Elsevier

Gynecologic Oncology

Volume 148, Issue 1, January 2018, Pages 79-85
Gynecologic Oncology

Letrozole may be a valuable maintenance treatment in high-grade serous ovarian cancer patients

https://doi.org/10.1016/j.ygyno.2017.10.036Get rights and content
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open access

Highlights

  • ESR1 and ER expression are similarly high in HGSOC and in breast cancer.

  • ER expression did not differ between platin-sensitive or –resistant HGSOC.

  • ER expression did not differ between matched primary or recurrent HGSOC.

  • Letrozole maintenance showed improved progression-free survival.

Abstract

Objectives

Endocrine therapy is used as maintenance in estrogen receptor (ER) positive breast cancers and has been proposed in low-grade serous ovarian cancers (LGSOC). Here we examine a rationale for its use as maintenance in high-grade serous ovarian cancers (HGSOC).

Methods

We accessed the TCGA PANCAN dataset to evaluate the expression of ESR1. ESR1 expression data on all cancers (n = 8901) and HGSOC (n = 527) were followed by investigation of ER expression via immunohistochemistry (IHC) (n = 4071). The same was performed in an independent cohort for matched primary and recurrent HGSOC (n = 80). Finally, newly diagnosed ER + HGSOC patients were offered a maintenance therapy with Letrozole.

Results

ESR1 was strongly expressed in similar levels in HGSOC as in breast cancer. We found a strong ER expression via IHC in both the primary and matched recurrent HGSOC, particularly in the Platinum-resistant subgroup. The additional use of Letrozole as maintenance treatment was associated with a significantly prolonged recurrence free interval (after 24 months 60% when taking Letrozole versus 38.5% in the control group; p = 0.035; RFS: IC50 reached by one subject versus 13.2 months). This effect was also present in patients treated additionally with Bevacizumab; 20.8% of patients had no recurrence after 12 months compared to 87.5% when taking Letrozole in addition to Bevacizumab (p = 0.026).

Conclusions

Primary HGSOC have a slightly higher ESR1 than and a similar ER expression breast cancer where aromatase inhibitor maintenance is routine for decades. Here we demonstrate evidence for the usefulness of Letrozole in HGSOC, particularly in patients with chemotherapy resistance or residual disease.

Keywords

Ovarian cancer
HGSOC
Letrozol maintenance
Aromatase inhibitor
ER

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1

Contributed equally.