Mammographic Breast Density In Women Research Articles

Associations of stem cell markers CD44, CD24 and ALDH1A1 with mammographic breast density in women with benign breast biopsies.

We examined associations of CD44, CD24 and ALDH1A1 breast stem cell markers with mammographic breast density (MBD), a well-established breast cancer (BCa) risk factor. We included 218 cancer-free women with biopsy-confirmed benign breast disease within the Nurses' Health Study (NHS) and NHSII. The data on BCa risk factors were obtained from biennial questionnaires. Immunohistochemistry (IHC) was done on tissue microarrays. For each core, the IHC expression was assessed using a semi-automated platform and expressed as percent of positively stained cells for each marker out of the total cell count. MBD was assessed with computer-assisted techniques. Generalised linear regression was used to examine the associations of each marker with square root-transformed percent density (PD), absolute dense and non-dense areas (NDA), adjusted for BCa risk factors. Stromal CD44 and ALDH1A1 expression was positively associated with PD (≥ 10% vs. <10% β = 0.56, 95% confidence interval [CI] [0.06; 1.07] and β = 0.81 [0.27; 1.34], respectively) and inversely associated with NDA (β per 10% increase = -0.17 [-0.34; -0.01] and β for ≥10% vs. <10% = -1.17 [-2.07; -0.28], respectively). Epithelial CD24 expression was inversely associated with PD (β per 10% increase = -0.14 [-0.28; -0.01]. Stromal and epithelial CD24 expression was positively associated with NDA (β per 10% increase = 0.35 [0.2 × 10-2; 0.70] and β per 10% increase = 0.34 [0.11; 0.57], respectively). Expression of stem cell markers is associated with MBD.

Breast density and the likelihood of malignant MRI-detected lesions in women diagnosed with breast cancer

ObjectivesTo assess whether mammographic breast density in women diagnosed with breast cancer correlates with the total number of incidental magnetic resonance imaging (MRI)-detected lesions and the likelihood of the lesions being malignant.MethodsPatients diagnosed with breast cancer meeting the EUSOBI and EUSOMA criteria for preoperative breast MRI routinely undergo mammography and ultrasound before MRI at our institution. Incidental suspicious breast lesions detected in MRI are biopsied. We included patients diagnosed with invasive breast cancers between 2014 and 2019 who underwent preoperative breast MRI. One reader retrospectively determined breast density categories according to the 5th edition of the BI-RADS lexicon.ResultsOf 946 patients with 973 malignant primary breast tumors, 166 (17.5%) had a total of 175 (18.0%) incidental MRI-detected lesions (82 (46.9%) malignant and 93 (53.1%) benign). High breast density according to BI-RADS was associated with higher incidence of all incidental enhancing lesions in preoperative breast MRIs: 2.66 (95% confidence interval: 1.03–6.86) higher for BI-RADS density category B, 2.68 (1.04–6.92) for category C, and 3.67 (1.36–9.93) for category D compared to category A (p < 0.05). However, high breast density did not predict higher incidence of malignant incidental lesions (p = 0.741). Incidental MRI-detected lesions in the contralateral breast were more likely benign (p < 0.001): 18 (27.3%)/48 (72.7%) vs. 64 (58.7%)/45 (41.3%) malignant/benign incidental lesions in contralateral vs. ipsilateral breasts.ConclusionWomen diagnosed with breast cancer who have dense breasts have more incidental MRI-detected lesions, but higher breast density does not translate to increased likelihood of malignant incidental lesions.Clinical relevance statementDense breasts should not be considered as an indication for preoperative breast MRI in women diagnosed with breast cancer.Key Points• The role of preoperative MRI of patients with dense breasts diagnosed with breast cancer is under debate.• Women with denser breasts have a higher incidence of all MRI-detected incidental breast lesions, but the incidence of malignant MRI-detected incidental lesions is not higher than in women with fatty breasts.• High breast density alone should not indicate preoperative breast MRI.

The Effect of Breast Size and Density in Turkish Women on Radiation Dose in Full-Field Digital Mammography.

The purpose of this study was to look into the relationship between breast size and mammographic breast density in women and breast radiation dose on full-field digital mammography (FFDM), as well as the factors that influence radiation dose. The study included a total of 2,060 FFDM images from 515 consecutive participants. The participants were divided into two groups: those exposed to high doses (>3 mGy) and those exposed to low doses (<3 mGy). Moreover, the researchers analyzed the relationship between mean glandular dose (MGD) of the breast and patient age, compressed breast thickness, compression force, mammographic breast composition, and mammographic breast size. The mean mammographic breast volume was 936.2 ± 425.2 (114.5-3,018) mL, and the mean compressed breast tissue thickness was 56.75 ± 10.44 mm. Moreover, the mean MGD in the high-dose group was 3.51 ± 0.48 mGy and 1.92 ± 0.56 mGy in the low-dose group. The high-dose group had greater breast thickness, diameters, volume, compression pressure, and surgical rate. However, the high-dose group was younger and had less dense breasts. In multivariate logistic regression analysis, the most important predictors of dose determination were breast thickness [odds ratio (OR): 1.178, 95% confidence interval (CI): 1.156-1.200, p<0.001], history of previous surgery (OR: 2.210, 95% CI: 1.417-3.447, p<0.001), compression force (OR: 1.008, 95% CI: 1.004-1.013, p<0.001), and breast density (OR: 1.873, 95% CI: 1.359-2.580, p<0.001). Women with larger breast volumes are subjected to higher doses of radiation. Therefore, breast-screening programs can be individualized to young women with larger breast volumes and women who have had breast-conserving surgery.

Lifestyle, Behavioral, and Dietary Risk Factors in Relation to Mammographic Breast Density in Women at High Risk for Breast Cancer.

Women at high risk for breast cancer due to genetics or risk factor profiles are counseled to adopt lifestyle, behavioral, and dietary changes to help reduce their risk. These recommendations are based on studies of women at average risk, so their effectiveness in high-risk women is unclear. We evaluated the impact of physical activity, smoking, alcohol consumption, and intake of folate and carotenoids on mammographic breast density-a proxy for breast cancer risk-among 387 high-risk women. Exposures were self-reported on questionnaires. Breast dense area, nondense area, and percent dense area were measured from screening mammograms with Library for Breast Radiodensity Assessment software. Cross-sectional associations were estimated with multivariable quantile regression models. After adjusting for age, adiposity, reproductive history, and use of postmenopausal hormones, no breast density measure was associated with physical activity level, smoking status, alcohol consumption, or estimated intake of folate, alpha-carotene, beta-carotene, lutein/zeaxanthin, and beta-cryptoxanthin. Lycopene intake was associated with lower dense area when comparing the highest and lowest intake categories (adjusted difference in median = -14 cm2, 95% confidence interval: -29 to 1.3 cm2). This association may be explained by incomplete adjustment for adiposity. Recommended lifestyle, behavioral, and dietary changes to mitigate personal risk of breast cancer do not substantially impact mammographic breast density measures. Alternative strategies, such as increased uptake of chemoprevention, may better serve risk reduction efforts in women at high risk for breast cancer.

Abstract P3-01-05: Influence of hormone replacement therapy following bilateral salpingo-oophorectomy on mammographic breast density in women newly diagnosed with breast cancer

Abstract Background: Studies have demonstrated that use of hormone replacement therapy (HRT) in post-menopausal women results in increased breast density. This is associated with increased risk of breast cancer and reduced sensitivity of mammography. The purpose of the present study was to compare breast densities of women following surgical menopause with and without use of HRT to women who had natural menopause without use of HRT. Methods: Our institutional Database was queried for post-menopausal women newly diagnosed with breast cancer from 01/2010 to 01/2016. Patients were divided into following groups: 1) natural menopause with no HRT use, 2) history of a bilateral salpingo-oophorectomy (BSO) with no HRT use, 3) history of a BSO with HRT use prior to diagnosis, or 4) history of BSO and use of HRT at the time of diagnosis. BSO may have occurred with or without concurrent hysterectomy. Results: 1106 women were eligible for analysis. 976 (88%) had natural menopause with no HRT, 63 (6%) had a BSO with no HRT, 51 (5%) had a BSO with previous history of HRT, and 16 (1%) had a BSO and were using HRT at time of malignancy diagnosis. Though not statistically significant, women who had a prior BSO and were on HRT at the time of diagnosis had more dense breasts (69% heterogeneously or extremely dense) than women who had natural menopause with no HRT (44% heterogeneously or extremely dense). However, women who had a prior BSO and were on HRT in the past had significantly less dense breasts (p=0.007) than women who underwent natural menopause without HRT use (67% vs. 56%). There were no differences observed in the tumor characteristics between all groups. Breast densities by groupVariablesNatural menopause, no HRT (N=976, 88%)BSO, no HRT (N=63, 6%)p-valueBSO, prior HRT (N=51, 5%)p-valueBSO, current HRT (N=16, 1%)p-valueMedian age at diagnosis, yr64 (39-95)64 (39-93)0.4865 (45-83)0.3462 (41-77)0.17Median age at menopause, yr51 (33-62)47 (32-60)&amp;lt;0.000146 (30-59)&amp;lt;0.000147 (39-55)&amp;lt;0.0001Breast densityEntirely fatty94 (10%)5 (8%)0.950 (0%)0.0070 (0%)0.17Scattered fibroglandular448 (46%)30 (47%) 34 (67%) 5 (31%) Heterogeneously dense393 (40%)25 (40%) 16 (31%) 11 (69%) Extremely dense41 (4%)3 (5%) 1 (2%) 0 (0%) Conclusion: In our study cohort, women with history of surgical menopause who were on HRT at the time of breast cancer diagnosis had a trend towards more dense breasts. Surprisingly, women who were prior users had less dense breasts than women who never used HRT. Despite the change observed in breast density, the tumor characteristics do not differ with HRT usage, suggesting that variability in breast density did not correlate with stage of disease at presentation. This may be related to heightened awareness among clinicians regarding risk associated with HRT use that led them to modify screening and surveillance in these patients. Citation Format: Pivo S, Schwartz S, Chun J, Guth A, Axelrod D, Shapiro R, Schnabel F. Influence of hormone replacement therapy following bilateral salpingo-oophorectomy on mammographic breast density in women newly diagnosed with breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-01-05.

The influence of inflammation on mammographic breast density in women at increased risk of breast cancer.

1566 Background: Mammographic density is an important risk factor for breast cancer but the etiology of density is not well understood. Studies suggest that inflammation may play a role in density....

Mammographic breast density in women with premature ovarian failure

This study aims to compare breast density between two mammograms in women with premature ovarian failure (POF). A cohort study evaluated 56 women with POF. Two mammograms performed at least 2 years apart were analyzed. Mammogram films were digitalized, and images were assessed using a computer-assisted method; the percentage of breast image that is radiologically dense is referred to as the percentage of mammographic density (PMD). Age at menarche, age at onset of POF, length of POF, length of estrogen-progestin therapy (EPT), body mass index (BMI), pregnancy, and age at the time of each mammogram were evaluated. The mean (SD) age at POF diagnosis was 32.35 (5.95) years. In the first mammogram, the mean (SD) age, BMI, and length of POF were 37.58 (3.72) years, 26.79 (4.86) kg/m, and 5.25 (4.61) years, respectively. EPT had been used for a mean (SD) of 2.71 (3.12) years. In the second mammogram, the mean (SD) age, BMI, and length of POF were 43.23 (4.98) years, 27.6 (5.39) kg/m, and 10.5 (5.11) years, respectively. EPT had been used for a mean (SD) of 7.25 (4.6) years. The mean (SD) interval between mammograms was 5.25 (3) years, and the mean (SD) PMD decreased from 27.78% (21.04%) to 17.53% (15.71%) (P = 0.007). Comparing PMD between women taking EPT and those not taking EPT, we observed no significant differences. In both instances, multiparous women had lower PMD than nulliparous women (P < 0.05). BMI, length of POF, and pregnancy were negatively correlated with PMD. Breast density in young women with POF decreases across a period of 5 years, regardless of EPT use. Further studies may elucidate how this result will correlate with decision-making in clinical therapeutics and breast cancer risk in POF.

Abstract B95: Higher breast density is positively associated with larger tumor size and lymph node metastasis: A cross-sectional study of 910 Korean breast cancer patients

Abstract Although many western studies have demonstrated high breast density as a strong risk factor for breast cancer, it is poorly understood whether breast density differentially affects the diverse phenotypes of breast cancer. We examined the association between various tumor characteristics and mammographic breast density in women with breast cancer. We conducted a cross-sectional analysis in 910 Korean women diagnosed with in situ or invasive breast cancer to evaluate the associations between breast density and tumor size, lymph node (LN) status, lymphatic or vascular invasion, histologic grade, estrogen receptor (ER), progesterone receptor (PR), HER2, p53, and CK5/6. Breast density was classified as fatty (percent density less than 50% by a computer-assisted thresholding program, named “Cumulus TM”; n = 470) or dense (percent density 50% or more; n = 440) for the cancer-free breast at the time of operation. A single pathologist measured all tumor markers. Blinded to the tumor markers' status, percent densities were also calculated by a single rater. Logistic regression was used to examine whether the relationships were modified by adjustment for body mass index, age at diagnosis, age at first birth, menopausal status, history of breast-feeding, and breast cancer staging. The mean age was 48 (range 20-82) years old and mean percent density was 49.1% (SD = 15.2%: normally distributed, Kolmogorov-Smirnov test p=0.32). Women with a tumor size &amp;gt;0.5cm were more likely to have dense breasts compared with women with a tumor size &amp;lt;=0.5 cm (ORadj = 4.2, 95% CI = 1.6-11.2 for tumor sizes 0.6-1.0cm; ORadj = 3.4, 95% CI = 1.4-8.2 for tumor sizes 1.1-1.5cm; ORadj = 3.3, 95% CI = 1.4-7.9 for tumor sizes 1.6-2.0cm; and ORadj = 2.0, 95% CI = 0.7-5.5 for tumor sizes 2.1cm or more). An association between LN positivity and percent density had borderline significance (ORadj = 1.8, 95% CI = 0.997-3.215 for positive LN status). Percent density was not significantly associated with lymphatic or vascular invasion (p = 0.77), ER (p = 0.39), PR (p = 0.83), HER2 (p = 0.40), p53 (p=0.22), and CK5/6 (p = 0.62). An inverse association was suggested between tumor grade and percent density (OR = 0.56, 95% CI = 0.33-0.97), but insignificant after the adjustment (ORadj = 0.65, 95% CI = 0.31-1.37). These results suggest that breast density is associated with tumor size and LN status. Additional studies are needed to address whether these associations are due to just density masking the detection of some tumors, biological causation, or both. Citation Format: Jong won Lee, Ja Young Cho, Sei-hyun Ahn. Higher breast density is positively associated with larger tumor size and lymph node metastasis: A cross-sectional study of 910 Korean breast cancer patients. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B95.

P829 The different effect of progestin on mammographic breast density in women on low-dose hormone therapy

P829 The different effect of progestin on mammographic breast density in women on low-dose hormone therapy

Testosterone addition during menopausal hormone therapy: effects on mammographic breast density

Objective To study the effect on mammographic breast density of testosterone addition during combined estrogen/progestogen therapy in postmenopausal women.Methods A prospective, randomized, double-blind, placebo-controlled trial. A total of 99 women were given 2 mg 17β-estradiol and 1 mg norethisterone acetate in combination with either a testosterone patch (300 μg/24 h) or a placebo patch. Mammographic breast density at baseline and after 6 months was assessed by visual classification scales and by digitized quantification. A standardized questionnaire was used to quantify subjective breast symptoms.Results Visual classifications showed an increase in mammographic density in 18–30% of the women, with no significant differences between the treatment groups. The mean increase of the area of dense breast during treatment according to digitized assessment was 7.4% in the placebo group and 5.4% in the testosterone group. Breast symptoms showed a positive association with the increase in density (rs = 0.34; p < 0.01). Symptoms were most pronounced at 2 months of treatment. Density, both at baseline (rs = −0.35; p < 0.01) and change during treatment (rs = −0.28; p < 0.01) showed a negative association with free testosterone levels.Conclusion The addition of testosterone does not appear to influence mammographic breast density in women concurrently treated with a common oral estrogen/progestogen regimen for a period of 6 months.

Breast cancer risk factors and mammographic breast density in women over age 70

Breast density is a strong risk factor for breast cancer, but little is known about factors associated with breast density in women over 70. Percent breast density, sex hormone levels and breast cancer risk factor data were obtained on 239 women ages 70-92 recruited from 1986 to 1988 in the United States. Multivariable linear regression was used to develop a model to describe factors associated with percent density. Median (range) percent density among women was 23.7% (0-85%). Body mass index (beta=-0.345, p<0.001 adjusted for age and parity) and parity (beta=-0.277, p<0.001 adjusted for age and BMI) were significantly and inversely associated with percent breast density. After adjusting for parity and BMI, age was not associated with breast density (beta=0.05, p=0.45). Parous women had lower percent density than nulliparous women (23.7 versus 34.7%, p=0.005). Women who had undergone surgical menopause had greater breast density than those who had had a natural menopause (33.4 versus 24.8%, p=0.048), as did women who were not current smokers (26.0 versus 17.3% for smokers, p=0.02). Breast density was not associated with age at menarche, age at menopause, age at first birth, breastfeeding, estrogen levels or androgen levels. In a multivariable model, 24% of the variance in percent breast density was explained by BMI (beta=-0.35), parity (beta=-0.29), surgical menopause (beta=0.13) and current smoking (beta=-0.12). Factors associated with breast density in older, post-menopausal women differ from traditional breast cancer risk factors and from factors associated with breast density in pre-menopausal and younger post-menopausal women.

Association between Mammographic Breast Density and Breast Cancer Tumor Characteristics

Few studies have examined the association between breast density and breast cancer tumor characteristics. We examined the association between hormonal, proliferative, and histologic tumor characteristics and mammographic breast density in women with breast cancer. We conducted a cross-sectional analysis in 546 women diagnosed with invasive breast cancer to evaluate the associations between breast density and tumor size, lymph node status, lymphatic or vascular invasion, histologic grade, nuclear grade, tumor differentiation, mitotic index, tumor necrosis, Ki-67 proliferation, estrogen receptor, progesterone receptor, p53, p27, cyclin E, Bcl-2, and C-erb-B2 invasion. Breast density was classified as fatty (Breast Imaging Reporting and Data System code 1 or 2; n = 373) or dense (Breast Imaging Reporting and Data System code 3 or 4; n = 173) for the cancer-free breast. A single pathologist measured all tumor markers. We examined whether the relationships were modified by interval cancer or screen-detected cancer. Women with a tumor size >1.0 cm were more likely to have dense breasts compared with women with a tumor size < or =1.0 cm after adjusting for confounders (odds ratio, 2.0; 95% confidence interval, 1.2-3.4 for tumor sizes 1.1-2.0 cm; odds ratio, 2.3; 95% confidence interval, 1.3-4.4 for tumor sizes 2.1-10 cm). Tumor size, lymph node status, and lymphatic or vascular invasion were positively associated with breast density among screen-detected cancers. Histologic grade and mitotic index were negatively associated with breast density in women diagnosed with an interval cancer. These results suggest that breast density is related to tumor size, lymph node status, and lymphatic or vascular invasion in screen-detected cancers. Additional studies are needed to address whether these associations are due to density masking the detection of some tumors, a biological relationship, or both.