# AMH decline during chemotherapy reflects breast cancer cell DNA damage response (DDR) proficiency: the ONCO AMH1 pilot study

## TL;DR

This study explores how breast cancer patients' AMH levels change during chemotherapy and how this relates to their genetic status and tumor response.

## Contribution

The study is the first to link AMH decline during chemotherapy to chemotherapy susceptibility differences between BRCA1/2 carriers and non-carriers.

## Key findings

- AMH decline during chemotherapy was steeper in BRCA1/2 pathogenic variant carriers compared to wild-type patients.
- Tumor size change correlated with AMH levels in BRCA1/2 carriers but not in wild-type patients.
- No significant conclusions were drawn about treatment response using histological criteria.

## Abstract

The impact of a germline BRCA1/2 pathogenic variant (gBRCApv) on baseline or late post-treatment AMH concentrations in breast cancer patients has been extensively studied, yielding mixed conclusions. However, whether the AMH decline during neo-adjuvant chemotherapy reflects differences in chemotherapy susceptibility between gBRCApv carriers and non-carriers remains unexplored.

A monocentric, retrospective, longitudinal study was conducted on breast cancer patients carrying a gBRCApv (n = 12) or wild-type (WT) (n = 35) who received a neo-adjuvant sequential chemotherapy (CT) with anthracyclines followed by taxanes. Serum AMH levels were measured at baseline (AMH0) and at three time points during CT by a hypersensitive assay. Tumor size change was assessed via imaging. The impact of genetic status on AMH decline was evaluated using a linear mixed model with post hoc analysis.

The change of AMH concentrations from baseline to the end of CT tended to be influenced by the genetic status (BRCA * time interaction, p = 0.058). The slope between AMH0 and the end of anthracyclines (after log transformation) was steeper in gBRCApv than in WT patients (mean (SE): − 5.54 (0.63) vs − 3.97 (0.62); p = 0.023). Tumor size change was positively and significantly correlated with the change in AMH levels (AMH MidCT-AMH0) in gBRCApv patients (r = 0.93, p < 0.001) but not in WT patients (r = − 0.05; p = 0.84).

Germline BRCA1/2 status influences AMH decline during neo-adjuvant CT with drugs inducing DNA lesions. AMH decay is positively related to tumor size change assessed by imaging in gBRCApv patients. However, no conclusions can be drawn regarding the relationship with treatment response assessed by histological criteria.