Although pharmacist counseling assumes an important role in the clinical setting, oncology pharmacy practitioners worldwide currently lack adequate guidance. This study aimed to identify the determinants and causal relationships that affect quality of life (QOL) in breast cancer patients before adjuvant systemic therapy for improving pharmacist counseling and guidance. This study analyzed 93 postoperative patients with breast cancer before pharmacist counseling for adjuvant systemic therapy. Patients were asked to complete questionnaires to assess QOL (the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 [EORTC QLQ-C30] and its breast cancer module [EORTC QLQ-BR23]) before pharmacist counseling. We analyzed factors affecting QOL by stepwise multiple linear regression analysis and evaluated causal association using path analysis. In the multiple linear regression model using variables selected by stepwise analysis, the factors affecting global health status (GHS)/QOL included fatigue, emotional functioning, systemic therapy side effects, future perspectives, and appetite loss. In the path analysis model, GHS/QOL were strongly influenced by fatigue directly; and emotional functioning, directly and indirectly via other factors. Our results indicated that fatigue and emotional functioning are strong factors affecting QOL. These factors may be able to predict poor QOL before initiating adjuvant systemic therapy. Thus, our findings suggest that these factors may be potentially useful for pharmacist counseling at the beginning of adjuvant systemic therapy.