Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in patients treated by breast-conserving therapy in five National Surgical Adjuvant Breast and Bowel Project protocols of node-negative breast cancer

Abstract

Purpose: Locoregional failure (LRF) after breast-conserving therapy (BCT) is associated with increased risk of distant disease and death. The magnitude of this risk has not been adequately characterized in patients with lymph node-negative disease.

Patients and methods: Our study population included 3,799 women randomly assigned to five National Surgical Adjuvant Breast and Bowel Project protocols of node-negative disease (ie, B-13, B-14, B-19, B-20, and B-23) who underwent lumpectomy and whole breast irradiation with or without adjuvant systemic therapy. Cumulative incidences of ipsilateral breast tumor recurrence (IBTR) and other locoregional recurrence (oLRR) were calculated, along with distant-disease-free interval (DDFI) and overall survival (OS) after these events. Cox models were employed to model mortality by using clinical and pathologic factors jointly with these events.

Results: Four hundred nineteen patients (11.0%) experienced LRF: 342 (9.0%) experienced IBTR, and 77 (2.0%) experienced oLRR. The 12-year cumulative incidences of IBTR and oLRR in patients treated with adjuvant systemic therapy were 6.6% and 1.8%, respectively. Overall, 37.1% of IBTRs and 72.7% of oLRRs occurred within 5 years of diagnosis. Older age, black race, higher body mass index (BMI), larger tumors, and occurrence of IBTR or oLRR were significantly associated with increased mortality. The 5-year OS after IBTR and oLRR were 76.6% and 34.9%, respectively. Adjusted hazard ratios for mortality associated with IBTR and oLRR were significantly higher in estrogen receptor (ER)-negative patients than in ER-positive patients (P = .002 and P < .0001, respectively). Patients with early LRF had worse OS and DDFI than those with later-occurring LRF.

Conclusion: Although LRF is uncommon in patients with node-negative breast cancer who are treated with lumpectomy, radiation, and adjuvant systemic therapy, those who do develop LRF have substantially worse OS and DDFI.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Outcomes after ipsilateral breast tumor recurrence (IBTR) and other locoregional recurrence (oLRR) by estrogen receptor (ER) status. (A) Distant-disease–free interval (DDFI) and (B) overall survival (OS) for the first 5 years after IBTR by ER status; and (C) DDFI and (D) OS for the first 5 years after oLRR by ER status. The total numbers of events and deaths are measured during all follow-up time after the diagnosis of IBTR or oLRR.

Fig A1.

Cumulative incidence of ipsilateral breast tumor recurrence (IBTR) in lumpectomy patients in five node-negative National Surgical Adjuvant Breast and Bowel Project protocols for known values of (A) age at surgery; (B) ethnicity; (C) clinical tumor size (CTS); (D) pathologic tumor size (PTS); (E) estrogen receptor (ER) status; and (F) assigned adjuvant therapy. The numbers of events are measured during all follow-up time. Rx, treatment; Tam, tamoxifen; Chemo, chemotherapy.

Fig A2.

Cumulative incidence of other locoregional recurrence (oLRR) in lumpectomy patients in five National Surgical Adjuvant Breast and Bowel Project protocols of node-negative disease by (A) age at surgery; (B) race; (C) clinical tumor size (CTS); (D) pathologic tumor size (PTS); (E) estrogen receptor (ER) status; and (F) assigned adjuvant therapy. The numbers of events are measured during all follow-up time. Rx, treatment; Tam, tamoxifen; Chemo, chemotherapy.