Available clinical and experimental data on the effect of HER-2/neu overexpression on chemosensitivity are controversial. It was the purpose of this in vitro study to define the association between HER-2/neu overexpression and the sensitivity to the chemotherapeutic drug combinations of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) and 5-fluorouracil, epirubicin and cyclophosphamide (FEC) of breast cancer cells derived from 140 chemotherapy-naïve patients at the time of primary surgery. Both drug combinations were tested at six different concentrations ranging from 6.25-200% peak plasma concentration (PPC). Immunohistochemical detection of HER-2/neu overexpression was performed with the HER-2/neu antibodies, CB11, TAB250 and AO485, in the same tumor specimens. Immunoreactions were determined as negative (0/1+), weakly positive (2+) and strongly positive (3+). However, the antibodies varied in their degrees of sensitivity. Breast cancer samples with strong (3+) HER-2/neu overexpression demonstrated 90% growth inhibition (IC90) at significantly lower PPC values, using the CB11 (p = 0.048), TAB250 (p = 0.007) and AO485 (p < or =0.01) antibodies, and showed 50% growth inhibition (IC50) at significantly lower PPC values, using the CB11 antibody (p = 0.01) compared to their counterparts with lower levels of HER-2/neu expression. When analyzing the group of patients with intermediate and strong HER-2/neu overexpression (2+ and 3+), an association between HER-2/neu overexpression and increased chemosensitivity was seen with the TAB250 (p = 0.044) and AO485 (p = 0.032) antibodies, but not with the CB11 antibody (p =0.8) at the IC90 level. Differences in chemosensitivity between samples with strong HER-2/neu overexpression and those with lower levels were then analyzed separately for CMF and FEC. Both regimens achieved 90% tumor growth inhibition at lower PPC values in samples with strong HER-2/neu overexpression (3+) compared to their counterparts with lower expression levels (AO485 p = 0.011 for CMF, and p = 0.09 for FEC). Cumulative concentration-response plots of tumors responding in vitro with 90% tumor cell inhibition showed a stronger dose dependence for both CMF and FEC among tumor samples with strong HER-2/neu overexpression compared to those with lower levels of expression. In conclusion, the data show that HER-2/neu overexpression was not associated with in vitro drug resistance to CMF or FEC. In contrast, tumors with strong HER-2/neu overexpression demonstrated increased dose-dependent in vitro sensitivity to both the FEC and CMF regimens.

Background: The study was undertaken to evaluate the prognosis and prognostic factors of women with breast cancer under routine conditions. One of the main questions was to show, how prognosis is influenced by the adjuvant systemic therapy (CMF chemotherapy or hormonal therapy) with or without adjuvant radiotherapy in patients with breast cancer and positive axillary nodes (≥4). Patients and Methods: All patients (n =2,802) with primary breast cancer treated at the Oncology Center of Stuttgart, between 1988 and mid 1994, were retrospectively evaluated. Results: Patients with 4 or more nodes involved receiving adjuvant systemic therapy had an equal prognosis, compared to patients with 1–3 axillary nodes. After further analysis, a benefit was observed only among patients with 4–9 nodes involved, but not among patients with 10 or more axillary nodes. Conclusions: In the retrospective evaluation of data of groups not well-matched, the results have to be interpreted carefully. Bearing this in mind, the data nevertheless indicate that the prognosis of patients with 4–9 nodes involved is not so bad as it has been published, when they are treated with adjuvant systemic therapy with radiotherapy. Furthermore, the data indicate that adjuvant systemic treatment helps to prolong survival time in patients aged 80 years or more.