Future possibilities in the prevention of breast cancer: Luteinizing hormone-releasing hormone agonists

The cyclic production of estrogen and progesterone by the premenopausal ovary accounts for the steep rise in breast cancer risk in premenopausal women. These hormones are breast cell mitogens. By reducing exposure to these ovarian hormones, agonists of luteinizing hormone-releasing hormone (LHRH) given to suppress ovarian function may prove useful in cancer prevention. To prevent deleterious effects of hypoestrogenemia, the addition of low-dose hormone replacement to the LHRH agonist appears necessary. Pilot data with such an approach indicates it is feasible and reduces mammographic densities.     

CHANGES IN FIBRINOGEN LEVELS IN PATIENTS UNDERGOING OPEN AND LAPAROSCOPIC NISSEN FUNDOPLICATION

Background: Venous thromboembolic complications may be more common after laparoscopic surgical techniques, possibly due to changes in venous flow and blood coagulability. Methods: This study assessed fibrinogen, cross-linked fibrin degradation products (D-dimer), prothrombin international normalized ratio (INR), activated partial thromboplastin time (APTT) and platelets, during and after both open and laparoscopic Nissen fundoplication to determine whether coagulability is increased by the laparoscopic approach. Results: Seven patients underwent open and thirteen underwent laparoscopic Nissen fundoplication. Fibrinogen levels following open fundoplication fell from 2.8 ± 0.3 g/L pre-operatively to 2.0 ± 0.3 g/L following skin incision, and then increased to 4.1 ± 0.4 g/L on the first postoperative day. Similar changes in fibrinogen occurred following laparoscopic fundoplication (2.7 ± 0.2, 2.5 ± 0.2 and 3.8 ± 0.4 g/L, respectively). No significant changes in the other coagulation indices were observed. Conclusions: These results demonstrate hypercoagulability on the first postoperative day, irrespective of the operative technique. No differences between the results following laparoscopic and open fundoplication were demonstrated.     

Breast-cancer incidence and mortality rates in different countries in relation to known risk factors and dietary practices.

Breast-cancer incidence and mortality rates in different countries were found to be correlated with height, weight and age at menarche, all of which have been identified as risk factors in cohort or case-control studies of breast cancer. There were, however, correlations with total fat and animal protein consumption per capita even after controlling for the 3 anthropometric variables. This suggests that, while some of the effects of diet on breast-cancer rates may be mediated through effects on these known risk factors, there may be more direct effects as well.     

Treatment of malignant ascitic and pleural effusion with Corynebacterium parvum

Six patients with malignant effusions, five from adenocarcinomas and one from a melanoma, were treated by intrapleural or intraperitoneal Corynebacterium parvum. In each case there was a definite reduction in the effusions with a significant decrease in the number of malignant cells; in most cases the effusions stopped completely. Although none of the patients lived for more than a year after treatment, they were undoubtedly more comfortable, as they no longer required frequent paracentesis. In some cases the patients lived for longer than originally expected in a state in which the quality of life was acceptable.     

Evidence for the clonal abortion theory of B-lymphocyte tolerance

This paper deals with the behavior of adult mouse bone marrow cells placed in tissue culture with or without antigen, and subsequently assessed for immune competence after adoptive transfer into lethally X-irradiated, syngeneic hosts. Attention was focussed on B lymphocytes through using hapten human gamma globulin (HGG) preparations as putative tolerogens in tissue culture, the T-cell-independent antigens DNP-POL and NIP-POL as challenge injections in adoptive hosts, and numbers of hapten-specific PFC in host spleens for the quantitation of immune competence. It was found that the capacity of bone marrow cells to mount an adoptive immune response rose by a factor of about fivefold over 3 days in tissue culture. This rise was completely abolished by the presence in the culture of hapten-HGG conjugates with about one mole of hapten per carrier molecule. The prevention of the emergence of immune competence amongst maturing B cells was termed clonal abortion tolerogenesis. Dose-response studies showed the lowest effective antigen concentration to be between 2.5 times 10- minus 10 and 2.5 times 10- minus 9 M, and a standard concentration of 2.5 times 10- minus 8 M was chosen as producing near maximal effects. The tolerance was antigen-specific and time-dependent, being maximal only when antigen was present continuously as the cultured cells was maturing. It did not depend on the presence of T lymphocytes in marrow, and was not of an "infectious" type. In contrast to tolerogenesis of mature B lymphocytes by high antigen concentrations, it could not be abolished by lipopolysaccharide. We speculate that clonal abortion may be a tolerance mechanism of great physiological significance for self-recognition, and discuss the results in the framework of other recent tolerance models, including those involving receptor blockade and suppressor T cells.     

An overview of menopausal oestrogen-progestin hormone therapy and breast cancer risk

Results from the Women's Health Initiative (WHI) trial support findings from observational studies that oestrogen-progestin therapy (EPT) use is associated with an increase in breast cancer risk. We conducted a meta-analysis using EPT-specific results from the Collaborative Group on Hormonal Factors in Breast Cancer (CGHFBC) pooled analysis and studies published since that report to obtain an overview of EPT use and breast cancer risk. We also assessed risk by histologic subtype of breast cancer, by schedule of the progestin component of EPT, and by recency of use. We estimate that overall, EPT results in a 7.6% increase in breast cancer risk per year of use. The risk was statistically significantly lower in US studies than in European studies - 5.2 vs 7.9%. There was a significantly higher risk for continuous-combined than for sequential EPT use in Scandinavian studies where much higher total doses of progestin were used in continuous-combined than in sequential EPT. We observed no overall difference in risk for lobular vs ductal carcinoma but did observe a slightly higher risk for current vs past EPT use.