Dense breast stromal tissue shows greatly increased concentration of breast epithelium but no increase in its proliferative activity

Hawes, Debra; Downey, Susan E.; Pearce, Celeste Leigh; Bartow, Sue A.; Wan, Peggy; Pike, Malcolm C.; Wu, Anna H.

doi:10.1186/bcr1408

Cited by 64 publications

(74 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High levels of the cholesterol metabolite 27-hydroxycholesterol were observed to increase estrogen-dependent breast cancer proliferation (8,9). Interestingly, mammographic density, a strong predictor of breast cancer development, is positively correlated with the number of epithelial cells (10), and mammographic density was recently linked to metabolic syndrome (11).…”

Section: Introductionmentioning

confidence: 99%

High-Density Lipoprotein-Cholesterol, Daily Estradiol and Progesterone, and Mammographic Density Phenotypes in Premenopausal Women

Flote

Frydenberg

Ursin

et al. 2015

Cancer Prevention Research

View full text Add to dashboard Cite

High-density lipoprotein-cholesterol (HDL-C) may influence the proliferation of breast tumor cells, but it is unclear whether low HDL-C levels, alone or in combination with cyclic estrogen and progesterone, are associated with mammographic density, a strong predictor of breast cancer development. Fasting morning serum concentrations of HDL-C were assessed in 202 premenopausal women, 25 to 35 years of age, participating in the Norwegian Energy Balance and Breast Cancer Aspects (EBBA) I study. Estrogen and progesterone were measured both in serum, and daily in saliva, throughout an entire menstrual cycle. Absolute and percent mammographic density was assessed by a computer-assisted method (Madena), from digitized mammograms (days 7-12). Multivariable models were used to study the associations between HDL-C, estrogen and progesterone, and mammographic density phenotypes. We observed a positive association between HDL-C and percent mammographic density after adjustments (P ¼ 0.030). When combining HDL-C, estradiol, and progesterone, we observed among women with low HDL-C (<1.39 mmol/L), a linear association between salivary 17b-estradiol, progesterone, and percent and absolute mammographic density. Furthermore, in women with low HDL-C, each one SD increase of salivary mid-menstrual 17b-estradiol was associated with an OR of 4.12 (95% confidence intervals; CI, 1.30-13.0) of having abovemedian percent (28.5%), and an OR of 2.5 (95% CI, 1.13-5.50) of having above-median absolute mammographic density (32.4 cm 2 ). On the basis of plausible biologic mechanisms linking HDL-C to breast cancer development, our findings suggest a role of HDL-C, alone or in combination with estrogen, in breast cancer development. However, our small hypothesis generating study requires confirmation in larger studies.Cancer Prev Res; 8(6); 535-44. Ó2015 AACR.

show abstract

Section: Introductionmentioning

confidence: 99%

High-Density Lipoprotein-Cholesterol, Daily Estradiol and Progesterone, and Mammographic Density Phenotypes in Premenopausal Women

Flote

Frydenberg

Ursin

et al. 2015

Cancer Prevention Research

View full text Add to dashboard Cite

show abstract

“…48 It has also been shown that breasts with high density and those with cancer exhibit similar biological characteristics such as increased concentration of epithelial and stromal cells and collagen. 32,33,51 Epithelial cell proliferation is necessary for breast density increases, however since breast cancer primarily evolve from epithelial cells, increased numbers of epithelial cells in the dense breast increase the possibility of cancer. 33 Stromal cells induce cancer by modulating epithelial cells through epidermal growth factor receptor, IGF-1, and TGF-β.…”

Section: Breast Composition and Radiographic Appearancesmentioning

confidence: 99%

“…32,33,51 Epithelial cell proliferation is necessary for breast density increases, however since breast cancer primarily evolve from epithelial cells, increased numbers of epithelial cells in the dense breast increase the possibility of cancer. 33 Stromal cells induce cancer by modulating epithelial cells through epidermal growth factor receptor, IGF-1, and TGF-β. 52 Stromal cells are also progenitors, of collagen and stromal matrix which promote mammary gland development and tumour invasion [52][53][54] and since collagen is linked to IGF-1 quantities and tumour reorganization, 53 there are increased opportunities for cell proliferation and transformation to cancer.…”

Section: Breast Composition and Radiographic Appearancesmentioning

confidence: 99%

“…48 The second mechanism involves biological interaction among epithelial and stromal cells, collagen and the breast microenvironment. 32,33 It has been shown that mitogenic followed by mutagenic activity are at least in part, responsible for high breast density and breast cancer, where individuals with both high breast density and breast cancer demonstrate similar mitogen 47 and mutagen characteristics. 48 It is well known that mitogens induce cell proliferation, primarily affecting epithelial and stromal cells leading to increased fibroglandular tissue and higher levels of breast density mostly in premenopausal women.…”

Section: Breast Composition and Radiographic Appearancesmentioning

confidence: 99%

“…3 The dense portion of the breast contains high concentration of epithelial and stromal cells and collagen. 3,32,33 Dense breasts are highly radiosensitive due to the high proliferation of epithelial and stromal cells in such breasts. 34 To reduce the potential effect of radiation on the breast, there is a need to optimise the imaging procedure.…”

Section: Breast Composition and Radiographic Appearancesmentioning

confidence: 99%

See 2 more Smart Citations

Breast composition: Measurement and clinical use

Ekpo¹,

Hogg²,

Highnam³

et al. 2015

Radiography

View full text Add to dashboard Cite

Breast density is a measure of the extent of radiodense fibroglandular tissue in the breast. The risk of developing breast cancer and the risk of missing cancer at screening rise with higher breast density. In this paper, the historical background to breast density measurement is outlined and current evidence based practice is explained. The relevance of breast density knowledge to mammographic practice and image interpretation is considered in the light of clinical assessment and notification of mammographic breast density (MBD). The current work also discusses risk stratification for decisionmaking regarding screening frequency and better modalities for earlier detection of breast cancer in the dense breast. Automated volumetric approaches are explained while ultrasound, digital breast tomosynthesis, molecular breast imaging, and magnetic resonance imaging are introduced as valuable adjuncts to digital mammography for imaging the dense breast. The work concludes on the important note that screened women should be notified of their breast density, and such notification should be accompanied with clear and adequate information about breast density and cancer risk, strategies associated with lower MBD, as well as best screening intervals and pathways for women with dense breasts. Adoption of these strategies may be crucial to early detection and treatment of cancer and improving survival from the disease.

show abstract

Baseline breast tissue characteristics determine the effect of tamoxifen on mammographic density change

Gabrielson,

Hammarström,

Bergqvist

et al. 2024

Intl Journal of Cancer

View full text Add to dashboard Cite

Tamoxifen prevents recurrence of breast cancer and is also approved for preventive, risk‐reducing, therapy. Tamoxifen alters the breast tissue composition and decreases the mammographic density. We aimed to test if baseline breast tissue composition influences tamoxifen‐associated density change. This biopsy‐based study included 83 participants randomised to 6 months daily intake of placebo, 20, 10, 5, 2.5, or 1 mg tamoxifen. The study is nested within the double‐blinded tamoxifen dose‐determination trial Karolinska Mammography Project for Risk Prediction of Breast Cancer Intervention (KARISMA) Study. Ultrasound‐guided core‐needle breast biopsies were collected at baseline before starting treatment. Biopsies were quantified for epithelial, stromal, and adipose distributions, and epithelial and stromal expression of proliferation marker Ki67, oestrogen receptor (ER) and progesterone receptor (PR). Mammographic density was measured using STRATUS. We found that greater mammographic density at baseline was positively associated with stromal area and inversely associated with adipose area and stromal expression of ER. Premenopausal women had greater mammographic density and epithelial tissue, and expressed more epithelial Ki67, PR, and stromal PR, compared to postmenopausal women. In women treated with tamoxifen (1–20 mg), greater density decrease was associated with higher baseline density, epithelial Ki67, and stromal PR. Women who responded to tamoxifen with a density decrease had on average 17% higher baseline density and a 2.2‐fold higher PR expression compared to non‐responders. Our results indicate that features in the normal breast tissue before tamoxifen exposure influences the tamoxifen‐associated density decrease, and that the age‐associated difference in density change may be related to age‐dependant differences in expression of Ki67 and PR.

show abstract

Dense breast stromal tissue shows greatly increased concentration of breast epithelium but no increase in its proliferative activity

Cited by 64 publications

References 10 publications

High-Density Lipoprotein-Cholesterol, Daily Estradiol and Progesterone, and Mammographic Density Phenotypes in Premenopausal Women

High-Density Lipoprotein-Cholesterol, Daily Estradiol and Progesterone, and Mammographic Density Phenotypes in Premenopausal Women

Breast composition: Measurement and clinical use

Baseline breast tissue characteristics determine the effect of tamoxifen on mammographic density change

Contact Info

Product

Resources

About