Extended Data Fig. 4: Age-correlated protein expression in normal breast epithelium and age-correlated distribution of estrogen receptor (ER) in breast cancer.

a, Age-correlated protein expression in a tissue microarray (TMA) from normal breast epithelium (Normal Breast 13 TMA, N = 537 cases). The red curves and tan confidence bands are described above in Extended Data Fig. 3. Since breast reduction mammoplasty is not performed as often for women over 65 years of age, trends in older cases are more variable, indicated by the wide confidence bands around age 70-80. b, Distribution of percent of tumour cells positively stained for ER proteins in immunohistochemistry tissue samples (Big Series TMA, N = 3991 cases). The youngest cases showed the lowest rates of percentages above 50%. The distribution of percent tumour cells positively stained was strongly associated with age (Pearson 𝜒2 ₍₁₅₎ = 348.3, p = 4.8×10⁻⁶⁵). c, Distribution of percent of tumour cells positively stained for ER proteins in immunohistochemistry tissue samples for ER positive cases only (from Big Series TMA, N = 3991 total cases, N = 2760 ER positive cases). Though all these cases were designated ER positive because they had 1% or more of tumour cells positively stained, the younger cases showed much fewer instances of 50% or more of tumour cells positively stained (Pearson 𝜒2 ₍₁₀₎ =215.7, p = 8.3×10⁻⁴¹). Younger ER positive cases had a much higher rate of individual tumour cells that did not show ER staining, which presumably would not be responsive to ER targeting therapies such as tamoxifen.