Involution of breast tissue and mammographic density

Abstract

BackgroundMammographic density decreases and involution of breast tissue increases with age; both are thought to be risk factors for breast cancer. The current study investigated the relationship between involution or hormone treatment (HT) and breast density among multiethnic patients with breast cancer in Hawaii.MethodsPatients with breast cancer cases were recruited from a nested case-control study within the Multiethnic Cohort. HT use was self-reported at cohort entry and at the time of the density study. Mammographic density and involution in adjacent non-tumor breast tissue were assessed using established methods. Linear regression was applied to evaluate the correlation between involution and four density measures and to compute adjusted means by involution status while adjusting for confounders.ResultsIn the 173 patients with breast cancer, mean percent breast density was 41.2% in mammograms taken approximately 1 year before diagnosis. The respective proportions of women with no, partial, and complete involution were 18.5, 51.4, and 30.1%, respectively and the adjusted density values for these categories were 32.5, 39.2, and 40.2% (p = 0.15). In contrast, the size of the dense area was significantly associated with involution (p = 0.001); the values ranged from 29.7 cm2 for no involution to 48.0 cm2 for complete involution. The size of the total breast area but not of the non-dense areas was also larger with progressive involution. Percent density and dense area were significantly higher in women with combined HT use.ConclusionsContrary to previous reports, greater lobular involution was not related to lower mammographic density but to higher dense area. Possibly, percent density during the involution process depends on the timing of mammographic density assessment, as epithelial tissue is first replaced with radiographically dense stromal tissue and only later with fat.

The relationship between terminal duct lobular unit features and mammographic density among Chinese breast cancer patients

“…In a recent study using data from The Breast Radiology Evaluation and Study of Tissues Stamp Project (Stamp), where benign biopsy tissues were annotated with more standardized and quantitative TDLU measures, the association of dense breast tissues with lower extent of TDLU involution was confirmed . In contrast, a report from Multiethnic Cohort showed that greater TDLU involution assessed in adjacent non‐tumor breast tissue was associated with a larger MD area . There may be several reasons to explain these conflicting results, such as the heterogeneity in the assessment of TDLU involution (standardized quantitative vs .…”

“…4 Contrary to these reports, a recent analysis of breast cancer cases within the Multiethnic Cohort, which was highly enriched for Japanese Americans (43%) and included participants who were older (mean age 59.7 years) and thinner than in other studies showed the opposite direction of the association (i.e., greater TDLU involution associated with higher dense area). 6 The explanation of this finding is unresolved but may suggest potential racial variation in the TDLU-MD relationship.…”

“…Mammographic density (MD) is a radiological representation of stromal and epithelial breast tissue content and extensive MD is a well‐established risk factor for breast cancer . Several studies have provided insight into the underlying mechanism of the MD and breast cancer risk association by examining histologic features of breast tissues . Terminal duct lobular unit (TDLU) involution is a histological measure of breast tissue characterized by a reduction in the epithelial component with aging .…”

“…Although these measures from the histologic (i.e., TDLU involution) and the radiologic (i.e., MD) assessments of breast tissues are correlated, increased TDLU involution has been associated with lower breast cancer risk independently of MD, suggesting that the relationship between TDLU involution and MD, and their associations with breast cancer risk are more complex. To date, most studies of MD in relation to TDLU features, including the one in Multiethnic Cohort, have been conducted among Western populations. Therefore, we examined the relationship between MD and TDLU features in non‐neoplastic breast tissues from breast cancer patients in China, where breast cancer incidence rates are historically low and the prevalence of dense breasts and other breast cancer risk factors are substantially different from high‐risk populations in Western countries …”

“…1,2 Several studies have provided insight into the underlying mechanism of the MD and breast cancer risk association by examining histologic features of breast tissues. [3][4][5][6] Terminal duct lobular unit (TDLU) involution is a histological measure of breast tissue characterized by a reduction in the epithelial component with aging. 7 Less extent of involution, characterized by greater number and size of observed TDLUs, has been associated with higher breast cancer risk among women with benign breast diseases.…”