Increase In Mammographic Density Research Articles

Factors Associated with Longitudinal Changes in Mammographic Density in a Multiethnic Breast Screening Cohort of Postmenopausal Women.

Breast density is an important risk factor for breast cancer and is known to be associated with characteristics such as age, race, and hormone levels; however, it is unclear what factors contribute to changes in breast density in postmenopausal women over time. Understanding factors associated with density changes may enable a better understanding of breast cancer risk and facilitate potential strategies for prevention. This study investigated potential associations between personal factors and changes in mammographic density in a cohort of 3,392 postmenopausal women with no personal history of breast cancer between 2011 and 2017. Self-reported information on demographics, breast and reproductive history, and lifestyle factors, including body mass index (BMI), alcohol intake, smoking, and physical activity, was collected by an electronic intake form, and breast imaging reporting and database system (BI-RADS) mammographic density scores were obtained from electronic medical records. Factors associated with a longitudinal increase or decrease in mammographic density were identified using Fisher's exact test and multivariate conditional logistic regression. 7.9% of women exhibited a longitudinal decrease in mammographic density, 6.7% exhibited an increase, and 85.4% exhibited no change. Longitudinal changes in mammographic density were correlated with age, race/ethnicity, and age at menopause in the univariate analysis. In the multivariate analysis, Asian women were more likely to exhibit a longitudinal increase in mammographic density and less likely to exhibit a decrease compared to White women. On the other hand, obese women were less likely to exhibit an increase and more likely to exhibit a decrease compared to normal weight women. Women who underwent menopause at age 55 years or older were less likely to exhibit a decrease in mammographic density compared to women who underwent menopause at a younger age. Besides obesity, lifestyle factors (alcohol intake, smoking, and physical activity) were not associated with longitudinal changes in mammographic density. The associations we observed between Asian race/obesity and longitudinal changes in BI-RADS density in postmenopausal women are paradoxical in that breast cancer risk is lower in Asian women and higher in obese women. However, the association between later age at menopause and a decreased likelihood of decreasing in BI-RADS density over time is consistent with later age at menopause being a risk factor for breast cancer and suggests a potential relationship between greater cumulative lifetime estrogen exposure and relative stability in breast density after menopause. Our findings support the complexity of the relationships between breast density, BMI, hormone exposure, and breast cancer risk.

The Correlation Between Progesterone and Mammographic Density in Postmenopausal Women: A Systematic Review of the Literature and Meta-Analysis.

Higher mammographic breast density in premenopausal and postmenopausal women is related to a higher breast cancer risk. In this review, we analyze the correlation between estrogen, progesterone, and mammographic density in postmenopausal women and clarify whether these findings are consistent across different types of mammographic breast density. We extracted data concerning mammographic density increases in the populations treated with estrogen-only hormone replacement therapy and those treated with estrogen and progestin hormone replacement therapy. Postmenopausal women treated with estrogen and progesterone regimens had a statistically significant lesser mammographic density increase than estrogen-only hormone replacement therapy regimens.

201TiP Density lowering effect of ovarian function suppression in premenopausal breast cancer patients who had no density change with one year of tamoxifen treatment (DELFINO study)

Mammographic density has been known to be a risk factor for breast cancer. Moreover, tamoxifen reduces mammographic density, and the change in mammographic density is a predictive surrogate marker for response to adjuvant tamoxifen therapy. If there is no change or rather an increase in mammographic density, the effect of tamoxifen therapy is considered to be less, and intervention for additional treatment such as ovarian function suppression (OFS) may be considered in the group with a low response to the treatment.

Abstract 5892: Factors associated with longitudinal changes in mammographic density in a multiethnic breast screening cohort of postmenopausal women

Abstract Mammographic density is an important risk factor for breast cancer and is known to differ in women by characteristics such as age and race/ethnicity. Women who experience longitudinal decreases in breast density have a reduced risk of breast cancer; however, besides age, which correlates with decreases in breast density, it is unclear what other factors contribute to changes in breast density over time. Understanding factors associated with density changes may enable a better understanding of breast cancer risk and potential strategies for prevention. This study investigated factors associated with changes in mammographic density in a cohort of 3,392 postmenopausal women (mean age=61.3±8.8 years) with no history of breast cancer who had at least two mammograms spaced at least three months apart at a University of California, Irvine Health breast imaging facility between 2011-2017. Self-reported information on demographics, breast and reproductive history, and lifestyle factors, including body mass index (BMI), alcohol intake, smoking, and physical activity, was collected by an electronic intake form, and Breast Imaging Reporting and Database System (BI-RADS) mammographic density scores were obtained from electronic medical records. 7.9% of women exhibited a longitudinal decrease in mammographic density, 6.7% exhibited an increase, and 85.4% exhibited no change. Longitudinal changes in mammographic density were statistically significantly correlated with age, race/ethnicity, and age at menopause by univariate analysis using the Fisher’s exact test. Multivariate conditional logistic regression using baseline mammographic density as strata was performed to identify factors associated with a longitudinal increase or decrease in mammographic density. Variables were selected if they were nominally significant (p < 0.10) in the initial univariate analyses of women who exhibited a longitudinal change in mammographic density (race/ethnicity, age at baseline, menopause age) or were otherwise selected a priori based on previous literature showing an association with mammographic density (alcohol, physical activity, BMI). Asian women were more likely to exhibit a longitudinal increase in mammographic density (OR=1.78, 95% CI=1.02-3.09, p=0.04) and less likely to exhibit a decrease (OR = 0.58, 95% CI = 0.40-0.83, p=0.003) compared to white women. On the other hand, overweight and obese women were less likely to exhibit an increase compared to normal weight women (OR = 0.52, 95% CI = 0.31-0.87, p=0.01; OR = 0.41, 95% CI = 0.23-0.75, p=0.004, respectively). Other lifestyle factors (alcohol intake, smoking, and physical activity) were not associated with longitudinal changes in mammographic density. The potential interactions of Asian race and BMI with longitudinal breast density changes in influencing breast cancer risk should be further studied. Citation Format: Roza L. Kirmizi, Christie J. Lee, Hannah Lui Park, Argyrios Ziogas, Andrea Alvarez, Rachel M. Lucia, Deborah Goodman, Kathryn M. Larsen, Richard Kelly, Hoda Anton-Culver, Stephen A. Feig. Factors associated with longitudinal changes in mammographic density in a multiethnic breast screening cohort of postmenopausal women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5892.

Vaginal estrogen and mammogram results: case series and review of literature on treatment of genitourinary syndrome of menopause (GSM) in breast cancer survivors.

To examine mammographic density before and after at least 1 year of vaginal estrogen use in a small cohort of healthy postmenopausal women and women with a personal history of breast cancer. We extracted data via chart review of patients from a single practitioner's menopause specialty clinic in Baltimore, MD. Mammographic change was primarily determined via the Bi-RADS scoring system, including the Bi-RADS density score. In addition, we conduct a narrative review of the current literature on the usage of local estrogen therapy, and systemic and local alternatives in the treatment of genitourinary syndrome of menopause (GSM) in breast cancer survivors. Twenty healthy postmenopausal women and three breast cancer survivors fit our inclusion criteria. Amongst these two groups, we did not find an increase in mammographic density after at least 1 year and up to 18 years of local vaginal estrogen. Ospemifene use in one patient did not appear to be associated with any change in Bi-RADS score. Our narrative review found little data on the effects of vaginal estrogen therapy or newer alternative systemic therapies such as ospemifene on mammographic density. Low-dose vaginal estrogen use for 1 or more years in a small cohort of women with GSM did not appear to be associated with any changes in breast density or Bi-RADS breast cancer risk scores in the majority of study participants, including three breast cancer survivors. Larger long-term controlled clinical trials should be conducted to examine the effects of low-dose vaginal estrogen on mammographic density in women with and without a personal history of breast cancer. Furthermore, relative efficacy and risk of vaginal estrogen compared with other forms of treatment for GSM should also be studied in long-term trials.

Mammographic density changes following discontinuation of tamoxifen in premenopausal women with oestrogen receptor-positive breast cancer.

To evaluate the changes in mammographic density after tamoxifen discontinuation in premenopausal women with oestrogen receptor-positive breast cancers and the underlying factors METHODS: A total of 213 consecutive premenopausal women with breast cancer who received tamoxifen treatment after curative surgery and underwent three mammograms (baseline, after tamoxifen treatment, after tamoxifen discontinuation) were included. Changes in mammographic density after tamoxifen discontinuation were assessed qualitatively (decrease, no change, or increase) by two readers and measured quantitatively by semi-automated software. The association between % density change and clinicopathological factors was evaluated using univariate and multivariate regression analyses. After tamoxifen discontinuation, a mammographic density increase was observed in 31.9% (68/213, reader 1) to 22.1% (47/213, reader 2) by qualitative assessment, with a mean density increase of 1.8% by quantitative assessment compared to density before tamoxifen discontinuation. In multivariate analysis, younger age (≤ 39 years) and greater % density decline after tamoxifen treatment (≥ 17.0%) were independent factors associated with density change after tamoxifen discontinuation (p < .001 and p = .003, respectively). Tamoxifen discontinuation was associated with mammographic density change with a mean density increase of 1.8%, which was associated with younger age and greater density change after tamoxifen treatment. • Increased mammographic density after tamoxifen discontinuation can occur in premenopausal women. • Mean density increase after tamoxifen discontinuation was 1.8%. • Density increase is associated with age and density decrease after tamoxifen.

Estrone – a partial estradiol antagonist in the normal breast

Oral hormone replacement therapy (HRT) based on estradiol-17β (E2) greatly increases circulating estrone (E1) levels. E1 is an estrogen receptor agonist but may also be a partial E2 antagonist. We investigated the effects of circulating E1 on the association between circulating E2 and the increase in mammographic density (∂MD) in 46 healthy post-menopausal women treated with E2 2 mg and norethisterone acetate 1 mg daily. MD and serum E1 and E2 were measured before and after 6 months of treatment. At high E1 levels, ∂MD showed significant positive correlations leading to increase (∂-values) in both E1 and E2. Lowering the upper serum E1 limit strengthened the correlations to ∂E2 while the significant correlations to ∂E1 disappeared. E1 at high concentrations may act as a partial E2 antagonist also in the normal breast in vivo and disturb relationships between circulating E2 and biological estrogen effects. When investigating the relations between circulating steroids and their effects, structurally related compounds, which may act as partial antagonists, have to be considered, at least when they are present in higher concentrations.

Rotating Night Shift Work and Mammographic Density

An increased risk of breast cancer has been observed in night shift workers. Exposure to artificial light at night and disruption of the endogenous circadian rhythm with suppression of the melatonin synthesis have been suggested mechanisms. We investigated the hypothesis that rotating night shift work is associated with mammographic density. We conducted a cross-sectional study on the association between rotating night shift work characteristics, 6-sulfatoxymelatonin (MT6s) creatinine adjusted in a spot morning urine sample, and a computer-assisted measure of mammographic density in 640 nurses and midwives ages 40 to 60 years. The associations were evaluated using regression models adjusted for age, body mass index, menopausal status, age at menopause, age at menarche, smoking, and the calendar season of the year when mammography was conducted. The adjusted means of percentage of mammographic density and absolute density were slightly higher among women working rotating night shifts but not statistically significant [percentage of mammographic density = 23.6%, 95% confidence interval (CI), 21.9%-25.4% vs. 22.5%, 95% CI, 20.8%-24.3%; absolute density = 23.9 cm(2), 95% CI, 21.4-26.4 cm(2) vs. 21.8 cm(2), 95% CI, 19.4-24.3 cm(2) in rotating night shift and day shift nurses, respectively). There were no significant associations between the current or cumulative rotating night shift work exposure metrics and mammographic density. No association was observed between morning MT6s and mammographic density. The hypothesis on the link between rotating night shift work, melatonin synthesis disruption, and mammographic density is not supported by the results of the present study. It is unlikely that the development of breast cancer in nurses working rotating night shifts is mediated by an increase in mammographic density.

Progestogen levels, progesterone receptor gene polymorphisms, and mammographic density changes

Estrogen plus progestin therapy (EPT) in postmenopausal women increases breast cancer risk and mammographic density to a higher extent than does estrogen therapy alone. Data from the randomized placebo-controlled Postmenopausal Estrogen/Progestinv Interventions trial showed that EPT-induced increases in serum estrone and estrone sulfate levels were positively correlated with increases in mammographic density. Here, after adjusting for serum estrone and estrone sulfate levels, we investigated the roles of posttreatment serum progestogen increase and of progesterone receptor gene (PGR) genetic variations on changes in mammographic density. We measured the percent mammographic density and serum progestogen levels in 280 Postmenopausal Estrogen/Progestin Interventions trial participants randomized to EPT treatment. Analyses of genetic variations in PGR were limited to 260 white women for whom we successfully obtained PGR genotypes. We used linear regression analyses to determine how an increase in progestogen levels and PGR genetic variation influenced mammographic density change after EPT. The increase in posttreatment serum progestogen level was positively associated with greater increases in mammographic density after adjustment for covariates (P trend = 0.044). Compared with women in the lowest quartile of serum progestogen level, women in the highest quartile experienced a 3.5% greater increase in mammographic density (P = 0.046). We did not find a strong indication that genetic variation in PGR was associated with mammographic density increase or modified the association with serum progestogen; however, confidence in these null findings is constrained by our small sample size. Our results suggest that higher serum progestogen levels resulting from EPT treatment lead to greater increases in mammographic density.

Breast tenderness after initiation of conjugated equine estrogens and mammographic density change

We examined the association between new-onset breast tenderness and change in mammographic density after initiation of conjugated equine estrogens (CEE). We analyzed baseline, year 1 and 2 data from 695 participants of the Women's Health Initiative Estrogen+Progestin (daily CEE 0.625mg+medroxyprogesterone acetate 2.5mg [MPA] or placebo) and Estrogen-Alone (CEE 0.625mg or placebo) trials who participated in the Mammogram Density Ancillary Study. Using multivariable repeated measures models, we analyzed the association between new-onset breast tenderness (i.e. absence of baseline tenderness and presence of tenderness at year 1 follow-up) and change from baseline in percent mammographic density. Active therapy increased the odds of new-onset breast tenderness (CEE+MPA vs. placebo risk ratio [RR] 3.01, 95% confidence interval [95% CI] 1.96-4.62; CEE vs. placebo RR 1.70, 95% CI 1.14-2.53). Among women assigned to CEE+MPA, mean increase in mammographic density was greater among participants reporting new-onset of breast tenderness than among participants without new-onset breast tenderness (11.3 vs. 3.9% at year 1, 9.4 vs. 3.2% at year 2, P<0.001). Among women assigned to CEE alone, increase in mammographic density at year 1 follow-up was not significantly different in women with new-onset breast tenderness compared to women without new-onset breast tenderness (2.4 vs. 0.6% at year 1, 2.2 vs. 1.0% at year 2, P=0.30). The new-onset of breast tenderness after initiation of CEE+MPA, but not CEE alone, is associated with greater increases in mammographic density.

Less mammographic density after nasal versus oral administration of postmenopausal hormone therapy

ABSTRACTObjective Nasal administration gives a more acute but shorter rise in serum hormone levels than oral administration and may therefore have less effect on the fibroglandular tissue in the breasts. We studied the change in mammographic breast density after nasal vs. oral administration of postmenopausal hormone therapy (PHT).Methods We studied participants in a randomized, controlled trial on the impact of nasal vs. oral administration of PHT (combined 17β-estradiol plus norethisterone) for 1 year. Two radiologists classified mammographic density at baseline and after 1 year into four categories. Also, the percentage density was calculated by a computer-based method. The main outcome measure was the difference in the proportion of women with an increase in mammographic density category after 1 year between the nasal and oral groups. Also, the change in the percentage density was calculated.Results The study group comprised 112 healthy postmenopausal women (mean age 56 years), of whom 53 received oral and 59 intranasal PHT. An increase in mammographic density category after 1 year was seen in 20% of the women in the nasal group and in 34% of the oral group. This resulted in a non-significant difference in the proportion of women in whom mammographic breast density had increased by 214% (95% confidence interval (CI) 230% to 2.7%). The mean change in percentage density was 21.2% in the nasal group and + 1.2% in the oral group, yielding a 22.4% differential effect (95% CI 27.3% to 2.5%).Conclusions One year of nasal PHT gave a smaller, although not statistically significant, increase in mammographic density than oral PHT. Remaining issues are the relation between the route of administration of PHT and breast complaints and breast cancer risk.

Childhood factors associated with mammographic density in adult women

Growth and development factors could contribute to the development of breast cancer associated with an increase in mammographic density. This study examines the influence of certain childhood-related, socio-demographic and anthropometric variables on mammographic density in adult woman. The study covered 3574 women aged 45-68 years, participating in breast cancer-screening programmes in seven Spanish cities. Based on a craniocaudal mammogram, blind, anonymous measurement of mammographic density was made by a single radiologist, using Boyd's semiquantitative scale. Data associated with the early stages of life were obtained from a direct survey. Ordinal logistic regression and generalised linear models were employed to estimate the association between mammographic density and the variables covered by the questionnaire. Screening programme was introduced as a random effects term. Age, number of children, body mass index (BMI) and other childhood-related variables were used as adjustment variables, and stratified by menopausal status. A total of 811 women (23%) presented mammographic density of over 50%, and 5% of densities exceeded 75%. Our results show a greater prevalence of high mammographic density in women with low prepubertal weight (OR: 1.18; 95% CI: 1.02-1.36); marked prepubertal height (OR: 1.25; 95% CI: 0.97-1.60) and advanced age of their mothers at their birth (>39 years: OR: 1.28; 95% CI: 1.03-1.60); and a lower prevalence of high mammographic density in women with higher prepubertal weight, low birth weight and earlier menarche. The influence of these early-life factors may be explained by greater exposure to hormones and growth factors during the development of the breast gland, when breast tissue would be particularly susceptible to proliferative and carcinogenic stimulus.

Effects of isoflavones on breast density in pre- and post-menopausal women: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUNDIsoflavones from soy and red clover exert modest hormonal effects in women, but the relevance to risk of breast cancer is unclear. The aim of this meta-analysis was to assess the effects of isoflavone-rich foods or supplements on a biomarker of breast cancer risk, women's mammographic density.METHODSElectronic searches were performed on The Cochrane Library, Medline and EMBASE (to June 2009), and reference lists and trial investigators were consulted to identify further studies. Randomized controlled trials (RCTs) of isoflavone-rich foods or supplements versus placebo with a duration of at least 6 months were included in our analysis. Inclusion/exclusion, data extraction and validity assessment were carried out independently in duplicate, and meta-analysis used to pool study results. Subgrouping, sensitivity analysis, assessment of heterogeneity and funnel plots were used to interpret the results.RESULTSEight RCTs (1287 women) compared isoflavones with placebo for between 6 months and 3 years. Meta-analysis suggested no overall effect of dietary isoflavones on breast density in all women combined [mean difference (MD) 0.69%, 95% confidence interval (CI) −0.78 to 2.17] or post-menopausal women (MD −1.10%, 95% CI −3.22 to 1.03). However, there was a modest increase in mammographic density in premenopausal women (MD 1.83%, 95% CI 0.25–3.40) without heterogeneity but this effect was lost in one of three sensitivity analyses.CONCLUSIONSIsoflavone intake does not alter breast density in post-menopausal women, but may cause a small increase in breast density in premenopausal women. Larger, long-term trials are required to determine if these small effects are clinically relevant.

Influence of High-Dose Estrogen Exposure during Adolescence on Mammographic Density for Age in Adulthood

High-dose estrogen exposure during adolescence has been hypothesized to increase a woman's breast cancer risk, possibly mediated through an increase in mammographic density, a well-established breast cancer risk factor. In 2006 to 2007, we conducted a retrospective study of women assessed for tall stature as an adolescent between 1959 and 1993. Eligible participants were ages > or =40 years and treated during adolescence with 3 mg diethylstilbestrol or 150 microg ethinyl estradiol daily or untreated. Mammograms from 167 treated and 142 untreated women were digitized. Total breast area, dense area, nondense area, and percent density were measured using a computer thresholding technique. Data on potential determinants were collected from medical records and telephone interview. Treated women had, on average, 17% lower dense area (P = 0.032). Means (95% confidence intervals) adjusted for age and body mass index for treated and untreated women were 24.5 cm(2) (21.8-27.2) and 29.1 cm(2) (26.0-32.4), respectively. There was no difference in adjusted means (95% confidence intervals) between treated and untreated women for nondense area [71.7 cm(2) (66.2-77.7) versus 70.5 cm(2) (64.7-76.9); P = 0.78], percent dense area [24.8% (22.4-27.4) versus 27.7% (24.8-30.7); P = 0.16], or total area [105.6 cm(2) (100.1-111.4) versus 109.3 cm(2) (103.1-115.8); P = 0.41], respectively. High-dose estrogen exposure during adolescence appears to curtail growth of mammographically dense tissue and therefore is unlikely to increase breast cancer risk through mechanisms related to mammographic density.

Conjugated Equine Estrogen Influence on Mammographic Density in Postmenopausal Women in a Substudy of the Women's Health Initiative Randomized Trial

Increased mammographic density is associated with increased breast cancer risk and reduced sensitivity of screening mammography and is related to hormone exposure. However, the effects of conjugated equine estrogens (CEEs) alone on mammographic density in diverse racial/ethnic populations are not established. We examined the effect of CEE alone on mammographic density in a subsample of the Women's Health Initiative (WHI) clinical trial participants. In the WHI trial, women were randomly assigned to daily CEE 0.625 mg or placebo. The effect of CEE on mammographic percent density was determined over 1 and 2 years in a stratified random sample of 435 racially and ethnically diverse participants from 15 of 40 WHI clinics. Use of CEE resulted in mean increase in mammographic percent density of 1.6 percentage points (95% CI, 0.8 to 2.4) at year 1 compared with a mean decrease of 1.0 percentage point (95% CI, -1.7 to -0.4) in the placebo group (P < .001). The effect persisted for 2 years, with a mean increase of 1.7 percentage points (95% CI, 0.7 to 2.7) versus a mean decrease of 1.2 percentage points (95% CI, -1.8 to -0.5; P < .001) in the hormone and placebo groups, respectively. These effects were greater in women age 60 to 79 years (P = .03 for interaction across age). Use of CEE results in a modest but statistically significant increase in mammographic density that is sustained over at least a 2-year period. The clinical significance of the CEE effect on mammographic density remains to be determined.

Breast density analysis for whole breast ultrasound images

Breast density has been established as an independent risk factor associated with the development of breast cancer. The terms mammographic density and breast density are often used interchangeably, since most breast density studies are performed with projection mammography. It is known that increase in mammographic density is associated with an increased cancer risk. A sensitive method that allows for the measurement of small changes in breast density may provide useful information for risk management. Despite the efforts to develop quantitative breast density measurements from projection mammograms, the measurements show large variability as a result of projection imaging, differing body position, differing levels of compression, and variation of the x-ray beam characteristics. This study used two separate computer-aided methods, threshold-based and proportion-based evaluations, to analyze breast density on whole breast ultrasound (US) imaging and to compare with the grading results of three radiologists using projection mammography. Thirty-two female subjects with 252 images per case were included in this study. Whole breast US images were obtained from an Aloka SSD-5500 ultrasound machine with an ASU-1004 transducer (Aloka, Japan). Before analyzing breast density, an adaptive speckle reduction filter was used for removing speckle noise, and a robust thresholding algorithm was used to divide breast tissue into fatty or fibroglandular classifications. Then, the proposed approaches were applied for analysis. In the threshold-based method, a statistical model was employed to determine whether each pixel in the breast region belonged to fibroglandular or fatty tissue. The proportion-based method was based on three-dimensional information to calculate the volumetric proportion of fibroglandular tissue to the total breast tissue. The experimental cases were graded by the proposed analysis methods and compared with the ground standard density classification assigned by a majority voting of three experienced breast radiologists. For the threshold-based method, 28 of 32 US test cases and for the proportion-based density classifier, 27 of 32 US test cases were found to be in agreement with the radiologist "ground standard" mammographic interpretations, resulting in overall accuracies of 87.5% and 84.4%, respectively. Moreover, the concordance values of the proposed methods were between 0.0938 and 0.1563, which were less than the average interobserver concordance of 0.3958. The experiment result showed that the proposed methods could be a reference opinion and offer concordant and reliable quantification of breast density for the radiologist.

Densité mammaire : un paramètre à surveiller lors de la prise d’un traitement hormonal de la ménopause

Mammographic density is a risk factor for breast cancer and it reflects variations in the tissue composition of the breast. It is notably influenced by body mass index and by endogenous hormones as well as hormone replacement therapy (HRT). The pathways that are responsible for the increase in mammographic density following exposure to hormones and those that increase risk of breast cancer are probably not the same. Careful clinical and mammographic follow-up is appropriate in women undergoing HRT because an increase in density is not only a risk factor for breast cancer but it also reduces screening sensitivity. We present a case in which mammographic density decreased after menopause, then dramatically increased after HRT and finally, surgical biopsy allowed the diagnosis of an infiltrative breast carcinoma. We discuss appropriate HRT changes in case of increasing mammographic density.

Increases in Serum Estrone Sulfate Level Are Associated with Increased Mammographic Density during Menopausal Hormone Therapy

Menopausal hormone therapy increases mammographic density. We determined whether increases in serum estrone sulfate (E(1)S) levels during menopausal hormone therapy predict increased mammographic density. We measured percent mammographic density and serum E(1)S levels in 428 participants of the Postmenopausal Estrogen/Progestin Interventions study who were randomly assigned to daily conjugated equine estrogen (CEE) 0.625 mg alone, CEE + daily medroxyprogesterone acetate (MPA) 2.5 mg, CEE + cyclical MPA (10 mg days 1-12 per 28-day cycle), or CEE + cyclical micronized progesterone (10 mg days 1-12). Serum E(1)S levels were determined by RIA. Information about covariates was determined by annual questionnaire. Using linear regression, we determined the association between change in E(1)S level from baseline to 12 months and change in percent mammographic density (by semiquantitative interactive threshold method). After controlling for baseline mammographic density, age, body mass index, alcohol intake, parity, smoking, ethnicity, physical activity, and age at first pregnancy, mammographic density increased by 1.3% for every 1 ng/mL increase in E(1)S level (P < 0.0001). The association between change in E(1)S level and change in mammographic density differed by treatment group (greater effect in CEE + cyclical MPA group versus CEE group; P = 0.05). After controlling for treatment group, change in the ratio of E(1)S to E(1) was also positively associated with change in mammographic density. Increases in serum E(1)S levels during menopausal hormone therapy are associated with increases in mammographic density. The relative contribution of E(1)S and E(1) to stimulation of breast tissue awaits further elucidation.

Serum prolactin levels are positively associated with mammographic density in postmenopausal women

Prolactin is a polypeptide hormone that promotes normal breast proliferation and differentiation, but it is also implicated in the development and growth of mammary tumors. Mammographic density is a strong, independent predictor of breast cancer and, therefore, a potential surrogate indicator of breast cancer risk. To test the hypothesis that serum prolactin is positively related to mammographic density, we conducted a cross-sectional analysis of baseline data from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Mammographic Density Study. Based on prior work, we further hypothesized that this association would be apparent only in women who had not recently used postmenopausal hormone therapy (HT). In linear regression models adjusted for age, body mass index, race, smoking, alcohol use, parity and physical activity, among the 400 women who were not recent users of HT, prolactin was positively and statistically significantly associated with mammographic density (Beta log base 2 prolactin 0.0369 [95% CI: 0.0094-0.0645]. Thus, for each doubling of serum prolactin, there was an absolute increase in mammographic density of 3.69%. Additional adjustment for serum levels of estradiol, progesterone, sex hormone binding globulin and age at first pregnancy did not affect this result. There was no association between prolactin and mammographic density among the 169 participants who had recently used HT. The correspondence between higher prolactin and higher mammographic density is consistent with prolactin's mitogenic properties and the associations between prolactin and breast tumor promotion. These results support the thesis that prolactin deserves investigation as a target for breast cancer risk reduction.

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.