The influence of mammographic density on breast tumor characteristics

Abstract

Mammographic density (MD) is a well-established risk factor for breast cancer. Whether MD influences the tumor phenotype remains to be clarified. Previous studies are highly inconsistent and most lack important covariate information. This is a case-only study within a population-based case-control study. Cases were all postmenopausal women, aged 50-74 years, with incident breast cancer, diagnosed 1993-1995, and with no history of previous cancer (n = 2,720). 1,747 women with mammograms and information on tumor characteristics were included in analyses. MD was assessed using a computer-assisted thresholding technique. We used linear, logistic, and multinomial logistic regression, adjusting for possible confounders, to study density and tumor characteristics. PD was only statistically significantly associated with tumor size in our study (regression coefficient 0.031, p = 0.017). The effect of PD on tumor size was greater when mode of detection was excluded from the model (regression coefficient 0.043, p = 0.001). No other associations between PD and the tumor characteristics studied (lymph node metastasis, ER-status, PR-status, grade, and histopathological classification) were observed. In summary, PD was positively associated with tumor size in postmenopausal women. However, the relationship was at least partially confounded by mode of detection. Although there may be a true biological relationship between MD and more highly proliferative tumors, it also seems that part of this relationship is due to masking delaying diagnosis. In conclusion, PD does not seem to be differentially associated with tumor phenotype, except for tumor size, after taking mode of detection into consideration.

Amount of stroma is associated with mammographic density and stromal expression of oestrogen receptor in normal breast tissues

“…Epidemiological studies have shown that mammographic density is not associated with any particular breast cancer sub-type [26,27], while some studies suggest that mammographic density is more strongly associated with ER-positive rather than ER-negative breast cancers [28,29]. Although the majority of human breast cancers are ERpositive and arise from epithelial tissues, we found no association between epithelial ER and proportions of epithelial and stromal tissue in any of the statistical models employed.…”

Mammographic density and survival in interval breast cancers

“…For this study, the inclusion criteria were further refined to include only postmenopausal women who had no prior diagnosis of cancer other than nonmelanoma skin cancer (see Eriksson et al [14] for details). The study base thus consisted of 2,720 breast cancer cases.…”

“…This is theoretically plausible because MD has consistently been shown to be associated with the stromal composition of the breast [5-9], and the stroma plays an important part in tumor progression [10]. There is also some evidence that MD is associated with more aggressive tumor characteristics [11-13], but most studies have found no association between MD and tumor characteristics [14-19]. …”

Will Supplemental Screening Ultrasound Increase Breast Cancer Overdiagnosis?

“…It has been established that tumors seen in BRCA1 carriers are more likely to be grade III and of the medullary subtype than sporadic cancers (25), but there are little data on association of other risk factors and histologic features. Reports on the associations of breast density with prognostic factors such as tumor grade, estrogen receptor (ER) status, and HER2 status have been inconclusive (26,27), although one recent study did show an association between breast density and high-grade tumors, ER-negative tumors, and in situ versus invasive tumors (27). Breast density has also been associated with an increased risk of local and locoregional recurrence (28) but not with distant metastasis or survival.…”