Biology and prognosis of 1,685 recently diagnosed HER2-positive breast carcinomas

Abstract

10501 Background: Understanding biology, prognosis and drug-sensitivity of HER2-positive breast cancer might help optimization of treatment of patients affected by this type of cancer. Most available studies are retrospective and suffer from the low frequency of this tumor subset. Methods: We conducted a large national retrospective/prospective study involving 1685 patients (cases) with HER2-positive (2+, 3+ score) primary breast carcinomas diagnosed in Italy in 2000/2001; for each case, in each participating center, a control was identified as the first consecutive patient with HER2-negative cancer (0, 1+ score). Results: In addition to the already known association with some pathologic parameters such as grade, hormone receptors, and ductal histotype, the four HER2 categories also displayed specific features, for example, a significantly higher frequency of p53-positivity among HER2–2+ tumors than in the other three categories, and a significantly lower frequency of lymphoid infiltration and desmoplasia, accompanied by a higher frequency of vascular invasion, in HER2–1+ as compared to HER2–0 tumors. Neither tumor size nor nodal involvement were associated with HER2 status. With a median follow-up of 4 yrs, the HER2-positive group showed a 20% relapse rate versus 14% in the HER2-negative group (p < 0.001). Analysis of relapse rates in the four HER2 categories indicated that only 3+ tumors show a significantly poorer prognosis, in both node-positive and node-negative subgroups; however, when patients who underwent invasive surgery are considered, the HER2–2+ patients also showed a significantly increased relapse rate as compared to negative cases, consistent with a stimulation of tumor cells by growth factors released at the time of surgery. Analysis of relapse rates according to type of therapy confirms the unresponsiveness to tamoxifen but sensitivity to chemotherapy, in particular taxanes, of HER2-positive tumors. Indeed, HER2-positive tumors were found to have a significantly better prognosis than HER2-negative when treated with taxanes. Conclusions: The present analysis conducted in a very large series of HER2-positive cases suggests innovative findings that can help optimization of treatment strategy for patients with HER2-positive breast cancer. No significant financial relationships to disclose.