Metformin increases mammographic breast density: a randomized controlled trial

What effect does mammographic breast density have on lesion detection in digital mammography?

Mammographic breast density as a predictor of breast cancer recurrence: a single centre longitudinal analysis of women with hormone receptor positive breast cancer Background Mammographic breast density has been associated with risk of development of breast cancer. To date clinical studies examining the use of tamoxifen and fall in mammographic breast density during this treatment have shown reduction in mammographic breast density examining change in mammographic breast density between baseline and a single follow-up mammogram to be predictive for disease recurrence. Aim To examine serial change in mammographic breast density over years to describe the changes which occur with use of aromatase inhibitors and tamoxifen, as well as changes following cessation of this treatment and to determine whether changes observed correlate with outcome. Method Eligible patients were identified from the Royal Perth Hospital breast unit database between January 1994-December 2011. Patient data was prospectively collected through the breast unit database. Additional data regarding endocrine therapy, adherence, weight, height and concomitant medications were obtained from case note review. Recurrence data was obtained from the hospital medical records system, as well as the breast unit database. Mammograms were obtained and mammographic breast density readings undertaken by a single reader using Cumulus. Percentage breast densities were obtained and statistical analysis undertaken to investigate changes in mammographic density on endocrine therapy, at switch of therapy, and cessation of therapy and correlation with disease free and overall survival. Results 1942 eligible patients were identified. 417 were premenopausal at time of diagnosis, 148 perimenopausal, 1328 postmenopausal and the remainder unknown status. 12 declined adjuvant endocrine therapy, 520 received both at least 1 aromatase inhibitor and tamoxifen during follow-up, 1189 tamoxifen only, 56 tamoxifen plus goserelin, and the remainder either aromatase inhibitor only or aromatase inhibitor with ovarian suppression. Over 10,000 mammograms were obtained for analysis. Currently results are available from 4301 mammograms from 689 patients. Mean density change between baseline scan and subsequent imaging after between 11-24 months of patient-reported endocrine adherence was -6.0%, with mean reduction of -11% in patients who were premenopausal at baseline and -4.5% in those who were postmenopausal at baseline. Kaplan Meier analysis showed late separation of overall survival curves favouring those with reduction in mammographic breast density however there was no statistically significant difference in the curves Conclusion Reduction in mammographic breast density was greatest in those who were premenopausal at baseline. Further multivariate analysis and assessment of the additional mammograms in this data set is required to assess the association between mammographic breast density and outcome in this cohort. Citation Format: Redfern AD, Martin HL, Stone J, Davidson JA, Yap F, Chung K. Mammographic breast density as a predictor of hormone receptor positive breast cancer recurrence: A single centre longitudinal analysis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD1-06.

BackgroundMonitoring metabolites of tamoxifen, such as endoxifen, has been suggested as a strategy to ascertain therapeutic effect of tamoxifen therapy, but clinical guidelines are missing. Herein, we aim to investigate the outcome of endoxifen concentrations of low-dose tamoxifen, using change in mammographic breast density as a proxy for therapy response.MethodsIn the randomized KARISMA-Tam (Karolinska Mammography project for risk prediction of breast cancer -Intervention Study with Tamoxifen) trial, including 5 doses of tamoxifen, measurements of plasma endoxifen concentrations, determination of CYP2D6 metabolizer status, and mammographic breast density change over the trial period were carried out. Association between endoxifen concentrations and relative mammographic breast density change after 6 months treatment was analyzed using linear regression in a spline model.ResultsA total of 824 women (335 premenopausal, 489 postmenopausal) were included. In analyses of premenopausal women, a spline model described a mammographic breast density decrease, equivalent to the mean (−18.5%) seen in women exposed to 20 mg tamoxifen, at endoxifen concentrations of 2-3 ng/mL. The mammographic breast density decrease reached a nadir at endoxifen levels of 3 ng/mL and did not decrease further at higher endoxifen concentrations. Most intermediate and normal tamoxifen metabolizers (about 90% of all participants) reached an endoxifen concentration of more than 2 ng/mL at tamoxifen doses of 5 and 10 mg. No mammographic breast density decrease was seen in the postmenopausal group.ConclusionsWe have identified a possible window of effect on mammographic breast density at endoxifen concentrations of 2-3 ng/mL in premenopausal women, which corresponds to the doses of 5 and 10 mg tamoxifen. Because mammographic breast density change was used as a surrogate marker for therapy response, results should be confirmed using clinically established outcomes measures.

Lobular Involution, Mammographic Density, and Breast Cancer Risk: Visualizing the Future?

IntroductionBenign breast disease (BBD) and high mammographic breast density (MBD) are prevalent and independent risk factors for invasive breast cancer. It has been suggested that temporal changes in MBD may impact future invasive breast cancer risk, but this has not been studied among women with BBD.MethodsWe undertook a nested case–control study within a cohort of 15,395 women with BBD in Kaiser Permanente Northwest (KPNW; 1970–2012, followed through mid-2015). Cases (n = 261) developed invasive breast cancer > 1 year after BBD diagnosis, whereas controls (n = 249) did not have breast cancer by the case diagnosis date. Cases and controls were individually matched on BBD diagnosis age and plan membership duration. Standardized %MBD change (per 2 years), categorized as stable/any increase (≥ 0%), minimal decrease of less than 5% or a decrease greater than or equal to 5%, was determined from baseline and follow-up mammograms. Associations between MBD change and breast cancer risk were examined using adjusted unconditional logistic regression.ResultsOverall, 64.5% (n = 329) of BBD patients had non-proliferative and 35.5% (n = 181) had proliferative disease with/without atypia. Women with an MBD decrease (≤ − 5%) were less likely to develop breast cancer (Odds Ratio (OR) 0.64; 95% Confidence Interval (CI) 0.38, 1.07) compared with women with minimal decreases. Associations were stronger among women ≥ 50 years at BBD diagnosis (OR 0.48; 95% CI 0.25, 0.92) and with proliferative BBD (OR 0.32; 95% CI 0.11, 0.99).DiscussionAssessment of temporal MBD changes may inform risk monitoring among women with BBD, and strategies to actively reduce MBD may help decrease future breast cancer risk.

Mammographic breast density is a strong risk factor for breast cancer. Tamoxifen, which reduces the risk of breast cancer in women at high risk, also reduces mammographic breast density. However, it is not known if tamoxifen-induced reductions in breast density can be used to identify women who will benefit the most from prophylactic treatment with this drug. We conducted a nested case-control study within the first International Breast Cancer Intervention Study, a randomized prevention trial of tamoxifen vs placebo. Mammographic breast density was assessed visually and expressed as a percentage of the total breast area in 5% increments. Case subjects were 123 women diagnosed with breast cancer at or after their first follow-up mammogram, which took place 12-18 months after trial entry, and control subjects were 942 women without breast cancer. Multivariable logistic regression was used to adjust for other risk factors. All statistical tests were two-sided. In the tamoxifen arm, 46% of women had a 10% or greater reduction in breast density at their 12- to 18-month mammogram. Compared with all women in the placebo group, women in the tamoxifen group who experienced a 10% or greater reduction in breast density had 63% reduction in breast cancer risk (odds ratio = 0.37, 95% confidence interval = 0.20 to 0.69, P = .002), whereas those who took tamoxifen but experienced less than a 10% reduction in breast density had no risk reduction (odds ratio = 1.13, 95% confidence interval = 0.72 to 1.77, P = .60). In the placebo arm, there was no statistically significant difference in breast cancer risk between subjects who experienced less than a 10% reduction in mammographic density and subjects who experienced a greater reduction. The 12- to 18-month change in mammographic breast density is an excellent predictor of response to tamoxifen in the preventive setting.

Background: Based on the results of a case-control study performed in Japan (Okayama and Kagawa), it was revealed that gene polymorphisms of the estrogen receptor (single nucleotide polymorphisms, SNPs), ESR1/6q25.1-rs2046210 and rs3757318, were closely related to breast cancer risk in Japanese women, and that the odds ratios per allele of individual SNPs were 1.37 [95% CI: 1.1 - 1.7] and 1.33 [1.04 - 1.7], respectively (San Antonio Breast Cancer Symposium 2012, Mizoo et al.). To examine the effects of these SNPs on the pathogenic mechanism of breast cancer, we analyzed the relationship of SNPs with reproductive/physiological factors (age of menarche and number of births), physical factors (height and Body Mass Index [BMI]), family history and mammographic breast density. Methods: Among the patients enrolled in the case-control study, the patients who could be evaluated regarding their lifestyle, SNPs and mammographic breast density were divided into the case group (N = 394) and the control group (N = 511) as the dataset for the study. SNPs were analyzed using the TaqMan genotyping assay® for blood samples. In the analysis of the relationship between SNPs and breast cancer risk, the odds ratios (OR) and 95% confidence intervals (95%CI) were calculated using logistic regression analysis. For the analysis of the relationship between SNPs and the factors, t-test and chi-square test were used. Results: In our dataset, the age-adjusted OR [95% CI] of ESR1/6q25.1-rs2046210 and rs3757318 were 2.22 [1.41 - 3.55] (AA vs. GG) and 2.12 [1.2 - 3.8] (AA vs. GG), respectively, suggesting that they would be significant risk factors. As a result of analyzing the relationship between SNPs and other factors, a significantly lower BMI was observed for the risk allele AA/AG of rs2046210, compared to GG (p = 0.014, t-test). Regarding the mammographic breast density, a significantly higher proportion of mammary glands with high density was confirmed for the risk allele AA/AG of rs2046210, compared to GG (p = 0.0389, chi-square test). The tendency towards a high mammographic breast density in the rs2046210 risk allele AA/AG was also confirmed based upon a stratified analysis of the case and control groups before and after menopause, and a significant correlation was observed, especially before menopause (p = 0.026, chi-square test). Conclusion: Mammographic high breast density is generally considered as one of the breast cancer risks, and it was suggested that gene polymorphisms of ESR1/6q25.1-rs2046210 might affect mammographic breast density. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-01-07.

Mammographic density changes during different postmenopausal hormone replacement therapies

BackgroundUnderstanding locoregional recurrence (LRR) risk is important in breast cancer, as it relates directly to breast cancer-associated mortality. Individualised LRR risk estimation should inform treatment and surveillance strategies. Increased mammographic breast density has been identified as a risk factor for the development of breast cancer. However, the precise relationship between mammographic density and breast cancer LRR remains unclear.AimsTo perform a systematic review and relative risk meta-analysis to explore the assocation between breast mammographic density and breast cancer LRR.MethodsA systematic review was performed as per PRISMA guidelines. Mammographic breast density (MBD) was classified as BI-RADs A-B (breast density < 50%, predominately fatty or scattered areas of fibroglandular density) or BI-RADs C-D breast density > 50%, heterogeneously dense or extremely dense). A meta-anlysis was performed using Meta-Disc and Statsdirect 2.8.0.ResultsSeven studies published between 2004 and 2023 met the inclusion criteria, comprising 3008 patients with reported mammographic breast density (MBD) (age range: 20–94 years). Overall, 59.1% (1779/3008) were classified as low MBD (BI-RADS A-B) and 40.9% (1229/3008) were classified as high MBD (BI-RADS C-D). Of these patients, 68.9% (2073/3008) were treated for invasive breast carcinoma and 31.1% had ductal carcinoma in-situ (DCIS). Breast-conserving surgery (BCS) was performed in 71.1% (2139/3008) of patients, mastectomy was performed in 28.2% (850/3008),. The median follow-up was 94.1 months, and the overall LRR rate was 12.8% (386/3008). Five of the seven studies reported a correlation between BI-RADs C-D and the development of LRR. LRR rates were lower in patients with low mammographic breast density (9.9% for BI-RADS A-B (177/1779)) compared to those with higher mammogaphic breast density (17.0% for BI-RADs C-D. (209/1229)) [P < 0.001, Chi Square]. BI-RADS C-D density on mammography was associated with an increased risk of locoregional recurrence (pooled relative risk 1.41; 95% confidence interval 1.17 to 1.70).ConclusionIncreased mammographic breast density may be associated with an increased risk of LRR. Multidisciplinary team discussions should consider MBD as a potential prognostic factor in when considering surveillance and locoregional control after breast cancer treatment.

Background: Higher mammographic breast density is a strong risk factor for breast cancer. Early-life factors may influence breast development and subsequent breast density in adulthood. Although childhood adiposity is inversely associated with breast cancer risk, the association of childhood adiposity with mammographic breast density in premenopausal women has not been adequately studied. This knowledge could provide insight into pathways linking mammographic density and breast cancer risk. We investigated the associations between adiposity at age 10 and mammographic density. Methods: We collected data from 370 premenopausal women during their routine screening mammograms at Washington University in St. Louis, MO from December 2015 to October 2016. Body size at age 10 was self-reported using the Stunkard 9-figure Somatotype pictogram. For these analyses, the Stunkard pictogram was collapsed into 4 groups: (i) body size 1 or 2, (ii) body size 3 or 4, (iii) body size 5, (iv) body size 6 or higher. Body mass index (BMI) at age 10 was imputed using BMI and Stunkard data from the Growing Up Today Study. Trained personnel collected womens' height and weight, which were used to calculate current BMI. We used the Volpara software to evaluate the following volumetric mammographic density measures: volumetric percent density (VPD), dense volume (DV) and non-dense volume (NDV). Age-adjusted Pearson correlations and multivariable linear regression models (adjusted for age, age at each given birth, family history, race, education, oral contraceptive use, and breast feeding history) were used to evaluate the associations between adiposity at age 10 and volumetric mammographic density measures. Results: The mean age at the time of screening mammogram was 47.1 years. The majority of the women (43.8%) reported having body size 1 or 2, followed by body size 3 or 4 (34.9%), body size 5 (13.8%) and body size 6 (7.6%) at age 10. We observed a negative correlation between BMI at age 10 (r= -0.28, p-value&amp;lt;0.001) and VPD, and a positive correlation between BMI at age 10 (r= 0.27, p-value&amp;lt;0.001) and NDV. In multivariable regression models, adiposity at age 10 was significantly inversely associated with VPD, and positively associated with NDV. A 1kg/m2 increase in BMI at age 10 was associated with a 6.3% decrease in VPD (p-value &amp;lt;0.001), and a 6.7% increase in NDV (p-value &amp;lt;0.001). Compared to women whose body sizes were 1 and 2 at age 10, women with body size 3 or 4 had a 17.6% decrease in VPD, and a 28.5% increase in NDV; women with body size 5 had a 32.3% decrease in VPD, and a 58.1% increase in NDV, and women with body sizes ≥6 had a 46.6% decrease in VPD, and a 75.1% increase in NDV (all p-values &amp;lt;0.05). The associations of body size at age 10 and VPD were attenuated, but still statistically significant when we adjusted for current BMI. No statistically significant associations were found between adiposity at age 10 and DV. Conclusions: Our findings of an inverse association between adiposity at age 10 and percent density suggest that adiposity at age 10 could impact breast cancer development via its effect on mammographic density. Mechanistic studies to understand how childhood adiposity reduces mammographic density and breast cancer development in premenopausal women are needed. Citation Format: Alimujiang A, Imm KR, Appleton CM, Colditz GA, Berkey CS, Toriola AT. Adiposity at age 10 and mammographic density among premenopausal women [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-01-01.

BackgroundHigher mammographic breast density (MBD) is associated with an increased risk of breast cancer when compared with lower MBD, especially in premenopausal women. However, little is known about the effectiveness of chemoprevention agents in reducing MBD in premenopausal women without a history of breast cancer. Findings from this review should provide insight on how to target MBD in breast cancer prevention in premenopausal women with dense breasts.MethodsWe searched 9 electronic databases for clinical trials in English, Spanish, French, or German published until January 2020. Articles evaluating the association of pharmacological agents and MBD were included. Data were extracted on methods, type and dose of intervention, outcomes, side effects, and follow up. Quality of the studies was assessed using the US Preventive Services Task Force criteria.ResultsWe identified 7 clinical trials evaluating the associations of 6 chemoprevention agents with changes in MBD in premenopausal women without history of breast cancer. The studies evaluated selective estrogen-receptor modulators (n = 1); gonadotropin-releasing hormone agonists (n = 2); isoflavones (n = 1); vitamin D (n = 1); and Boswellia, betaine, and mayo-inositol compound (n = 1). Hormonal interventions were associated with net reductions in percent density (tamoxifen [13.4%], leuprolide acetate [8.9%], and goserelin [2.7%]), whereas nonhormonal (vitamin D and isoflavone) interventions were not. However, MBD returned to preintervention baseline levels after cessation of gonadotropin-releasing hormone agonists.ConclusionsA limited number of chemoprevention agents have been shown to reduce MBD in premenopausal women. Identification of new and well-tolerated chemoprevention agents targeting MBD and larger studies to confirm agents that have been studied in small trials are urgent priorities for primary breast cancer prevention in premenopausal women with dense breasts.

e21160 Background: Previous studies showed that anti-estrogen therapy lowers mammographic breast density (MD). We hypothesized that the short-term change of breast density can be a surrogate marker predicting response to adjuvant endocrine therapy (ET) for breast cancer. Methods: We analyzed data of 1,065 estrogen receptor (ER)-positive breast cancer patients who underwent surgery between 2003 and 2006 and received at least 2 years of ET including tamoxifen and aromatase inhibitor. MD was measured using Cumulus software 4.0 and expressed as a percentage. MD reduction was defined as an absolute difference between the MD of two mammography images: taken preoperatively and 8-20months after the start of adjuvant ET.. Results: After median follow up of 68.8 months, overall recurrence rate was 7.5% (80/1065). Mean MD reduction was 5.9% (-17.2 to 36.9). In a logistic regression analysis, age&lt;50, high preoperative MD, and longer interval between start of ET to the 2nd mammogram were significantly associated with higher MD reduction (p value&lt;0.05). In a survival analysis using Cox model, tumor size (&gt;2cm), lymph node positive, high Ki-67 (≥10%), and lower MD reduction were independent factors significantly associated with recurrence-free survival (p&lt;0.05). The hazard of recurrence increased proportionally according to the less degree of MD reduction. Conclusions: MD change during short-term use of adjuvant ET was a significant predictive factor for long-term recurrence in ER-positive breast cancer. It is urgent to develop effective treatment strategy in patients who have less MD reduction in spite of about 1 year of ET.

Several studies suggest antidepressant medications can increase prolactin levels. Some, but not all, studies suggest prolactin levels are positively associated with mammographic breast density, an established risk factor for breast cancer. We evaluated 29,284 women with two routine screening mammograms 9 to 28 months apart between 1996 to 2006 to examine whether antidepressant use was associated with changes in mammographic breast density. Mammographic breast density was assigned by radiologists and coded according the Breast Imaging Reporting and Data System classification. Exposure to antidepressants was ascertained based on electronic pharmacy dispensing data, including dispensings from claims data. We used polytomous logistic regression to estimate the odds of an increase or decrease in density categories between mammograms associated with antidepressant initiation, continuation, and discontinuation compared with nonusers of any antidepressants. Initiation, continuation, and discontinuation of antidepressant medications were not associated with changes in mammographic density. The lack of association between antidepressant use and breast density is consistent with recent studies that do not suggest an association between antidepressant use and breast cancer risk.

Introduction: High mammographic breast density (MBD) is a strong risk factor for breast cancer, but the biological mechanisms underlying high MBD are not well understood. We, therefore, comprehensively investigated for the first time the associations of lipid species with volumetric measures of MBD to elucidate potential biological mechanisms of high MBD in premenopausal women. Methods: We performed lipidomic profiling on 705 premenopausal women recruited during their annual screening mammogram at Washington University School of Medicine, St. Louis, MO. Lipidomic profiling for 982 lipid species was completed at Metabolon (Durham, NC®). Lipid species with greater than 300 missing values (N=125) were excluded from the analysis. Using nearest neighbor methods, we imputed the lipid species missing less than 300 values. We used Volpara 1.5 (Volpara Health®) to quantify volumetric measures of MBD - volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV). We investigated the associations of the lipid species with MBD measures using multivariable linear regression models adjusting for age, age at menarche, body shape at age 10, race/ethnicity, body fat %, family history of breast cancer, oral contraceptive use, parity/age at first birth, and alcohol use. MBD measures were log10-transformed, and lipid species were standardized. Linear coefficients were back-transformed to the original scale and considered significant if the Bonferroni corrected p&amp;lt;0.05. Results: In multivariable linear regression models, 34 lipid species were inversely associated with VPD. The lipid species belong to the triacylglycerol (TAG, N=26), diacylglycerol (DAG, N=6), phosphatidylcholine (PC, N=1), and cholesterol ester (N=1) pathways. DAG(16:0/18:2) and TAG54:6-FA20:4 displayed the largest inverse associations with one standard deviation increase in DAG(16:0/18:2), and TAG54:6-FA20:4 corresponding to 9.9% (p=0.002), and 9.6% (p=0.007) decrease in VPD, respectively. Eleven lipid species were significantly associated with NDV, with 10 species (all TAG) having a positive association and 1 inverse association PC(18:1/18:1). The strongest positive association was observed with TAG54:6-FA20:4. One standard deviation increase in TAG54:6-FA20:4 was associated with a 9.8% increase in NDV (p=0.01). Several of the lipid species (N=8, 23.5%) that were associated with VPD were also associated with NDV, but in opposite directions. No lipid species were significantly associated with DV. Conclusions: Our study identified many lipid species, especially in TAG and DAG pathways, that were associated with VPD and NDV and offer new insights into the biological mechanisms underlying high MBD in premenopausal women. Future studies are needed to validate our results and the translational potential. Citation Format: Kayla R. Getz, Myung S. Jeon, Chongliang Luo, Jingqin Luo, Adetunji T. Toriola. Lipidome of mammographic breast density in premenopausal women. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4173.

Background Women with atypical hyperplasia (AH) are at an approximately four-fold increased risk of subsequent breast cancer (BC). Mammographic breast density (MBD) is a well-established risk factor for BC, but its contribution to BC risk in women with AH remains an open question. We previously reported no association between MBD [measured by Wolfe's parenchymal pattern (PP)] and BC risk in a cohort of 147 women with AH. Here, we present results in an expanded cohort of 459 women diagnosed with AH between 1985 and 2001. Methods The Mayo Clinic Benign Breast Disease Cohort includes 13,485 women who had benign core and/or excisional biopsy 1967-2001. Biopsy tissues were reviewed by our study pathologist to determine presence of AH. MBD was available from clinical records starting in 1985, coded as PP (the standard for 1985-1996) or BI-RADS (1997-2001) density criteria. The original four-level PP (N1-fatty, P1-ductal prominence &amp;lt;25% of breast, P2-ductal prominence &amp;gt;25%, DY-dysplasia) and BI-RADS (fatty, scattered densities, heterogeneously dense, extremely dense) measures were re-categorized as low, moderate or high MBD by combining the middle two categories for each. BC events and clinical information were obtained by questionnaires, medical records and the Mayo Clinic Tumor Registry. Women were followed from benign biopsy to date of BC, death or last contact. Standardized incidence ratios (SIRs) were generated overall and within subgroups defined by density measure (PP vs. BI-RADS), number of atypical foci, and BMI by dividing the observed number of BCs by population-based expected values. Cox regression was used to estimate MBD hazard ratios after adjustment for demographic and clinical variables. Results Of the 551 women diagnosed with AH between 1985 and 2001, 459 (83%) had MBD data within 1 year prior to biopsy. Of these, 68 (15%) had low, 221 (48%) had moderate, and 170 (37%) had high MBD, respectively. Over a median follow-up of 11.7 years, 80 BCs were observed. SIRs for breast cancer did not differ significantly across density categories, overall or within any subgroups examined (see Table). Cox regression adjusting for age, BMI and density measure (PP vs. BI-RADS) also failed to identify an association with MBD (p=0.55). Low MBDModerate MBDHigh MBD N / BCsSIR (95% CI)N / BCsSIR (95% CI)N / BCsSIR (95% CI)P-valueOverall68/123.5 (1.8,6.1)221/393.6 (2.5,4.9)170/293.4 (2.3,4.8)0.97MBD Measure PP59/113.6 (1.8,6.5)85/153.0 (1.7,5.0)130/243.3 (2.2,5.0)0.87BI-RADS9/12.7 (0.1,14.7)136/244.0 (2.6,6.0)40/53.4 (1.1,7.9)0.90No. Atypical Foci 147/62.3 (0.9,5.1)123/182.8 (1.7,4.4)96/163.5 (2.0,5.8)0.63214/47.5 (2.0,19.1)58/134.8 (2.6,8.3)41/62.5 (0.9,5.5)0.213+7/26.7 (0.8,24.0)40/84.4 (1.9,8.6)33/74.0 (1.0,8.2)0.83BMI &amp;lt;2525/21.5 (0.2,5.4)75/184.9 (2.9,7.7)101/173.4 (2.0,5.5)0.1625-2919/54.9 (1.6,11.3)68/92.8 (1.3,5.2)36/42.1 (0.6,5.4)0.4530+23/54.8 (1.6,11.2)76/123.0 (1.6,5.3)32/74.0 (1.6,8.2)0.67SIRs compare observed numer of BCs to expected using Iowa SEER data. Analyses account for the effects of age and calendar period. P-value is test of heterogeneity in SIRs across columns. Conclusions We found no evidence of an association between MBD and subsequent BC in women with AH. Citation Format: Vierkant RA, Degnim AC, Hartmann LC, Frank RD, Radisky DC, Visscher DW, Frost MH, Winham SJ, Ghosh K, Vachon CM. No evidence of association between mammographic breast density and risk of breast cancer in women with atypical hyperplasia. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-09-05.