Impact of the menstrual cycle on commercial prognostic gene signatures in oestrogen receptor-positive primary breast cancer.
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Embargo End Date
ICR Authors
Authors
Haynes, BP
Schuster, G
Buus, R
Alataki, A
Ginsburg, O
Quang, LH
Han, PT
Khoa, PH
Van Dinh, N
Van To, T
Clemons, M
Holcombe, C
Osborne, C
Evans, A
Skene, A
Sibbering, M
Rogers, C
Laws, S
Noor, L
Cheang, MCU
Cleator, SJ
Smith, IE
Dowsett, M
Schuster, G
Buus, R
Alataki, A
Ginsburg, O
Quang, LH
Han, PT
Khoa, PH
Van Dinh, N
Van To, T
Clemons, M
Holcombe, C
Osborne, C
Evans, A
Skene, A
Sibbering, M
Rogers, C
Laws, S
Noor, L
Cheang, MCU
Cleator, SJ
Smith, IE
Dowsett, M
Document Type
Journal Article
Date
2021-11-01
Date Accepted
2021-08-26
Abstract
PURPOSE: Changes occur in the expression of oestrogen-regulated and proliferation-associated genes in oestrogen receptor (ER)-positive breast tumours during the menstrual cycle. We investigated if Oncotype® DX recurrence score (RS), Prosigna® (ROR) and EndoPredict® (EP/EPclin) prognostic tests, which include some of these genes, vary according to the time in the menstrual cycle when they are measured. METHODS: Pairs of test scores were derived from 30 ER-positive/human epidermal growth factor receptor-2-negative tumours sampled at two different points of the menstrual cycle. Menstrual cycle windows were prospectively defined as either W1 (days 1-6 and 27-35; low oestrogen and low progesterone) or W2 (days 7-26; high oestrogen and high or low progesterone). RESULTS: The invasion module score of RS was lower (- 10.9%; p = 0.098), whereas the ER (+ 16.6%; p = 0.046) and proliferation (+ 7.3%; p = 0.13) module scores were higher in W2. PGR expression was significantly increased in W2 (+ 81.4%; p = 0.0029). Despite this, mean scores were not significantly different between W1 and W2 for any of the tests and the two measurements showed high correlation (r = 0.72-0.93). However, variability between the two measurements led to tumours being assigned to different risk categories in the following proportion of cases: RS 22.7%, ROR 27.3%, EP 13.6% and EPclin 13.6%. CONCLUSION: There are significant changes during the menstrual cycle in the expression of some of the genes and gene module scores comprising the RS, ROR and EP/EPclin scores. These did not affect any of the prognostic scores in a systematic fashion, but there was substantial variability in paired measurements.
Citation
Breast cancer research and treatment, 2021, 190 (2), pp. 295 - 305
Source Title
Publisher
SPRINGER
ISSN
0167-6806
eISSN
1573-7217
Research Team
Clinical Trials & Statistics Unit
Endocrinology
Endocrinology