Clinical significance of immunohistochemistry in breast cancer diagnostics

Abstract: For patients with breast cancer, modern patient-tailored treatment depends on tumor- specific characteristics, i.e., estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and the proliferation marker Ki67. These biomarkers are used in different combinations to classify breast cancer into subtypes on which treatment recommendations are based. Although modern multi-gene tests are available, the cornerstone for assessing these biomarkers remains immunohistochemistry (IHC). This thesis is aimed at investigating various clinical aspects of IHC and breast cancer subtypes in breast cancer diagnostics and treatment. In Paper I, the mRNA-based assessment tool STRAT4 was compared with IHC, and the potential changes in adjuvant treatment recommendations based on the differences between tests were compared. The results indicated that adjuvant treatment decisions based on STRAT4 rather than IHC were more aggressive. Paper II investigated whether IHC assessment on more foci than only the largest focus in patients with multifocal breast cancer would affect adjuvant treatment recommendations. The results suggest that all detected foci within a breast specimen should be assessed with IHC. Because guidelines do not recommend IHC assessment of lymph node metastasis (LNM), Paper III investigated whether treatment recommendations might differ if the biomarker status in the LNMs were known. Although both biomarker and subtype discordance was observed, no additional treatment was recommended according to these changes. Paper IV, a national population-based registry study, investigated the effects of chemotherapy on survival outcomes in women ?:70 years of age with a breast cancer subtype lacking ER, PR, and HER2 biomarker expression, i.e., those with triple- negative breast cancer. Statistically significant survival benefits were shown for women treated with adjuvant chemotherapy, thus highlighting the importance of considering chemotherapy in this group of older patients.