PD04-02: Recovery of Ovarian Function in Breast Cancer Patients with Chemotherapy-Induced Amenorrhea Receiving Anastrozole in the Dutch DATA Study.
Authors: Tjan-Heijnen VC , Smorenburg CH , de Graaf H , Erdkamp F , Honkoop A , Wals J , van Gastel S , van der Sangen M , Seynaeve C , Nortier JW , Borm G 
Published: June 2012

Background: In early stage hormone receptor positive breast cancer, aromatase inhibitors (AIs) are established as adjuvant therapy for postmenopausal women. In daily practice AIs are also offered to patients with chemotherapy-induced amenorrhea (CIA). The impact of AIs on estrogen (E2) levels in these patients has not extensively been studied, although this could be very relevant for the efficacy and safety of the adjuvant hormonal treatment. The Dutch phase III DATA study is assessing the impact on disease-free survival of 3 vs. 6 years of anastrozole after 2–3 years of tamoxifen (N=1900 patients in total), and has included both postmenopausal patients and patients with CIA. The current analysis reports on the hormonal data in the CIA group.

Patients and methods: We identified patients from the DATA study &lt; 55 years of age at randomization who had received adjuvant chemotherapy and developed CIA, and excluded patients with ovariectomy or use of LHRH agonist. Patients were considered as having CIA if they were in amenorrhea since 3 months before start of chemotherapy up to 6 months after start of chemotherapy, and did not resume menses during tamoxifen therapy. Patients were eligible if postmenopausal E2 levels were confirmed within the last three months before randomization. Plasma FSH and E2 levels were serially determined at 6-month intervals.

Results: A total of 285 patients with CIA were identified in the DATA study. Median age was 50.8 years (range 35.9 - 54.9). Results on E2 and FSH levels are presented in the Table. During treatment with anastrazole, FSH levels tended to increase over time and E2 levels didn't decline. Of note, FSH increased in nearly all patients with significantly elevated (premenopausal) E2 levels, in contrast to the pattern seen in spontaneous recovery of ovarian function. During follow-up, 4 patients had vaginal bleeding, 2 of them having postmenopausal E2 levels. In 8 (2.8%) patients E2 levels became ≥ 200 pmol/l (considered premenopausal) after 12–30 months use of AI. Using a more strict cutoff value of E2 (≥ 100 pmol/l), 62 (21.8%) patients had elevated levels of E2 during AI treatment. With 70 pmol/l as cutoff value, 117 (41.0%) patients had at some point during treatment an increased E2 level. Updated and detailed analyses will be presented at the meeting.

Conclusion: In this first series of a large number of CIA patients with available data on E2 and FSH levels during anastrozole therapy, we observed high E2 levels in a substantial number of patients. The combination of increased E2 and FSH levels may indicate continuous stimulation of remaining ovarian follicles. The efficacy of AIs in women with CIA without strict E2 monitoring and adequate treatment modification in the presence of increasing E2 can be questioned. Further data hereon are warranted.

Supported by: AstraZeneca NL and the Dutch Breast Cancer Trialists’ Group (BOOG).

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD04-02.