The main aim for preoperative chemotherapy for operable breast cancer is to reduce tumour size and improve the chance of breast conserving surgery. In cases of locally advanced and inoperable tumours, primary chemotherapy may reduce tumour size and improve local control following radiation.
The randomised NSABP B-18 study treated 747 patients with 4 cycles of preoperative AC then surgery and 759 patients with surgery and post-operative AC.r
Disease specific and overall survival was identical in the two groups. A clinical response rate of 80% [36% CR, 44% PR] was seen with 13% complete pathological response. Less mastectomies (60% versus 67%, p=0.002) performed in patients undergoing preoperative chemotherapy.
The incorporation of a sequential taxane following an anthracycline-based regimen has improved patient outcomes in the neoadjuvant setting.r
The follow-up study to B-18 was NSABP B-27 which compared preoperative AC for 4 cycles to preoperative AC for 4 cycles followed by 4 cycles of docetaxel and then surgery.rr (Link to the evidence for neoadjuvant AC-docetaxel protocol)
Weekly paclitaxel given before or after an anthracycline-based regimen has also been used pre-operatively. (Link to the evidence for neoadjuvant AC-paclitaxel protocol)
Efficacy
Dieras et al r |
Doxorubicin and paclitaxel
(AP) (%) |
Doxorubicin and cyclophosphamide
(AC) (%) |
Pathological complete response (pCR) |
8 |
6 |
Clinical complete response |
15 |
7 |
Partial response |
74 |
63 |
Stable disease |
11 |
30 |
Progressive disease |
0 |
0 |
Breast conserving surgery |
58 |
45 |
Greater objective clinical response (CR+PR) was found in those with no axillary node involvement in both treatment groups.
Disease-free survival was 87% in the AP group and 79% in the AC group at 18 months.
At 31.3 months median follow up, 30% AP arm and 30% in the AC arm had experienced disease relapse or died.r
Fisher et al r |
Preoperative AC (n=693) (%) |
Clinical complete response |
36 |
Partial response |
44 |
Stable disease |
17 |
Progressive disease |
3 |
Toxicity
Adverse events r |
Doxorubicin and paclitaxel (AP)
(n=132) (%) |
Doxorubicin and cyclophosphamide (AC)
(n=67) (%) |
Neutropenia (grades 3/4) |
97 |
76 |
Thrombocytopenia (grades 3/4) |
1 |
0 |
Neutropenic fever |
11 |
0 |
Fatigue (grade 3) |
10 |
10 |
Nausea (grade 3) |
3 |
10 |
Stomatitis (grade 3) |
4 |
0 |
Vomiting (grades 3/4) |
3 |
11 |
Sensory neuropathy (grade 3) |
2 |
0 |
Arthralgia (grade 3) |
4 |
0 |
Myalgia (grade 3) |
5 |
1 |