Human Epidermal growth factor Receptor 2 positive (HER2+) breast cancers have a high risk of recurrence in the absence of systemic treatment. The monoclonal antibody trastuzumab in combination with chemotherapy has significantly improved survival. Randomized trials have given trastuzumab both concurrently and sequentially with chemotherapy. To date, only one study reported a comparison between concurrent and sequential trastuzumab, with a numerically but not statistically significant benefit for concurrent use.

Our aim is to evaluate whether there is a difference in survival between patients who received trastuzumab sequentially to chemotherapy compared to concurrently with chemotherapy using data from the population-based, Netherlands Cancer Registry (NCR).


All women diagnosed in the Netherlands with a HER2+, TanyNanyM0 breast tumor between 2005 and 2007 who received both chemotherapy and trastuzumab were identified from the NCR.

Kaplan Meier survival estimates and Cox regression were used to compare recurrence free survival (RFS) and overall survival (OS) by trastuzumab sequence. Hazard ratios (HR) were adjusted for grade, pathological T-stage, pathological N-stage, estrogen receptor (ER), progesterone receptor, radiotherapy, hormonal therapy and ovarian ablation.


A total of 1,849 patients were identified, with a mean follow-up of 7.8 years. Of these, 1,260 received concurrent trastuzumab and 589 sequential trastuzumab. Most tumors were grade 3, node positive and ER+. During follow-up 358 RFS events occurred, 231 in the concurrently treated patients compared to 127 in sequentially treated patients. Regarding OS, 290 deaths were observed, 188 deaths in concurrently treated patients compared to 102 deaths in sequentially treated patients, respectively.

OS and RFS were similar among sequentially versus concurrently treated patients (adjusted HR 1.11; 95% CI 0.87-1.42; P=0.420 and adjusted HR 1.15; 95% CI 0.92-1.44; P=0.209, respectively).


We observed no significant difference in OS and RFS between patients who received sequential trastuzumab compared to patients treated concurrently. Based on our results no recommendation can be made favoring either of the two treatment sequences for the adjuvant treatment of HER2+ breast cancer patients.

Citation Format: Dackus GMHE, Jóźwiak K, Van der Wall E, Van Diest PJ, Hauptmann M, Siesling S, Sonke GS, Linn SC. Adjuvant treatment of HER2+ breast cancer: Should trastuzumab be given sequentially or concurrently with chemotherapy? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-13-10.