Short-term Femara (letrozole) treatment and suppression of Ki67 expression in postmenopausal endometrial carcinoma

Lloyd H Smith,Guibo Xing,Gary Leiserowitz,John Bishop

doi:10.4236/ojog.2013.33064

Lloyd H Smith, Guibo Xing + Show 2 more

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https://doi.org/10.4236/ojog.2013.33064

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Abstract

Objective: To determine if short-term treatment with Femara (letrozole) induces measurable reduction in tumor Ki67 expression in postmenopausal women with FIGO grade 1 and 2 endometrial carcinoma. Methods: In this non-randomized prospective study, 12 patients were given Femara (letrozole) 2.5 mg daily for approximately 3 weeks prior to planned hysterectomy for FIGO grade 1 or 2 endometrial carcinoma. A group of 12 demographically similar patients were enrolled as no-treatment controls. Ki67 expression in tumor cells was quantitated by immunohistochemistry with mechanical scanning within the initial endometrial biopsy and compared to that in the hysterectomy specimen for each patient in the treatment and control groups. Results: The treatment and control groups were similar in age, tumor grade and FIGO stage. When “aromatase inhibitor responsiveness” was defined as proportionate decline in Ki67% stained tumor cells of at least 70% between the pre-treatment endometrial biopsy and post-treatment hysterectomy specimens, 5 of 12 patients were found to be “responsive” in the treatment group with none of the controls fulfilling these criteria. Conclusion: Femara (letrozole) 2.5 mg daily for approximately 3 weeks induced a significant reduction in tumor cell Ki67 expression among 5 of 12 (41%) postmenopausal women with FIGO grade 1 or 2 endometrial carcinoma. We postulate that Ki67 may be a useful marker during aromatase inhibitor medical treatment of patients with endometrial cancer who are not candidates for surgical treatment.

Highlights

In 2012, cancers of the uterine corpus remain the fourth most common incident malignancy and the eighth most frequent cause of cancer mortality among women in the USA [1]
Twelve patients enrolled in this study completed Femara treatment and were found to have FIGO grade 1 or 2 endometrial carcinoma within their hysterectomy specimen
High potency progestins have been extensively studied in the setting of young women with endometrial carcinoma seeking treatments which allow preservation of fertility, and most knowledge of endocrine therapy for this disease comes from these studies [12]

Summary

Introduction

In 2012, cancers of the uterine corpus remain the fourth most common incident malignancy and the eighth most frequent cause of cancer mortality among women in the USA [1]. Hysterectomy remains the initial treatment recommendation for most patients, women with endometrial cancer who are old and frail, or who have other serious medical conditions, experience increased risk of perioperative morbidity and mortality [3,4,5]. Effective medical treatments are needed as an alternative to surgery for the oldest and sickest women with endometrial cancer. The development of aromatase inhibitors (AIs) for the treatment of breast cancer potentially provides such a therapeutic alternative since AIs block the synthesis of estradiol, depriving the estrogen receptor of its ligand which promotes proliferation of both breast and endometrial malignant neoplasms. There are no AIs in the USA which are currently FDA approved for treatment of endometrial cancer, their use for this purpose is rational and supported by previous clinical research observations

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