Modified Bi-Rads Scoring of Breast Imaging Findings Improves Clinical Judgment.

In contrast with the reporting requirements currently mandated under the Federal Mammography Quality Standards Act (MQSA), we propose a modification of the Breast Imaging Reporting and Data System (Bi-Rads) in which a concluding assessment category is assigned, not to the examination as a whole, but to every potentially malignant abnormality observed. This modification improves communication between the radiologist and the attending clinician, thereby facilitating clinical judgment leading to appropriate management. In patients with breast cancer eligible for breast conserving therapy, application of this modification brings to attention the necessity for such patients to undergo pretreatment biopsies of all secondary, synchronous ipsilateral lesions scored Bi-Rads 3-5. All contralateral secondary lesions scored Bi-Rads 3-5 also require pretreatment biopsies. The application of this modification of the MSQA demonstrates the necessity to alter current recommendations ("short-interval follow-up") for secondary, synchronous Bi-Rads 3 ("probably benign") image-detected abnormalities prior to treatment of the index malignancy.

The relative importance of genetics and environment on mammographic density.

BACKGROUND: Although several environmental factors predict mammographic density, estimates of its heritability have been quite high. We investigated whether part of the presumed heritability might be attributed to differential sharing of modifiable risk factors in monozygotic (MZ) and dizygotic (DZ) twins. METHODS: We measured percent and absolute mammographic density using mammograms from 257 MZ and 296 DZ twin pairs. The correlation of intrapair mammographic density was compared according to zygosity across strata of modifiable risk factors. Portions of variance attributable to additive genetic factors, shared environment, and individual environment were calculated using a variance component methodology in the entire set, and within twin pairs stratified by environmental trait similarity. RESULTS: Both percent density and absolute mammographic density were more highly correlated between MZ twins than DZ twins, but the correlations varied across strata. Body mass index (BMI) and parity strongly predicted differences in mammographic density within MZ twin pairs. After adjusting for covariates, 53% of the total variance in percent density and 59% of that in absolute density seemed attributable to genetic effects, but these estimates varied greatly by stratum. For twins dissimilar on BMI (difference >2.5 kg/m(2)), the additive genetic component of absolute density was estimated at only 20% (+/-19%), and the common and individual environment at 21% (+/-14%) and 49%, respectively (P value for heterogeneity across BMI = 0.0001). CONCLUSION: Our results confirm that the genome is an important determinant of mammographic density but suggest that an unknown portion of the mammographic density effect attributed to the genome may be due to shared modifiable environmental factors.

Greatly increased occurrence of breast cancers in areas of mammographically dense tissue.

INTRODUCTION: Mammographic density is a strong, independent risk factor for breast cancer. A critical unanswered question is whether cancers tend to arise in mammographically dense tissue (i.e. are densities directly related to risk or are they simply a marker of risk). This question cannot be addressed by studying invasive tumors because they manifest as densities and cannot be confidently differentiated from the densities representing fibrous and glandular tissue. We addressed this question by studying ductal carcinoma in situ (DCIS), as revealed by microcalcifications. METHOD: We studied the cranio-caudal and the mediolateral-oblique mammograms of 28 breasts with a solitary DCIS lesion. Two experienced radiologists independently judged whether the DCIS occurred in a mammographically dense area, and determined the density of different areas of the mammograms. RESULTS: It was not possible to determine whether the DCIS was or was not in a dense area for six of the tumors. Of the remaining 22 lesions, 21 occurred in dense tissue (test for difference from expected taken as the percentage of density of the 'mammographic quadrant' containing DCIS; P < 0.0001). A preponderance of DCIS (17 out of 28) occurred in the mammographic quadrant with the highest percentage density. CONCLUSION: DCIS occurs overwhelmingly in the mammographically dense areas of the breast, and pre-DCIS mammograms showed that this relationship was not brought about by the presence of the DCIS. This strongly suggests that some aspect of stromal tissue comprising the mammographically dense tissue directly influences the carcinogenic process in the local breast glandular tissue.

Polymorphisms in genes involved in estrogen and progesterone metabolism and mammographic density changes in women randomized to postmenopausal hormone therapy: results from a pilot study.

INTRODUCTION: Mammographic density is a strong independent risk factor for breast cancer, and can be modified by hormonal exposures. Identifying genetic variants that determine increases in mammographic density in hormone users may be important in understanding hormonal carcinogenesis of the breast. METHODS: We obtained mammograms and DNA from 232 postmenopausal women aged 45 to 75 years who had participated in one of two randomized, double-blind clinical trials with estrogen therapy (104 women, taking 1 mg/day of micronized 17beta-estradiol, E2), combined estrogen and progestin therapy (34 women, taking 17beta-estradiol and 5 mg/day of medroxyprogesterone acetate for 12 days/month) or matching placebos (94 women). Mammographic percentage density (MPD) was measured on baseline and 12-month mammograms with a validated computer-assisted method. We evaluated polymorphisms in genes involved in estrogen metabolism (catechol-O-methyltransferase (COMT (Val158Met)), cytochrome P450 1B1 (CYP1B1 (Val432Leu)), UDP-glucuronosyltransferase 1A1 (UGT1A1 (<7/>or= 7 TA repeats))) and progesterone metabolism (aldo-keto reductase 1C4 (AKR1C4 (Leu311Val))) with changes in MPD. RESULTS: The adjusted mean change in MPD was +4.6% in the estrogen therapy arm and +7.2% in the combined estrogen and progestin therapy arm, compared with +0.02% in the placebo arm (P = 0.0001). None of the genetic variants predicted mammographic density changes in women using estrogen therapy. Both the AKR1C4 and the CYP1B1 polymorphisms predicted mammographic density change in the combined estrogen and progestin therapy group (P < 0.05). In particular, the eight women carrying one or two low-activity AKR1C4 Val alleles showed a significantly greater increase in MPD (16.7% and 29.3%) than women homozygous for the Leu allele (4.0%). CONCLUSION: Although based on small numbers, these findings suggest that the magnitude of the increase in mammographic density in women using combined estrogen and progestin therapy may be greater in those with genetically determined lower activity of enzymes that metabolize estrogen and progesterone.

Mammographic density and breast cancer in three ethnic groups.

The extent of radiodense tissue on a mammogram (mammographic densities) is strongly associated with breast cancer risk among (non-Latina) white women, but few data exist for African-American and Asian-American women. We collected prediagnostic mammograms from 622 breast cancer patients and 443 control subjects ages 35-64 years from three different ethnic groups (whites, African Americans, and Asian Americans) who participated as cases and controls in one of two ongoing breast cancer studies. Percent and absolute mammographic density were assessed using a previously validated computer-assisted method. In all three ethnic groups combined, breast cancer risk increased with increasing percent mammographic density. After adjustment for ethnicity, age, body mass index, age at menarche, breast cancer family history, age at and number of full-term pregnancies, menopausal status, and hormone replacement therapy use, women with the highest percent density had 5-fold greater breast cancer risk than women with no density (P(trend) = 0.0001). The impact of percent density on risk was stronger for older than for younger women (>/=50 versus <50 years; P = 0.05). Risk estimates did not differ significantly by ethnicity, with breast cancer risk (95% confidence interval) increasing 15% (4-27%) in whites, 30% (5-61%) in Asian Americans, and 11% (-2-26%) in African Americans for each 10% increase in density. The trends were similar for absolute density. Our results confirm that increases in computer-assisted mammographic density measurements are associated with a strong gradient in breast cancer risk. Furthermore, our findings suggest that mammographic density is as strong a predictor of risk for African-American and Asian-American women as for white women.

Racial differences in mammographic breast density.

BACKGROUND: African American women have a lower incidence but a higher mortality from breast carcinoma than Caucasians. A proposed explanation for this discrepancy is the decreased efficacy of screening among African American women. Increased breast density in African American women may result in decreased sensitivity of mammography. The purpose of this article is to determine whether there is a difference in mammographic breast density between African American and Caucasian women. METHODS: A series of 769 women were recruited from 5 sites. Mammograms were reviewed centrally by seven reviewers using Breast Imaging Reporting and Data System categories converted to numeric values. The mean mammographic densities for Caucasian, African American, and Latina patients were compared using a two-way analysis of covariance. The mean values for each race were estimated adjusting for the reader as well as for each patient's age and body mass index (BMI). RESULTS: African American women had the lowest mean breast density. The reported density in this group was 2.43, compared with 2.69 among Caucasians and 2.65 among Latina patients. After adjusting for age and BMI as well as the reader, there was still an independent racial effect on breast density (P = 0.0050). CONCLUSIONS: Mammographic breast density was lower in African American women than in Caucasians and Latinas. This discrepancy may be an intrinsic racial difference due to undetermined causes. Factors, such as the growth rate of tumors and the incidence of calcifications, must be studied to confirm that other forces do not have a negative impact on the efficacy of screening mammograms in African American women.