Neoadjuvant Chemotherapy and Targeted Therapy in Breast Cancer: Past, Present, and Future

Table 1

Trials comparing the same chemotherapeutic regimen pre- and postoperatively.

Trial	Phase (𝑛)	Tumors	NA versus adjuvant	Primary endpoint	Other outcomes	Ref.
IBBGS	III (272)	T2 > 3 cm or T3 N0-1	3 × EVM → 3 × ETV	BCT 63% (33% RT only, 30% S + RT) versus 0%	No difference in DFS or OS; 34% local recurrence with RT only	[40, 41]
Institut Curie S6	III (390)	T2-3, N0-1	4 × FAC	BCT 82 versus 77% (ns); (S only if no cCR after RT)	No difference in DFS and OS,; short-term OS benefit (𝑃=.02) for NA	[42, 43]
Royal Marsden	III (293)	T0–4, N0-1	4 × 2MT	BCT 89 versus 78% (𝑃=.004)	No difference in DFS, OS, and local recurrence; pCR 7%	[44, 45]
NSABP B-18	III (1493)	T1–3, N0-1	4 × AC	5 y-OS: 80 versus 81% (ns); 5 y-DFS: 67 versus 67% (ns)	BCT 68 versus 60% (𝑃=.001); LRR 13 versus 10% (𝑃=.21); ORR 78%, pCR 13%; pCR associated with better 9 y-DFS (75 versus 58%); pCR associated with better 9 y-OS (85 versus 73%); trends in favor of NA for DFS and OS in women <50 y	[1, 46, 47]
EORTC 10902	III (698)	T1c–T4b	4 × FEC	4 y-OS 82 versus 84% (𝑃=.38)	4 y-PFS 65 versus 70% (𝑃=.27); LRR 5 versus 5% (ns); pCR 4%; downstaging to BCT in 23%	[2]
ABCSG-7	III (423)	T1–3, N0-1 HR− + high risk HR+	3 × CMF	RFS better with adjuvant therapy (HR 0.7; 𝑃=.02); no difference in OS (HR 0.8; 𝑃=.21)	cORR 56%, pCR 6%; LRR 13 versus 8% (𝑃=.1)	[48]
Meta-analysis	IV (3946)	9 randomized trials	Same regimen	No difference in OS (RR 1.0); no difference in DFS (RR 0.99)	LRR higher for NA (RR 1.22; 𝑃=.015) especially if no S was done; pCR range 4–29%	[3]

EVM: epirubicin, vincristin, methotrexat; ETV: mitomycin, thiotepa, vindesine; FAC: 5-FU, doxorubicin, cyclophosphamide; 2MT: mitoxantrone, methotrexat, tamoxifen; AC: doxorubicin, cyclophosphamide; FEC: 5-FU, epirubicin, cyclophosphamide; CMF: cyclophosphamide, methotrexat, 5-FU.