Abstract P4-08-29: Lymphatic invasion is an independent risk factor in patients with small node-negative luminal breast cancer
Authors: Abe T , Ito Y , Fukada I , Shibayama T , Ono M , Kobayashi T , Kobayashi K , Takahashi S , Horii R , Akiyama F , Iwase T , Ueno T , Ohno S 
Published: May 2019

Abstract
[Background]
In patients with node-negative (N0), hormone receptor-positive, human epidermal growth factor receptor (HER2) -negative (luminal) breast cancer, the impact of lymphatic invasion (ly) on the prognosis remains to be clarified.
[Methods]
Among 3,158 patients with primary breast cancers who underwent surgery in our institute from January 2007 to December 2009, we analyzed 1027 N0 luminal invasive breast cancers without preoperative systemic therapy. The luminal breast cancer was defined as hormone receptor-positive (ER of ≥ 10% or PgR of ≥ 10%) and HER2-negative (immunohistochemistry: 0, 1+ or FISH: ratio &lt; 2.0) cancer in the postoperative pathological specimen. ly was defined as positive when cancer cell nests were detected within the lymph duct in the whole specimen. N0 was confirmed pathologically by the sentinel lymph node biopsy in all the patients. The Fisher's exact test was used for comparison between different categories. The distant recurrence rate (DRR) was analyzed using the Kaplan-Meier method and the log-rank test. For multivariate analysis, Cox's regression analysis was performed.
[Results]
The median follow-up period was 103.8 months (range: 5.6-128.8). Recurrence with distant metastasis occurred in 26 patients (2.5%). There were 5 (0.7%) deaths related to breast cancer. ly was detected in 240 patients (23.4%). In the ly-positive group, the tumor size was larger (p = 0.007), and the nuclear grade (NG) was higher (p &lt; 0.001) than in the ly-negative group. Postoperative endocrine therapy (p &lt; 0.001) and postoperative chemotherapy (p &lt; 0.001) were more frequently employed for patients with ly-positive tumor. The univariate analysis showed that ly positivity (p &lt; 0.001), large tumor size (p &lt; 0.001), high NG (p &lt; 0.001), PgR negativity (p = 0.002) and the history of adjuvant chemotherapy (p &lt; 0.001) were associated with high DRR. In the multivariate analysis, large tumor size (p = 0.007) and PgR negativity (p = 0.015) remained significant. Although positive ly had a risk ratio of 2.2, it was not an independent risk factor.When restricted to T1 tumor (n = 899), the aforementioned factors still showed prognostic value in the univariate analysis, among which ly positivity (p = 0.004)remained significant together with PgR negativity (p = 0.047)in themultivariate analysis.The 8-year DRR was very favorable (0.8%) in patients with ly-negative T1N0 tumor while it was modest (6.6%) in patients with ly-positive T1N0 tumor (p &lt; 0.001). Only 1.3% of the patients had received adjuvant chemotherapy in the ly-negative group while 27% of the patients had in the ly-positive group.
[Conclusion]
Lymphatic invasion was associated with higher DRR although it was not independent in the multivariate analysis among patients with N0 luminal breast cancer. When restricted to patients with T1N0 luminal breast cancer, the presence of ly was independently associated with higher risk of distant recurrence. It suggests that the assessment of ly is clinically more relevant when considering treatment options for small luminal breast cancer.
Citation Format: Abe T, Ito Y, Fukada I, Shibayama T, Ono M, Kobayashi T, Kobayashi K, Takahashi S, Horii R, Akiyama F, Iwase T, Ueno T, Ohno S. Lymphatic invasion is an independent risk factor in patients with small node-negative luminal breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-29.