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DCIS and aromatase inhibitors
J Michael Dixon1, Dana Faratian, Sharon White
1Edinburgh Breast Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom. jmd@ed.ac.uk
Abstract:
In patients with hormone receptor positive DCIS tamoxifen reduces recurrence rates by almost 50%. Few data are available with aromatase inhibitors from randomised studies. In the ATAC study there were three DCIS lesions in the anastrozole arm and four in the tamoxifen arm in the women with ER positive invasive cancer. In the MA17 study which randomised patients to up to 5 years of letrozole or placebo there was only one DCIS event in the contralateral breast in patients taking letrozole and five on placebo. There were also four patients in this study who had DCIS in the conserved breast on placebo and none in the letrozole treated group. The few clinical data that are available therefore suggest the aromatase inhibitors are likely to be effective in DCIS. A histological review of a study of 206 postmenopausal women with invasive oestrogen receptor positive breast cancer who were randomised as part of a 14 day preoperative study to receive 2.5mg of letrozole or 1mg of anastrozole identified 27 patients with 28 pairs of tumours in whom there was sufficient ER positive DCIS in invasive cancer in the initial core biopsy and in the subsequent surgery specimen, to evaluate for PgR activity and proliferation. Within the DCIS both aromatase inhibitors significantly reduced PgR expression and both drugs also produced a significant fall in proliferation. There was a moderate degree of agreement between the fall in PgR in both the invasive cancer and DCIS (Kappa=0.5; p=0.0013) and between the fall in proliferation and between the invasive and in situ components (correlation coefficient=0.68; p<0.001). This study has shown significant effects of aromatase inhibitors on DCIS indicating that these agents are therapeutically active in this condition.
Insights
Aromatase inhibitors show therapeutic activity in ductal carcinoma in situ (DCIS), significantly reducing progesterone receptor (PgR) expression and proliferation. These findings suggest aromatase inhibitors are effective agents for treating DCIS.
Area of Science:
- Oncology
- Endocrinology
- Pathology
Background:
- Tamoxifen is effective in reducing recurrence rates for hormone receptor-positive ductal carcinoma in situ (DCIS).
- Limited randomized study data exist for aromatase inhibitors (AIs) in DCIS.
- Previous studies suggest AIs may be effective in DCIS, with low event rates observed in ATAC and MA17 trials.
Purpose of the Study:
- To evaluate the therapeutic activity of aromatase inhibitors (letrozole and anastrozole) in ductal carcinoma in situ (DCIS).
- To assess the impact of AIs on progesterone receptor (PgR) expression and proliferation within DCIS.
Main Methods:
- Histological review of 27 patients with ER-positive invasive breast cancer and DCIS from a preoperative study.
- Patients received either letrozole (2.5mg) or anastrozole (1mg) for 14 days.
- Evaluated PgR activity and proliferation in DCIS from core biopsies and surgical specimens.
Main Results:
- Both letrozole and anastrozole significantly reduced PgR expression in DCIS.
- Both AIs significantly decreased proliferation within DCIS.
- Moderate agreement was observed between changes in PgR and proliferation in invasive cancer and DCIS components.
Conclusions:
- Aromatase inhibitors demonstrate significant therapeutic effects on DCIS.
- These findings indicate that aromatase inhibitors are active agents in the treatment of DCIS.
- Further research into AI efficacy for DCIS is warranted.
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