title: Effect of infertility treatment and pregnancy-related hormones on breast cell proliferation in vitro.
abstract: BACKGROUND
  Breast cancer development involves a series of mutations in a heterogeneous group of proto-oncogenes/tumor suppressor genes that alter mammary cells to create a microenvironment permissive to tumorigenesis. Exposure to hormones during infertility treatment may have a mutagenic effect on normal mammary epithelial cells, high-risk breast lesions and early-stage breast cancers. Our goal was to understand the association between infertility treatment and normal and cancerous breast cell proliferation.
  
  
  METHODS
  MCF-10A normal mammary cells and the breast cancer cell lines MCF-7 [estrogen receptor (ER)-positive, well differentiated] and HCC 1937 (ER-negative, aggressive, BRCA1 mutation) were treated with the weak ER activator clomiphene citrate and hormones that are increased during infertility treatment. Direct effects of treatment on cell proliferation and colony growth were determined.
  
  
  RESULTS
  While clomiphene citrate had no effect on MCF-10A cells or MCF-7 breast cancer cells, it decreased proliferation of HCC 1937 versus untreated cells (P= 0.003). Estrogen had no effect on either MCF-10A or HCC 1937 cells but, as expected, increased cell proliferation (20-100 nM; P≤0.002) and colony growth (10-30 nM; P< 0.0001) of MCF-7 cells versus control. Conversely, progesterone decreased both proliferation (P= 0.001) and colony growth (P= 0.01) of MCF-10A cells, inhibited colony size of MCF-7 cells (P= 0.01) and decreased proliferation of HCC 1937 cells (P= 0.008) versus control. hCG (100 mIU/ml) decreased both proliferation (P ≤ 0.01) and colony growth (P ≤ 0.002) of all three cell lines.
  
  
  CONCLUSIONS
  Although these data are preclinical, they support possible indirect estrogenic effects of infertility regimens on ER-positive breast cancer cells and validate the potential protective effect of pregnancy-related exposure to hCG.
authors.affiliation: Department of Surgery, Northwestern University Feinberg School of Medicine, 250 East Superior Street, Prentice, 4-420, Chicago, IL 60611, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Cooley
authors.forename: Laura
authors.initials: L
authors.lastname: Matthews
authors.forename: Stanislav
authors.initials: S
authors.lastname: Zelivianski
authors.forename: Ashley
authors.initials: A
authors.lastname: Hardy
authors.forename: Jacqueline S
authors.initials: JS
authors.lastname: Jeruss
mesh_terms: D001940:Breast / Q000166:cytology / Q000473:pathology*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D002996:Clomiphene / Q000008:administration & dosage; D003094:Collagen; D018450:Disease Progression; D004338:Drug Combinations; D005260:Female; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D007246:Infertility / Q000473:pathology / Q000628:therapy*; D007797:Laminin; D011247:Pregnancy; D011509:Proteoglycans; D027724:Reproductive Techniques, Assisted; D013997:Time Factors
chemical_list: D004338:Drug Combinations; D006728:Hormones; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D002996:Clomiphene; D003094:Collagen
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