Changes In Breast Density Research Articles

The Effect of Weight Change on Volumetric Measures of Mammographic Density

Abstract The association between changing body mass index (BMI) and mammographic breast density is important to better evaluate how to adjust for BMI gain/loss in longitudinal studies of density and breast cancer risk. Increasing BMI has been associated with decreasing percent dense area but the effect on absolute dense area is unclear. No studies have explored a longitudinal association using volumetric density measurement. Methods: We examined the association between change in BMI and change in volumetric breast density among 24,556 women who received breast imaging at the San Francisco Mammography Registry from 2007–2013. Height and weight were self-reported at the time of mammography. Breast density was assessed using single x-ray absorptiometry (SXA) volumetric measurement. The cross-sectional and longitudinal associations between BMI and absolute dense volume (DV) and percent dense volume (PDV) were assessed using multivariable adjusted regression. Results: Women were primarily Caucasian (66%) or Asian (25%) and most were postmenopausal (64%) at time of first mammogram. In cross-sectional analysis, BMI was positively associated with DV (β = 2.95 cm3, 95% CI, 2.69–3.21) and inversely associated with PDV (β = −2.03%, 95% CI, −2.09–−1.98). In longitudinal analysis, an annual increase in BMI was associated with an annual decrease in both DV (β = −1.01 cm3/year, 95% CI, −1.59–−0.42) and PDV (β = −1.17%/year, 95% CI, −1.31–−1.04). Findings were consistent between pre- and postmenopausal women. The annual decrease in DV was strongest among premenopausal women who were initially overweight or obese (P < 0.01 for interaction by initial BMI). Conclusion: Our findings support an inverse association between change in BMI and change in PDV. Longitudinal studies of PDV and breast cancer risk, or those using PDV as an indicator of breast cancer risk, should consider adjusting for change in BMI. The association between increasing BMI and decreasing DV is unexpected and will require confirmation using volumetric methods.

Minimal impact of adjuvant exemestane or tamoxifen treatment on mammographic breast density in postmenopausal breast cancer patients: A Dutch TEAM trial analysis

Background. Mammographic breast density is one of the strongest independent risk factors for developing breast cancer. We examined the effect of exemestane and tamoxifen on breast density in Dutch postmenopausal early breast cancer patients participating in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial.Material and methods. Analogue mammograms of selected TEAM participants before start, and after one and two (and if available after three) years of adjuvant endocrine therapy were collected centrally and reviewed. Study endpoints were change in breast density over time, and correlations between breast density and locoregional recurrence (LRR), distance recurrence (DR), and contralateral breast cancer (CBC).Results. Mammograms of 378 patients (181 tamoxifen, 197 exemestane) were included in the current per protocol analyses. Baseline breast density was low (breast density score < 50% in 75% of patients) and not different between patients randomised to exemestane or tamoxifen (coefficient 0.16, standard error 0.17). Breast density did not change during treatment in exemestane (p = 0.25) or tamoxifen users (p = 0.59). No relation was observed between breast density and the occurrence of a LRR [hazards ratio (HR) 0.87, 95% CI 0.45–1.68, p = 0.67], a DR (HR 1.02, 95% CI 0.77–1.35, p = 0.90), or CBC (HR 1.31, 95% CI 0.63–2.72, p = 0.48).Conclusion. The in general low breast density score in early postmenopausal breast cancer patients did not substantially change over time, and this pattern was not different between tamoxifen and exemestane users. Breast density was not a predictive marker for efficacy of adjuvant endocrine therapy.

PB.24. How does volumetric breast density change with time?

Breast density is a well-established independent risk factor for breast cancer, but risk may also relate to the rate at which breast density changes over time. Here we aim to establish the baseline rate of change in volumetric breast density in postmenopausal women undergoing mammographic screening.

How Mammographic Breast Density Affects Radiologists' Visual Search Patterns

To determine the impact of mammographic breast density on the visual search process of radiologists when reading digital mammograms. Institutional review board approval was obtained. A set of 149 craniocaudal digital mammograms were read by seven radiologists, and observer search patterns were recorded. Total time examining each case, time to first hit the lesion, dwell time, and number of hits per area were calculated. The nonparametric Mann-Whitney U test was used for statistical evaluation. In both low- and high-mammographic density cases, significant increases were observed in the time to first hit lesions when they were located outside, compared to overlying fibroglandular dense tissue (P = .001). Significantly longer dwell time (P = .003) and greater number of fixations (P = .0003) were observed when the lesions were situated within--rather than outside--the dense fibroglandular tissue. Increased mammographic breast density changes radiologists' visual search patterns. Dense areas of the parenchyma attracted greater visual attention in both high- and low-mammographic density cases, resulting in faster detection of lesions overlying the fibroglandular dense tissue, along with longer dwell times and greater number of fixations, as compared to lesions located outside the dense fibroglandular regions.

Development of conjugated estrogens/bazedoxifene, the first tissue selective estrogen complex (TSEC) for management of menopausal hot flashes and postmenopausal bone loss

Conjugated estrogens (CE) combined with the selective estrogen receptor modulator (SERM) bazedoxifene (BZA) is a new option for alleviating menopausal symptoms and preventing postmenopausal bone loss. The rationale for developing the tissue selective estrogen complex (TSEC) CE/BZA was to combine CE’s benefits with the SERM’s tissue-specific properties to offset estrogenic stimulation of endometrial and breast tissue. TSECs provide a progestin-free alternative to traditional estrogen–progestin therapy (EPT) in women with a uterus. Preclinical studies supported bazedoxifene as the SERM of choice and demonstrated that CE/BZA provided an optimal balance of estrogen receptor agonist/antagonist activity compared with other potential TSEC pairings. Initial clinical development of CE/BZA focused on determining the appropriate dose ratio that would demonstrate efficacy with minimal to no stimulation of the breast or endometrium. Clinical studies confirmed the efficacy of the selected doses for maintaining bone mass; relieving vasomotor symptoms, vulvar–vaginal atrophy, and dyspareunia; and improving sexual function in postmenopausal women. Reduction of hot flashes also translated into improved menopause-specific quality of life and sleep. Unlike EPT, the FDA-approved dose of CE 0.45mg/BZA 20mg does not cause a change in breast density or the endometrium, or increase breast pain compared with placebo. In clinical trials up to 2years, CE 0.45mg/BZA 20mg has a favorable tolerability profile and rates of coronary heart disease, venous thromboembolism, and amenorrhea similar to placebo. Therefore, CE 0.45mg/BZA 20mg is an effective, well-tolerated alternative to EPT for menopausal symptom relief and osteoporosis prevention for postmenopausal women with a uterus.

Change in breast density as a response to adjuvant endocrine treatment: An American cohort.

e11523 Background: Anti-estrogen treatment is the cornerstone in adjuvant therapy of estrogen receptor (ER) positive breast cancer. Previous work has demonstrated that endocrine therapy (ET) reduces breast density on subsequent mammograms. Research from Korea and Sweden has shown that decreased mammographic density (MD) after ET is a positive prognostic marker for long-term survival. We seek to validate this finding in a North American cohort. Methods: We identified 102 patients treated at our institution with ER positive breast cancer from 2003-2006, with mammograms available in our system and an intact contralateral breast. MD was measured as percentage volume density using Volpara software (v. 1.2); MD reduction (MDR) was defined as Follow up MD - Baseline MD*100 / Baseline MD. Baseline MD was measured from a preoperative mammogram, and Follow up MD from mammograms taken 1-2 years after start of ET. Logistic regression analysis was performed with endpoint defined as locoregional or distant breast cance...

Treating Multiple Myeloma: The Cause for Optimism

process. “People in the top 5%–10% [for breast cancer risk] are identified, contacted by breast health specialists, and counseled about their options,” she said. To the extent that cost is a disincentive, the Affordable Care Act will, starting next year, require new health insurance plans to cover chemoprevention with no copayment or deductible in high-risk women. That typically means a 5-year breast cancer risk of 1.67% or higher, which includes nearly all American women older than 55 years. Meanwhile, European researchers are investigating reduced doses of tamoxifen to alleviate some side effects. Per Hall, M.D., Ph.D., of the Karolinska Institute in Stockholm, was among the researchers who showed that a change in breast density might be a useful surrogate for therapeutic effect. Now his group is about to launch another trial to learn whether women who take lower doses of tamoxifen can achieve the same benefit with fewer side effects. The group plans to randomize 1,000 Swedish women to receive placebo or one of four daily doses

Volumetric quantification of the effect of aging and hormone replacement therapy on breast composition from digital mammograms

ObjectiveTo assess the physiological changes in breast composition with aging using volumetric breast composition measurement from digital mammograms and to assess the effect of hormone replacement therapy (HRT). MethodsA total of 764 consecutive mammograms of 208 non-HRT using women and 508 mammograms of 134 HRT-using women were analyzed using a volumetric breast composition assessment software (Quantra™, Hologic Inc.). Fibroglandular tissue volume (FTV), breast volume (BV), and percent density (PD) were measured. For statistical analysis, women were divided into a premenopausal (<46 years), a perimenopausal (46–55 years), and a postmenopausal (>55 years) age group. More detailed graphical analysis was performed using smaller age brackets. Women using HRT were compared to age-matched controls not using HRT. ResultsWomen in the postmenopausal age group had a significantly lower FTV and PD and a significantly higher BV than women in the premenopausal age group (FTV: 77 vs. 120cm3, respectively; PD: 16% vs. 28%, respectively; BV 478 vs. 406cm3, respectively; p<0.01 for all). Median FTV was nearly stable in consecutive mammograms in the premenopausal and postmenopausal age groups, but declined at a rate of 3.9% per year in the perimenopausal period. Median PD was constant in the premenopausal and postmenopausal age groups and declined at a rate of 0.57% per year in the perimenopausal age group. BV continuously increased with age. Women using HRT throughout the study had a 5% higher PD than women not using HRT (22% vs. 17%, respectively; p<0.001). ConclusionsAccurate knowledge of normal changes in breast composition are of particular interest nowadays due to the importance of breast density for breast cancer risk evaluation. FTV and PD change significantly during the perimenopausal period but remain relatively constant before and thereafter. Median total breast volume consistently increases with age and further contributes to changes in breast density. HRT use is associated with a significantly higher PD.

Early Discussion of Breast Density and Supplemental Breast Cancer Screening: Is it Possible?

The purpose of this study is to determine whether it is possible to make breast cancer screening more efficient in those with dense breasts. Over 12 states require that patients with dense breasts receive notification about their breast density in lay letters that are sent after the screening mammogram. Some of these letters advise patients to speak with their primary care providers about the possibility of supplemental breast cancer screening. We sought to determine whether primary care providers can discuss breast density and recommend supplemental breast cancer screening using the density of the previous mammography. This would reduce the burden of additional appointments and might increase the number of patients choosing to have supplemental screening. The mammographic breast density of 250 consecutive patients from May 2011 to September 2011 was compared with the immediate prior mammogram. Patients whose prior mammograms were more than 36months prior or less than 8months prior to the current exam were excluded, leaving 217 patients. The proportion of patients with breast density change was analyzed. The concordance of breast density between the two exams was assessed and the effects of patient age and the length of time between mammograms were examined. The breast density of the current and most recent prior mammogram was stable for 86.6% of patients. Neither age nor length of time between mammograms affected concordance. Primary care providers can decrease the need for multiple appointments and decrease patient anxiety by discussing breast density and screening choices prior to the patient's screening mammography. The great majority of patients will receive the correct information about their breast density by using a prior report.

Smaller Reduction in 3D Breast Density Associated With Subsequent Cancer Recurrence in Patients With Breast Cancer Receiving Adjuvant Tamoxifen Therapy

The purpose of this study was to retrospectively investigate whether 3D breast density changes measured using MRI were associated with recurrent cancer in patients with breast cancer who received adjuvant tamoxifen. A search of the breast MRI database (2007-2008) revealed a dataset that included 80 women (mean age, 44 years; range, 27-68 years) with breast cancer who underwent breast-conserving surgery, adjuvant tamoxifen treatment, and breast MRI before and after tamoxifen. The following clinicopathologic variables were collected: age, body mass index, menopausal status, family history, tumor stage, tumor grade, hormonal receptor status, and adjuvant chemotherapy status. MRI variables (total breast volume, fibro-glandular volume, and breast density) were measured for the contralateral untreated breast before and after tamoxifen treatment, and the percentage changes were recorded. A multivariate logistic regression analysis was performed to identify independent factors that were associated with cancer recurrence. Overall, 12 (15%) of the 80 women developed recurrence. No recurrent cancers were found in the remaining 68 patients (85%) at a median follow-up of 48 months (range, 37-60 months). Percentage reduction of breast density after tamoxifen was the only independent factor associated with recurrence (adjusted odds ratio [OR] = 0.848, 95% CI = 0.769-0.935, and p = 0.001 for observer 1; adjusted OR = 0.957, 95% CI = 0.919-0.996, and p = 0.032 for observer 2) in the multivariate analysis. Three-dimensional breast density changes measured using MRI during tamoxifen treatment were an independent factor associated with cancer recurrence in patients with breast cancer who received adjuvant tamoxifen.

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

BackgroundNeoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer.Methods/DesignPatients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively.DiscussionThis study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer.Trial registrationClinicalTrials.gov Identifier NCT01589367

Abstract ES02-2: Who should receive preventive therapy?

Abstract Several options are now becoming available for preventive therapy in women at increased risk for breast cancer. A major challenge is to determine which women are at sufficiently high risk to warrant treatment, and who will benefit from such treatment. Standard risk factors have been combined in several models to develop a risk score, and the spread in 10-year risk associated with these models will be examined. Two new features which offer improved prognostic discrimination are breast density and SNP profiles. The former can be routinely read visually, but there is a substantial inter-reader variability, and a goal is to develop automated testing which is reproducible and highly prognostic for risk. SNP profiles consist of panels (now over 70) of low risk but common genes that individually are not useful, but as a panel may add useful information. A discussion of the relative amount of information in classic models, mammographic density, and SNP scores will be presented along with initial estimates of their combined utility. Lastly we look at markers which may be able to predict response to endocrine prophylactic treatment. Currently change in breast density offers the most promise in this arena. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr ES02-2.

Abstract P4-01-12: Optical imaging of breast density correlates with magnetic resonance imaging in patients undergoing neoadjuvant chemotherapy

Abstract Background: In addition to being a strong risk factor for breast cancer, data from recent studies suggests that breast density changes correlate with response to preventative or adjuvant tamoxifen treatment for breast cancer. Breast density may be a surrogate biomarker for survival and indication of the need for additional treatments such as radiotherapy. However, quantitative methods to assess breast density in the clinic are limited. In this study, we assess how Diffuse Optical Spectroscopic Imaging (DOSI) may be used to evaluate and understand changes in breast density in patients undergoing neoadjuvant chemotherapy. Methods: DOSI was used to measure hemodynamic and metabolic information from the contralateral normal breast of 28 breast cancer patients undergoing neoadjuvant chemotherapy. DOSI uses near-infrared light to determine absolute tissue molar concentrations of oxyhemoglobin (ctO2Hb), deoxyhemoglobin (ctHHb), water, and lipid content without requirement of an exogenous contrast agent. DOSI measurements were compared to 3.0T MRI measured fibroglandular density before and during therapy. Results: Water (r = 0.843; P&amp;lt;0.001), ctHHb (r = 0.785; P = 0.003), and lipid (r = -0.707; P = 0.010) concentration measured with DOSI correlated strongly with MRI-measured density before therapy. During neoadjuvant treatment measured at ∼90 days after treatment commenced, significant reductions were observed in ctO2Hb for pre- (-20.0%; 95% confidence interval (CI), -32.7 to -7.4) and postmenopausal subjects (-20.1%; 95% CI, -31.4 to -8.8), and water concentration for premenopausal subjects (- 1.9%; 95% CI, -17.1 to -6.7) compared to baseline. Lipid content increased slightly in premenopausal subjects (3.8%; 95% CI, 1.1 to 6.5) and water increased slightly in postmenopausal subjects (4.4%; 95% CI, 0.1 to 8.6). Percentage change in water at the end of therapy compared with baseline correlated strongly with percentage change in MRI-measured density (r = 0.864; P = 0.012). Discussion: For this patient cohort, non-invasive optical measurement may provide an assessment of breast density and yield additional information that complements MRI and mammography techniques. We demonstrate a strong baseline correlation between water and ctHHb with breast density, reflecting the increased water content and rate of metabolism in fibroglandular breast tissue. Significant changes in optical markers for vascular density and supply (ctO2Hb and water) are observed during treatment. A significant decrease in ctO2Hb is observed in both menopausal groups. The steady reduction of ctO2Hb without a corresponding decrease in ctHHb suggests that chemotherapy agents act directly on the normal breast tissue, perhaps by causing a reduction of perfusion. The greater reduction in breast-tissue water in premenopausal subjects suggests that chemo-reduced ovarian hormone levels may exert a role in reducing breast-tissue density. Although from a limited patient dataset, these results suggest that DOSI may provide new functional indices of breast density based on hemoglobin and water that could be used at the bedside to assess response to therapy. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-01-12.

Abstract C28: Effects of vitamin D supplementation on breast imaging and blood-based biomarkers of breast cancer risk

Abstract Background: Vitamin D deficiency is a potentially modifiable risk factor that may be targeted for breast cancer prevention. Observational studies have demonstrated an inverse association between breast cancer and vitamin D status, including the main circulating form of serum 25-hydroxyvitamin D [25(OH)D]. The relationship between vitamin D and mammographic density (MD), a strong predictor of breast cancer risk, remains unclear. Despite a number of clinical trials of vitamin D supplementation, the efficacy, optimal dose of vitamin D, and target level of serum 25(OH)D for breast cancer prevention remain unclear. We examined the effects of high-dose vitamin D on breast imaging and circulating biomarkers among women at high risk for breast cancer. Methods: Forty high-risk women [defined as a 5-year breast cancer risk per the Gail model of ≥1.67%, lobular or ductal carcinoma in situ (LCIS/DCIS)] were assigned to a 1-year intervention of vitamin D3 20,000 IU or 30,000 IU weekly. Other eligibility criteria included baseline MD ≥25%, serum 25(OH)D ≥32 ng/ml, no current tamoxifen or raloxifene use, and no history of kidney stones. Women underwent a digital mammogram at baseline and 12 months, and serial blood draws at baseline, 6 and 12 months. In addition, postmenopausal women underwent a breast MRI at baseline and 12 months. Participants were monitored for toxicity during follow-up visits every 3 months. Biomarker endpoints included changes in breast density by mammography and breast MRI, serum 25(OH)D, 1,25(OH)D , PTH , IGF-1 , IGFBP-3. MD was evaluated by the Cumulus technique and fibroglandular tissue volume was measured using a novel segmentation method on noncontrast T1-weighted images from breast MRIs. Paired t-tests were used to compare biomarker changes from baseline to follow-up. Multivariate linear regression was used to determine the association between breast density and blood biomarkers with adjustment for known confounders. Results: From Nov 2007 to Jan 2011, 40 women were enrolled. Median age 50 years (range, 37-73); pre/postmenopausal: 20/20; Non-Hispanic white/Hispanic/Non-Hispanic black/Asian: 18/20/1/1; median body mass index (BMI) 26.6 kg/m2 (20-39.6); elevated Gail risk/LCIS/DCIS: 20/10/10; baseline serum 25(OH)D 19.9 ng/ml (9.4-30.4); baseline MD 14.5% (0.9-60.4). At baseline, 6 and 12 months, mean serum 25(OH)D rose from 20.0 to 43.8 to 46.8 ng/ml, respectively; and mean serum 1,25(OH)D increased from 69.7 to 86.8 to 98.1 pg/ml, respectively (p&amp;lt;0.01). Compared to baseline, serum PTH decreased significantly at 6 months (35.0 vs. 29.2 pg/ml, p&amp;lt;0.01) and IGF-1/IGFBP-3 ratio decreased at 12 months (0.0341 vs. 0.0327, p=0.01). After 1 year of high-dose vitamin D, there was no significant change in MD (19.2% vs. 20.8%, p=0.54), regardless of menopausal status or dose level. In univariate analysis, serum 25(OH)D was inversely correlated with MD at 12 months (p=0.02), however, the association was no longer significant after adjustment for age, race, BMI, and menopausal status. Discussion: We demonstrated that a 1-year intervention of high-dose vitamin D3 was associated with a significant increase in serum 25(OH)D above a target level of 40 ng/ml. Previous studies have shown a direct association with IGF-1/IGFBP-3 ratio and breast cancer risk. We found a decrease in serum IGF-1/IGFBP-3 ratio with vitamin D supplementation. However, no significant change in MD was noted. Analysis of breast MRI fibroglandular tissue volume is ongoing in a subset of postmenopausal women. These early phase chemoprevention trials are designed to enhance our understanding of the biologic effects of vitamin D on intermediate biomarkers of breast cancer risk. Citation Format: Parijatham S. Sivasubramanian, Tong Xiao, Dawn L. Hershman, Matthew Maurer, Kevin Kalinsky, Sheldon Feldman, Sr., Lois Brafman, Susan Refice, Grace Kranwinkel, Katherine D. Crew. Effects of vitamin D supplementation on breast imaging and blood-based biomarkers of breast cancer risk. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C28.

Aromatase inhibitor-induced modulation of breast density: clinical and genetic effects

Background:Change in breast density may predict outcome of women receiving adjuvant hormone therapy for breast cancer. We performed a prospective clinical trial to evaluate the impact of inherited variants in genes involved in oestrogen metabolism and signalling on change in mammographic percent density (MPD) with aromatase inhibitor (AI) therapy.Methods:Postmenopausal women with breast cancer who were initiating adjuvant AI therapy were enrolled onto a multicentre, randomised clinical trial of exemestane vs letrozole, designed to identify associations between AI-induced change in MPD and single-nucleotide polymorphisms in candidate genes. Subjects underwent unilateral craniocaudal mammography before and following 24 months of treatment.Results:Of the 503 enrolled subjects, 259 had both paired mammograms at baseline and following 24 months of treatment and evaluable DNA. We observed a statistically significant decrease in mean MPD from 17.1 to 15.1% (P<0.001), more pronounced in women with baseline MPD ⩾20%. No AI-specific difference in change in MPD was identified. No significant associations between change in MPD and inherited genetic variants were observed.Conclusion:Subjects with higher baseline MPD had a greater average decrease in MPD with AI therapy. There does not appear to be a substantial effect of inherited variants in biologically selected candidate genes.

Assessment of mammographic density in postmenopausal women during long term hormone replacement therapy

Objective: To assess long-term effects of different hormone replacement therapy (HRT) regimens on mammographic density.Methods: One hundred sixty-five postmenopausal women were treated with the same HRT during 5 years: 38 received transdermal estradiol, 78 cyclic combined therapy and 49 continuous combined therapy. Mammograms were obtained at baseline, at 1-year and 5-year treatment. Breast density changes were categorized as slight focal increased density, considerable focal increased density, slight diffuse increased density and considerable diffuse increased density.Results: Mammographic density increased in 7.9% of women receiving estrogen alone versus 25.2% of women receiving combined therapy (p < 0.022) during 1 year, and in 7.9% of women versus 28.3% of women (p < 0.009) after 5 years of therapy, respectively. There were significant statistical differences in women treated with estrogen alone versus those treated with combined HRT after 1 and 5 years. After 5 years of HRT, breast density increased 21.8% in women receiving cyclic combined therapy versus 38.8% in those under continuous combined therapy (p < 0.039).Conclusion: An increase in breast density is significantly more frequent in women receiving combined estrogen-progestin therapy than in women receiving estrogen alone. There are differences between cyclic and continuous combined therapy at 5 years of treatment.

Effect of taxane‐based neoadjuvant chemotherapy on fibroglandular tissue volume and percent breast density in the contralateral normal breast evaluated by 3T MR

The aim of this study was to evaluate the change of breast density in the normal breast of patients receiving neoadjuvant chemotherapy (NAC). Forty-four breast cancer patients were studied. MRI acquisition was performed before treatment (baseline), and 4 and 12 weeks after treatment. A computer-algorithm-based program was used to segment breast tissue and calculate breast volume (BV), fibroglandular tissue volume (FV), and percent density (PD) (the ratio of FV over BV × 100%). The reduction of FV and PD after treatment was compared with baseline using paired t-tests with a Bonferroni-Holm correction. The association of density reduction with age was analyzed. FV and PD after NAC showed significant decreases compared with the baseline. FV was 110.0 ml (67.2, 189.8) (geometric mean (interquartile range)) at baseline, 104.3 ml (66.6, 164.4) after 4 weeks (p < 0.0001), and 94.7 ml (60.2, 144.4) after 12 weeks (comparison with baseline, p < 0.0001; comparison with 4 weeks, p = 0.016). PD was 11.2% (6.4, 22.4) at baseline, 10.6% (6.6, 20.3) after 4 weeks (p < 0.0001), and 9.7% (6.2, 17.9) after 12 weeks (comparison with baseline, p = 0.0001; comparison with 4 weeks, p = 0.018). Younger patients tended to show a higher density reduction, but overall correlation with age was only moderate (r = 0.28 for FV, p = 0.07, and r = 0.52 for PD, p = 0.0003). Our study showed that breast density measured from MR images acquired at 3T MR can be accurately quantified using a robust computer-aided algorithm based on non-parametric non-uniformity normalization (N3) and an adaptive fuzzy C-means algorithm. Similar to doxorubicin and cyclophosphamide regimens, the taxane-based NAC regimen also caused density atrophy in the normal breast and showed reduction in FV and PD. The effect of breast density reduction was age related and duration related.

Abstract 2286: Short term reduction in mammographic density predicts survival in breast cancer.

Abstract Back ground: Identification of the factors that predict response to treatment in breast cancer patients early after diagnosis is important in guiding the treatment strategy. High mammographic density (MD) is a risk factor for breast cancer. However no study has examined the association between change in MD and death in breast cancer survivors. We hypothesized that a short-term change in breast density may be a surrogate biomarker predicting risk of death from breast cancer and all causes. Methods: We evaluated the relationship between reduction in MD and risk of death from all causes within the Health, Eating, Activity, and Lifestyle (HEAL) Study. In a prospective observational study, we studied 403 women diagnosed with primary invasive breast carcinoma between 1995 and 1998 and followed until death or September 2009. We collected mammograms and prognostic, demographic, and lifestyle factors as well as treatments at the time of diagnosis and two years after the diagnosis was made. Mammograms were digitized and MD was measured on cranio-caudal (CC) images of the unaffected breast using a computer assisted program developed at the University of Toronto. MD reduction (MDR) was evaluated based on two mammograms; the first was taken 12 months before diagnosis, and the second approximately 24 months after diagnosis. MDR was defined as the difference between the MD of these two images (% MDR = % preMD -% postMD). Reduction in MD was categorized into a binary variable as women who had a MDR ≥5% compared to those with less than 5% reduction in MD. Cox proportional hazards models were used to estimate the Hazard ratios and 95% confidence intervals. Results: Breast cancer patients with 5% or more reduction in MD were younger (mean age was 55.7 compared to 58.9), more likely to be premenopausal at diagnosis (36.7% compared to 24.0%), and more likely to have a history of oral contraception (73.9% compared to 63.3%). Women with MDR ≥5% were 49% less likely to die from any cause after adjustment for age, BMI, estrogen receptor status, progesterone receptor status, menopausal status at baseline, smoking, stage, tamoxifen use, chemotherapy, radiation therapy, and study center (HR=0.51 CI: 0.3-0.86). The results were stronger when we restricted the analysis to women who were premenopausal at diagnosis. When we restricted the analysis to women who had taken tamoxifen a similar direction was observed but the results were not statistically significant. Conclusion: Result from our data suggests that reduction in mammographic density few years after breast cancer diagnosis may be used as a predictor of overall survival. Citation Format: Ali Ozhand, Roberta Mckean-Cowdin, Leslie Bernstein, Rachel Ballard-Babash, Anne McTiernan, Kathy B. Baumgartner. Short term reduction in mammographic density predicts survival in breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2286. doi:10.1158/1538-7445.AM2013-2286

Breast density measurements using ultrasound tomography for patients undergoing tamoxifen treatment.

Women with high breast density have an increased risk of developing breast cancer. Women treated with the selective estrogen receptor modulator tamoxifen for estrogen receptor positive breast cancer experience a 50% reduction in risk of contralateral breast cancer and overall reduction of similar magnitude has been identified among high-risk women receiving the drug for prevention. Tamoxifen has been shown to reduce mammographic density, and in the IBIS-1 chemoprevention trial, risk reduction and decline in density were significantly associated. Ultrasound tomography (UST) is an imaging modality that can create tomographic sound speed images of the breast. These sound speed images are useful because breast density is proportional to sound speed. The aim of this work is to examine the relationship between UST-measured breast density and the use of tamoxifen. So far, preliminary results for a small number of patients have been observed and are promising. Correlations between the UST-measured density and mammographic density are strong and positive, while relationships between UST density with some patient specific risk factors behave as expected. Initial results of UST examinations of tamoxifen treated patients show that approximately 45% of the patients have a decrease in density in the contralateral breast after only several months of treatment. The true effect of tamoxifen on UST-measured density cannot yet be fully determined until more data are collected. However, these promising results suggest that UST can be used to reliably assess quantitative changes in breast density over short intervals and therefore suggest that UST may enable rapid assessment of density changes associated with therapeutic and preventative interventions.

Breast density changes in a randomized controlled trial evaluating bazedoxifene/conjugated estrogens

Breast density is associated with an increased risk of breast cancer. This study assessed changes in mammographic breast density after 24 months of treatment with bazedoxifene (BZA)/conjugated estrogens (CE) in postmenopausal women. This was an ancillary study in a subset of nonhysterectomized postmenopausal women enrolled in a randomized, double-blind, placebo-controlled, and active-controlled phase 3 study. Treatments evaluated were BZA 20 mg/CE 0.45 mg, BZA 20 mg/CE 0.625 mg, raloxifene 60 mg, and placebo. Women who were eligible for participation in the ancillary study must have completed 24 months of treatment and have mammograms at baseline and 24 months. The left craniocaudal views from each mammogram pair were digitized and analyzed by a radiologist who was blinded to treatment arm and mammogram date. The percent breast density was determined using validated software. Mammogram pairs were obtained from 507 evaluable participants (mean age range, 55.2-56.3 y). The mean changes (95% CI) in mammographic breast density from baseline to 24 months were comparable among groups (-0.39% [-0.69 to -0.08], -0.05% [-0.38 to 0.27], -0.23% [-0.54 to 0.08], and -0.42% [-0.72 to -0.11] for BZA 20 mg/CE 0.45 mg, BZA 20 mg/CE 0.625 mg, raloxifene 60 mg, and placebo, respectively). These reductions from baseline were statistically significant for BZA 20 mg/CE 0.45 mg and placebo. The effect of both BZA/CE doses on breast density was generally consistent among subgroups based on age, body mass index, and years since menopause. Treatment with BZA 20 mg/CE 0.45 mg or BZA 20 mg/CE 0.625 mg for 24 months did not affect mammographic breast density in this population of postmenopausal women.