reference to a potential role for CSF-1 in breast tumour invasion.