Effect of estrogen and estrogen-progestin replacement regimens on mammographic breast parenchymal density.

Persson, Ingemar; Thurfjell, Erik; Holmberg, Lars

doi:10.1200/jco.1997.15.10.3201

Cited by 166 publications

(76 citation statements)

References 29 publications

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“…The influence on breast density varies among different compositions of the medicament, but there is agreement that use of HRT increases breast density among a substantial proportion of the users (17-73% depending on how the changes are measured). 6,30 We found a significant relation in our material between ever-use of HRT and high breast density. A recent article reported that breast density decreased when HRT use was discontinued, 31 so this increased breast density may be a transient problem dependent on the prescription practice.…”

Section: Breast Density and Use Of Hrtmentioning

confidence: 49%

Interval cancers in the Norwegian breast cancer screening program: Frequency, characteristics and use of HRT

et al. 2001

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Key words: mammography screening; interval cancer; breast density; HRTAs a result of the mortality reduction found in several randomized controlled clinical trials, 1,2 breast cancer screening programs have been implemented in several western countries. 3 The Norwegian Breast Cancer Screening Program is a population-based program that offers women aged 50 -69 years biannual mammography screening. The program started as a pilot project in 4 counties in 1996, and the results from the first screening round were reported earlier. 4 Interval cancers can be defined as breast cancer diagnosed in screened women during the interval between 2 screening rounds, where the diagnosis does not follow from the screening examination. 5 The benefit of attending a screening program is reduced for women diagnosed with interval cancer. Thus the effect of a screening program in terms of mortality reduction can diminish if the frequency of interval cancer is high. This frequency depends, among other factors, on sensitivity of the test and length of the screening interval.Most interval cancers are diagnosed because of symptoms, hence interval and screening-detected cancers might be expected to have different characteristics. High breast density and use of hormone replacement therapy (HRT) have been discussed as possible contributors to reduction of screening sensitivity, and this may be related to occurrence of interval cancers. 6 -11 The purpose of our study was to quantify the interval cancers in the pilot project and to explore characteristics and factors that may be associated with interval cancer. To study the relations between use of HRT, breast density and interval cancer, data from a blinded review (breast density) and a questionnaire (use of HRT) were linked. MATERIAL AND METHODS Screening populationThe Norwegian Breast Cancer Screening Program is population based and covers women aged 50 -69 years. The screening population is identified through the Central Population Register, in which each inhabitant in Norway has a unique 11-digit number. Women are invited into the Norwegian Breast Cancer Screening Program irrespective of previous breast cancer history. The screening interval is 2 years. Two-view mammograms and independent double reading are standard. The pilot project included 4 counties with about 40% of the Norwegian female population aged 50 -69 years. During the first round (1996-97), 159,887 women born from 1927-46 were invited and 127,064 women were examined (79.5%). 4 Study subjectsWomen who had their first screening examination within the pilot project after July 31, 1998 (n ϭ 411) and women who experienced recurrence in the same breast as a previous lesion (n ϭ 6) were excluded from the study. Women who received a cancer diagnosis in the first screening round (n ϭ 854) were not included as being at risk of interval cancer. However, women who were screen-positive but cleared after assessment were included. This left 125,793 women at risk of developing interval cancer. The women were followed until the date an in...

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Section: Breast Density and Use Of Hrtmentioning

confidence: 49%

Interval cancers in the Norwegian breast cancer screening program: Frequency, characteristics and use of HRT

et al. 2001

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“…Data on BC mortality by breast density have not been reported earlier, although hormone use is known to delay breast tissue transition from M/D to F (Persson et al, 1997). Current hormone users at recruitment to the Million Women Study had, during a follow-up period of about 4 years, a relative risk of BC incidence of 1.66 (95% CI 1.60 -1.72) compared with never users, whereas their relative BC mortality risk was only 1.22 (95%CI 1.05 -1.41) (Beral et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Breast density and outcome of mammography screening: a cohort study

et al. 2009

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The purpose of this study was to investigate the effect of breast density on breast cancer (BC) mortality in a mammography screening programme. The cohort included 48 052 women participating in mammography screening in Copenhagen, Denmark, where biennial screening is offered to women aged 50 -69 years. We collected information for the years 1991 -2001 on screening outcome, incident BCs (screen-, interval-, and later detected), and BC deaths. Breast density was dichotomised into fatty (F) and mixed/dense (M/D) breasts. Screening sensitivity was measured as the odds ratio of interval versus screen-detected cancer for dense versus F breasts. Poisson regression was used to estimate the ratios for BC incidence, case fatality, and mortality between women with M/D and F breasts. For women with M/D breasts, the odds ratio of an interval cancer was 1.62 (95% confidence interval, CI, 1.14 -2.30), and the age-adjusted rate ratios were 2.45 (95% CI 2.14 -2.81) for BC incidence, 0.60 (95% CI 0.43 -0.84) for case fatality, and 1.78 (95% CI 1.17 -2.72) for BC mortality. The study shows that BC in women with M/D breasts is more frequent, but on average less severe, than in women with F breasts. British Journal of Cancer (2009) Breast density is a measure of the composition of the breast tissue. Breasts with low density have a high proportion of fatty (F) tissue, whereas breasts with high density have a high proportion of epithelial and connective tissue. Mammography has a lower sensitivity in women with mixed/dense (M/D) breasts than in women with F breasts (Mandelson et al, 2000, Ciatto et al, 2004Chiarelli et al, 2006), and women with M/D breasts have a higher incidence of breast cancer (BC) than women with F breasts (McCormack and dos Santos Silva, 2006;Boyd et al, 2007). We therefore examined whether breast density affects the outcome of mammography screening using data from the organised mammography screening programme in Copenhagen, Denmark, earlier shown to reduce BC mortality in targeted women by 25% and in participating women by 37% (Olsen et al, 2005).We tested the following hypotheses: compared with women with F breasts, (1) the sensitivity of mammography is lower in women with M/D breasts, and (2) women with M/D breasts have a higher BC incidence. Our results were well in accordance with those of earlier studies. We further tested whether: (3) because of the lower sensitivity the case fatality rate of BC patients with M/D breasts will be higher than that of patients with F breasts, and (4) screened women with M/D breasts will experience a higher BC mortality than screened women with F breasts. This study is the first to report on the effect of breast density on BC mortality in screened women.

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“…The increment was greater in response to EPT than to ET in the terminal ductal lobular unit. Greendale et al 20 , 21 and others 13 have shown that HT and particularly EPT increase mammographic density substantially over that with use of placebo or no therapy. However, no studies have correlated breast density and histologic changes in women using HT.…”

mentioning

confidence: 99%

“…11 Menopausal HT increases mammographic density as assessed by quantitative methods, although this finding varies by regimen. 12 , 13 Similar to breast cancer risk, a higher percentage of women experience increased mammographic breast density when using EPT than those who use only estrogen therapy (ET). 13 Likewise, women using therapies that reduce breast cancer risk, such as tamoxifen 14 , 15 and raloxifene, 16 -18 experience a decrease in mammographic breast density.…”

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confidence: 99%

Histologic changes in the breast with menopausal hormone therapy use

Harvey¹,

Santen²,

Petroni

et al. 2008

Menopause

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Objective-This retrospective study systematically compared mammographic density with histology in women receiving or not receiving menopausal hormone therapy (HT).Design-This study was approved by the institutional review board. Twenty-eight postmenopausal women using HT were matched with 28 postmenopausal women not using HT at the time of breast cancer diagnosis. Noncancerous tissue from mastectomy specimens was examined histologically to quantitate the content of fibrous stroma, ducts, and lobule types 1, 2, and 3. Tissue samples were also evaluated for estrogen receptor, progesterone receptor, and Ki67 activity in the ducts and lobules. Breast density was quantified by digitizing the contralateral mammogram and computer-assisted interactive thresholding.Results-High breast density in women using HT was correlated with greater fibrous stroma (P = 0.020) and lobule type 1 (P = 0.016). Breast density also correlated with Ki67 activity in the ducts (P = 0.031) and lobules (P = 0.023) for both groups combined. Estrogen and progesterone receptors did not correlate with either breast density or HT use.Conclusions-Increased fibrous stroma and lobule type 1 are associated with increasing mammographic density in women using HT, independent of estrogen and progesterone receptor up-regulation. These findings suggest that increased breast density may be mediated through a paracrine effect. The increase in breast cancer risk with HT use may be due to an increase in target lobule type 1 cells.

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Effect of estrogen and estrogen-progestin replacement regimens on mammographic breast parenchymal density.

Abstract: HRT with estradiol-progestin regimens, especially continuously combined, may increase the mammographic density in a substantial proportion of women.

Cited by 166 publications

References 29 publications

Interval cancers in the Norwegian breast cancer screening program: Frequency, characteristics and use of HRT

Interval cancers in the Norwegian breast cancer screening program: Frequency, characteristics and use of HRT

Breast density and outcome of mammography screening: a cohort study

Histologic changes in the breast with menopausal hormone therapy use

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