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Original Research |
1 Division of Gynecologic Oncology, Massachusetts General Hospital, 55 Fruit
St., Yawkey 9E, Boston, MA 02114.
2 Department of Radiology, Massachusetts General Hospital and Harvard Medical
School, Boston, MA.
3 Cancer Center, Massachusetts General Hospital and Harvard Medical School,
Boston, MA.
4 Division of Surgical Oncology, Department of Surgery, Massachusetts General
Hospital and Harvard Medical School, Boston, MA.
Received May 8, 2006;
accepted after revision October 4, 2006.
Address correspondence to M. G. del Carmen
(mdelcarmen{at}partners.org).
Abstract
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MATERIALS AND METHODS. A retrospective review of data collected from 15,292 women was conducted. A stepwise multiple regression for an ordered response (breast density) was used to test for a relationship between race or ethnicity and breast density. We then determined whether differences in breast density by race might be caused by differences among races and ethnic groups in the age at imaging and BMI. We informally assessed the strength of the contribution of each term by means of the incremental change in the percent concordance. We also compared models using bra and cup sizes and age with models using BMI and age to try to determine whether the effects of breast size are local or systemic.
RESULTS. We did not find evidence that mammographic breast density differences exist across racial groups (p < 0.0001) other than those associated with BMI and age at screening. Ignoring age and BMI, breast density depends on race for all comparisons (p < 0.0001). To generalize, we found that breast density appears to be greater in Asian women and least in African American women. However, when controlling for BMI and age, breast density differences by race disappeared in all groups except Asians (p < 0.0001). In all racial groups, bra and cup size in addition to age correlated with breast density after controlling for BMI (p < 0.0001). Except in Asian women, in women of any racial group, age and any of the following parameters accounted for all of the breast density differences: BMI, bra size, and cup size.
CONCLUSION. Although breast density is associated with breast cancer risk, our results indicate that innate mammographic breast density differences across racial groups do not explain the risk differences known for the development of breast cancer. Age and BMI or age, bra size, and cup size can account for the reported density differences except among Asians. There may be no innate racial differences in breast density beyond those associated with racial differences in age and body habitus.
Keywords: breast • breast cancer • breast density • mammography
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The question is whether racial differences in mammographic breast density might explain these differences. Mammographically dense breast tissue may make it more difficult to detect cancers on screening mammography, which would lead to lower rates of detection and higher stage at presentation [4, 5].
Breast density has also been reported to be an independent predictor of breast cancer risk [6-11]. Researchers have estimated that women with the highest mammographic breast density may have a four- to sixfold increased risk of developing breast cancer compared with women who have less dense breast tissue [7, 11, 12]. Thus, the relationship of race to mammographic density may explain differences in breast cancer risk among racial groups.
A number of studies have documented a relationship between breast density and race. Chen and colleagues [13] reported that absolute mammographic density, when controlling for age and body mass index (BMI), was statistically lower in Asian Americans than African Americans but not compared with white women. Other series have noted a lower breast density among African American women when compared with Latino and Caucasian women [14]. These studies controlled for different factors, including age, BMI, selected menstrual or reproductive factors, family history, and hormone replacement therapy use.
The goal of this study was to determine whether race is an independent factor in determining breast density and, if so, whether racial differences in breast density parallel differences in breast cancer incidence across racial groups.
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Dates of birth were collected from a series of 20,638 women, and their breast density was categorized prospectively by the interpreting radiologist. From this initial group, 2,864 of patients with a personal history of prior breast cancer were excluded. An additional 2,482 patients were excluded because of incomplete data regarding density, date of birth, height, or weight. We analyzed the data collected from the remaining 15,292 women who presented for scanning from May 12, 2003, to October 7, 2004, using information from which the patient identifiers had been removed.
Mammographic breast density was categorized by the interpreting radiologist, as part of clinical care, using BI-RADS categories converted to numeric values as follows: 1, breast is almost entirely fat (< 25% fibroglandular tissue); 2, breast has scattered fibroglandular dense tissue (25-50% fibroglandular tissue); 3, breast tissue is heterogeneously dense (51-75% fibroglandular tissue); and 4, breast tissue is extremely dense (> 75% fibroglandular tissue) [15].
The National Institutes of Health (NIH) definition of BMI and weight categories were used [16]. According to the NIH, underweight is defined as a BMI of 18.5 kg/m2 or less; normal, as 18.6-24.9 kg/m2; overweight, as 25-29.9 kg/m2; and obesity, as 30 kg/m2 or greater [16]. Four BMI categories were created. BI-RADS frequency counts were calculated across the four different categories for each race and were reported as a percentage of the total number of women in each BI-RADS category for each race.
We used a stepwise multiple regression for an ordered response (breast
density) to test for a relationship of race and ethnicity with breast density
over and above any association that might be caused by differences among races
and ethnic groups in the age at imaging and BMI. We used the incremental
effects of race and ethnicity after including age and BMI in the models to
test the null hypothesis that all differences among racial groups in breast
density were due to age and BMI. Having determined the significant effects
(p 
0.05), if any, we informally assessed the strength of the
contribution of each term by means of the incremental change in the percent
concordance. We also compared models using bra and cup sizes and age with
models using BMI and age to try to determine if the effects of breast size are
local or systemic.
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Using logistic regression analysis, age and BMI predict density with a 73.4% concordance level. Adding a term for Asian race to the logistic regression model while controlling for both BMI and age improved the prediction of breast density significantly (73.5% concordance). When data for the other races were entered into this model, no additional effects were observed at a 0.05 significance level. That is, even after controlling for BMI and age, the breast density among Asians was documented to be statistically greater than the breast density of other groups. However, in all of the other groups, breast density did not correlate with race beyond what can be attributed to differences in age and BMI.
Using age and breast size or cup size resulted in a 74.1% predictive concordance of breast density. Using BMI in addition to age, breast size, or cup size yielded 75.4% concordance. Bra size and cup size in addition to age correlated with breast density even after controlling for BMI (p < 0.0001). Except among Asian women, age and any of the following parameters account for all of the differences in breast density noted in the current study (Table 2): BMI, bra size, and cup size.
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Multiple studies of the relationship between breast density and race have been reported with conflicting results. Ursin et al. [17] concluded that absolute mammographic density is significantly higher in Asians than in African Americans. However, after adjusting for age, BMI, and other factors, they determined that the percent mammographic density was significantly lower in Asian Americans than in African Americans, but was not significantly different from Caucasians [13]. These racial differences in absolute mammographic density were most pronounced among women older than 50 years but were reduced after adjusting for breast size [13].
Other investigators have concluded that the size of the dense areas in the breast is a better indicator of racial differences than percent densities [17, 18]. Maskarinec et al. [18] compared mammographic density in three groups of women: white and Japanese women in Hawaii and Japanese women in Japan. The percent densities among Japanese women in Hawaii were significantly higher than among Japanese women in Japan [18]. The authors concluded that the size of the total breast differs primarily by race and that the size of the dense areas differs primarily by place of residence [18].
We found that breast density was greater among Asian women than among African American and white women. However, when we controlled for BMI and age, these differences disappeared. Age along with BMI or age along with breast or cup size accounted for the differences in breast density among the racial groups in this study with the possible exception of Asian women. This statistically significant difference in Asian women, as compared with white women and all others, may largely be an effect of our large sample size rather than a clinically significant difference. From the percentage concordance for the models, the racial difference in Asian women may be a factor in approximately 0.1% of all women. Our analysis suggests that breast density is related to breast size, as indicated by BMI, bra size, or cup size. Breast density in the current study does not appear to be related to race.
Our series, one of the largest in the literature, shows that racial differences in breast density are little more than the result of racial differences in breast size as indicated by BMI, bra size, or cup size. Thus, although one might predict that racial groups with lower breast cancer risk should have lower mammographic breast density, we did not find that relationship. This does not mean that density and risk are not related, but only that racial differences in risk do not seem to correlate with racial differences (or the lack thereof) in breast density. For example, our current series has one of the largest number of Asian women, with 435 Asian women responding to our questionnaire, compared with the other reports in the published literature. If breast density is related to breast cancer risk, either Asian women should have a higher incidence of breast cancer or they should have the least dense breasts. This study shows that Asians have the highest breast density, whereas the incidence of breast cancer among Asian women is lower than that among Caucasians [19].
Most of the investigations that focus on breast cancer risk as it relates to mammographic breast density have included North American women as the study subjects [20]. However, other racial groups such as Asians have distinctly different physical proportions, including breast size, cup size, and BMI. Therefore, breast density may not be as predictive of breast cancer risk across racial groups. However, density may still be predictive of risk within racial groups or within groups with similar BMI or breast size.
Our group has previously reported a series of 769 women and noted a lower mean mammographic breast density among the 207 African American women in that group when compared with Caucasians and Latinas [14]. Although most of this difference appeared to be due to differences in BMI, our data suggested an additional difference due to race. The results of our current study failed to confirm our previous observation. Instead, this larger series of African Americans showed that all differences in density can be explained by BMI, bra size, or cup size. There is no difference in breast density in African Americans based on race alone. Importantly, with the larger data set and our current analysis, we are unable to corroborate previous reports that differences in breast density explain racial variations in cancer risk [14, 15].
The results of the current series, reporting on 15,292 women, fail to support the suggestion that innate breast density differences explain risk differences across racial groups [13, 14, 17, 21]. According to our data, age plus BMI or bra size plus cup size could account for the reported differences in breast density. There may be no innate racial differences in breast density beyond those associated with racial differences in age and body habitus. Our results do not support the use of mammographic density as a suitable surrogate of breast cancer risk differences across racial groups. Future studies are needed to explore relationships of mammographic breast density to the risk of developing breast cancer and to explore relationships of race and the risk of developing breast cancer.
Acknowledgments
We thank Elizabeth Rafferty and James S. Michaelson for their contributions
to the manuscript.
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