Pain and increased mammographic density in women receiving hormone replacement therapy: a prospective study.

127

105

Objectives: Few studies have examined the association between breast density and breast cancer tumor characteristics. We examined the association between hormonal, proliferative, and histologic tumor characteristics and mammographic breast density in women with breast cancer. Methods: We conducted a cross-sectional analysis in 546 women diagnosed with invasive breast cancer to evaluate the associations between breast density and tumor size, lymph node status, lymphatic or vascular invasion, histologic grade, nuclear grade, tumor differentiation, mitotic index, tumor necrosis, Ki-67 proliferation, estrogen receptor, progesterone receptor, p53, p27, cyclin E, Bcl-2, and C-erb-B2 invasion. Breast density was classified as fatty (Breast Imaging Reporting and Data System code 1 or 2; n = 373) or dense (Breast Imaging Reporting and Data System code 3 or 4; n = 173) for the cancer-free breast. A single pathologist measured all tumor markers. We examined whether the relationships were modified by interval cancer or screen-detected cancer.Results: Women with a tumor size >1.0 cm were more likely to have dense breasts compared with women with a tumor size V V 1.0 cm after adjusting for confounders (odds ratio, 2.0; 95% confidence interval, 1.2-3.4 for tumor sizes 1.1-2.0 cm; odds ratio, 2.3; 95% confidence interval, 1.3-4.4 for tumor sizes 2

Section: Introductionmentioning

confidence: 99%

Association between Mammographic Breast Density and Breast Cancer Tumor Characteristics

Aiello

Buist

White

et al. 2005

127

105

“…This suggests that postmenopausal hormone therapy use slows down the natural reduction in mammographic density. Other studies have shown that postmenopausal hormone therapy use even increases breast density (6)(7)(8)(9)(10)(11)(12)(13)(14)(15). These effects, however, are not seen in all women who use hormone therapy (6)(7)(8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Influence of Estrogen Receptor α and Progesterone Receptor Polymorphisms on the Effects of Hormone Therapy on Mammographic Density

Duijnhoven

Peeters

Warren

et al. 2006

Postmenopausal hormone therapy increases mammographic density, a strong breast cancer risk factor, but effects vary across women. We investigated whether the effect of hormone therapy use is modified by polymorphisms in the estrogen receptor (ESR1) and progesterone receptor (PGR) genes in the Dutch Prospect-EPIC and the English EPICNorfolk cohorts. Information on hormone therapy use was obtained through questionnaires at recruitment and after 5 years. Blood samples were collected and consecutive mammograms were available through breast cancer screening programs. For 795 hormone therapy users, one mammogram before and a second mammogram during hormone therapy use was included. For 781 never hormone therapy users, mammograms with similar time intervals were included. Mammographic density was assessed using a computerassisted method. Changes in density were analyzed using linear regression. A statistically significant difference in percentage density change between hormone therapy users and never users was seen in women with the ESR1 PvuII Pp or pp genotype (2.24%; P < 0.01), but not in those with the PP genotype (0.90%; P = 0.47). Similarly, effects of hormone therapy on percentage density were observed in women with the ESR1 XbaI Xx or xx genotype (2.20%; P < 0.01), but not in those with the XX genotype (À0.65%; P = 0.70). Also, effects were seen in women with the PGR +331 GG genotype (2.04%; P < 0.01), but not in those with the GA or AA genotype (0.98%; P = 0.53). The PGR PROGINS polymorphism did not seem to make women more susceptible to the effects of hormone therapy use. In conclusion, our results suggest that specific polymorphisms in the ESR1 and PGR genes may make women more susceptible to the effects of hormone therapy use on mammographic density.

“…However, the pathway through which this occurs is not clearly defined. One hypothesis is that increased endogenous sex hormone levels may play a role, as several studies have noted that the use of exogenous hormones, particularly estrogen plus progesterone therapy, is associated with an increase in mammographic density (7)(8)(9)(10)(11)(12)(13) and breast cancer risk (14)(15)(16). We are aware of only two studies that have examined the association of blood or urine levels of estradiol and estrone with mammographic density (17,18); however, the reported results were inconsistent.…”

Section: Introductionmentioning

confidence: 99%

Associations among Circulating Sex Hormones, Insulin-Like Growth Factor, Lipids, and Mammographic Density in Postmenopausal Women

Aiello

Tworoger

Yasui

et al. 2005

Objective: Hormone therapy use has been positively associated with mammographic density in several studies. However, few studies have examined the association between endogenous hormone levels and mammographic density. Therefore, we evaluated the relationship of endogenous sex hormones, insulin-like growth factor (IGF), and lipids with mammographic density in 88 overweight, postmenopausal women not taking hormone therapy. Methods: Percent density and dense area were evaluated as continuous measures using a computer-assisted program. We used multiple linear regression to evaluate the associations of sex hormones, IGF, and cholesterol with mammographic density, adjusting for confounders, including adiposity. We evaluated stratification by history of hormone therapy use (former versus never) and hormone therapy latency (<5 versus z5 years). Results: Among former hormone therapy users, mammographic density was inversely associated with circulating levels of estrone (P = 0.01), estradiol (P = 0.003), free estradiol (P = 0.004), testosterone (P = 0.04), free testosterone (P = 0.02), androstenedione (P < 0.001), dehydroepiandrosterone (P = 0.01), and the ratio of IGF-I to its binding protein (IGF-I/IGFBP-3; P = 0.04). We found similar associations when we limited the analyses to women who had used hormone therapy within the past 5 years. We also noted positive associations of mammographic density with total cholesterol (P = 0.03) and low-density lipoprotein (P = 0.03) among former hormone therapy users. No associations were noted among women who had never used hormone therapy. Conclusions: These results suggest that there is an inverse relationship between endogenous sex hormones and mammographic density in postmenopausal women among former users of hormone therapy. This is not consistent with the hormone therapy literature and should be confirmed in larger studies. (Cancer Epidemiol Biomarkers Prev 2005;14(6):1411 -7)