Oral Presentation ESA-SRB-AOTA 2019

The impact of menstrual cycling on OncotypeDx recurrence scores in premenopausal breast cancer patients (#34)

Sarah M Bernhardt 1 2 , Pallave Dasari 1 2 , Danielle J Glynn 1 2 , Amanda R Townsend 3 , Timothy J Price 3 , Wendy V Ingman 1 2
  1. Discipline of Surgery, School of Medicine, The University of Adelaide, Woodville, SA, Australia
  2. The Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia
  3. Department of Medical Oncology, The Queen Elizabeth Hospital, Woodville, SA, Australia

OncotypeDx is a genomic test used to help guide adjuvant chemotherapy treatment decisions for hormone receptor (HR)–positive breast cancers. There is a scarcity of literature on whether OncotypeDx is suitable for use in premenopausal women, where ovarian hormones estrogen and progesterone fluctuate during the menstrual cycle. This project aimed to determine how variable OncotypeDx recurrence scores are between paired breast cancer samples from premenopausal women, compared to postmenopausal women, and whether recurrence scores are affected by ovarian cycle stage.

To investigate the variability in OncotypeDx recurrence scores within the same tumour collected on different days of the menstrual cycle, paired HR-positive breast cancer samples were collected from premenopausal women (<50 years old; n=19) and compared to non-menstrual cycling postmenopausal women (≥50 years old; n=13). Samples were collected an average of 18 days apart and in the absence of any intervention. OncotypeDx recurrence scores were calculated and compared between paired samples. There was increased variability in recurrence scores between paired samples from premenopausal women (3.1±2.5; mean±stdev) compared to postmenopausal women (2.4±1.7; p=0.03).

To determine whether the ovarian cycle contributes to the greater variability in OncotypeDx recurrence scores observed in premenopausal women, HR-positive mammary tumours from naturally cycling MMTV-PyMT mice were dissected at either the estrus or diestrus phase of the ovarian cycle (n=25, 28 respectively). Tumours collected from mice at diestrus showed significant differences in 6/16 OncotypeDx signature genes (p≤0.05), and a significant increase in their OncotypeDx recurrence score (21.1±2.4; mean±SEM), compared to tumours dissected at estrus (15.5±1.9; p=0.03).

This study demonstrates that OncotypeDx recurrence scores are more variable in young women and that ovarian cycle stage significantly alters OncotypeDx recurrence scores in mouse models. We propose that hormonal fluctuations during the menstrual cycle impact OncotypeDx recurrence scores, and may affect the clinical utility of this test in premenopausal women.