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Effects of tamoxifen on normal breast tissue histological composition: Results from a randomised six-arm placebo-controlled trial in healthy women.
Gabrielson, Marike; Hammarström, Mattias; Bäcklund, Magnus; Bergqvist, Jenny; Lång, Kristina; Rosendahl, Ann H; Borgquist, Signe; Hellgren, Roxanna; Czene, Kamila; Hall, Per.
Afiliación
  • Gabrielson M; Department of Medical Epidemiology and Biostatics, Karolinska Institutet, Stockholm, Sweden.
  • Hammarström M; Department of Medical Epidemiology and Biostatics, Karolinska Institutet, Stockholm, Sweden.
  • Bäcklund M; Department of Medical Epidemiology and Biostatics, Karolinska Institutet, Stockholm, Sweden.
  • Bergqvist J; Department of Medical Epidemiology and Biostatics, Karolinska Institutet, Stockholm, Sweden.
  • Lång K; Breast Centre, Department of Surgery, Capio St Görans Hospital, Stockholm, Sweden.
  • Rosendahl AH; Department of Translational Medicine, Diagnostic Radiology, Lund University, Lund, Sweden.
  • Borgquist S; Department of Clinical Sciences Lund, Oncology, Lund University and Skåne University Hospital, Lund, Sweden.
  • Hellgren R; Department of Clinical Sciences Lund, Oncology, Lund University and Skåne University Hospital, Lund, Sweden.
  • Czene K; Department of Oncology, Aarhus University Hospital and Aarhus University, Aarhus, Denmark.
  • Hall P; Department of Radiology, Södersjukhuset, Stockholm, Sweden.
Int J Cancer ; 152(11): 2362-2372, 2023 06 01.
Article en En | MEDLINE | ID: mdl-36637153
ABSTRACT
Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to "no dose" (0-1 mg), "low-dose" (2.5-5 mg) or "high-dose" (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 1_ASSA2030 / 2_ODS3 Problema de salud: 1_doencas_nao_transmissiveis / 2_muertes_prematuras_enfermedades_notrasmisibles Asunto principal: Tamoxifeno / Neoplasias de la Mama Tipo de estudio: Clinical_trials Límite: Female / Humans Idioma: En Revista: Int J Cancer Año: 2023 Tipo del documento: Article País de afiliación: Suecia

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 1_ASSA2030 / 2_ODS3 Problema de salud: 1_doencas_nao_transmissiveis / 2_muertes_prematuras_enfermedades_notrasmisibles Asunto principal: Tamoxifeno / Neoplasias de la Mama Tipo de estudio: Clinical_trials Límite: Female / Humans Idioma: En Revista: Int J Cancer Año: 2023 Tipo del documento: Article País de afiliación: Suecia
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