Tinne Laurberg1, Trine Tramm2, Torsten Nielsen3, Jan Alsner1, Silje Nord4, Simen Myhre4, Therese Sørlie4, Samuel Leung3, Cheng Fan5, Charles Perou5, Karen Gelmon3, Jens Overgaard1, David Voduc3, Aleix Prat6,7, Maggie Chon U Cheang8. 1. a Department of Experimental Clinical Oncology , Aarhus University Hospital , Aarhus , Denmark. 2. b Department of Pathology , Aarhus University Hospital , Aarhus , Denmark. 3. c British Columbia Cancer Agency , Vancouver , British Columbia , Canada. 4. d Department of Genetics, Institute for Cancer Research , Oslo University Hospital , Oslo , Norway. 5. e Lineberger Comprehensive Cancer Center , University of North Carolina , Chapel Hill , NC , USA. 6. f Department of Medical Oncology , Hospital Clinic , Barcelona , Spain. 7. g Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) , Barcelona , Spain. 8. h Clinical Trials and Statistics Unit , Institute of Cancer Research , London , UK.
Abstract
BACKGROUND: The study of the intrinsic molecular subtypes of breast cancer has revealed differences among them in terms of prognosis and response to chemotherapy and endocrine therapy. However, the ability of intrinsic subtypes to predict benefit from adjuvant radiotherapy has only been examined in few studies. METHODS: Gene expression-based intrinsic subtyping was performed in 228 breast tumors collected from two independent post-mastectomy clinical trials (British Columbia and the Danish Breast Cancer Cooperative Group 82b trials), where pre-menopausal patients with node-positive disease were randomized to adjuvant radiotherapy or not. All patients received adjuvant chemotherapy and a subgroup of patients underwent ovarian ablation. Tumors were classified into intrinsic subtypes: Luminal A, Luminal B, HER2-enriched, Basal-like and Normal-like using the research-based PAM50 classifier. RESULTS: In the British Columbia study, patients treated with radiation had an overall significant lower incidence of locoregional recurrence compared to the controls. For Luminal A tumors the risk of loco-regional recurrence was low and was further lowered by adjuvant radiation. These findings were validated in the DBCG 82b study. The individual data from the two cohorts were merged, the hazard ratio (HR) for loco-regional recurrence associated with giving radiation was 0.34 (0.19 to 0.61) overall and 0.12 (0.03 to 0.52) for Luminal A tumors. CONCLUSIONS: In both postmastectomy trials, patients with Luminal A tumors turned out to have a significant lower incidence of loco-regional recurrence when randomized to adjuvant radiotherapy, leaving no indication to omit postmastectomy adjuvant radiation in pre-menopausal high-risk patients with Luminal A tumors. It was not possible to evaluate the effect of radiotherapy among the other subtypes because of limited sample sizes.
RCT Entities:
BACKGROUND: The study of the intrinsic molecular subtypes of breast cancer has revealed differences among them in terms of prognosis and response to chemotherapy and endocrine therapy. However, the ability of intrinsic subtypes to predict benefit from adjuvant radiotherapy has only been examined in few studies. METHODS: Gene expression-based intrinsic subtyping was performed in 228 breast tumors collected from two independent post-mastectomy clinical trials (British Columbia and the Danish Breast Cancer Cooperative Group 82b trials), where pre-menopausal patients with node-positive disease were randomized to adjuvant radiotherapy or not. All patients received adjuvant chemotherapy and a subgroup of patients underwent ovarian ablation. Tumors were classified into intrinsic subtypes: Luminal A, Luminal B, HER2-enriched, Basal-like and Normal-like using the research-based PAM50 classifier. RESULTS: In the British Columbia study, patients treated with radiation had an overall significant lower incidence of locoregional recurrence compared to the controls. For Luminal A tumors the risk of loco-regional recurrence was low and was further lowered by adjuvant radiation. These findings were validated in the DBCG 82b study. The individual data from the two cohorts were merged, the hazard ratio (HR) for loco-regional recurrence associated with giving radiation was 0.34 (0.19 to 0.61) overall and 0.12 (0.03 to 0.52) for Luminal A tumors. CONCLUSIONS: In both postmastectomy trials, patients with Luminal A tumors turned out to have a significant lower incidence of loco-regional recurrence when randomized to adjuvant radiotherapy, leaving no indication to omit postmastectomy adjuvant radiation in pre-menopausal high-risk patients with Luminal A tumors. It was not possible to evaluate the effect of radiotherapy among the other subtypes because of limited sample sizes.
Authors: Thomas Hehr; René Baumann; Wilfried Budach; Marciana-Nona Duma; Jürgen Dunst; Petra Feyer; Rainer Fietkau; Wulf Haase; Wolfgang Harms; David Krug; Marc D Piroth; Felix Sedlmayer; Rainer Souchon; Frederick Wenz; Rolf Sauer Journal: Strahlenther Onkol Date: 2019-08-26 Impact factor: 3.621
Authors: Beryl McCormick; Kathryn A Winter; Wendy Woodward; Henry M Kuerer; Nour Sneige; Eileen Rakovitch; Barbara L Smith; Isabelle Germain; Alan C Hartford; Mark A O'Rourke; Eleanor M Walker; Eric A Strom; Judith O Hopkins; Lori J Pierce; Anthony T Pu; Kenneth N M Sumida; Danny Vesprini; Jennifer Moughan; Julia R White Journal: J Clin Oncol Date: 2021-08-18 Impact factor: 50.717
Authors: Won Kyung Cho; Won Park; Doo Ho Choi; Yong Bae Kim; Jin Ho Kim; Su Ssan Kim; Kyubo Kim; Jin Hee Kim; Sung-Ja Ahn; Sun Young Lee; Jeongshim Lee; Sang-Won Kim; Jeanny Kwon; Ki Jung Ahn Journal: J Breast Cancer Date: 2019-05-13 Impact factor: 3.588