Impact of systemic adjuvant therapy and CYP2D6 activity on mammographic density in a cohort of tamoxifen-treated breast cancer patients

Breast Cancer Res Treat. 2021 Dec;190(3):451-462. doi: 10.1007/s10549-021-06386-2. Epub 2021 Sep 27.

Abstract

Purpose: Change in mammographic density has been suggested to be a proxy of tamoxifen response. We investigated the effect of additional adjuvant systemic therapy and CYP2D6 activity on MD change in a cohort of tamoxifen-treated pre- and postmenopausal breast cancer patients.

Methods: Swedish breast cancer patients (n = 699) operated 2006-2014, genotyped for CYP2D6, having at least three months postoperative tamoxifen treatment, a baseline, and at least one follow-up digital mammogram were included in the study. Other systemic adjuvant treatment included chemotherapy, goserelin, and aromatase inhibitors. Change in MD, dense area, was assessed using the automated STRATUS method. Patients were stratified on baseline characteristics, treatments, and CYP2D6 activity (poor, intermediate, extensive, and ultrarapid). Relative density change was calculated at year 1, 2, and 5 during follow-up in relation to treatments and CYP2D6 activity.

Results: Mean relative DA decreased under the follow-up period, with a more pronounced MD reduction in premenopausal patients. No significant effect of chemotherapy, aromatase inhibitors, goserelin, or CYP2D6 activity on DA change was found. DA did not revert to baseline levels after tamoxifen discontinuation.

Conclusion: Our results indicate that other systemic adjuvant therapy does not further reduce MD in tamoxifen-treated breast cancer patients. We could not confirm the previously suggested association between CYP2D6 activity and MD reduction in a clinical setting with multimodality adjuvant treatment. No rebound effect on MD decline after tamoxifen discontinuation was evident.

Keywords: Adjuvant treatment; Breast cancer; CYP2D6; Chemotherapy; Mammographic density; Tamoxifen.

MeSH terms

  • Antineoplastic Agents, Hormonal / therapeutic use
  • Breast Density
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Chemotherapy, Adjuvant
  • Cytochrome P-450 CYP2D6 / genetics
  • Female
  • Genotype
  • Humans
  • Tamoxifen* / therapeutic use

Substances

  • Antineoplastic Agents, Hormonal
  • Tamoxifen
  • Cytochrome P-450 CYP2D6