Relationship between mammographic breast density and tamoxifen in women with breast cancer.

Previous studies have reported that tamoxifen use is associated with a decrease in mammographic breast density. This is a potentially valuable finding since mammographic sensitivity is limited by breast density. Anything that reduces breast density would theoretically enhance the sensitivity of mammography for the detection of breast cancer in women at an earlier stage when it is more curable. We performed a retrospective study investigating the potential effect of tamoxifen on breast density. The data for this retrospective study were collected from the records of 52 charts from a single medical oncologist. Patients with breast cancer were selected regardless of stage or age at the time of diagnosis or treatment, as long as their charts had records of bilateral mammograms. For each breast on each woman, both mediolateral oblique and craniocaudal views were reviewed independently by two radiologists on two separate occasions to obtain inter- and intraobserver variability. Two methods of classifying breast density were used: the Breast Imaging Reporting and Data System (BI-RADS), and measurements of percent density. Only age and menopausal status were found to be associated with breast density. There was no correlation between breast density and tamoxifen use (past or present). Our study shows no association between tamoxifen use and breast density. We confirm previous observations that breast density is inversely correlated with age and postmenopausal status.

A phase II trial of docetaxel and estramustine in patients with refractory metastatic breast carcinoma.

BACKGROUND: The similarity between the mechanism of action between docetaxel and estramustine generated the hypothesis of synergistic antimicrotubule effects and cytotoxicity when the two agents are combined. In addition, it has been demonstrated that estramustine binds P-glycoprotein in vitro and, thus, may prevent the efflux of taxanes in tumors that over-express P-glycoprotein. To further evaluate the combinations clinical efficacy and safety, a trial was performed in heavily pretreated patients with metastatic breast carcinoma (MBC). METHODS: Thirty-six patients with MBC were treated with estramustine 900 mg/m(2) per day divided into 3 doses given on Days 1-3 and docetaxel 70 mg/m(2) given by intravenous administration over 1 hour on Day 3 after the first dose of estramustine, every 21 days. Patients may have received any number of prior chemotherapy regimens for MBC. RESULTS: Nine partial responses were observed in 31 assessable patients, for an objective response rate of 29% (95% confidence interval, 14-48%). The median progression free survival was 4 months (range, 1-41 months), and the median overall survival was 17 months (range, 2-45 months). Severe toxicities (Grade 3 or 4) were neutropenia, hypophosphatemia, and thrombosis. Seventy-five percent of patients experienced either an improvement or no change in quality of life. CONCLUSIONS: The combination of docetaxel and estramustine produced responses in heavily pretreated women with MBC while maintaining quality of life.

Ku86 is essential in human somatic cells.

Ku86 plays a key role in nonhomologous end joining in mammals. Functional inactivation in rodents of either Ku86 or Ku70, which form the heterodimeric DNA end-binding subunit of the DNA-dependent protein kinase complex, is nevertheless compatible with viability. In contrast, no human patient has been described with mutations in either Ku86 or Ku70. This has led to the hypotheses that either these genes are performing an additional essential role(s) and/or redundant pathways exist that mask the phenotypic expression of these genes when they are mutated in humans. To address this issue, we describe here the construction of human somatic cell lines containing a targeted disruption of the Ku86 locus. Human HCT116 colon cancer cells heterozygous for Ku86 were haploinsufficient with an increase in polyploid cells, a reduction in cell proliferation, elevated p53 levels, and a slight hypersensitivity to ionizing radiation. Functional inactivation of the second Ku86 allele resulted in cells with a drastically reduced doubling time. These cells were capable of undergoing only a limited number of cell divisions, after which they underwent apoptosis. These experiments demonstrate that the Ku86 locus is essential in human somatic tissue culture cells.