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BCIRG-001 trial
The Breast Cancer International Research Group (BCIRG) trial was published in 2005. BCIRG-001 compared
6 cycles of doxorubicin-cyclophosphamide-5-fluorouracil (5FU) regimen (FAC) vs. 6 cycles of docetaxel-
doxorubicin-cyclophosphamide (TAC) regimen in 1480 breast cancer patients with positive LNs after
surgery. Ninety-one percent of the patients completed the full TAC course despite the fact that there was no
routine use of granulocyte-colony stimulating factor (G-CSF) primary prophylaxis. It reported 5-year OS of
87% in the TAC arm compared to 81% in the FAC arm (P = 0.008), and 5-year DFS of 75% in the TAC arm
compared to 68% in the FAC arm (P = 0.001). Also, there were 25% of patients in the TAC arm developed
[3]
neutropenia with fever (NF) vs. 2% in the FAC arm .
It examined the concurrent use of taxanes-anthracyclines rather than sequential administration which was
the case in both the NSABP and CALGB trials. Docetaxel, the second member in taxanes family was used
unlike the CALGB and NSABP trial, which is going to be discussed later.

An update of the BCIRG-001 trial was published in 2013, and showed a maintained DFS and OS advantage,
after 10-year of follow-up, in favor of the TAC arm. Ten-year OS was 76% vs. 69% in the TAC and FAC arm
(P = 0.002), respectively. In subgroup analysis, TAC improved DFS relative to FAC irrespective of the nodal,
hormone receptor, and HER2 status. Grade 3-4 heart failure occurred in 3% in the TAC arm vs. 2% in the
[4]
FAC arm, and it caused death in 2 patients in the TAC arm and 4 patients in the FAC arm .
PACS-01 trial
This is a French trial that was published in 2006 and randomized 1999 breast cancer patients with positive
2
nodes to 3 cycles of adjuvant docetaxel (100 mg/m ) after 3 cycles of epirubicin-cyclophosphamide-5FU (FEC)
regimen (FEC-D arm) compared to 6 cycles adjuvant FEC. Five-year DFS in the FEC-D arm was 78.4% vs.
73.2% in the FEC only arm (P = 0.11). Five-year OS was 90.7% in the FEC-D arm compared to 86.7% in the
FEC arm (P = 0.14). It is noteworthy that G-CSF primary prophylaxis was not allowed in this trial and grade
3-4 neutropenia was 11.2% in the FEC-D vs. 8.4% (P = 0.03). Also, cardiac toxicity was less in the FEC-D arm
when compared to the FEC arm (P = 0.03). Patients with 1-3 positive nodes as well as patients aged 50 years
[5]
or more had better DFS in subgroup analyses .

WSG-AGO trial
WSG-AGO Trial was published in 2014 from Germany where it randomized 2011 eligible patients to receive
either adjuvant 6 cycles FEC regimen (or oral-cyclophosphamide-epirubicin-5FU, which is also known as the
oral-CMF, which was received in 9 % of this arm) vs. 4 cycles of adjuvant EC followed by 4 cycles docetaxel
2
100 mg/m (EC-D arm). It included only patients with 1-3 positive level I/II axillary LNs (pN1) disease, and
the results showed that 5-year event-free survival (EFS) was 87.3% in the FEC/CMF arm compared to 89.8%
in the EC-D arm (P = 0.038), and 5-year OS was 92.8% in the FEC/CMF arm compared to 94.5% in the
EC-D arm (P = 0.034). Primary G-CSF prophylaxis was allowed, and NF occurred in 3.7% in the EC-D arm
vs. 2.1% in the FEC/CMF arm. It was noted that patients with estrogen receptor (ER) positive tumors plus
[6]
Ki-67 ≥ 20% had the most benefit from adding taxanes in subgroup analyses .

RANDOMIZED TRIALS SHOWED ONLY SIGNIFICANT DFS BENEFIT FROM ADDING TAXANES
NSABP-B28 trial
The National Surgical Adjuvant Breast and Bowel Project (NSABP-B28) trial, which was published in
2005, is one of the landmark adjuvant taxanes’ trials. It included 3060 patients with early breast cancer and
positive axillary (LNs), then the eligible patients were randomized to receive either 4 cycles AC (AC arm) or
4 cycles AC followed by 4 cycles paclitaxel (AC-T arm). This trial was characterized by using a higher dose
2
of paclitaxel which is 225 mg/m without primary G-CSF prophylaxis. There was a DFS benefit in the AC-T
arm compared to the AC arm, where 5-year DFS was 76% in the AC-T arm compared to 72% in the AC arm (P