Background: Patients with HER2−positive metastatic disease used to show a more unfavorable prognosis compared to patients with HER2−negative tumors. With the introduction of trastuzumab, patients with HER2−positive metastatic breast cancer show an improved survival compared to patients with HER2−negative tumors (Dawood et al. 2010). So far it has not been shown, if such a switch in prognosis is also achieved in early breast cancer. Methods: 6377 patients from 7 neoadjuvant German studies with operable or locally advanced, non-metastatic breast cancer were analyzed (for details see von Minckwitz G et al, BCRT 2010). In earlier studies patients (pts) with HER2−positive disease did not receive trastuzumab. Trastuzumab was given in 2 trials parallel to chemotherapy for 12–36 weeks and completed after surgery for up to one year of treatment. All patients with endocrine responsive disease received adjuvant endocrine therapy according to institutional standard. We compared the overall and disease free survival in three subgroups, HER2−negative patients, HER2−positive w/o trastuzumab and HER2−positive patients with trastuzumab according to pCR defined as ypT0, ypN0. Results: 6377 patients were evaluable. During a median follow up of 46.3 (0-127) months and observation of 22.869 patient years, 1466 (23%) relapses and 775 (12.2%) deaths were observed. 3060 had HER2−negative disease, 665 patients had HER2−positive disease w/o trastuzumab and 662 patients with HER2−positive disease received trastuzumab. No data on HER2 status were available in 1990 (31.2%) patients as measurement of HER2 was only implemented in the study procedures since 2001.Median age of patients at time of study entry was 50.1 (21-81) years. Median tumor size was 4.0 (range 1.2 − 33.0) cm. Overall 15% (955) of patients had a pCR. The pCR rate in HER2−positive pts was 24% in those with trastuzumab and 15.8% in those without. There was no difference in overall DFS in the three groups achieving a pCR (log rank p=0.251). There was a strong trend towards a better OS in pCR HER2+pts being treated with trastuzumab (overall log rank p= 0.067). Cox regression analysis revealed HER2 positive patients with trastuzumab had a better OS than HER2−positive pts w/o trastuzumab (HR: 7.44; 95%CI [0.92−60.1; p=0.06) and HER2negative pts (HR: 3.86; 95% CI [0.5−29.41], p=0.19). However, for non-pCR pts, DFS was significantly inferior for pts treated with trastuzumab compared to patients without trastuzumab (HR: 0.81, 95% CI [0.63−1.04), p=0.102) or pts with HER2−negative tumors (HR: 0.75; 95% CI [0.61−0.92] p=0.006.)(overall log-rank p=0.022). However, OS was not significantly different between the three groups of non-pCR pts. Conclusion: Patients with HER2−positive primary breast cancer treated with trastuzumab achieve a higher pCR rate. This higher absolute number of pCRs in trastuzumab-treated patients lead to a DFS at least as good as that of HER2−positive not trastuzumab treated and HER2−negative patients and OS even tended to be superior to the other two groups. This supports that pCR can be considered as a surrogate marker in HER2−positive disease. However, HER2−positive, trastuzumab-treated patients without a pCR are at high risk of relapse and are at high medical need for new treatment options. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S5-4.

The presence of receptors for epidermal growth factor (EGF-R), the percentage of cells in S-phase and DNA-ploidy measured by flow-cytometry are new prognostic factors in breast cancer. In order to investigate the relationship between EGF-R, S-Phase/DNA-ploidy and clinical data, we measured these parameters in 68 tumors from patients with operable breast cancer. 11 Patients had positive EGF-R's (specific binding greater than 10 fmol/mg membrane-protein) and 37 patients had a positive S-Phase (more than 5% of cells in S-Phase). 10 of 44 carcinomas of ductal type were EGF-R positive, while only 1 of 18 lobular-type tumor displayed positive EGF-R's. We found significant inverse correlations between EGF-R's and estrogen receptors (p less than 0.00001) and between EGF-R's and age (p less than 0.0001): EGF-R positive tumors were found more often in young patients and in patients with estrogen-receptor-negative tumors. The EGF-R's and flow-cytometric data did not correlate with tumor size and/or nodal status. There was no correlation between EGF-R and S-Phase/DNA-ploidy in the breast cancer specimens suggesting that these two prognostic parameters are independent from each other.