Preoperative Chemotherapy in Patients With Operable Breast Cancer: Nine-Year Results From National Surgical Adjuvant Breast and Bowel Project B-18

TLDR

NSABP B‑18 was launched to evaluate whether preoperative doxorubicin/cyclophosphamide improves survival and disease‑free survival compared with postoperative administration. The study aimed to assess whether preoperative chemotherapy downstages tumors and lymph nodes, increases lumpectomy rates, affects ipsilateral breast tumor recurrence, and whether tumor response predicts outcomes. The analysis extends the original 5‑year follow‑up to 9 years to reassess outcomes. Over nine years, survival and disease‑free survival were similar between preoperative and postoperative groups (70% vs 69% survival, 55% vs 53% DFS), although preoperative therapy increased lumpectomy rates, slightly raised ipsilateral breast tumor recurrence, and the link between tumor response and outcome strengthened, with possible age‑dependent benefits.

Abstract

National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-18 was initiated in 1988 to determine whether four cycles of doxorubicin/cyclophosphamide given preoperatively improve survival and disease-free survival (DFS) when compared with the same chemotherapy given postoperatively. Secondary aims included the evaluation of preoperative chemotherapy in downstaging the primary breast tumor and involved axillary lymph nodes, the comparison of lumpectomy rates and rates of ipsilateral breast tumor recurrence (IBTR) in the two treatment groups, and the assessment of the correlation between primary tumor response and outcome. Initially published findings were based on a follow-up of 5 years; this report updates results through 9 years of follow-up. There continue to be no statistically significant overall differences in survival or DFS between the two treatment groups. Survival at 9 years is 70% in the postoperative group and 69% in the preoperative group (P = .80). DFS is 53% in postoperative patients and 55% in preoperative patients (P = .50). A statistically significant correlation persists between primary tumor response and outcome, and this correlation has become statistically stronger with longer follow-up. Patients assigned to preoperative chemotherapy received notably more lumpectomies than postoperative patients, especially among patients with tumors greater than 5 cm at study entry. Although the rate of IBTR was slightly higher in the preoperative group (10.7% versus 7.6%), this difference was not statistically significant. Marginally statistically significant treatment-by-age interactions appear to be emerging for survival and DFS, suggesting that younger patients may benefit from preoperative therapy, whereas the reverse may be true for older patients.