Survival of BRCA1/BRCA2-associated pT1 breast cancer patients, a cohort study

Abstract

Purpose: Intensive screening in BRCA1/2 mutation carriers aims to improve breast cancer (BC) prognosis. Our aim is to clarify the prognostic impact of tumor size in BRCA mutation carriers with a pT1 BC, which is currently unclear. We are especially interested in differences between pT1a, pT1b, and pT1c regarding the prognosis of node-negative breast cancer, the effect of chemotherapy, and the prevalence of lymph node involvement.

Methods: For this study, BRCA1/2-associated BC patients were selected from a nationwide cohort. Primary outcomes were 10-year overall survival (OS) per pT1a-b-c group and the effect of chemotherapy on prognosis of node-negative BC, using Kaplan-Meier and Cox models. Finally, we evaluated lymph node involvement per pT1a-b-c group.

Results: 963 women with pT1 BRCA1/2-associated BC diagnosed between 1990 and 2017 were included, of which 679 had pN0 BC. After a median follow-up of 10.5 years, 10-year OS in patients without chemotherapy was 77.1% in pT1cN0 and lower than for pT1aN0 (91.4%, p = 0.119) and pT1bN0 (90.8%, p = 0.024). OS was better with than without chemotherapy for pT1cN0 (91.6% vs. 77.1%, p = 0.001; hazard ratio (HR) 0.56, 95% confidence interval (CI): 0.21-1.48). Lymph node involvement was 24.9% in pT1c, 18.8% in pT1b, and 8.6% in pT1a.

Conclusion: Smaller tumor size is associated with better OS and less lymph node involvement in pT1 BRCA1/2-associated BC patients. The results suggest that early detection in BRCA1/2 mutation carriers of pT1a/b BC may reduce mortality and the need for systemic therapy.

Keywords: BRCA1; BRCA2; Breast cancer; Survival; Tumor size.

Fig. 1

Flowchart of patient selection. BC breast cancer, pTNM pathological assessment of tumor size, lymph nodes and metastasis (pT1a = 0.1–0.5 cm, pT1b ≥ 0.5–1.0 cm, pT1c ≥ 1.0–2.0 cm)

Fig. 2

Kaplan–Meier of overall survival in node-negative pT1 (≤ 2.0 cm) breast cancer patients who did not receive chemotherapy. Abbreviations: pT, pathological tumor assessment (pT1a = 0.1–0.5 cm, pT1b ≥ 0.5–1.0 cm, pT1c =  > 1.0–2.0 cm)

Fig. 3

Percentage lymph node involvement in screened and non-screened patients. *known to be screened or not, missing values imputed based on DNA diagnosis (see methods for details). Abbreviations: pN, pathological lymph node assessment (pN ± lymph nodes are tumor-positive); pT, pathological tumor assessment (pT1a = 0.1–0.5 cm, pT1b ≥ 0.5–1.0 cm, pT1c ≥ 1.0–2.0 cm)