If HER-2/neu-specific IFN-γ producing T cells are involved in HER-2/neu loss and tumor recurrence, we might be able to detect such immune responses in patients with HER-2/neu negative breast cancer, who might have had undetectable HER-2/neu positive premalignant tumors in the past, that had lost HER-2/neu expression and progressed to invasive carcinoma under the immune pressure. The gene discussed is ERBB2; the disease is invasive carcinoma.