Endocrine Treatment of Advanced Breast Cancer

Dowsett, Mitchell

doi:10.3109/02841869609083973

Cited by 9 publications

(3 citation statements)

References 23 publications

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“…depletion of in situ estrogen production which results in impaired estrogenic stimulation is an important mechanism in the antitumor activity of aromatase inhibitors (de Jong et al 1997). Newly developed aromatase inhibitors are specific and associated with minimum side effects (Dowsett 1996(Dowsett , 1997. Very recently, one of these newly developed aromatase inhibitors has been shown to exert a more potent antitumor activity compared with other antiestrogens including tamoxifen (Brodie a et al 1998).…”

Section: Introductionmentioning

confidence: 99%

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Effects of aromatase inhibitors on the pathobiology of the human breast, endometrial and ovarian carcinoma.

Sasano¹,

Sato²,

Itō³

et al. 1999

Endocrine-Related Cancer

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It is very important to examine the influence of inhibition of in situ estrogen production on the pathobiology of human sex steroid-dependent tumors in order to understand the clinical effects of aromatase inhibitors. We have examined the biological changes before and after aromatase inhibitor treatment in vitro (endometrial and ovarian cancer) and in vivo (breast cancer). First, we analyzed these changes using histoculture of 15 human endometrial cancers and 9 ovarian cancers. Five of the fifteen endometrial cancers and four of the nine ovarian cancers demonstrated decreased [3 H]thymidine uptake or Ki67 labeling index after 14α-hydroxy-4-androstene-3,6,17-trione (NKS01) treatment.In ovarian cancer cases, the responsive cases tended to be associated with higher aromatase and estrogen receptor α (ER) expression compared with the other cases but this was not seen in the endometrial cancer cases. There were no changes in ER and aromatase expression before and after NKS01 treatment in either ovarian or endometrial cancer cases. We then studied the same primary human breast tumors before and after aminoglutethimide (AMG, n=3) and 4-hydroxyandrostenedione (4-OHA, n=3) treatment. Tumor aromatase activity increased in 3 cases and decreased or was unchanged in 3 cases but aromatase immunoreactivity in stroma and adipocytes was unaltered in 5 cases. There were no changes in the ER labeling index before or after treatment. Five of the six cases including the responsive cases tended to be associated with decreased cell proliferation or Ki67 expression and increased apoptosis when examined by the TUNEL method. These results indicate that aromatase inhibitors may exert their effects on human breast and other cancers through Endocrine-Related Cancer (1999) 6 197-204 decreasing proliferation and increasing apoptosis, possibly without altering ER status.

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Section: Introductionmentioning

confidence: 99%

“…An increasing number of aromatase inhibitors are being introduced into clinical practice (Dowsett 1996(Dowsett , 1997. These inhibitors are at present considered to act on sex steroid-dependent neoplasms by suppressing intratumoral aromatase activity, i.e.…”

Section: Introductionmentioning

confidence: 99%

Effects of aromatase inhibitors on the pathobiology of the human breast, endometrial and ovarian carcinoma.

Sasano¹,

Sato²,

Itō³

et al. 1999

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…This intratumoral 17␤-estradiol production by in situ aromatisation of estradiol precursors may function as an autocrine growth and mitogenic factor and give a growth advantage to these cells, regardless of serum estrogen concentrations. This is further substantiated by the fact that in human breast cancer an increased activity and/or expression of the aromatase enzyme is found associated with a malignant phenotype [16][17][18][19], supporting the use of aromatase inhibitors for postoperative adjuvant endocrine treatment of patients with breast carcinoma [20,21].…”

Section: Introductionmentioning

confidence: 95%