Abstract S6-06: The effect of trastuzumab-based therapy on overall survival in small, node-negative HER2-positive breast cancer: To treat or not to treat?
Authors: MS van Ramshorst, M van der Heijden-van der Loo, GMHE Dackus, SC Linn, GS Sonke
Journal: Cancer Research (2016)

Abstract Background Since the addition of trastuzumab to (neo)adjuvant chemotherapy, the prognosis of patients with stage II and III HER2-positive breast cancer has significantly improved. Several reports have subsequently shown that small, node-negative tumors also carry a relatively poor prognosis and patients with HER2-positive tumors of 2cm or less increasingly receive trastuzumab-based chemotherapy. We sought to provide evidence for the effect of this approach in a population-based cohort. Methods All patients diagnosed with T1N0 HER2-positive breast cancer in the Netherlands between 2006 and 2012 were identified from the nationwide Netherlands Cancer Registry. Patient, tumor, and treatment characteristics were recorded. The primary outcome was overall survival and analyses were performed for the whole group and for T1a, T1b, and T1c tumors separately. Kaplan-Meier survival rates were compared between groups with and without systemic treatment and multivariate cox regression analysis was performed to adjust for baseline characteristics. Results A total of 3512 eligible patients were identified of whom 385 had a T1a tumor (≤0.5cm, including 54 micro-invasive), 800 had a T1b tumor (&amp;gt;0.5 to 1cm), and 2327 had a T1c tumor (&amp;gt;1cm to 2cm). Systemic treatment with chemotherapy and/or trastuzumab was administered in 45% of patients: 7% in T1a, 19% in T1b, and 60% in T1c tumors. Of the treated patients, the majority (92%) received both chemotherapy and trastuzumab. The use of systemic treatment increased significantly over time and varied according to geographic region. Other factors associated with receiving systemic treatment in multivariate analysis were younger age, negative hormone receptor status, higher tumor grade, larger tumor size and presence of isolated tumor cells in the lymph nodes. At a median follow-up of 49 months (interquartile range [IQR] 30-69), 186 deaths had occurred. Treatment with chemotherapy and/or trastuzumab significantly improved overall survival at seven years follow-up (95% versus 87%; hazard ratio [HR] 0.30; 95% confidence interval [CI] 0.20-0.44, p&amp;lt;0.001). This effect was seen in all three tumor size groups: 100% versus 91% in T1a, 99% versus 91% in T1b, and 95% versus 83% in T1c tumors. When corrected for age the beneficial effect of systemic treatment on overall survival remained highly significant (HR 0.46; 95% CI 0.30-0.70, p&amp;lt;0.001). Due to the small number of events in the treated group, correction for additional variables in multivariate analysis was not feasible. However, the otherwise unfavorable prognostic profile in the treated patients (hormone receptor status, grade, size, isolated tumor cells), suggests an even stronger actual effect of systemic treatment. To ensure that the excess mortality in the non-treated group was due to breast cancer and not the result of other causes, breast-cancer specific survival analyses will follow. Conclusion Systemic treatment with chemotherapy and/or trastuzumab improves overall survival in T1a, T1b, and T1c node-negative HER2-positive breast cancer. Citation Format: van Ramshorst MS, van der Heijden-van der Loo M, Dackus GMHE, Linn SC, Sonke GS. The effect of trastuzumab-based therapy on overall survival in small, node-negative HER2-positive breast cancer: To treat or not to treat?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr S6-06.