[Long-term results of exclusive radiotherapy and brachytherapy of breast cancer]. / Cancer du sein traité exclusivement par l'association d'une irradiation externe et d'une curiethérapie exclusive: résultats à long terme.

PURPOSE: To report retrospective long-term results of historical experience of breast radiotherapy (RT) including external beam radiotherapy (EBRT) followed by low dose rate (LDR) brachytherapy. PATIENTS AND METHODS: Between 1971 and 1983, at our service 474 breast cancer patients underwent exclusive conserving radiotherapy treatment. The RT included an initial external irradiation followed by interstitial LDR brachytherapy (37Gy) to the residual tumour. The local regional nodes received 47.5Gy followed by a 15Gy boost delivered to the mammary nodes internal (IMN) and 25Gy axilla. RESULTS: Median follow-up was 139months (8-342). There were 40 T1, 356 T2, and 78 T3. Local recurrences (LR) were observed in 20% of cases. The rate of recurrences free at 5, 10, 15 and 20years were 86%, 77%, 73% and 67% respectively. At 5, 10, 15 and 20-year, the disease-free survival rates were 63%, 42%, 32% and 24%. Overall survival rates at 5, 10, 15 and 20-years were 75%, 53%, 34% and 25% respectively. CONCLUSION: Although the historical retrospective character of these series, it is interesting to have this experience and to analyse it according to our new knowledge and advances. The described technique was a standard for many years and could be still used in some cases.

Combination of vinorelbine, epirubicin, and cyclophosphamide as neoadjuvant chemotherapy for locally advanced breast cancer: phase II study.

Achievement of a pathologic complete response after primary chemotherapy in breast cancer can predict long-term outcome. We have investigated a combination of epirubicin, cyclophosphamide, and vinorelbine as neoadjuvant chemotherapy in locally advanced breast cancer (LABC). From January 1997 to May 1999, 30 chemonaive patients were treated (T2 or T3 histologically proven invasive breast carcinoma). Treatment was vinorelbine 25 mg/m2 day 1 and day 3, epirubicin 30 mg/m2/d, days 1 to 3, cyclophosphamide 350 mg/m2/d, days 1 to 3, every 14 days for 4 courses. Twenty-nine patients were evaluable. Median age: 48 years (range: 28-66 years); 26 had ductal invasive carcinoma and 4 lobular invasive carcinoma; median tumor size: 7 cm; median number of induction cycles: four. Clinical objective response was seen in 24 patients (relative risk: 86%), 14 complete responses, 10 partial responses, four stable disease (no significant changes). Twenty-nine patients had surgical treatment. Pathologic response rate was complete response in 32% (no residual tumor), in situ carcinoma: 11%, invasive or unchanged tumor remaining: 57%. Ninety-eight cycles were administered; major toxicities were hematologic: grade IV Hb in 5% and grade IV neutropenia in 60% of cycles. Ten patients required hospitalization for febrile neutropenia. Other toxicities were mild to moderate. The vinorelbine/epirubicin/cyclophosphamide regimen resulted in a high pathologic complete response rate in LABC with a good tolerance profile, and warrants further evaluation.

Long-term results of neoadjuvant radiation therapy for breast cancer.

Our aim was to determine the long-term outcome and the possible role of neoadjuvant (preoperative) radiation therapy for breast cancers unsuitable for primary conservative surgery. From 1977 to 1992, 75 unifocal non-inflammatory and non-metastatic T2 and T3 breast cancers were treated in our department. All these patients underwent initial radiotherapy, followed by secondary limited surgery. A population of 74 patients, aged from 32 to 82 years (median 56 years), presenting 49 T2 and 26 T3 tumors, was studied. Seventy-two patients (96%) underwent secondary tumorectomy and three patients (4%) reduction mammaplasty. The secondary tumorectomy was followed by a postoperative boost. There were nine recurrences, treated by mastectomy in eight cases and by tumorectomy in one case. Twenty-five patients showed secondary dissemination. Forty-seven patients are still alive and free of disease. The cosmetic results were considered excellent or satisfactory in 71 cases. Under good conditions, preoperative radiotherapy (as well as preoperative chemotherapy) allows the possibility of conservative surgery for cancers of more than 3 cm. The choice between the two modalities depends on the patient's condition and on a precise analysis of all prognostic factors that would justify the need for systemic treatment.

First-line high-dose sequential chemotherapy with rG-CSF and repeated blood stem cell transplantation in untreated inflammatory breast cancer: toxicity and response (PEGASE 02 trial).

Despite the generalization of induction chemotherapy and a better outcome for chemosensitive diseases, the prognosis of inflammatory breast cancer (IBC) is still poor. In this work, we evaluate response and toxicity of high-dose sequential chemotherapy with repeated blood stem cell (BSC) transplantation administered as initial treatment in 100 women with non-metastatic IBC. Ninety-five patients (five patients were evaluated as non-eligible) of median age 46 years (range 26-56) received four cycles of chemotherapy associating: cyclophosphamide (C) 6 g m(-2) - doxorubicin (D) 75 mg m(-2) cycle 1, C: 3 g m(-2) - D: 75 mg m(-2) cycle 2, C: 3 g m(-2) - D: 75 mg m(-2) - 5 FU 2500 mg m(-2) cycle 3 and 4. BSC were collected after cycle 1 or 2 and reinfused after cycle 3 and 4. rG-CSF was administered after the four cycles. Mastectomy and radiotherapy were planned after chemotherapy completion. Pathological response was considered as the first end point of this trial. A total of 366 cycles of chemotherapy were administered. Eighty-seven patients completed the four cycles and relative dose intensity was respectively 0.97 (range 0.4-1.04) and 0.96 (range 0.25-1.05) for C and D. Main toxicity was haematological with febrile neutropenia ranging from 26% to 51% of cycles; one death occurred during aplasia. Clinical response rate was 90% +/- 6%. Eighty-six patients underwent mastectomy in a median of 3.5 months (range 3-9) after the first cycle of chemotherapy; pathological complete response rate in breast was 32% +/- 10%. All patients were eligible to receive additional radiotherapy. High-dose chemotherapy with repeated BSC transplantation is feasible with acceptable toxicity in IBC. Pathological response rate is encouraging but has to be confirmed by final outcome.

Metastasis of a breast carcinoma in a mature teratoma of the ovary.

Metastatic tumors in ovaries from breast carcinoma are well known. Breast carcinoma metastases in primary ovarian tumors are much more uncommon. The authors present a case of a primary breast carcinoma, with a lobular component (signet ring cells), which metastasized into a mature cystic teratoma of the ovary. The problem of differential diagnosis with other primary ovarian tumors or metastatic tumors and the problem of particular behavior of metastatic lobular components are discussed.

Stewart-Treves syndrome after treatment for breast cancer.

This study reviews 3 cases of angiosarcoma of the upper extremity after mastectomy and radiotherapy for breast cancer (Stewart-Treves syndrome). Angiosarcoma was diagnosed an average 14 years (from 6.5 to 26 years) after treatment for breast cancer. Presenting signs included a red raised lesion, a palpable mass, a blister appearance (in one case). Two of our three patients underwent surgical treatment: one patient underwent local excision followed by chemotherapy, and the other patient wide excision, followed by external beam radiotherapy. Local recurrence occurred in one of these two patients and was followed by the development of lung metastases. The second patient who had treatment is free of disease without problems. The third patient refused any treatment and died 5 months later. The purpose of this article is to add to the literature 3 new cases of Stewart-Treves syndrome and to discuss some specific problems of this rare tumour.

[Radiation-induced sarcoma after breast cancer. Apropos of 8 cases and review of the literature]. / Sarcomes radio-induits après cancer du sein. A propos de huit cas et revue de la littérature.

PURPOSE: Retrospective analysis of eight new cases of radiation-induced sarcomas following radiotherapy for breast carcinoma and literature review. PATIENTS AND METHODS: Eleven patients presenting with radiation-induced sarcoma after radiotherapy for breast cancer have been treated between 1983 and 1997 at Henri Mondor University Hospital (France). Eight of these patients respected the criteria established by Cahan et al. The others had Stewart-Treves Syndrome and were thus excluded from the analysis. Only one of the eight patients had received chemotherapy. All of the patients at the time of diagnosis of radiation-induced sarcoma were free of breast cancer recurrence. Radiation-induced sarcoma appeared with a latency period of 5 to 18 years (mean: 10.3 years). Patients' ages ranged from 39 to 88 years (mean: 57.6 years) at the time of diagnosis of sarcoma. Three sarcomas occurred in the treated breast, two in the chest wall, one in the preclavicular area and two in the axillary region. There were two angiosarcomas, three fibrosarcomas, one osteosarcoma, one malignant fibrous histiocytoma (MFH), and one undifferentiated sarcoma. All patients have received treatment for their sarcoma: all of them underwent surgery, one patient combined radiotherapy and chemotherapy, and three patients chemotherapy. RESULTS: Two patients were alive and free from disease. Six patients died (5-34 months); all six had local and/or metastatic recurrence. CONCLUSIONS: Radiotherapy can induce malignancies after a latent period of several years. Radiation-induced sarcomas are associated with poor overall prognosis. The treatment in most of the cases is late and ineffective, therefore careful follow-up is needed. There are still many uncertainties and questions about radiation-induced sarcomas.

Intrauterine device--associated pelvic actinomycosis: a rare disease mimicking advanced ovarian cancer: a case report.

A case report of intrauterine device (IUD)-associated tubo-ovarian actinomycosis is presented. The patient was a 37-year-old nulliparous woman with IUD usage for the last four years. She presented anemia and weight lost of 8 kg. Ultrasound and computed tomography showed an unilateral large mass in the right adnexum adherent to the uterus and compressing the urinary bladder. Preoperative diagnosis of ovarian cancer with liver metastases was made. Bilateral salpingoophorectomy and total abdominal hysterectomy were performed. After pathological and biological analyses, actinomycosis was diagnosed and the patient was treated postoperatively with penicillin. The purpose of this article is to add to the literature a new case of this rare disease which clinically mimics ovarian cancer.

Management of breast cancer in the elderly.

The management of breast cancer in elderly women was analysed by a retrospective study of 150 women over 70 years old referred to our department between 1984 and 1988. 80 were T1-T2, 33 were T3 and 34 were T4. 107 were N0 and 43 were N1-N2. 16 women (11%) were in poor health, preventing conventional treatment. Treatment choice varied with age: 60% of the women aged 70-79 (group 1) and 23% of the oldest women (group 2) were treated conventionally. The use of surgery decreased with age and surgical procedures were conventional in only 85% of the group 1 women and in 56% of the group 2 women. Definitive radiation therapy was used more frequently in the oldest women, as was primary hormone therapy. Quality of follow-up also varied with age. Five-year survival rates were still high in both groups while relapses were frequent. Breast cancer was consequently a frequent cause of death. The increase in the proportion of elderly people with breast cancers over the next few years will require validated guidelines. Specific protocols and specific rules of management must be drawn up.

Comparison of the selective aromatase inhibitor formestane with tamoxifen as first-line hormonal therapy in postmenopausal women with advanced breast cancer.

A total of 409 postmenopausal patients with advanced metastatic breast cancer were randomized to receive either formestane (Lentaron) 250 mg every 2 weeks by intramuscular injection, or tamoxifen 30 mg/day orally. Treatment continued until tumor progression. The groups were well matched for pretreatment characteristics including age, performance status, hormone receptor status (patients with known negative receptor status of their primary tumor were excluded), site and extent of metastases, disease-free interval, and previous primary and adjuvant therapy. Patients were assessed for antitumor efficacy at 3-monthly intervals using UICC criteria. Of the 348 patients evaluable for response, 33% had an objective response to formestane (14 complete and 43 partial responses), while 37% had an objective response to tamoxifen (10 complete and 54 partial responses). Median duration of response was 15 months for formestane and 20 months for tamoxifen; survival was 35 and 38 months respectively. There were no statistically significant differences between the treatments for all these variables, but time to disease progression and time to treatment failure significantly favoured tamoxifen. Systemic tolerability was excellent for both treatments. Local side effects due to intramuscular injection of formestane were mild and transient. In this comparative trial of first-line therapy for advanced breast cancer, formestane gave results comparable to tamoxifen for both efficacy and tolerability. We conclude that formestane is an effective and well tolerated addition to the therapeutic options available for the treatment of postmenopausal women with advanced breast cancer.

Induction chemotherapy in head and neck cancer: results of a phase III trial.

Between December 1982 and October 1986, 131 patients with stage II-III-IV squamous cell carcinoma of the oropharynx or oral cavity were randomized to induction chemotherapy, consisting of bleomycin (10 mg/m2/day in continuous infusion from day 1 to day 5), methotrexate (120 mg/m2 on day 2) followed by folinic acid, 5-fluorouracil (5 FU) (600 mg/m2 on day 2), and cisplatin (120 mg/m2 on day 4) every 4 weeks for a total of three cycles followed by definitive locoregional treatment versus locoregional treatment alone. The modalities of definitive treatment (radiotherapy +/- surgery) were chosen prior to randomization. A total of 116 patients were evaluable. Of 55 patients in the chemotherapy arm, four (7%) had a complete response (CR) and 23 (42%) a partial response (PR) following the induction regimen. At the completion of locoregional treatment, 76% (42 of 55) of patients in the experimental group were in CR compared to 89% (54 of 61) in the control group. There was no difference in survival, cause-specific survival, and pattern of relapse between both groups. The median survival was 22 months in the chemotherapy group and 29 months in the control group. Responders to chemotherapy did not fare better than nonresponders. Chemotherapy-related toxicities were few and most of them related to cisplatin which was reduced to 100 mg/m2 for 35 patients. There were no treatment-related deaths and, in the experimental arm of the trial, no increased morbidity from locoregional treatment. This induction regimen does not offer any advantages over standard treatment.

New cell lines of human breast cancer origin.

Established human mammary tumor cell lines constitute an important tool in the study of breast cancer. The aim of this work was to isolate and characterize two new mammary tumor cell lines, JCK and GCS, which were obtained from the pleural effusion and ascitic fluid, respectively, from two breast cancer patients. Both cell lines had some properties of transformed cells, namely immortalization and growth in soft agar. The carcinoma cells presented epithelial morphology shown by light and electron microscopy, and antigenic properties shown by different tumor markers such as a cytokeratin cocktail, carcinoembryonic antigen, epithelial membrane antigen, and human milk fat globule membrane antigen. A significant increase was also found (P greater than 0.05) in cell growth and 3H-thymidine incorporation into DNA in the JCK and GCS cell lines in the presence of 17 beta estradiol at concentrations of 10(-9) and 10(-7) M, respectively, after 5 days in culture. These cells presented estradiol receptor levels which were similar in the biopsies and the resulting cell lines. The aromatase activity was also similar in the JCK cell line and the original patient biopsy. However, there was a considerably higher aromatase activity in the GCS cell line than in the biopsy specimen. Southern hybridizations with the neu oncogene showed an additional 12 kb fragment in both cell lines, as also seen in patients with breast cancer. We conclude from these studies that this in vitro system may provide us with a way to study metastatic cells and improve clinical management of breast cancer patients.

External irradiation prior to conservative surgery for breast cancer treatment.

From 1981 to 1987, 138 patients with breast cancer unsuitable for primary tumorectomy received initial external radiotherapy (45 Gy/25f/35d) in order to reduce the tumor volume so that secondary limited surgery could be performed. There were 81 T2 and 57 T3. Fifty-seven percent of the patients had a tumor larger than 4.5 cm. After completion of the radiotherapy, 22 patients (16%) showed no more evidence of a tumor either clinically or radiologically and received a boost of 25 Gy. In 52 cases (38%) the tumor regression allowed for secondary tumorectomy followed by a boost of 20 Gy. Sixty-four patients (46%) showed either little or no tumor regression: radical surgery was performed in 14 cases (10%) and high dose boost curietherapy (37 Gy) in the 50 (36%) remaining patients who refused mastectomy. Breast conservation in good condition was thus obtained in 74 patients (54%). Sufficient tumor regression to allow secondary tumorectomy was more often observed in T2 than in T3, in poorly differentiated tumors or mucinous type, and in tumor with well defined mammographic aspects. Actuarial 5-year local control and disease-free survival rates after limited surgery were, respectively, 90% and 73%. No particular complications were observed after secondary tumorectomy. This therapeutic approach is encouraging in patients with large T2 and T3 breast tumors, but a longer follow-up is required to assess definitive conclusions.

[Effectiveness of hemodialysis in a case of acute methotrexate poisoning]. / Efficacité de l'hémodialyse dans un cas d'intoxication aiguë par le méthotrexate.

In a case of acute intoxication with high-dose methotrexate, a kinetic study of plasma methotrexate concentrations enabled the authors to begin treatment with high-permeability membrane haemodialysis combined with intensive folic acid loading before the clinical signs of iatrogenic toxicities developed, and to continue with haemodialysis rather than using other depurative methods. In this case, the post-depuration course was favourable: dermatological signs and febrile pancytopenia regressed within 4 days, and these was no sign of hepatic toxicity.

[Can tumors of the breast larger than 3 centimeters be treated conservatively?]. / Peut-on être conservateur pour les tumeurs du sein supérieures à 3 centimètres?

Unlike small breast cancers, which are now treated conservatively by primary tumorectomy, the most important lesions (T2 and T3) as usually treated tumorectomy, the most important lesions (T2 and T3) as usually treated by mastectomy. However, in patients with these large lesions attempts may be made at conserving the breast with reliable oncological safety and good cosmetic results. Depending on clinical presentation, one or the other of two therapeutic approaches may be considered. The most common treatment is preoperative radiotherapy of 45 Gy which, in more than 50 p. 100 of the cases results in a tumoral regression that is sufficient for secondary tumorectomy to be performed. In some patients, the first-line treatment consists of wide tumoral excision as part of a reductive mammaplasty, followed by radiation.

[Arterial stenosis after radiotherapy]. / Les sténoses artérielles après radiothérapie.

Published reports of arterial stenosis following radiotherapy are reviewed. In oncological practice, this complication is rare but experimental studies have demonstrated the role of irradiation in producing arterial lesions. The histological specificity and the mechanisms of radiation and related arterial lesions are discussed. Atherosclerosis risk factors and chemotherapy could have a synergic role on artery stenosis. Cases reported of arterial stenosis after radiotherapy include subclavicular artery after breast cancer, carotid artery after head and neck cancer, coronary artery and abdominal aorta or its trunks after pelvic and abdominal irradiation. The radiotherapy parameters described are not unusual. Therapeutical modalities and their indications are presented.