On prognostic and treatment predictive factors in early stage breast cancer

Abstract: Breast cancer is the most common malignant tumor in Swedish women and the incidence is increasing with 1-2% per year in the Stockholm area. A subgroup of patients is women diagnosed with primary inoperable disease. This group constitutes about 15% of all women affected by breast cancer. Primary systemic (neoadjuvant) therapy either with chemotherapy or endocrine therapy is frequently used in these patients. Prognostication is especially important in identifying patients whose prognosis is so favorable that adjuvant systemic therapy is unnecessary. Prognostic factors can also be useful in identifying patients with poor prognosis that warrants an aggressive approach. In the ncoadjuvant setting the patients receive preoperative treatment and the behavior of the tumor during treatment may act as a biological model. Beside the earlier described prognostic factors additional factors such as clinical tumor response and early or late changes in biological markers during therapy may be of help in deciding the most beneficial therapy for the individual patient. However, the determination of a patient's clinical response to neoadjuvant therapy is sometimes difficult. An inaccurate response evaluation may prevent an early identification of non responders. The conclusions from the thesis are: Proliferation fraction (PF) (assessed in preoperative FNA biopsies) has a significant prognostic value which is independent of lymph node status, PgR status and tumor size. To our knowledge this is the first study demonstrating that PF can contribute prognostic information when analyzed in preoperative smears. PAI-1 (assessed in surgical specimen) is a significant independent prognosticator independent of lymph node status. A decrease in PF > 25% (assessed in fine neele aspiration (FNA) biopsies) during preoperative chemotherapy have a predictive value and may be of value in selecting postoperative adjuvant systemic treatment. In elderly patients, a high initial PF (assessed in FNA biopsies) may predict a decreased probability of response. Moreover, a decrease in the percentage of ER positive cells > 50% after 3 months tamoxifen therapy significantly predicted a lower probability of a long-term clinical response Cathepsin D (assessed in surgical specimen) may predict the benefit of tamoxifen amongst ER- positive patients. There is a poor correlation between clinically and mammographically assessed tumor size. Menopausal status, BMI and use of HRT are factors that could influence the correlation between the two assessments. Clinical assessment may not be the optimal method for response evaluation of preoperative systemic therapy. Mammographic assessment contributes with changes in size as well as density and gives a reproducible information.