title: The role of hormones and aromatase inhibitors on breast tumor growth and general health in a postmenopausal mouse model.
abstract: BACKGROUND
  Breast cancer is the most frequently diagnosed cancer in women in the United States. Approximately 70% of breast cancers are diagnosed in postmenopausal women. Major clinical trials and experimental studies showed that aromatase inhibitors are effective against postmenopausal breast cancer. Despite their effectiveness in reducing tumor recurrence, aromatase inhibitors have adverse effects on the cardiovascular system and increase osteoporosis and bone fractures. Our study is aimed at investigating the role of natural steroid hormones on serum cardiovascular and bone resorption markers in an established mouse model mimicking postmenopausal breast cancer.
  
  
  METHODS
  Ovariectomized nude mice were transplanted with MCF-7 breast cancer cells constitutively expressing aromatase. The mice were treated with different combinations and doses of steroids, [estrogen (25 pg, 40 pg, 100 pg), progesterone (6 ng) and testosterone (50 ng)] along with dehydroepiandrostenedione (100 ug). Serum levels of HDL, LDL/VLDL, free and total cholesterol, total and bone specific alkaline phosphatase and triglycerides were analyzed after 5, 10 and 15 months.
  
  
  RESULTS
  Free cholesterol and LDL/VLDL levels in serum were reduced in groups mimicking estrous cycle and menstrual cycle hormones treatment. HDL cholesterol was increased in all the hormone treated groups except the estrous cycle-mimicking group. Bone specific alkaline phosphatase was decreased in menstrual cycle levels of estrogen and progesterone treatment.
  
  
  CONCLUSIONS
  All together our results show that use of natural hormones in appropriate combinations have beneficial effects on cardiac and bone toxicity, along with better tumor reduction than current treatments.
authors.forename: Arunkumar
authors.initials: A
authors.lastname: Arumugam
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Lissner
authors.affiliation: Center of Excellence in Cancer Research, Department of Biomedical Sciences, Paul L, Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas 79905, USA. rajkumar.lakshmanaswamy@ttuhsc.edu.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Lakshmanaswamy
mesh_terms: D000375:Aging; D000818:Animals; D001141:Aromatase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000517:prevention & control*; D003687:Dehydroepiandrosterone / Q000009:adverse effects / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000517:prevention & control*; D061986:MCF-7 Cells; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000517:prevention & control*; D011374:Progesterone / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D011897:Random Allocation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013739:Testosterone / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D047072:Aromatase Inhibitors; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D013739:Testosterone; D003687:Dehydroepiandrosterone; D011374:Progesterone; D004958:Estradiol; D001141:Aromatase; C561410:CYP19A1 protein, human