Hanna Fredholm1, Kristina Magnusson2, Linda S Lindström3, Nicholas P Tobin4, Henrik Lindman5, Jonas Bergh6, Lars Holmberg7, Fredrik Pontén2, Jan Frisell8, Irma Fredriksson8. 1. Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden; Department of Breast- and Endocrine Surgery, Karolinska University Hospital, Stockholm, Sweden. Electronic address: hanna.fredholm@ki.se. 2. Uppsala University, Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala, Sweden. 3. Karolinska Institutet, Department of Biosciences and Nutrition, Stockholm, Sweden. 4. Karolinska Institutet, Department of Oncology and Pathology, Cancer Center Karolinska, Stockholm, Sweden. 5. Uppsala University, Department of Radiology, Oncology and Radiation Science, Uppsala University Hospital, Uppsala, Sweden. 6. Karolinska Institutet, Department of Oncology and Pathology, Cancer Center Karolinska, Stockholm, Sweden; Karolinska Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden. 7. Uppsala University, Department of Surgical Sciences, Regional Cancer Center, Uppsala University Hospital, Uppsala, Sweden; King's College London, Faculty of Life Sciences and Medicine, Division of Cancer Studies, London, UK. 8. Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden; Department of Breast- and Endocrine Surgery, Karolinska University Hospital, Stockholm, Sweden.
Abstract
AIM: Compared to middle-aged women, young women with breast cancer have a higher risk of systemic disease. We studied expression of proliferation markers in relation to age and subtype and their association with long-term prognosis. METHODS: Distant disease-free survival (DDFS) was studied in 504 women aged <40 years and 383 women aged ≥40 years from a population-based cohort. Information on patient characteristics, treatment and follow-up was collected from medical records. Tissue microarrays were produced for analysis of oestrogen receptor, progesterone receptor (PR), Her2, Ki-67 and cyclins. RESULTS: Young women with luminal tumours had significantly higher expression of Ki-67 and cyclins. Proliferation markers were prognostic only within this subtype. Ki-67 was a prognostic indicator only in young women with luminal PR+ tumours. The optimal cut-off for Ki-67 varied by age. High expression of cyclin E1 conferred a better DDFS in women aged <40 years with luminal PR- tumours (hazard ratio [HR] 0.47 [0.24-0.92]). Age <40 years was an independent risk factor of DDFS exclusively in women with luminal B PR+ tumours (HR 2.35 [1.22-4.50]). Young women with luminal B PR- tumours expressing low cyclin E1 had a six-fold risk of distant disease compared with luminal A (HR 6.21 [2.17-17.6]). CONCLUSIONS: The higher expression of proliferation markers in young women does not have a strong impact on prognosis. Ki-67 is only prognostic in the subgroup of young women with luminal PR+ tumours. The only cyclin adding prognostic value beyond subtype is cyclin E1. Age is an independent prognostic factor only in women with luminal B PR+ tumours.
AIM: Compared to middle-aged women, young women with breast cancer have a higher risk of systemic disease. We studied expression of proliferation markers in relation to age and subtype and their association with long-term prognosis. METHODS: Distant disease-free survival (DDFS) was studied in 504 women aged <40 years and 383 women aged ≥40 years from a population-based cohort. Information on patient characteristics, treatment and follow-up was collected from medical records. Tissue microarrays were produced for analysis of oestrogen receptor, progesterone receptor (PR), Her2, Ki-67 and cyclins. RESULTS: Young women with luminal tumours had significantly higher expression of Ki-67 and cyclins. Proliferation markers were prognostic only within this subtype. Ki-67 was a prognostic indicator only in young women with luminal PR+ tumours. The optimal cut-off for Ki-67 varied by age. High expression of cyclin E1 conferred a better DDFS in women aged <40 years with luminal PR- tumours (hazard ratio [HR] 0.47 [0.24-0.92]). Age <40 years was an independent risk factor of DDFS exclusively in women with luminal B PR+ tumours (HR 2.35 [1.22-4.50]). Young women with luminal B PR- tumours expressing low cyclin E1 had a six-fold risk of distant disease compared with luminal A (HR 6.21 [2.17-17.6]). CONCLUSIONS: The higher expression of proliferation markers in young women does not have a strong impact on prognosis. Ki-67 is only prognostic in the subgroup of young women with luminal PR+ tumours. The only cyclin adding prognostic value beyond subtype is cyclin E1. Age is an independent prognostic factor only in women with luminal B PR+ tumours.
Authors: Hege Russnes; Giske Ursin; Anna L V Johansson; Cassia B Trewin; Irma Fredriksson; Kristin V Reinertsen Journal: Breast Cancer Res Date: 2021-02-01 Impact factor: 6.466
Authors: Sara S Oltra; Maria Peña-Chilet; Kirsty Flower; María Teresa Martinez; Elisa Alonso; Octavio Burgues; Ana Lluch; James M Flanagan; Gloria Ribas Journal: Sci Rep Date: 2019-10-18 Impact factor: 4.379