V Heinzelmann-Schwarz1, A Knipprath Mészaros2, S Stadlmann3, F Jacob4, A Schoetzau5, K Russell6, M Friedlander7, G Singer3, M Vetter2. 1. Gynecological Cancer Center, University Hospital Basel, University of Basel, Spitalstrasse 21, 4031 Basel, Switzerland; Ovarian Cancer Research, Department of Biomedicine, University of Basel, Hebelstrasse 20, 4056 Basel, Switzerland. Electronic address: viola.heinzelmann@usb.ch. 2. Gynecological Cancer Center, University Hospital Basel, University of Basel, Spitalstrasse 21, 4031 Basel, Switzerland. 3. Institute of Pathology, Cantonal Hospital Baden, Im Ergel 1, 5404 Baden, Switzerland. 4. Glyco-Oncology Group, Ovarian Cancer Research, Department of Biomedicine, University Hospital Basel and University of Basel, Hebelstrasse 20, 4056 Basel, Switzerland; Ovarian Cancer Research, Department of Biomedicine, University of Basel, Hebelstrasse 20, 4056 Basel, Switzerland. 5. Ovarian Cancer Research, Department of Biomedicine, University of Basel, Hebelstrasse 20, 4056 Basel, Switzerland. 6. Caris Life Sciences, Jakobsstrasse 199, 4052 Basel, Switzerland. 7. Department of Medical Oncology, Prince of Wales Hospital, Prince of Wales Clinical School, University of New South Wales, Barker St, Randwick NSW 2031, Sydney, Australia.
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 24months 60% when taking Letrozole versus 38.5% in the control group; p=0.035; RFS: IC50 reached by one subject versus 13.2months). This effect was also present in patients treated additionally with Bevacizumab; 20.8% of patients had no recurrence after 12months 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.
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 24months 60% when taking Letrozole versus 38.5% in the control group; p=0.035; RFS: IC50 reached by one subject versus 13.2months). This effect was also present in patients treated additionally with Bevacizumab; 20.8% of patients had no recurrence after 12months 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.
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