Faculty Bibliography

The World Health Organization recently reported that breast cancer has become the most common cancer in women throughout the world. Known risk factors account for less than half of all cases of breast cancer, and inherited germ line mutations occur in at most only 10% of all cases. Cumulative exposure to estradiol and other hormones links many of the established risk factors for breast cancer. This paper reviews epidemiologic and toxicologic evidence on breast cancer risks and presents a comprehensive construct of risk factors intended to focus on the identification of those factors that can be controlled or modified. We attempt to provide a framework for interpreting the etiologic interplay of endogenous metabolic changes and environmental changes in the etiology of breast cancer. The construct we develop distinguishes between those risk factors that are directly causal, such as ionizing radiation and inherited germ cell defects, those vulnerability factors that extend the time period during which the breast undergoes development, and those contributing factors that increase total hormonal stimulation of the breast. Some hormonally active compounds, such as those in soy and broccoli and other phytoestrogen-containing foods, can be protective against breast cancer, while others, such as some environmental contaminants, appear to increase the risk of the disease by increasing levels of harmful hormones. Efforts to explain patterns of breast cancer should distinguish between these different risk factors. Identification of vulnerability and contributing risk factors can foster the development of public policy to reduce the burden of this prevalent cancer. Prudent precautionary principles suggest that reducing exposure to avoidable or modifiable risk factors should receive high priority from the public and private sectors

BACKGROUND: Pure mucinous carcinoma (PMC) of the breast has a better prognosis than does invasive ductal carcinoma not otherwise specified and is more prevalent in older patients. We investigated the correlation between prognostic indices and clinical outcome in this histologic subset. METHODS: A retrospective review was done of patients with PMC treated between 1989 and 1996. Demographic data, pathologic indices of prognosis, axillary nodal status, and outcome were assessed. RESULTS: Out of 6083 cases of breast carcinoma, 30 were PMC. Only 3 of 25 (12%) axillary dissections were positive. The average age of the group with positive nodes was 57 years, as compared to 69.5 years (95% CI; 63.24-75.76) in the group with negative nodes. All the tumors with positive nodes were aneuploid and had a high nuclear grade, compared to a 31.25% aneuploidy rate in the group without nodal disease (P = .058). Negative ER receptors were found in only 2 of 20 (10%) of the patients tested. Both had axillary disease (P = .016). Tumor size did not correlate with axillary metastasis. Two of the 29 patients died from unrelated diseases. The other 27 patients are alive with no evidence of disease. CONCLUSIONS: Axillary nodal disease is rare in PMC and correlates with a younger age, aneuploidy, high nuclear grade, or a negative ER receptor status. Sentinel lymph node biopsy may help identify the need for axillary dissection

In light of the changing trends in the diagnosis and management of invasive breast cancer, the practice of routine axillary dissection should be reevaluated. A growing number of patients with breast cancer are diagnosed as having small tumors with an associated low risk of lymph node metastases. The pathologic features of the primary tumor are increasingly being used as a prognostic guide for recommendations about adjuvant systemic therapy, and there are recent reports suggesting a superior prognostic value for tumor cells detected in bone marrow, as compared to axillary lymph node metastases. Consequently, axillary lymph node status is no longer the single prognostic guide for recommendations about adjuvant systemic therapy. For treatment of the axilla, there is evidence that, in clinical N0 patients, radiation therapy to the axilla is an effective alternative to axillary dissection. Finally, there are cost and morbidity considerations for patients undergoing axillary dissection in whom the indications of the procedure are equivocal. In the management of invasive breast cancer, a selective policy toward axillary lymph node dissection should be considered. This review discusses the nonsurgical management of the axilla; ie, radiation therapy to the axilla and observation of the axilla as an alternative to axillary dissection

In vivo experiments on strains of mice that differ in the risk of developing mammary cancer have demonstrated a correlation between the extent of 16 alpha-hydroxylation of estradiol and incidence of mammary cancer. The ability of human mammary terminal duct lobular unit (TDLU), the site of neoplastic transformation, to metabolize estradiol or to accumulate estradiol metabolites has not been unequivocally established. Using a newly developed human mammary TDLU explant culture system and a radiometric assay for estradiol metabolism, we compared the site-specific metabolism of estradiol by the 17-oxidation, 2-hydroxylation, and 16 alpha-hydroxylation pathways in noninvolved human mammary tissue. The relative extent of estradiol 16 alpha-hydroxylation was found to be increased in TDLU from patients in the luteal phase of the menstrual cycle in relation to either those from patients in the follicular phase or from postmenopausal subjects. This study demonstrates that TDLU can metabolize estradiol extrahepatically and that 16 alpha-hydroxylation in the target tissue is dependent on the phase of the menstrual cycle. Furthermore, the specific, risk-related increase in 16 alpha-hydroxylation suggests that intrinsic metabolic ability of the target tissue leading to the formation of 16 alpha-hydroxyestrone from estradiol may be a determinant in, or a marker for, the relative risk of developing mammary cancer

A patient with intermittent epigastric pain was found to have a hamartomatous polyp of the jejunum as the lead point of an intussusception. The bowel adjacent to the hamartoma had intramural and subserosal mucinous cysts consistent with jejunitis cystica profunda. To our knowledge, this is the second case described in the English literature