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. 2022 Feb 22;23:52. doi: 10.1186/s13059-022-02603-3

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 5 — Menopause as a turning point for the WID-relative-epithelial-age: distinct impacts of hormonal exposure or genetic factors on the WID-relative-epithelial age before or after menopause. Before menopause, factors increasing breast cancer risk (e.g., BRCA mutations) result in a reduced WID-relative-epithelial-age, while anti-progestins (such as ulipristal acetate or mifepristone) increase the WID-relative-epithelial-age. After menopause, this pattern is switched: HRT responders exhibit a reduced WID-relative-epithelial-age, but this effect is not observed in HRT non-responders and may indicate an increased risk for breast cancer in these women. Therefore, an acceleration or deceleration of the WID-relative-age (age discordance) has different effects before and after menopause