MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

Inhibice estrogenní aktivity

Diindolylmethane (DIM)


Endocrine therapy + CDK4/6 inhibitors - palbociclib, ribociclib and abemaciclib

  • Cyclin-dependent kinase (CDK) 4/6 inhibitors + ER-regulated cyclin D1
  • Critical role in regulating transition from G1 to S phase
  • In ER-positive, advanced breast cancer effective
  • CDK inhibitors improve survival in women with metastatic ER-positive breast cancer
    • When combined with aromatase inhibitors (letrozole and anastrozole)
      • Or fulvestrant (Finn et al. 2016, Hortobagyi et al. 2016, Goetz et al. 2017)

Phase II trial in ovarian and endometrial cancer (n = 40)

  • LGSC patients were among those showing the most significant benefit
  • With all three women achieving durable responses
    • One CR and two with partial responses over 2 years (Colon-Otero et al. 2020)

GOG 3026 (NCT03673124), a phase II trial - ribociclib + letrozole

NCT03531645, a phase II trial - fulvestrant + abemaciclib in LGSC

  • Currently recruiting

Aromatase inhibitors in relapsed LGSC

  • Similar at ~13%

Gershenson’s retrospective analysis, in 54 women

  • Aromatase inhibitors
    • Response rate was 13.0% (letrozole, 6/33; anastrozole, 1/21) (Gershenson et al. 2012)

PARAGON

  • Objective response rate to anastrazole was 13.9% (36 patients) (Tang et al. 2019)

GOG 0281 trial

  • 6/44 (13.6%) patients responded to letrozole (Gershenson et al. 2020a).

Aromatase inhibitors + CDK4/6 inhibitors

Breast-fed girls


The estrobolome

  • Aggregate effect of bacteria in the gut capable of metabolizing estrogens
    • Thereby modifying estrogen levels in the blood
    • Affect the risk of breast cancer risk
    • Affecting the age of puberty
  • Early antibiotic use + lack of fiber in the modern diet
    • Appear to bring puberty forward
  • drpaulclayton.eu/blog/wasted-on-the-young/

Prebiotic fibers


Food deprivation


Reduce endocrine disrupters

  • Also linked to an increased risk of obesity and metabolic disorders
  • Dietary strategies designed to reduce exposure to such compounds
    • Likely to further improve our offspring’s sexual health and body composition.
  • Encouraging our children to avoid fast foods such as
    • Hamburgers,
    • Fries and chicken nuggets
    • Excessive use of plastic packaging
  • Effects of endocrine disruptors on pubertal timing
    • Are compound specific
    • Vary according to the window of exposure
    • Making them unlikely to be a major factor in pubertal acceleration as a whole
  • drpaulclayton.eu/blog/wasted-on-the-young/

Tamoxifen

GOG 198 trial, which enrolled 139 patients


O úroveň výše

Poslední aktualizace: 10. 12. 2023 20:36:04