Effects of mammographic density and benign breast disease on breast cancer risk (United States).

BACKGROUND: Having either a history of benign breast disease, particularly atypical hyperplasia or extensive mammographic breast density, is associated with increased breast cancer risk. Previous studies have described an association between benign breast disease histology and breast density. However, whether these features measure the same risk, or are independent risk factors, has not been addressed. METHODS: This case-control study, nested within the prospective follow-up of the Breast Cancer Detection Demonstration Project, evaluated both benign histologic and mammographic density information from 347 women who later developed breast cancer and 410 age- and race-matched controls without breast cancer. Multivariate logistic regression analyses provided maximum-likelihood estimates of the odds ratios (OR) and 95% confidence intervals (CI) to evaluate the relative risk of breast cancer associated with each exposure. RESULTS: Adjusting for mammographic density, the OR for atypical hyperplasia was 2.1 (95% CI: 1.3-3.6), and adjusting for benign breast histology, the OR for > or = 75% density was 3.8 (95% CI: 2.0-7.2). Women with nonproliferative benign breast disease and > or = 75% density had an OR of 5.8 (95% CI: 1.8-18.6), and women with < 50% density and atypical hyperplasia had an OR of 4.1 (95% CI: 2.1-8.0). CONCLUSIONS: In this study, both benign breast disease histology and the percentage of the breast area with mammographic density were associated with breast cancer risk. However, women with both proliferative benign breast disease and > or = 75% density were not at as high a risk of breast cancer due to the combination of effects (p = 0.002) as women with only one of these factors.

The detection of changes in mammographic densities.

We previously reported reductions in mammographic densities in women participating in a trial of a gonadotropin-releasing hormone agonist (GnRHA)-based regimen for breast cancer prevention. In our previous report, we compared (by simultaneous evaluation) three basic elements of mammographic densities. The purpose of the present study was to evaluate whether a standard (expert) method of measuring mammographic densities would detect such changes in densities and whether a novel nonexpert computer-based threshold method could do so. Mammograms were obtained from 19 women at baseline and 12 months after randomization to the GnRHA-based regimen. The extent of mammographic densities was determined by: (a) a standard expert outlining method developed by Wolfe and his colleagues (Am. J. Roentgenol., 148: 1087-1092, 1987); and (b) a new computer-based threshold method of determining densities. The results from both the expert outlining method and the computer-based threshold method were highly consistent with the results of our original (simultaneous evaluation) method. All three methods yielded statistically significant reductions in densities from baseline to the 12-month follow-up mammogram in women on the contraceptive regimen. The difference between the treated and the control group was statistically significant with the expert outlining method and was of borderline statistical significance with the computer-based threshold method. The computer-based results correlated highly (r > 0.85) with the results from the expert outlining method. Both the standard expert outlining method and the computer-based threshold method detected the reductions we had previously noted in mammographic densities induced by the GnRHA-based regimen.

Mammographic features and breast cancer risk: effects with time, age, and menopause status.

BACKGROUND: Mammographic images from women with a high proportion of epithelial and stromal breast tissues are described as showing high-density parenchymal patterns. Most past studies that noted an increase in breast cancer risk associated with mammographic parenchymal patterns showing high density either 1) lacked information on other breast cancer risk factors, 2) were too small, or 3) included insufficient follow-up time to adequately resolve persisting doubts whether mammographic features are "independent" measures of breast cancer risk and not a detection artifact. PURPOSE: The purpose of this study was twofold: 1) to evaluate the associations between mammographic features and other breast cancer risk factors and 2) to assess effects of mammographic features on breast cancer risk by time, age, and menopause status. METHODS: To address these questions, we analyzed detailed information from a large, nested case-control study with 16 years of follow-up. This study used information from both screening and follow-up phases of the Breast Cancer Detection Demonstration Project, a nationwide program that offered annual breast cancer screening for more than 280,000 women from 1973 to 1980. Mammographic features were assessed from the base-line screening mammographic examination for 1880 incident case subjects and 2152 control subjects. Control subjects were randomly selected from women of the same age and race as each case subject. Control subjects attended the same screening center as the case subject and were free of breast cancer at the case subject's date of diagnosis. Odds ratios (ORs) with 95% confidence intervals (CIs) provided estimates of the relative risk of breast cancer. RESULTS: Mammographic features were associated with known breast cancer risk factors. However, the high-density parenchymal pattern effects were independent of family history, age at first birth, alcohol consumption, and benign breast disease. The increase risk for women with Wolfe's two high-density parenchymal patterns, P2 (OR = 3.2; 95% CI = 2.5-4.0) and Dy (OR = 2.9; 95% CI = 2.2-3.9), was explained primarily by measured percent of the breast with dense mammographic appearance. Compared with women with no visible breast density, women who had a breast density of 75% or greater had an almost fivefold increased risk of breast cancer (95% CI = 3.6-7.1). These effects persisted for 10 or more years and were noted for both premenopausal and postmenopausal women of all ages. CONCLUSIONS: Of the breast cancer risk factors assessed in the participants, high-density mammographic parenchymal patterns, as measured by the proportion of breast area composed of epithelial and stromal tissue, had the greatest impact on breast cancer risk. Of the breast cancers in this study, 28% were attributable to having 50% or greater breast density.

Mammographic densities and risk of breast cancer.

To determine the relation of mammographic densities to subsequent breast cancer risk, a case-control study was undertaken using prediagnostic mammograms of screening program participants. Mammograms of cases (n = 266) and controls (n = 301) were blindly assessed for mammographic densities, which were measured by planimetry. The odds of breast cancer increased steadily with increasing breast density (test for trend, P less than 0.0001). Breast cancer odds was 1.7 for densities between 5% and 24.9%, 2.5 for 25% through 44.9%, 3.8 for 45% through 64%, and 4.3 for densities of 65% and greater (referent = less than 5% densities). Odds ratios also increased with increasing densities among women with the P2 and DY mammographic patterns. These findings suggest that the percentage of mammographic densities in the breast can predict breast cancer risk more accurately than a qualitative assessment of mammographic patterns.

Mammographic parenchymal patterns as indicators of breast cancer risk.

Mammographic parenchymal patterns have been suggested as indicators of breast cancer risk. However, few well-controlled studies have used prediagnostic mammograms to determine the pattern classification. The authors studied 266 cases of breast cancer and 301 controls from 25 screening centers of the Breast Cancer Detection and Demonstration Project, a nationwide screening program conducted between 1973 and 1980 to evaluate the risk associated with mammographic patterns using mammograms taken four years before the detection of breast cancer. Mammograms of the cancerous breast of cases and of the ipsilateral breast in the control matched to each case were blindly assessed by one of the investigators (J.N.W.), originator of the mammographic pattern classification. The breast cancer odds ratio among women with the combined P2 + DY patterns, compared with women with the N1 pattern, was 2.8 (95% confidence interval (CI): 1.6-5.1). This estimate of relative risk was comparable with the risk associated with other recognized breast cancer risk factors. The odds ratio among P2 + DY women with a first-degree family history of breast cancer was 5.5 (95% CI: 2.6-11.8) compared with N1 women without a family history. These data provide additional evidence that mammographic patterns are indicators for subsequent development of breast cancer, particularly among women with a first-degree family history of this malignancy.

Xeroradiography of the breast: overview of 21,057 consecutive cases.

Xeroradiography was performed on 21,057 new patients referred over a 5 1/2-year period. For purposes of analysis, mammograms reported as "benign" or "follow-up suggested" were considered negative and those reported as "suspicious" or "strongly suggestive of cancer" were considered positive. All patients were followed up for 12 months. After 6 months, 773 breast cancers were diagnosed. An additional 19 cancers were proved to exist during the 6-12-month period. The cancer rate increased progressively with age and ranged from 1.2% at age 30-39 years, to 4.5% at age 50-59 years, to 11.8% at age 70 years and over. Mammography had a sensitivity of 91.1%, a specificity of 89.9%, and a predictive value of 25.5%. Sensitivity increased with age, ranging from 78.5% at age 30-39 to 95.1% at age 70 and over. Predictive value increased dramatically with age, varying from 12.4% at age 30-39, to 28.4% at age 50-59, to 49.4% at age 70 years and over.

Mammographic parenchymal patterns and quantitative evaluation of mammographic densities: a case-control study.

The classification of breast parenchymal patterns (N1, P1, P2, DY) and the percentage of the breast containing radiographic densities are two highly correlated radiographic measures proposed as predictors of the risk of breast cancer. In this case-control study, 160 cases of breast cancer and 160 matched controls from a mammography referral practice were compared to determine the risk of breast cancer associated with each of these two radiographic measures. The mammographic densities were quantified on caudal projections by means of a compensating polar planimeter. A relative risk estimate of 3.3 (p less than .05) was associated with the P2 + DY patterns compared with the N1 + P1 patterns. Significantly elevated risks of 4.3 to 5.5 also were observed among women whose breasts contained at least 25% mammographic densities, compared with women with less than 25% involvement. These radiographic measures tended to be more predictive of the risk of breast cancer in black women than in white women. Although the precise clinical roles of breast parenchymal patterns and densities have not been defined fully, the results of this study suggest that they are useful in the recognition of women at high risk of breast cancer. We make no claims that the findings of this study are sufficiently developed to be used as a basis for screening strategies.

Breast parenchymal patterns: analysis of 332 incident breast carcinomas.

A detailed analysis of 332 incident breast carcinomas is presented. The study results indicate that there is validity to the breast parenchymal patterns as an indication of risk for developing breast cancer and that risk is independent of length of follow-up and age of patient. All cases were drawn from a referral-type practice at Hutzel Hospital, Detroit, MI. The cases were compared to controls for computation of relative risk up to and beyond a follow-up period of 48 months. They were also compared to a consecutive series of prevalent breast carcinomas seen at Hutzel Hospital during the 6 years 1975-1980. The extent of disease in the cases described in this report is somewhat more favorable than in a consecutive series of prevalent cancers operated on a Hutzel Hospital. Most breast cancers occur in the P2 breast, a smaller number in the DY, and only 12% in the combined N1P1 type. The conclusions of other investigators regarding parenchymal patterns as risk indicators are reviewed. Particular attention was paid to comparing the length of follow-up and age of patient. There was no diminution of proportions of cases in the P2/N1-P1 or DY/N1-P1 after a 48 month follow-up. There was a significant diminution in the proportion of cases falling into DY/N1-P1 after age 50, and less so in P2/N1-P1. Furthermore, relative risk was unaffected by time or age.

Familial influences on breast parenchymal patterns.

Some studies accomplished thus far have indicated that mammographic patterns may serve as risk indices for breast cancer. The present investigation was undertaken to determine whether patterns are familial. Mammograms from 110 mothers and their daughters and 122 sister pairs and a like number of unrelated controls matched for patient age, reproductive history, and personal and family history of breast cancer and drawn from the files of the Radiology Department of Hutzel Hospital, Detroit, Michigan, were compared. A familial influence was indicated by the finding that pattern similarities were significantly stronger in test cases than in unrelated controls. This influence appeared to be manifested by premature age changes in daughters and younger sisters and consisted, primarily, of a decrease in DY and an increase in P2 patterns. The data suggest that performing mammography on first degree relatives of women with high risk P2 and DY patterns should be considered.