Prospective endometrial assessment of breast cancer patients treated with third generation aromatase inhibitors

Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 82%

“…It has been shown that administration of aromatase inhibitors can decrease endometrial thickness in patients previously treated with TAM [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…However, most of these studies were performed on a relatively small number of patients [9][10][11][12], and patients were followed by TVS for relatively short periods of time [9,10,12].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Long-term “protective” effect of aromatase inhibitors on the endometrium of postmenopausal breast cancer patients

Markovitch

Tepper

Fishman

et al. 2008

“…Although most of these changes are benign, the wide range of abnormalities induced by tamoxifen has led to a number of gynecological interventions in symptomatic women to exclude malignant disease. The third generation aromatase inhibitors (AIs) which are increasingly used as an alternative or as an additional treatment to tamoxifen [5][6][7] do not have an estrogenic effect on the uterus and may even reverse tamoxifen-associated endometrial pathologies as shown in several studies [8][9][10][11][12][13][14][15]. The potential use of AIs specifically for the management of endometrial pathologies is promising [16].…”

Section: Introductionmentioning

confidence: 99%

Prospective assessment of the endometrium in postmenopausal breast cancer patients treated with fulvestrant

Morales

Neven

Timmerman

et al. 2008

This prospective study assessed the endometrial effects of fulvestrant, a pure estrogen-receptor antagonist, in postmenopausal women with breast cancer. This singlecenter study enrolled postmenopausal patients who had an intact uterus at baseline with progressive metastatic breast cancer on tamoxifen followed by an oral aromatase inhibitor (AI). Fulvestrant (250 mg) was administered every 28 ± 3 days via IM injection. Transvaginal ultrasonography (TVUS) was performed at baseline and after 3 months of therapy. Primary and secondary endpoints were changes from baseline in double endometrial thickness (DET) and uterine volume (UV), respectively. No interventions were performed on any asymptomatic uterine abnormalities that were detected at baseline. In total, 32 women were enrolled. Five patients had no repeat TVUS because of early progression before 3 months, leaving 27 evaluable patients for final analysis. After 3 months therapy, mean DET had significantly decreased by 23.08% (P = 0.010). Mean UV also decreased by 10.88%, although this change was not significant (P = 0.119). After 3 months of therapy, none reported vaginal bleeding, there were no changes noted in most of the uterine pathologies present at baseline and no new uterine abnormalities were detected. We observed that 3 months of fulvestrant treatment resulted in a significant decrease in endometrial growth and a non-significant decrease in UV in postmenopausal women with metastatic breast cancer previously exposed to tamoxifen and AIs. Furthermore, no new uterine pathologies were detected, indicating that fulvestrant behaves as a pure antiestrogen at the uterine level.

The oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with hormone receptor-positive HER2-negative (HR + /HER2 −) advanced/metastatic breast cancer

Bardia

Mayer

Winer

et al. 2022

Purpose GDC-0810 (ARN-810) is a novel, non-steroidal, orally bioavailable, selective estrogen receptor degrader (SERD) that potentially inhibits ligand-dependent and ligand-independent estrogen receptor (ER)-mediated signaling. Methods A phase Ia/Ib/IIa dose escalation, combination treatment with palbociclib or a luteinizing hormone-releasing hormone, and expansion study determined the safety, pharmacokinetics, and recommended phase 2 dose (RP2D) of GDC-0810 in postmenopausal women with ER + (HER2 −) locally advanced or metastatic breast cancer (MBC). Baseline plasma ctDNA samples were analyzed to determine the ESR1 mutation status. Results Patients (N = 152) received GDC-0810 100–800 mg once daily (QD) or 300–400 mg twice daily, in dose escalation, expansion, as single agent or combination treatment. Common adverse events regardless of attribution to study drug were diarrhea, nausea, fatigue, vomiting, and constipation. There was one dose-limiting toxicity during dose escalation. The maximum tolerated dose was not reached. GDC-0810 600 mg QD taken with food was the RP2D. Pharmacokinetics were predictable. FES reduction (> 90%) highlighting pharmacodynamic engagement of ER was observed. Outcomes for the overall population and for patients with tumors harboring ESR1 mutations included partial responses (4% overall; 4% ESR1), stable disease (39% overall; 42% ESR1), non-complete response/non-progressive disease (13% overall; 12% ESR1), progressive disease (40% overall; 38% ESR1), and missing/unevaluable (5% overall; 5% ESR1). Clinical benefit (responses or SD, lasting ≥ 24 weeks) was observed in patients in dose escalation (n = 16, 39%) and expansion (n = 24, 22%). Conclusion GDC-0810 was safe and tolerable with preliminary anti-tumor activity in heavily pretreated patients with ER + advanced/MBC, with/without ESR1 mutations, highlighting the potential for oral SERDs. Clinical Trial and registration date April 4, 2013. NCT01823835 .