Association between HER-2/neu and the progesterone receptor in oestrogen-dependent breast cancer is age-related

In oestrogen receptor-positive (ER+) breast cancer, HER-2/neu and the progesterone receptor (PR) are inversely associated. This explains a lower response to anti-oestrogens if ER+ breast cancers are HER-2/neu positive. One randomized study however, showed that premenopausal women with an ER+ breast cancer respond to anti-oestrogens independent of HER-2/neu. We therefore hypothesized an age-related association between HER-2/neu and PR in ER+ breast cancers. Receptors for ER, PR and HER-2/neu were analysed by immunohistochemistry (IHC). A uni- and multivariate analyses was carried out to assess this relationship in 1104 women with an ER+ breast cancer. We observed an inverse association between HER-2/neu and PR only after age 45. There were 173 women of age <= 45 and 931 of age >45 years. In multivariate analysis, only tumour grade (p=0.005) but not PR status was associated with HER-2/neu in women age <= 45 years. However, in age > 45 years group, both PR status (p=0.001) and tumour grade (p=0.001) were independently associated with HER-2/neu. In ER+ breast cancers from women age > 45, PR was positive in 76.9% if HER-2/neu negative but in 53.4% if HER-2/neu positive (p < 0.001) and the median quantitative PR levels are 150 and 75 respectively in HER-2/neu negative and HER-2/neu positive tumours (p=0.002). This age effect of HER-2/neu on the PR status was not seen in women age <= 45 years and the median quantitative PR levels are 200 and 220 respectively in HER-2/neu negative and HER-2/neu positive tumours (p=0.518). The study confirms an age-related inverse relationship between HER-2/neu and PR only in women age > 45 years but not in women age <= 45 years.