Genetics, biomarkers, and control of breast cancer: a review.

More has been written about the epidemiology of breast cancer than possibly any other form of cancer affecting mankind. However, in the face of this intense interest, only a paucity of attention has been given to the role of genetics in its etiology. This review represents an attempt by the investigators to provide a comprehensive coverage of hereditary breast cancer. Included are pertinent endogeneous and exogeneous risk factors, which in certain circumstances, may significantly influence the role of primary genetic factors. Hereditary breast cancer is heterogeneous. When discussing the subject, therefore, one must be precise relevant to the particular heterogeneous form of concern, based on differing tumor associations. It is probably not appropriate to discuss "hereditary breast cancer" without qualification of the specific hereditary breast cancer syndrome of concern; i.e., the SBLA syndrome, breast/ovarian cancer syndrome, and others. This reasoning also applies to attempts at linking biomarkers to hereditary breast cancer. Finally, in addition to ongoing discussions on the cardinal principles that associate with hereditary forms of breast cancer, its frequency, and new developments in biomarkers, we have provided surveillance/management programs that embrace those facets of the natural history of this disease.

PIP: More has been written about the epidemiology of breast cancer than perhaps any other form of cancer affecting mankind. However, in light of this intense interest, only a paucity of attention has been given to the role of genetics in its etiology. This review represents an attempt by the investigators to provide comprehensive coverage of hereditary breast cancer. Included are pertinent edogeneous and exogeneous risk factors, which in certain circumstances, may signficantly influence the role of primary genetic factors. Hereditary breast cancer is heterogeneous. When discussing the subject, therefore, one be must precise with regard to the particular heterogeneous form of concern, based on differing tumor associations. It is probably not appropriate to discuss hereditary breast cancer without qualification of the specific hereditary breast cancer syndrome of concern; i.e., the SBLA syndrome, breast/ovarian syndrome, and others. This reasoning applies to attempts at linking biomarkers to hereditary breast cancer. Finally, in addition to ongoing discussion on the cardinal principles that associate with hereditary forms of breast cancer, its frequency, and new developments in biomarkers, the authors have provided surveillance/management programs which embrace those facets of the natural history of this disease.

Polyarthritis, rash and lymphadenopathy: case reports of two patients with angioimmunoblastic lymphadenopathy presenting to a rheumatology clinic.

Two patients presented with a symmetrical inflammatory polyarthropathy. Both patients fulfilled the diagnostic criteria for angioimmunoblastic lymphadenopathy. We present the two case histories and review the current literature. Although an uncommon disease, the diagnosis of angioimmunoblastic lymphadenopathy should be considered in a patient presenting with polyarthritis and skin rash.

Breast cancer, genetics, and age at first pregnancy.

Hereditary breast cancer shows a distinctive natural history characterised by an earlier age of onset, excess bilaterality, vertical transmission, heterogeneous tumour associations, and improved survival when compared to its sporadic counterpart. To date, very little attention has been given to interrelationships between breast cancer risk factors and genetics. In the general population, early age of first term pregnancy has been generally accepted as protective against breast cancer. In addition, recent findings suggest that an early age of first pregnancy may be associated with an earlier age of breast cancer diagnosis. We studied the age at first pregnancy and age at onset of breast cancer among 162 females at 50% genetic risk, 72 of whom had already developed the disease. We then compared them to 154 consecutively ascertained breast cancer patients from the Creighton Cancer Center. In the hereditary subset (1) early first term pregnancy did not alter the frequency of breast cancer; (2) early age at first term pregnancy was not associated with an earlier age at cancer diagnosis; and (3) age of breast cancer onset in nulliparous females was not significantly lower than that in females having at least one term pregnancy. We speculate, therefore, that in our hereditary population, pregnancy does not influence the natural history of breast cancer in the same way that it does in the population at large.

The therapeutic response to D-penicillamine in rheumatoid arthritis: influence of glutathione S-transferase polymorphisms.

OBJECTIVES: To investigate whether the therapeutic response of rheumatoid arthritis (RA) patients to D-penicillamine is associated with polymorphisms in genes of the glutathione S-transferase (GST) supergene family. METHODS: Disease activity in 81 patients with RA treated with D-penicillamine monotherapy was assessed using the Stoke Index, a validated index of disease activity, prior to treatment and at 6 months. GST typing was performed using a polymerase chain reaction-based approach and a logistic regression model was used to investigate any possible association between the therapeutic response to D-penicillamine and the GST genotype. RESULTS: A poor therapeutic response was associated with the GSTM1 null genotype [odds ratio (OR) 3.94], and in particular with the GSTM1*0/GSTM3*A haplotype (OR 7.63). CONCLUSIONS: Our results suggest that GST polymorphisms may influence the response to D-penicillamine in RA, and that patients in possession of the GSTM1*0/GSTM3*A haplotype are significantly less likely to show a beneficial response to the drug.

Genetic predisposition to breast cancer.

Breast cancer risk factors are closely intertwined with the patient's cultural background, which may contribute to breast cancer aggregations within families. The difficult questions are: (1) does a truly hereditary breast cancer subset exist; (2) which familial aggregations are hereditary; and (3) is the hereditary form distinctive from its sporadic counterpart? These queries will be resolved once biomarkers are identified that show high sensitivity and specificity with genotype. The authors provide a review of this subject and will focus on their recent discovery of increased in vitro hyperdiploidy in cultured skin fibroblasts from patients with or at risk for hereditary breast cancer. The authors discuss findings from their study of family histories in 225 consecutively ascertained patients with verified breast cancer from the Creighton University School of Medicine Oncology Clinic. Findings consistent with an hereditary breast cancer syndrome were identified in 5% of the patients. Given the 112,000 new cases of breast cancer in the United States in 1982, the authors estimate that with a confidence coefficient of 0.95 between 2410 and 8790 of these individuals will manifest hereditary breast cancer. Specific surveillance/management programs should be geared to high-risk members of these families in which cancer yield will be predictable.