Patterns of Recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: results from international breast cancer study group trials VIII and IX

Abstract

Purpose: To retrospectively evaluate the pattern of recurrence and outcome of node-negative breast cancer (BC) according to major subtypes.

Patients and methods: In all, 1,951 patients with node-negative, early-stage BC randomly assigned in International Breast Cancer Study Group Trials VIII and IX with centrally reviewed pathology data were included. BC subtypes were defined as triple negative (TN; n = 310), human epidermal growth factor receptor 2 (HER2) positive (n = 369), and hormone receptor positive with high (luminal B-like [LB-like]; n = 763) or low (luminal A-like [LA-like]; n = 509) proliferative activity by Ki-67 labeling index. BC-free interval (BCFI) events were invasive BC recurrence in local, contralateral breast, nodal, bone, or visceral sites. Time to first site-specific recurrence was evaluated by using cumulative incidence and competing risks regression analysis.

Results: Median follow-up was 12.5 years. The 10-year BCFI was higher for patients with LA-like (86%) BC compared with LB-like (76%), HER2 (73%), and TN (71%; P < .001) BC. TN and HER2 cohorts had higher hazard of BCFI event in the first 4 years after diagnosis (pre-trastuzumab). LB-like cohorts had a continuously higher hazard of BCFI event over time compared with LA-like cohorts. Ten-year overall survival was higher for LA-like (89%) compared with LB-like (83%), HER2 (77%), and TN (75%; P < .001) BC. LB-like subtypes had higher rates of bone as first recurrence site than other subtypes (P = .005). Visceral recurrence as first site was lower for the LA-like subgroup, with similar incidence among the other subgroups when treated with chemotherapy (P = .003).

Conclusion: BC subtypes have different distant recurrence patterns over time. Defining different patterns of BC recurrence can improve BC care through surveillance guidelines and can guide the design of clinical studies.

Fig 1.

CONSORT diagram showing the numbers of patients enrolled onto International Breast Cancer Study Group Trials VIII and IX, and the derivations of the 1,951 patients in the analysis population. ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; PgR, progesterone receptor.

Fig 2.

(A) Kaplan-Meier estimates of breast cancer–free interval (BCFI) according to breast cancer subtype; (B) hazard rate of BCFI over time; (C) Kaplan-Meier estimates of overall survival (OS) according to breast cancer subtype. HER2, human epidermal growth factor receptor 2; TN, triple negative.

Fig 3.

Estimated cumulative incidence of (A) local recurrence, (B) contralateral breast recurrence, and (C) bone recurrence over time according to breast cancer subtype. For time to first local recurrence, contralateral breast recurrence, and bone recurrence, no significant interaction of treatment group and breast cancer subtype was observed. The P values are based on Gray's test for comparing the distribution for each site-specific recurrence across subtypes. HER2, human epidermal growth factor receptor 2; TN, triple negative.

Fig 4.

Estimated cumulative incidence of nodal recurrence and visceral recurrence over time according to subtype for patients who were randomly assigned to receive no chemotherapy (A, B) or chemotherapy (C, D). The P values were based on Gray's test for comparing the distribution for each site-specific recurrence across subtype within treatment group. HER2, human epidermal growth factor receptor 2; TN, triple negative.