Abstract

Abstract Background: Lymph node positivity (LNP) is among the most important prognostic factors in breast cancer. Counterintuitively, a negative association of LNP with age has been shown in different cancers. The goal of this study is to determine the influence of age and tumor size on lymph node positivity in breast cancer in a large real-world population setting. Methods: Patients aged 0-85 years with primary invasive breast cancer who underwent primary surgery and lymph node dissection between 2010 and 2018 were selected using the U.S. Surveillance, Epidemiology, and End Results (SEER) database. Patients with systemic therapy before surgery or patients not receiving surgery for the breast tumor and/or lymph nodes were excluded. We used a multivariate logistic regression model to determine the association of age with regional LNP. We corrected for grade, tumor size, ER-, PR- and HER2-positivity and race. Based on previous studies and exploratory analysis on the current database, we used a piecewise effect of age with cutoff at 70y, and an interaction term between age and tumor size. We also introduced a piecewise linear effect for tumor size, with cut-off at 50mm. Results: (see table) 177,866 patients were included. The multivariate model suggests that LNP strongly decreases with age in patients with breast cancer ≤ 70y. This effect is stronger for smaller tumor sizes. The effects in patients >70 years are less clear, and may be more biased by delay in diagnosis or selection bias as older patients with small tumors are less likely to undergo surgery (of both breast tumor and lymph nodes).Concerning impact of tumor size, our analysis shows that LNP strongly increases with tumor size in tumors ≤ 50 mm as expected, but that this association is not present anymore in tumors > 50 mm. Conclusion: We found a clear negative association of LNP with age in patients ≤ 70 years, when corrected for grade, tumor size, ER-, PR- and HER2-positivity and race. This points to differences in biological mechanisms of lymph node invasion in young versus older persons that are counterintuitive and poorly understood. We also found that LNP strongly increases with tumor size in tumors ≤ 50 mm, but not in larger tumors. The impact of age on tumor biology, micro-environment and the lymphatic system may each play a role. However, these areas are understudied and further research is needed to understand the mechanism behind the current results. Impact of age on Lymph node positivity (LNP), according to tumor sizeAge expressed per 10-year increaseTumor sizeOdds Ratio (95% CI)≤70y15mm0.852 (0.841;0.863)25mm0.871 (0.860;0.881)40mm0.900 (0.885;0.914)>70y15mm0.980 (0.939;1.023)25mm1.002 (0.960;1.046)40mm1.035 (0.990;1.082)Impact of tumor size on Lymph node positivity (LNP), according to ageTumor size expressed by 1 cm increaseAgeOdds Ratio (95% CI)≤50mm50y2.041 (2.016;2.066)60y2.086 (2.063;2.109)70y2.132 (2.105;2.159)80y2.179 (2.143;2.215)>50mm50y0.957 (0.945;0.970)60y0.978 (0.967;0.990)70y1.000 (0.987;1.013)80y1.022 (1.005;1.039)OR: odds ratio, CI: confidence interval OR>(<)1: increased (decreased) risk with increasing level (ordinal variables)/for first category (binary variables) Citation Format: Michael Pinchuk, Annouschka Laenen, Sigrid Hatse, Kevin Punie, Patrick Neven, Ines Nevelsteen, Hans Wildiers. Influence of age and tumor size on lymph node positivity in breast cancer: A retrospective population study on the US SEER database [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-01-05.

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