Adjuvant tamoxifen in postmenopausal breast cancer: preliminary results of a randomized trial.

Between May 1978 and March 1982, 179 postmenopausal women with operable breast cancer were randomized to receive either adjuvant tamoxifen, 40 mg daily for three years (TAM group), or no further treatment (controls). The difference in five-year survival rates (61% in the control group, 72% in the TAM group) was not statistically significant. However, there was a significant improvement in disease-free survival in the TAM group (61%) relative to the controls (44%) (p = 0.008). In estrogen receptor positive patients, tamoxifen improved both the disease-free rate (47% controls, 80% with tamoxifen) and the survival rate (63% to 83%). Similar results were observed in progesterone receptor positive patients. In patients that were estrogen receptor negative, tamoxifen modified neither the survival rate nor the disease-free interval.

[Renal toxicity of 9-hydroxy-2-methyl-ellipticinium]. / Toxicité rénale du 9-hydroxy-2-méthylellipticinium.

9-hydroxy-2-methyl-ellipticinium (HME) is an intercaling agent mainly potent in metastatic breast cancer. Its almost complete lack of bone marrow toxicity is of greatest value. However, among 385 patients 20 cases of renal failure were observed: renal failure is gradual, non reversible except in four cases with acute renal failure. Histological and ultrastructural studies, performed in 8 cases, showed exclusively proximal tubular lesions, without glomerular or interstitial lesions. We have evidence that there is a relation between the cumulative dose and the severity of the lesions. A prospective study was done in 30 patients. An increase in enzymuria, proteinuria and glycosuria was observed in most patients after HME infusion. HME is an efficient drug in the treatment of bone metastases of breast cancer. Renal function should be carefully monitored during HME administration.

[Reliability of cytologic puncture. Who should perform the puncture of breast tumors?]. / Fiabilité de la ponction cytologique. Qui doit ponctionner les tumeurs du sein?

In a period of 18 months, 187 cytology aspiration biopsies of the breast were performed at the Centre François Baclesse by clinicians and radiologists, using the conventional technique. Comparison of the results with clinical, radiological and histological findings by different specialists showed that one out of two aspiration biopsies gave an erroneous diagnosis. The authors believe that this failure was due to the fact that the biopsies were not performed by a cytologist. This prime condition of success should be more clearly expressed in the literature.

Hydroxy-9-methyl-2-ellipticinium for osseous metastases from breast cancer: a 5-year experience.

A group of 135 patients with osseous metastases from breast cancer were treated with hydroxy-9-methyl-2-ellipticinium (100 mg/m2 weekly). Although it was impossible to grade the response precisely, because only indirect criteria are available for assessing the course of bone metastases (radiographs, quantified 99mTc pyrophosphate scintigrams, CEA), it was considered that an objective response was obtained in 44 cases. These responses lasted from 3 to 17 months. The main characteristic of the compound is its lack of marrow toxicity, a valuable property in osseous lesions, where frequent marrow involvement makes it difficult to use conventional drugs. The major and most unpleasant side effect was an inhibition of salivary secretion, which causes other complications such as tongue mycosis, anorexia, and asthenia. Immunologic disorders were less frequent, and four patients developed severe tubular renal insufficiency.

[Hydroxy-9-methyl-2-ellipticinium (NSC 264-137) for osseous metastases from breast cancer. A 4 year experience (author's transl)]. / L'hydroxy-9-methyl-2-ellipticinium (NSC 264-137) dans le traitement des métastases osseuses du cancer du sein. Bilan d'une expérimentation de 4 années.

In 96 patients (95 women--1 man) with osseous metastases from breast cancer suitable for analysis an objective remission was obtained with hydroxy-9-methyl-2-ellipticinium (100 mg/m2 weekly) in 31 cases. These responses lasted from 3 to 17 months. The main characteristic of this compound is its lack of marrow toxicity, a property of value in osseous lesions where marrow is so frequently involved, making difficult the use of conventional chemical drugs. The principal unpleasant drawback is an inhibition of the salivary secretion which causes other side effects such as tongue mycosis, anorexia, and asthenia. Less frequently immunologic disorders and a few cases of renal insufficiency were observed.

Antitumor activity, pharmacology, and toxicity of ellipticines, ellipticinium, and 9-hydroxy derivatives: preliminary clinical trials of 2-methyl-9-hydroxy ellipticinium (NSC 264-137).

Ellipticine and some derivatives are highly cytotoxic substances which kill L1210 cells at concentrations ranging form 10(-8) to 10(-6)M. Some compounds in this series bind with high affinity to DNA (affinity constant between 10(7) M-1 and 10(5) M-1) by intercalation between base pairs. The antitumoral properties of these derivatives are thought to be related to their DNA-binding ability. Both 9-hydroxylation of ellipticine and quaternarization of 2-pyridinic nitrogen tend to increase DNA binding and antitumor activity. 2-Methyl-9-hydroxyellipticine (NSC 264-137) was selected for a phase I and later for a phase II trial in human cancer. This drug does not affect blood cell counts in animals or in man. It is not mutagenic in the Ames' test nor teratogenic in mice, but is endowed with anti-inflammatory properties and induces a marked decrease of motoricity in mice. Transient bradycardia and decrease of blood pressure are the most noticeable cardiovascular effects in dogs. This compound administered at 80-100 mg/m2/week in 1-h intravenous (IV) infusion induces objective remissions in about 25% of patients suffering from advanced breast cancer refractory to all other treatment. These remissions, which occurred after 3-4 weeks, lasted for 1-18 months. This drug seems particularly to improve the condition of patients suffering from oesteolytic breast cancer metastasis. Activity against anaplastic thyroid carcinoma and ovarian carcinoma has also been observed in some cases. Toxic side effects are nausea and vomiting (one-third of the patients), hypertension (less than 10% of the patients), muscular cramp (one-third of the patients), fatigue which can be very pronounced (in most patients after 3 months of treatment), mouth dryness, and mycosis of the tongue and esophagus (less than 20% of the patients).

[Hydroxy 9-methyl 2-ellipticinium acetate (NSC 264-137). Toxicologic study and therapeutic effect in 100 cancers (author's transl)]. / L'acétate d'hydroxy 9-méthyl 2-ellipticinium (NSC 264-137). Etude toxicologique et thérapeutique chez 100 cancéreux.

A new derivative of ellipticine, hydroxy-9-methyl-2-ellipticinium acetate, was found to be a useful anti-tumor drug in advanced cancers which could not be treated any longer successfully by any other procedure. In our series of 100 patients, the best results were obtained with bone metastases from breast carcinomas and with anaplastic thyroid carcinomas. Most patients usually received a weekly perfusion of 80 mg/m2. The main characteristic of this drug is its lack of hematologic, and hepatic toxicity. No renal trouble was observed during the first year, but 2 deaths from renal insufficiency occured during the 18th and 15th month of treatment. The most frequent side effect consists of digestive troubles (nausea, vomiting) which rarely compelled to stop the treatment (4 times in 100 patients).

Sex of first child as a prognostic factor in breast cancer.

The sex of the first child of patients who underwent mastectomy for potentially curable breast cancer appeared to be a valuable prognostic factor: patients whose first child was a boy had a better outcome than those whose first child was a girl. The difference was statistically significant. This may have been because the male/female sex ratio among first children was significantly higher in those patients without node involvement than in those with node involvement. But the favourable effect of a male first birth was still seen when only patients with an equal degree of node involvement (greater than or equal to 4 nodes) were studied. The "protection" resulting from a male first-born could be the result of fetal testicular secretions. This protection did not apply to the risk of breast cancer--the male/female sex ratio of first children in our series was 1.08, a figure not statistically different from that of the overall French population (1.05).

[Stewart-Treves syndrome. Apropos of a case with ultrastructural study]. / Syndrome de Stewart-Treves. A propos dun cas avec étude ultrastructurale.

An optical and ultrastructural study was performed on biopsy and autopsy specimens of Stewart Treves syndrome cutaneous tumours and their metatases. Various histological aspects are described: territories presenting typical vascular differentiation, spindle cell "Kaposi type" territories and undifferentiated territories. The ultrastructural study confirmed the angiomatous differentiation of these tumors and revealed a certain number of arguments in favor of blood rather than lymphatic capillary differentiation of the newly formed vessels. Upon completion of this study, it appeared possible to confirm that the Stewart Treves syndrome corresponds to an anatomo-clinical entity whose histological features are very close to those of primitive cutaneous angiosarcomas.

[Pregnancy and breast cancer: 2 entities with complex interferences. Critical study of the dossier]. / Grossesse et cancer du sein: deux entités aux interférences complexes. Etude critique du dossier

The author reviews the epidemiological, biological and clinical data concerning the association of carcinoma of the breast and pregnancy. He discusses, in particular, the therapeutic problems raised by this association. The author attracts attention to the fact that in certain circumstances, pregnancy may aggravate the disease, whilst in others, it seems to protect with regard to the cancer. As far as the therapeutic problems are concerned, he emphasizes in particular, the following conclusions: 1) in cases which require surgery, the prognosis is less poor than generally believed; 2) the total inefficacy of therapeutic abortion is now certain; 3) radiotherapy and chemotherapy should be prohibited during pregnancy; 4) a pregnancy occurring during the years following mastectomy for carcinoma, does not seem to have the unfavourable prognosis which was originally believed.

[Regression of an adenocarcinoma of the breast treated by progesteroid agents. Anatomical-clinical study]. / Régression d'un adenocarcinome du sein traité par les progestatifs. Etude anatomo-pathologique

PIP: A 61-year old woman with breast adenocarcinoma was treated with hormonotherapy for 1 year. After this treatment the tumor had regressed and a mastectomy was performed. The macroscopic and histological examinations of the tumor showed similarities between the changes observed in this case and the ones which have been described by Emerson and his colleagues following estrogenotherapy and androgenotherapy in the case of clinically hormone-dependent breast cancers.^ieng

[Age at the time of the first birth: a variable with simple, double, or triple significance in breast cancer studies]. / L'âge à la première naissance: une variable à la signification simple, double ou triple en cancérologie mammaire

I.--The inverse relationship of risk with parity is one of the earliest known features of the epidemiology of human mammary cancer. But recently knowledge of this relationship was refined when Mac Mahon and his colleagues found that the protective effect is actually correlated to the age of the mother at the first birth rather than to the total number of children, so that a woman who has a child before the age of 18 is one third as likely to suffer breast cancer in later life as a woman first delivered at 35. II.--A study was undertaken in the Centre Francois Baclesse on the hypothesis that age at first birth may also be related to the age of the patient at clinical onset of the mammary malignancy. One would expect to find a retardative effect of early delivery since this factor was found to be protective as far as mammary cancer risk is concerned. The conclusions of our investigations are in complete opposition to the original hypothesis: in our series, breast cancer appears to occur significantly earlier in women whose first delivery occurred early. III.--Thus the same process appears to be protective as far as total mammary cancer risk is concerned but accelerating as far as age at tumor onset is concerned. These apparently inconsistent observations led to the hypothesis that both studies might express the same biologic process which, in the case of early delivery, inhibits the mechanism of carcinogenic induction and therefore reduces the total number of cancer but which subsequently quickens the evolution of the inducted disease. Such a conjecture implies that breast cancer should be more severe following early first birth. The analysis of our series, as well as the series of Ontario Cancer Clinics, substantiates this hypothesis. But these conclusions are built on indirect proofs or direct proofs which are still short of statistical significance.