Response to HER-2 pulsed DC1 vaccines is predicted by both HER-2 and estrogen receptor expression in DCIS
ABSTRACT
BACKGROUND: Patients with estrogen-independent (ER(neg)) human epidermal growth factor receptor-2 (HER-2)-positive ductal carcinoma in situ (DCIS) treated with lumpectomy alone or lumpectomy and radiation are at increased risk of developing subsequent breast cancer events.
METHODS: Thirty-eight patients with HER-2 expressing DCIS received a HER-2 pulsed autologous dendritic cell (DC1) vaccine administered over 4-6 weeks before surgical resection. HER-2 and estrogen receptor (ER) expression were determined by immunohistochemistry. In 35 patients, CD4(pos) T-cell sensitization to HER-2 peptides was identified by ELISPOT. In 19 patients, CD8(pos) T-cell responses were identified by ELISA. Clinical and immune responses postvaccination were compared between intermediate-expressing HER-2 (2+) and high-expressing HER-2 (3+) patients, as well as ER(neg) and estrogen-dependent (ER(pos)) patients.
RESULTS: There was no significant difference in immune response after HER-2 vaccination in patients with HER-2 (2+) and (3+) tumors or ER(neg) and ER(pos) tumors. Complete tumor regression rates were similar in patients with HER-2 (2+) and (3+) DCIS. Overall, clinical response rates were similar in patients with ER(neg) and ER(pos) DCIS, but complete tumor regression was significantly more common in patients with ER(neg) DCIS.
CONCLUSIONS: Despite equivalent immune responses after vaccination in patients with HER-2 (2+), HER-2 (3+), ER(neg) and ER(pos) DCIS, HER-2 pulsed DC1 induces more complete responses in patients with ER(neg) DCIS. These data provide a rationale for developing vaccinations to reduce recurrence in patients with ER(neg) DCIS for whom there are currently limited adjuvant options.