TY - JOUR
T1 - High-Risk Premenopausal Luminal A Breast Cancer Patients Derive no Benefit from Adjuvant Cyclophosphamide-based Chemotherapy
T2 - Results from the DBCG77B Clinical Trial
AU - Nielsen, Torsten O
AU - Jensen, Maj-Brit
AU - Burugu, Samantha
AU - Gao, Dongxia
AU - Jørgensen, Charlotte L Tykjaer
AU - Balslev, Eva
AU - Ejlertsen, Bent
N1 - ©2016 American Association for Cancer Research.
PY - 2017/2/15
Y1 - 2017/2/15
N2 - Purpose: Luminal A breast cancers have better prognosis than other molecular subtypes. Luminal A cancers may also be insensitive to adjuvant chemotherapy, although there is little high-level evidence to confirm this concept. The primary hypothesis in this formal prospective-retrospective analysis was to assess interaction between subtype (Luminal A vs. other) and treatment (chemotherapy vs. not) for the primary endpoint (10-year invasive disease-free survival) of a breast cancer trial randomizing women to adjuvant chemotherapy, analyzed in multivariate Cox proportional hazards models using the Wald interaction test.Experimental Design: The Danish Breast Cancer Cooperative Group 77B clinical trial randomized 1,072 premenopausal women to no systematic treatment (control), levamisole, cyclophosphamide, or cyclophosphamide-methotrexate-fluorouracil arms. All arms included radiotherapy but no endocrine therapy. Researchers with no access to clinical data performed intrinsic subtype analysis on tissue microarrays using published immunohistochemical methods based on estrogen receptor, progesterone receptor, HER2, Ki67, and basal markers.Results: Patients (n = 709) had tissue available; chemotherapy benefit in these patients was similar to the original trial (HR, 0.56). Immunohistochemistry classified 165 as Luminal A, 319 Luminal B, 58 HER2-enriched, and 82 core basal (among 91 triple-negative). Patients with Luminal A breast tumors did not benefit from chemotherapy [HR, 1.06; 95% confidence interval (CI), 0.53-2.14; P = 0.86], whereas patients with non-luminal A subtypes did (HR, 0.50; 95% CI, 0.38-0.66; P < 0.001; Pinteraction = 0.048).Conclusions: In a prospective-retrospective analysis of a randomized trial, patients with Luminal A breast cancers did not benefit from adjuvant cyclophosphamide-based chemotherapy. Clin Cancer Res; 23(4); 946-53. ©2016 AACR.
AB - Purpose: Luminal A breast cancers have better prognosis than other molecular subtypes. Luminal A cancers may also be insensitive to adjuvant chemotherapy, although there is little high-level evidence to confirm this concept. The primary hypothesis in this formal prospective-retrospective analysis was to assess interaction between subtype (Luminal A vs. other) and treatment (chemotherapy vs. not) for the primary endpoint (10-year invasive disease-free survival) of a breast cancer trial randomizing women to adjuvant chemotherapy, analyzed in multivariate Cox proportional hazards models using the Wald interaction test.Experimental Design: The Danish Breast Cancer Cooperative Group 77B clinical trial randomized 1,072 premenopausal women to no systematic treatment (control), levamisole, cyclophosphamide, or cyclophosphamide-methotrexate-fluorouracil arms. All arms included radiotherapy but no endocrine therapy. Researchers with no access to clinical data performed intrinsic subtype analysis on tissue microarrays using published immunohistochemical methods based on estrogen receptor, progesterone receptor, HER2, Ki67, and basal markers.Results: Patients (n = 709) had tissue available; chemotherapy benefit in these patients was similar to the original trial (HR, 0.56). Immunohistochemistry classified 165 as Luminal A, 319 Luminal B, 58 HER2-enriched, and 82 core basal (among 91 triple-negative). Patients with Luminal A breast tumors did not benefit from chemotherapy [HR, 1.06; 95% confidence interval (CI), 0.53-2.14; P = 0.86], whereas patients with non-luminal A subtypes did (HR, 0.50; 95% CI, 0.38-0.66; P < 0.001; Pinteraction = 0.048).Conclusions: In a prospective-retrospective analysis of a randomized trial, patients with Luminal A breast cancers did not benefit from adjuvant cyclophosphamide-based chemotherapy. Clin Cancer Res; 23(4); 946-53. ©2016 AACR.
KW - Journal Article
U2 - 10.1158/1078-0432.CCR-16-1278
DO - 10.1158/1078-0432.CCR-16-1278
M3 - Journal article
C2 - 27601592
VL - 23
SP - 946
EP - 953
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 4
ER -