Comparative value of tumour grade, hormonal receptors, Ki-67, HER-2 and topoisomerase II alpha status as predictive markers in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy.

The aim of this study was to evaluate the predictive value of five different biological factors in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy: (1) tumour grade scored according to the Elston-Ellis classification, (2) hormonal receptor (HR) status; (3) tumour cell proliferation evaluated by Ki-67 staining, (4) HER-2 and topoisomerase II alpha (TopoIIalpha) expression evaluated by immunohistochemistry (IHC), (5) HER-2 and TopoIIalpha amplification evaluated by real-time polymerase chain reaction (PCR). 119 patients with operable breast cancer were treated with six cycles of FEC (100 5-fluorouracil (5-FU) 500 mg/m2, Epirubicin 100 mg/m2, Cyclophosphamide 500 mg/m2). Tumour response was assessed clinically and by computed tomography (CT) scan, then by pathological assessment. The clinical overall response (OR) was 80%, with 19% of complete responders (CR). The radiological OR was 71%, with 16% of CR. A pathological CR was demonstrated in 13% of the patients according to the Sataloff classification. In the multivariate analysis, the absence of HR expression and Ki-67 > or = 20% were predictive for a clinical CR. A high tumour grade was predictive for a pathological CR. Overexpression or amplification of HER2 or Topollcalpha were not predictive of response.

Systematic esophageal endoscopy screening in patients previously treated for head and neck squamous-cell carcinoma.

BACKGROUND: An attempt was made to improve metachronous oesophageal cancer prognosis through bi-annual systematic esophageal endoscopy screening in patients treated for head and neck cancer. PATIENTS AND METHODS: Bi-annual esophageal endoscopy, without a staining procedure, was performed in 1560 patients from 1987 to 1997. The distribution of previous head and neck cancer was oral cavity (20%), oropharynx (30%), hypopharynx (34%), and larynx (16%). All patients had initial panendoscopic inspection before HNSCC treatment. Esophageal tumors were considered to be second synchronous primaries when discovered within the first six months of initial tumor diagnosis. RESULTS: Fifty metachronous esophageal asymptomatic cancers (42 T1 and 7 in situ carcinomas) were diagnosed by endoscopy. The median time between the HNC and the esophageal carcinoma was 43 months (7-137 months). Metachronous esophageal carcinoma was discovered in 2.6% of patients with oral cavity tumor, 5.7% of patients with oropharynx tumor, 2.3% of patients with hypopharynx tumor, and 1.7% of patients with larynx tumor. Causes of death were: 41.1% related to esophageal tumor with tumor progression, metastatic evolution, or treatment toxicity; 28.9% related to non malignant causes; 26.6% related to a cancer that was not of esophageal origin. CONCLUSIONS: Over a 10-year period, systematic bi-annual esophageal endoscopy uncovered metachronous esophageal tumors in 3.2% of 1560 patients originally treated for head and neck carcinoma, developing in a median time of 47 months. Patients with initial oropharyngeal tumors had a significantly higher risk of metachronous esophageal SCC, compared to the other tumor sites (P < 0.02 with Fisher exact test). Given the elevated death rate not related to the esophageal cancer and the median survival of 16 months, any potential benefit from this time-consuming procedure is debatable.

Chemotherapy response of breast cancer depends on HER-2 status and anthracycline dose intensity in the neoadjuvant setting.

We evaluated the predictive value of a tumor's HER-2 status for chemotherapy response in the neoadjuvant setting and the effect of anthracycline dose intensity on this predictive value. HER-2 status was evaluated by immunochemistry on microbiopsy before neoadjuvant chemotherapy (monoclonal antibody CB-11; Novocastra) in 39 patients (group A) treated with FEC50 (500 mg/m(2) 5-fluorouracil, 50 mg/m(2) epirubicin, and 500 mg/m(2) cyclophosphamide) and 40 patients (group B) treated with FEC100 (500 mg/m(2) 5-fluorouracil, 100 mg/m(2) epirubicin, and 500 mg/m(2) cyclophosphamide). All tumors were stage II or noninflammatory stage III adenocarcinoma. Overall response rate (OR) was evaluated through ultrasound and mammographic measurements. Pathological complete response was evaluated by tumor excision and axillary node resection after six cycles of chemotherapy. Patient and tumor characteristics (age, tumor size, clinical nodal status, SBR grade, hormonal receptor status, and HER-2 expression) were similar in the two groups. In univariate analyses, anthracycline dose was the only factor predictive of response (OR = 61.5% with FEC50; OR = 82.5% with FEC100; P = 0.038). When anthracycline dose was correlated with HER-2 status, an OR of 73.9% was demonstrated in HER-2- tumors (tumors without HER-2 overexpression), and an OR of 12.5% was demonstrated in HER-2+ tumors (tumors with HER-2 with overexpression) in group A. In group B, an OR of 69.5% was demonstrated in HER-2- tumors, and an OR of 100% was demonstrated in HER-2+ tumors. There was no difference in OR for HER-2- tumors treated with FEC50 or FEC100 (P = 0.74). On the other hand, erbB-2+ tumors treated with FEC100 had a significantly better OR than HER-2+ tumors treated with FEC50 (P = 0.0003). In a multivariate analysis, the most powerful predictive factor of OR was a conditional variable associating anthracycline dose with HER-2 status. Low-dose anthracycline and HER-2+ predicted a poor OR, low- or high-dose anthracycline and HER-2- predicted an intermediate OR, and high-dose anthracycline and HER-2+ predicted a high OR. Our results merit additional studies, given the possibility for choosing anthracycline dose according to a tumor's HER-2 status.

Prospective randomised study of split-course radiotherapy versus cisplatin plus split-course radiotherapy in inoperable squamous cell carcinoma of the oesophagus.

Between 1983 and 1989, 211 patients with inoperable squamous cell carcinoma of the oesophagus were randomised in a study comparing split-course irradiation (two courses of 20 Gy in five fractions of 4 Gy, separated by a rest of 2 weeks) (arm A) and the same split-course irradiation in combination with cisplatin (CDDP) (3-4 days before each of the two courses of radiotherapy, repeated every 3-4 weeks, for a total of six cycles) (arm B). The Cox's regression model with retrospective stratification was used to compare the two arms to correct for the imbalance at randomisation of the T classification. The median overall survival was 7.9 (95% confidence interval (CI) 7.3-9.4) months in arm A and 9.6 (95% CI 8-13.5) months in arm B. The difference in overall survival was only borderline significant (P=0.048) with a reduction of the instantaneous rate of death of 24%. The 1 and 2 year overall survival rate were respectively 29% (95% CI 21-37%) and 15% (95% CI 8-22%) in arm A and 45% (95% CI 36-54%) and 20% (95% CI 13-27%) in arm B; thereafter, the survival curves became similar. The median progression free survival (PFS) was 5.0 (95% CI 4.6-5.7) versus 6.9 (95% CI 5.3-8.7) months (P=0.028) and the median time to local progression was 6.2 (95% CI 5.1-7.6) months versus 10.9 (95% CI 8.1-15.5) months (P=0.018), respectively, in arms A and B. Haematological toxicities were slightly more commonly observed in the combined group (1% versus 6%). This study shows that split-course irradiation in combination with CDDP is very well tolerated and should be preferred to radiotherapy alone.

[Germ-line mutations of the BRCA1 gene in northeastern France]. / Mutations germinales du gène BRCA1 dans le Nord-Est de la France.

Thirty-seven breast/ovarian or breast-only cancer families selected on a regional basis have been analyzed for mutations at BRCA1. By combining direct sequence analysis and protein truncation test, mutations were detected in 14 families (38%). We found seven different mutations, two of which have not been described before. Mutations at BRCA1 were present in 60% of breast/ovarian and 32% of breast-only cancer families. Mutations were frequent in families with at least one breast cancer case before age 40 (44%) and/or one bilateral breast cancer case (54%). Two mutations, namely 3600del11 and G1710X, are frequent in the population native from northeastern France. Oriented BRCA1 analysis should facilitate carrier detection in breast and/or ovarian cancer families stemming from this French area.

Uterine metastases from primary breast-cancer - report of 2 cases.

The authors report on 2 cases of uterine dissemination from primary breast carcinoma. Special emphasis is made on this atypical site of metastases and on the necessity of a gynecological work-up in patients previously treated for breast cancer.

Progress in the assessment of lymphatic spread in rectal cancer. Rectal endoscopic lymphoscintigraphy.

Rectal endoscopic lymphoscintigraphy was performed in 10 control subjects and in a series of 85 patients with adenocarcinoma of the rectum as a prospective study to evaluate lymphatic drainage of the rectum and lymphatic spread in rectal cancer. Complete cranial drainage was demonstrated in all control subjects, and internal iliac nodes were also visible in 50 percent of cases. Results were correlated with histologic node examination in all patients operated upon for rectal cancer. Rectal endoscopic lymphoscintigraphy was assessed for sensitivity (85 percent), specificity (68 percent), overall accuracy (76 percent), positive predictive value (71 percent), and negative predictive value (83 percent). False-negative and false-positive results are discussed. Rectal endoscopic lymphoscintigraphy represents the only method currently available for evaluation of lymphatic spread in rectal cancer.

[Progress in the evaluation of lymphatic involvement in cancer of the rectum: endoscopic rectal lymphoscintigraphy]. / Un passo avanti nella valutazione dell'estensione linfonodale del cancro del retto: la linfoscintigrafia rettale endoscopica.

The preoperative evaluation of lymphatic spread in rectal cancer constitutes a considerable problem. A prospective study including 45 patients operated for rectal cancer, was carried out in order to assess the diagnostic value of a new technique: endoscopic rectal lymphoscintigraphy. The results of the preoperative assessment were compared with histological data according to Dukes' classification (Dukes A/B: 22 cases, Dukes C: 23 cases). Analysis of these results revealed the sensitivity (80%), specificity (73%) and accuracy (80%) of this new technique. If, combined with endorectal ultrasonography, rectal lymphoscintigraphy might play highly significant role in identifying the indications for local excisions of small tumours; similarly, the effect of preoperative radiotherapy might be more thoroughly assessed.

Randomized phase II study of a combination of cisplatin (DDP), 5-fluorouracil (5-FU), and allopurinol (HPP) versus 5-FU in advanced colorectal carcinoma. An EORTC Gastrointestinal Tract Cancer Cooperative Group study.

In order to improve the therapeutic index of fluorouracil (5-FU), it has been combined with cisplatin (DDP) as synergistic agent and with allopurinol (HPP) as toxicity modulator. Patients with measurable colorectal carcinoma, previously untreated by chemotherapy, were randomized to receive either 5-FU alone 500 mg/m2 push iv days 1-5 or HPP 3 x 300 mg po, days 1-5, 5-FU 800 mg/m2 push iv, days 3-5 and DDP 50 mg/m2 d6. Treatment was repeated every 4 weeks. Of 104 patients randomized, 82 were evaluable for response and survival. Six partial responses were seen in each treatment group (15%) and the median survival time was 7 months. Hematologic toxicities were comparable in both treatment groups, with a mean nadir white blood cell count of 3500/ vs. 3800/mm3 and a mean nadir platelet count of 148,000/ vs, 203,000/mm3 for HPP-5-FU-DDP and 5-FU, respectively. This study suggests that the addition of both HPP and DDP does not improve the activity of 5-FU.

[Gastric metastases of cancer of the breast. Apropos of a case. Review of the literature]. / Les métastases gastriques des cancers du sein. A propos d'un cas. Revue de la littérature.

Since they are rare and often latent, gastric metastases from breast cancer, principally lobular, are difficult to diagnose particularly at the isolated stage. The primitive and non specific nature of their symptomatology and the negativity of endoscopic biopsies should lead to early explorative laparotomy. Surgery is often palliative to reduce tumor load and seldom involves complete excision, and can only hope to obtain prolonged survival if followed by chemotherapy, hormone therapy or indeed radiotherapy. Following a recent personal case a review of the worldwide literature was carried out and the principal pathogenic hypotheses were analysed.

[Progress in evaluating lymphatic spread in cancer of rectum: endoscopic rectal lymphoscintigraphy]. / Un progrès dans l'évaluation de l'extension ganglionnaire des cancers du rectum: la lymphoscintigraphie rectale endoscopique.

The preoperative evaluation of lymphatic spread in rectal cancer constitutes a problem of difficult solution. A prospective study including 45 patients operated for rectal cancer, has been carried out in order to evaluate the diagnostic value of a new technique: The endoscopic rectal lymphoscintigraphy. The results of preoperative assessment were compared with histological date according to Dukes' classification (Dukes A/B: 22 cases, Dukes C: 23 cases). Analysis of these results allowed to accurate sensitivity (80%), specificity (73%) and accuracy (80%) of this new technique. Combined to endorectal ultrasonography, rectal lymphoscintigraphy might play an overwhelming role in characterising the indications for local excisions of small tumors; similarly, the effect of preoperative radiotherapy might be further evaluated.

Palliative therapy of inoperable oesophageal carcinoma with radiotherapy and methotrexate: final results of a controlled clinical trial.

Between May 1976 and January 1982, 170 patients were entered in a randomized study comparing a combined treatment consisting of methotrexate followed by irradiation versus radiotherapy alone in patients with non metastatic inoperable oesophageal cancer. Methotrexate was administered subcutaneously in 4 days to a total dose of 24 mg/m2. Radiotherapy was performed, in both groups, at a dose of 56.25 Gy in 25 fractions (5 weeks). The administration of methotrexate did not lead to an increased intolerance to radiotherapy but severe hematological toxicities were observed in 7.8% of the cases. No difference in the duration of survival was detected. Initial performance status of the patients and their weight loss prior to entry on trial were the factors that were most predictive of the patient's prognosis.

[Secondary cardiac localizations in different cancers. Comparison of clinical, electrocardiographic and autopsy data. Apropos of 51 cases]. / Localisations cardiaques secondaires au cours de différents cancers. Confrontation des données cliniques, électrocardiographiques et nécropsiques. A propos de 51 cas.

The authors have investigated 910 post-mortem examinations of different primary cancers. Fifty-one cases (5.6% of the autopsies) presented cancer lesions of the heart. They have found the accuracy of clinical and paraclinical diagnostics by comparing them with autopsy findings in case of pericardial lesions, but very rarely in case of myocardial location.

[Immunologic tests in the prognosis of solid malignant tumors]. / Apport des tests immunologiques pour l'établissement du pronostic des tumeurs malignes solides.

Survival at 6, 12 and 24 months was studied in relation to the immunological findings before treatment and its variations after treatment in 600 patient and its variations after treatment in 600 patients with solid malignant tumours. Any change in any of these tests is a sign of poor prognosis proportional to the degree of this change. The most precise prognosis is given by an association of these tests. These two year survival rate for tumours without apparent spread was 87% if the tests were normal, 43% if one group of tests was disturbed and 11% if two groups of tests were abnormal. With local or regional spread, the survival was 52% in cases with normal tests, 12% if one group was disturbed, and 4% if both groups of tests were abnormal. With multiple metastases, the survival rates were respectively 24%, 4% and 0%. Thus the prognosis is less unfavourable for a tumour with general spread and normal immunological tests (24%) than for a localised tumour with a disturbance of two groups of immunological tests (11%). These immunological tests carried out before any treatment are thus very valuable in prognosis, independant of the apparent extension of the tumour. This indications are important in deciding on treatment.