title: Immunohistochemical Phenotype of Breast Cancer during 25-Year Follow-up of the Royal Marsden Tamoxifen Prevention Trial.
abstract: The randomized, double-blinded Royal Marsden Tamoxifen Breast Cancer Prevention Trial in healthy high-risk women started in 1986 and is still blinded. Eligible participants (n= 2,471) were randomly assigned to tamoxifen (20 mg/d) or placebo for 8 years. Analysis in 2006 showed a 30% risk reduction of estrogen receptor (ER)-positive invasive breast cancer mostly in the posttreatment period. Biomarker analysis in this population may identify any subgroup-specific preventive effects tamoxifen. After a median follow-up of 18.4 years, 242 patients had developed invasive cancer, 134 on placebo and 108 on tamoxifen. From these, 180 tissue blocks were available and ER, progesterone receptor (PgR), Ki67, HER2, and EGFR were immunohistochemically analyzed. A 32% reduction in ER+and PgR+invasive cancers resulted after 8 years of treatment. Quantitative levels of ER and PgR were lower in the tamoxifen-treated group, significantly so for ER (P= 0.001). These lower ER levels were restricted to the posttreatment period (P= 0.018). Among the ER+group, there was a similar proportional decrease in PgR+and PgR-tumors by tamoxifen. The median levels of Ki67 were similar in both arms. The numbers of HER2-positive and EGFR-positive cancers were higher in the tamoxifen arm but not significantly so. In conclusion, the preventive effects of tamoxifen result in reduced ER-positive but not ER-negative tumors and reduced ER expression in the ER-positive cases largely confined to the posttreatment period. Overall reductions in PgR expression are explained by lower frequency of ER-positive cases. Impact on Ki67, HER2, and EGFR was modest.Cancer Prev Res; 10(3); 171-6. ©2017 AACR.
authors.affiliation: Ralph Lauren Centre for Breast Cancer Research, Royal Marsden Hospital NHS Trust, London, United Kingdom.
authors.forename: Simone I
authors.initials: SI
authors.lastname: Detre
authors.affiliation: RDSU - Research and Development, Royal Marsden Hospital NHS Trust, Sutton, United Kingdom.
authors.forename: Susan
authors.initials: S
authors.lastname: Ashley
authors.affiliation: RDSU - Research and Development, Royal Marsden Hospital NHS Trust, Sutton, United Kingdom.
authors.forename: Kabir
authors.initials: K
authors.lastname: Mohammed
authors.affiliation: Breast Unit, Royal Marsden Hospital NHS Trust, London, United Kingdom.
authors.forename: Ian E
authors.initials: IE
authors.lastname: Smith
authors.affiliation: Cancer Centre London, Wimbledon, London, United Kingdom.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Powles
authors.affiliation: Ralph Lauren Centre for Breast Cancer Research, Royal Marsden Hospital NHS Trust, London, United Kingdom. mitch.dowsett@icr.ac.uk.
authors.forename: Mitch
authors.initials: M
authors.lastname: Dowsett
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000517:prevention & control*; D004311:Double-Blind Method; D066246:ErbB Receptors / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis / Q000096:biosynthesis; D008875:Middle Aged; D010641:Phenotype; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000032:analysis / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000032:analysis / Q000096:biosynthesis; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C512478:EGFR protein, human; C508053:ERBB2 protein, human