Does Breast Size Modify the Association between Mammographic Density and Breast Cancer Risk?

Stuedal, Anne; Ma, Hui; Bernstein, Leslie; Pike, Malcolm C.; Ursin, Giske

doi:10.1158/1055-9965.epi-07-2554

Cited by 29 publications

(27 citation statements)

References 22 publications

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“…Consistent with the trends and effects seen in our studies, the association of absolute dense area with BC risk was found to be decreased for larger breasts [50]. Investigators in two large case-control studies (634 cases:1880 controls [51] and 1424 cases:2660 controls [52]) and a prospective study of 111 cases of BC [53] all found statistically significant inverse associations of non-dense breast area with BC risk.…”

Section: Discussionsupporting

confidence: 88%

Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis

et al. 2016

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BackgroundHigh mammographic density (HMD) not only confers a significantly increased risk of breast cancer (BC) but also is associated with BCs of more advanced stages. However, it is unclear whether BC progression and metastasis are stimulated by HMD. We investigated whether patient-derived HMD breast tissue could stimulate the progression of MCF10DCIS.com cells compared with patient-matched low mammographic density (LMD) tissue.MethodsSterile breast specimens were obtained immediately after prophylactic mastectomy from high-risk women (n = 10). HMD and LMD regions of each specimen were resected under radiological guidance. Human MCF10DCIS.com cells, a model of ductal carcinoma in situ (DCIS), were implanted into silicone biochambers in the groins of severe combined immunodeficiency mice, either alone or with matched LMD or HMD tissue (1:1), and maintained for 6 weeks. We assessed biochamber weight as a measure of primary tumour growth, histological grade of the biochamber material, circulating tumour cells and metastatic burden by luciferase and histology. All statistical tests were two-sided.ResultsHMD breast tissue led to increased primary tumour take, increased biochamber weight and increased proportions of high-grade DCIS and grade 3 invasive BCs compared with LMD. This correlated with an increased metastatic burden in the mice co-implanted with HMD tissue.ConclusionsOur study is the first to explore the direct effect of HMD and LMD human breast tissue on the progression and dissemination of BC cells in vivo. The results suggest that HMD status should be a consideration in decision-making for management of patients with DCIS lesions.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0767-4) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 88%

Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis

et al. 2016

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“…Prior findings published by Stuedal and colleagues [14] lend indirect to support to the notion that nondense mammographic area is inversely associated with breast cancer risk. Stuedal and colleagues examined if the association between mammographic density and breast cancer risk differs according to the size of the breasts.…”

Section: Discussionmentioning

confidence: 95%

“…Stuedal and colleagues examined if the association between mammographic density and breast cancer risk differs according to the size of the breasts. They used the total breast area on a mammogram as a proxy for breast size and found that the association between absolute dense area and breast cancer risk was significantly lower in larger breasts [14]. For percentage dense area, the results were similar, although weaker and nonsignificant.…”

Section: Discussionmentioning

confidence: 99%

Nondense mammographic area and risk of breast cancer

et al. 2011

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IntroductionThe mechanisms underlying the strong association between percentage dense area on a mammogram and the risk of breast cancer are unknown. We investigated separately the absolute dense area and the absolute nondense area on mammograms in relation to breast cancer risk.MethodsWe conducted a nested case-control study on prediagnostic mammographic density measurements and risk of breast cancer in the Nurses' Health Study and the Nurses' Health Study II. Premenopausal mammograms were available from 464 cases and 998 controls, and postmenopausal mammograms were available from 960 cases and 1,662 controls. We used a computer-assisted thresholding technique to measure mammographic density, and we used unconditional logistic regression to calculate OR and 95% CI data.ResultsHigher absolute dense area was associated with a greater risk of breast cancer among premenopausal women (ORtertile 3 vs 1 = 2.01, 95% CI = 1.45 to 2.77) and among postmenopausal women (ORquintile 5 vs 1 = 2.19, 95% CI = 1.65 to 2.89). However, increasing absolute nondense area was associated with a decreased risk of breast cancer among premenopausal women (ORtertile 3 vs 1 = 0.51, 95% CI = 0.36 to 0.72) and among postmenopausal women (ORquintile 5 vs 1 = 0.46, 95% CI = 0.34 to 0.62). These associations changed minimally when we included both absolute dense area and absolute nondense area in the same statistical model. As expected, the percentage dense area was the strongest risk factor for breast cancer in both groups.ConclusionsOur results indicate that absolute dense area is independently and positively associated with breast cancer risk, whereas absolute nondense area is independently and inversely associated with breast cancer risk. Since adipose tissue is radiographically nondense, these results suggest that adipose breast tissue may have a protective role in breast carcinogenesis.

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“…Mammographic density may reflect cumulative exposure to endogenous estrogens, which may increase breast cancer risk through its mitogenic effects (40). Breast size has been reported to modify the association of dense area with breast cancer, with weaker associations found in larger breasts (48). Thus, the inverse associations of late adolescent BMI with breast density and cancer risk may be mediated by increased non-dense (fatty) area and adipocytes that support normal breast epithelial proliferation throughout puberty and inhibit later carcinogenesis (40).…”

Section: Discussionmentioning

confidence: 99%

Age at Menarche and Late Adolescent Adiposity Associated with Mammographic Density on Processed Digital Mammograms in 24,840 Women

Alexeeff

Odo

Lipson

et al. 2017

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background High mammographic density is strongly associated with increased breast cancer risk. Some, but not all, risk factors for breast cancer are also associated with higher mammographic density. Methods The study cohort (N=24,840) was drawn from the Research Program in Genes, Environment and Health of Kaiser Permanente Northern California and included non-Hispanic white females aged 40–74 years with a full-field digital mammogram (FFDM). Percent density (PD) and dense area (DA) were measured by a radiological technologist using Cumulus. The association of age at menarche and late adolescent BMI with PD and DA were modeled using linear regression adjusted for confounders. Results Age at menarche and late adolescent BMI were negatively correlated. Age at menarche was positively associated with PD (p-value for trend<0.0001) and DA (p-value for trend <0.0001) in fully adjusted models. Compared to the reference category of age 12–13 years at menarche, menarche at age >16 years was associated with an increase in PD of 1.47% [95% CI: (0.69, 2.25)] and an increase in DA of 1.59cm2 [95% CI: (0.48, 2.70)]. Late adolescent BMI was inversely associated with PD (p-value <0.0001) and DA (p-value <0.0001) in fully adjusted models. Conclusions Age at menarche and late adolescent BMI are both associated with Cumulus measures of mammographic density on processed FFDM images. Impact Age at menarche and late adolescent BMI may act through different pathways. The long-term effects of age at menarche on cancer risk may be mediated through factors besides mammographic density.

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Does Breast Size Modify the Association between Mammographic Density and Breast Cancer Risk?

Cited by 29 publications

References 22 publications

Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis

Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis

Nondense mammographic area and risk of breast cancer

Age at Menarche and Late Adolescent Adiposity Associated with Mammographic Density on Processed Digital Mammograms in 24,840 Women

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