High-Risk Premenopausal Luminal A Breast Cancer Patients Derive no Benefit from Adjuvant Cyclophosphamide-based Chemotherapy: Results from the DBCG77B Clinical Trial.
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.
Genetic Pathology Evaluation Centre, University of British Columbia, Vancouver, Canada. torsten@mail.ubc.ca.
Torsten O
TO
Nielsen
Danish Breast Cancer Cooperative Group, Copenhagen, Denmark.
Maj-Brit
MB
Jensen
Genetic Pathology Evaluation Centre, University of British Columbia, Vancouver, Canada.
Samantha
S
Burugu
Genetic Pathology Evaluation Centre, University of British Columbia, Vancouver, Canada.
Dongxia
D
Gao
Danish Breast Cancer Cooperative Group, Copenhagen, Denmark.
Charlotte L Tykjaer
CL
Jørgensen
Danish Breast Cancer Cooperative Group, Copenhagen, Denmark.
Eva
E
Balslev
Danish Breast Cancer Cooperative Group, Copenhagen, Denmark.
Bent
B
Ejlertsen
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000145:classification / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007978:Levamisole / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics
D003520:Cyclophosphamide; D007978:Levamisole; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone