Mammographic calcifications and risk of subsequent breast cancer.

BACKGROUND: Women with proliferative benign breast lesions are at increased risk of breast cancer, and some studies have provided evidence that microscopic calcifications in such lesions enhance the risk. PURPOSE: This study was performed to determine whether calcifications on mammograms are predictive of subsequent breast cancer. METHODS: Data for this study were collected on women enrolled at four of the clinics that participated in the Breast Cancer Detection and Demonstration Project (BCDDP). The presence, morphology, and distribution of calcifications visualized on baseline mammograms for 686 women who developed breast cancer over a 7- to 10-year period of follow-up were compared with those for 1357 controls who remained cancer free. We also compared presence and types of calcifications in breasts in which cancer subsequently developed with those in the contralateral breast. RESULTS: Calcifications were evident at baseline in at least one breast in 381 (55.5%) of 686 cases and in 606 (44.7%) of 1357 controls. The estimated relative risk (RR) of breast cancer was 1.68 in women with calcifications, compared with those having none. There was a statistically significant trend of increasing risk with number of breasts with calcifications; RR increased from 1.28 to 2.14 in women with calcifications in one and both breasts, respectively. In women with unilateral calcifications, RR was greater for the breast in which the calcification occurred (1.48) than for the opposite breast (1.08). The elevated risk persisted for more than 6 years from identification of the calcification, suggesting that these lesions were not indicative of existing carcinomas detected later. Risk was greatest in women with clustered calcifications of any morphology or linearly distributed punctate calcifications (RR = 3.64), and the cancer in women with such calcifications was 4.65 times more likely to occur in the involved breast than in the contralateral breast. Multiple and scattered punctate calcifications, and those of any number or distribution that were ring-shaped or linear, were also associated with subsequent risk of breast cancer (RR = 2.09 and 1.76, respectively) but were not strongly predictive of the side on which the breast cancer occurred. Risk was not altered in women with single punctate or large conglomerate calcifications, although the cancers that subsequently occurred in women with the latter lesions were over three times more likely to develop in the breast with the calcification than in the opposite breast. CONCLUSIONS: These findings are consistent with previously reported relationships between breast cancer and specific histologic types of noninvasive breast lesions. Some types of mammographic calcifications appear to be independent risk factors for breast cancer. IMPLICATIONS: If these results are confirmed by other investigators, mammographic calcifications could serve as an additional indicator of women at high risk for breast cancer who may benefit from intensified follow-up.

Observer variation in the classification of mammographic parenchymal patterns.

Wolfe has described different cancer risks associated with a classification of four patterns of the breast parenchyma on mammography, but there is however little information available on the ability of radiologists to agree on the classification of the different patterns. We have assessed inter-rater agreement on the assignment of films to one of the four mammographic patterns described by Wolfe. One hundred xeromammograms were selected, copied and distributed to 10 radiologists who were experts in mammography. Films were classified according to the presence or absence of several radiological signs, according to diagnosis and recommendation, and according to mammographic pattern. Agreement was assessed after correction for agreement expected by chance, using the Kappa statistic. In general, high levels of agreement were found for the classification of mammographic pattern. Agreement on the classification of mammographic pattern was substantially greater than agreement for any other feature of mammographic interpretation, including diagnosis and recommendation.

The relationship between Wolfe's classification of mammograms, accepted breast cancer risk factors, and the incidence of breast cancer.

Data collected between 1973 and 1984 on 696 incident cases of breast cancer and 1,376 matched controls from four Breast Cancer Detection Demonstration Project clinics in the United States were used to assess the role of mammographic parenchymal pattern as a risk factor and its relationship with other, accepted, risk factors. The data confirm previous reports of the influence of benign breast biopsy, age at first live birth, family history of breast cancer, and duration of menstruation on the incidence of breast cancer. Height is also found to be an influential factor. Parenchymal pattern is found to be a risk factor with effects comparable in magnitude to the other factors studied. It operates separately from them, except for its relationship with height and weight. After adjustment for parenchymal pattern, weight is seen to have a significant effect on breast cancer incidence, and height is no longer needed in a model for risk. A model which simultaneously incorporates all of the risk factors considered, including parenchymal pattern, is presented. While these factors are of interest in the epidemiology of breast cancer, it is demonstrated that they are insufficient to allow reliable prediction of the disease in an individual woman.

Wolfe mammographic parenchymal patterns. A study of the masking hypothesis of Egan and Mosteller.

Wolfe defined four different classes of breast parenchymal patterns and claimed that they were associated with different risks for the subsequent development of breast cancer. Egan and Mosteller suggested that these patterns did not constitute a true risk factor, rather the effect was caused by the greater difficulty of detecting breast cancers in the dense (P2, DY) patterns compared with the fatty (N1, P1) patterns. Similarly, Mendell believed that a bias was introduced into Wolfe's work by requiring a negative mammogram before a patient entered the study. This study of 221 prevalent and 706 incident cancers followed for up to 10 years indicates that a masking effect does exist, but that it operates in addition to a difference in risk of breast cancer within the four Wolfe classes. Wolfe's hypothesis is found to be valid.

Breast cancer prediction and the Wolfe classification of mammograms.

Mammographic parenchymal patterns have been proposed as a method of determining women at high risk of developing breast cancer. Wolfe's original report of relative risks as high as 37:1 for "dysplastic" breasts (DY) as compared with adipose breasts (N1), with intermediate values of P1 and P2, were not uniformly confirmed by others. (Relative risks are used here as the equivalent of odds ratios.) A case-control study of 706 breast cancers, each with two matching controls, drawn from 40,000 participants in four Breast Cancer Detection Demonstration Project clinics, was conducted to assess the role of the Wolfe classification of breast parenchymal patterns as a breast-cancer risk factor together with a set of well-established risk factors for breast cancer. Relative risks of 3.1 for DY to N1, 3.5 for P2 to N1, and 2.0 for P1 to N1 were determined. These are comparable to or greater than other known risk factors found in the same population. The Wolfe classification of parenchymal patterns strengthens the basis for clinical judgment, but should not be used exclusively to determine intervention in an individual patient's care.

Reproducibility and consistency in classification of breast parenchymal patterns.

The Wolfe Classification System of evaluating risk of developing breast cancer from analysis of mammographic parenchymal patterns (MPP) has received worldwide attention. In addition to confirming its validity, it is necessary to establish the ability of radiologists to apply the classification of mammograms consistently and reproducibly. This paper reports the results of 12 radiologists associated with the former Breast Cancer Detection Demonstration Projects (BCDDP) in Ann Arbor, Honolulu, Seattle, and Tucson. The participating radiologists had all had some experience with classifying mammograms, then were exposed to more intensive instruction, and finally worked with atlases developed at each institution. The results reported here show the comparisons of the radiologists' readings with Dr. Wolfe in a series of three separate exercises and also three tests of intraobserver consistency. Two of the participating institutions used xeromammograms and two, film mammograms. The study was designed and supervised by an independent data coordinating center with masking of mammograms, without benefit of information of previous readings and no information available except age. The results indicate that this group of radiologists could classify mammograms in the method of Wolfe at an acceptable level compared to other similar exercises.

Observer variation in the interpretation of xeromammograms.

We have examined variation in the interpretation of xeromammograms among radiologists designated to take part in a Canadian multicenter randomized controlled trial of screening for breast cancer. Radiologists read 100 xeromammograms comprising 10 histologically proved cancers, 40 benign abnormalities, and 50 normal films. Radiologists' opinions differed widely on the frequency of suspected or identified cancer. The diagnostic category "suspicion of cancer" or "cancer" was selected by radiologists for 10-55% of the films, and biopsy or aspiration was recommended for 21 to 53% of patients whose films were examined. Agreement on specific diagnostic categories was greatest for the diagnosis of cancer; agreement was least for the diagnosis of benign abnormalities and intermediate for the diagnosis of normality. Known cancers were in general correctly identified. These results indicate a need for development of methods to reduce observer variation in a interpretation of xeromammograms while preserving diagnostic sensitivity and validity. Results also emphasize the importance of developing strategies to ensure quality control in multicenter trials.

Breast cancer detection.

This review of methods of breast cancer detection refers briefly to some methodologies, which the author refers to as unestablished, and then comments on the role of physical examination and breast self-examination and mammography. Reference is made to risk factors in determining frequency of examination and the current recommendations of the American Cancer Society for guidelines of breast cancer examinations.

Mammographic parenchymal patterns as a risk indicator for prevalent and incident cancer.

Different mammographic parenchymal patterns have been found to be associated with significantly different rates for the development of breast cancer in a screening program of self-referred women. These differences are qualitatively similar but of lesser magnitude than those in previous reports by Wolfe which were based on symptomatic women who had had a previous negative mammogram. In addition, this report indicates a small difference in the rate of breast cancer at first mammographic examination, using the same parenchymal classifications. These findings, coupled with other risk factors, may permit the concentration of mammographic screening on a smaller segment of the population at risk, thus improving the benefit to risk ratio.