Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials.
Pathological complete response (pCR) to neoadjuvant treatment correlates with outcome in breast cancer. We determined whether characteristics of neoadjuvant therapy are associated with pCR. We used multi-level models, which accounted for heterogeneity in pCR across trials and trial arms, to analyze individual patient data from 3332 women included in 7 German neoadjuvant trials with uniform protocols. PCR was associated with an increase in number of chemotherapy cycles (odds ratio [OR] 1.2 for every two additional cycles; P = 0.009), with higher cumulative anthracycline doses (OR 1.6; P = 0.002), higher cumulative taxane doses (OR 1.6; P = 0.009), and with capecitabine containing regimens (OR 1.62; P = 0.022). Association of pCR with increase in number of cycles appeared more pronounced in hormone receptor (HR)-positive tumors (OR 1.35) than in HR-negative tumors (OR 1.04; P for interaction = 0.046). Effect of anthracycline dose was particularly pronounced in HER2-negative tumors (OR 1.61), compared to HER2-positive tumors (OR 0.83; P for interaction = 0.14). Simultaneous trastuzumab treatment in HER2-positive tumors increased odds of pCR 3.2-fold (P < 0.001). No association of pCR and number of trastuzumab cycles was found (OR 1.20, P = 0.39). Dosing characteristics appear important for successful treatment of breast cancer. Longer treatment, higher cumulative doses of anthracyclines and taxanes, and the addition of capecitabine and trastuzumab are associated with better response. Tailoring according to breast cancer phenotype might be possible: longer treatment in HR-positive tumors, higher cumulative anthracycline doses for HER2-negative tumors, shorter treatment at higher cumulative doses for triple-negative tumors, and limited number of preoperative trastuzumab cycles in HER2-positive tumors.
German Breast Group, c/o GBG Forschungs GmbH, Martin-Behaim-Str. 12, 63263 Neu-Isenburg, Germany. gunter.vonminckwitz@germanbreastgroup.de
Gunter
G
von Minckwitz
Michael
M
Untch
Eveline
E
Nüesch
Sibylle
S
Loibl
Manfred
M
Kaufmann
Sherko
S
Kümmel
Peter A
PA
Fasching
Wolfgang
W
Eiermann
Jens-Uwe
JU
Blohmer
Serban Dan
SD
Costa
Keyur
K
Mehta
Jörn
J
Hilfrich
Christian
C
Jackisch
Bernd
B
Gerber
Andreas
A
du Bois
Jens
J
Huober
Claus
C
Hanusch
Gottfried
G
Konecny
Werner
W
Fett
Elmar
E
Stickeler
Nadia
N
Harbeck
Volkmar
V
Müller
Peter
P
Jüni
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D005260:Female; D005858:Germany; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D016017:Odds Ratio; D018579:Patient Selection; D010641:Phenotype; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
D014408:Biomarkers, Tumor