Hormone Replacement Therapy With Estrogen or Estrogen Plus Medroxyprogesterone Acetate Is Associated With Increased Epithelial Proliferation in the Normal Postmenopausal Breast

Hofseth, Lorne J.; Raafat, Ahmed; Osuch, Janet; Pathak, Dorothy R.; Slomski, Carol; Haslam, Sandra Z.

doi:10.1097/00006254-200005000-00023

Cited by 75 publications

(97 citation statements)

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“…The results of our study differ from those of Hofseth et al, 19 who found a significant increase in proliferation in the breast lobules of women using HT compared with those not using HT as observed by proliferating cell nuclear antigen activity and the trend observed with Ki67 activity. These differences may be due to the use of Ki67 to assess proliferation rather than proliferating cell nuclear antigen.…”

Section: Discussioncontrasting

confidence: 99%

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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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Section: Discussioncontrasting

confidence: 99%

“…Hofseth et al 19 have shown increased proliferation in the terminal ductal lobular unit as measured by proliferating cell nuclear antigen in women using HT as compared with nonusers. The increment was greater in response to EPT than to ET in the terminal ductal lobular unit.…”

mentioning

confidence: 99%

Histologic changes in the breast with menopausal hormone therapy use

Harvey¹,

Santen²,

Petroni

et al. 2008

Menopause

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“…A recent study on proliferation of breast epithelial cells found an increased epithelial cell proliferation following use of the combined estrogen/progestin treatment, together with increased epithelial density, localized to the terminal duct lobular unit, which is the site of development for most breast cancers. 24 Furthermore, the discontinuation of progestins seems to reduce the estradiolinduced proliferation of breast epithelial cells and trigger the apoptotic mechanism. 25 This could explain the lower risk of breast cancer following the cyclical regimens.…”

Section: Discussionmentioning

confidence: 99%

Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe

Stahlberg

Pedersen

Lynge

et al. 2004

Intl Journal of Cancer

198

124

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“…By contrast, a substantial increase in breast cancer risk was noticed in women taking combinations of an oestrogen and various synthetic progesterone agonists (progestins), despite this being standard of care in the United States and the United Kingdom [20][21][22] . This could be related to the increase in cell proliferation in the breast epithelium that has been reported with combination therapy 23 .…”

Section: At a Glancementioning

confidence: 89%