HER‐2 pulsed dendritic cell vaccine can eliminate HER‐2 expression and impact ductal carcinoma in situ

• Published in: Cancer Vol. 118; no. 17; pp. 4354 - 4362
• Main Authors: Sharma, Anupama, Koldovsky, Ursula, Xu, Shuwen, Mick, Rosemarie, Roses, Robert, Fitzpatrick, Elizabeth, Weinstein, Susan, Nisenbaum, Harvey, Levine, Bruce L., Fox, Kevin, Zhang, Paul, Koski, Gary, Czerniecki, Brian J.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2012; Wiley-Blackwell
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - therapy; cancer vaccine; Cancer Vaccines - adverse effects; Cancer Vaccines - therapeutic use; Carcinoma, Intraductal, Noninfiltrating - genetics; Carcinoma, Intraductal, Noninfiltrating - therapy; dendritic cell vaccine; Dendritic Cells - immunology; ductal carcinoma in situ; Female; Gynecology. Andrology. Obstetrics; HER‐2/neu; Humans; Mammary gland diseases; Medical sciences; Middle Aged; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Tumors; Pulsed dendritic cell; Dendritic cell; Ductal carcinoma; Breast disease; Carcinoma in situ; cancer vaccine; erbB2 Gene; Breast cancer; Vaccine; Malignant tumor; Human Epidermal growth factor Receptor 2; ductal carcinoma in situ; Mammary gland diseases; Cancerology; Antigen presenting cell; dendritic cell vaccine; C-Onc gene; HER-2/neu; Protooncogene; Cancer
• ISSN: 0008-543X; 1097-0142; 1097-0142
• DOI: 10.1002/cncr.26734

BACKGROUND: HER‐2/neu overexpression plays a critical role in breast cancer development, and its expression in ductal carcinoma in situ (DCIS) is associated with development of invasive breast cancer. A vaccine targeting HER‐2/neu expression in DCIS may initiate immunity against invasive cancer. METHODS: A HER‐2/neu dendritic cell vaccine was administered to 27 patients with HER‐2/neu–overexpressing DCIS. The HER‐2/neu vaccine was administered before surgical resection, and pre‐ and postvaccination analysis was conducted to assess clinical results. RESULTS: At surgery, 5 of 27 (18.5%) vaccinated subjects had no evidence of remaining disease, whereas among 22 subjects with residual DCIS, HER‐2/neu expression was eradicated in 11 (50%). When comparing estrogen receptor (ER)neg with ERpos DCIS lesions, vaccination was more effective in hormone‐independent DCIS. After vaccination, no residual DCIS was found in 40% of ERneg subjects compared with 5.9% in ERpos subjects. Sustained HER‐2/neu expression was found in 10% of ERneg subjects compared with 47.1% in ERpos subjects (P = .04). Postvaccination phenotypes were significantly different between ERpos and ERneg subjects (P = .01), with 7 of 16 (43.8%) initially presenting with ERposHER‐2/neupos luminal B phenotype finishing with the ERposHER‐2/neuneg luminal A phenotype, and 3 of 6 (50%) with the ERnegHER‐2/neupos phenotype changing to the ERnegHER‐2/neuneg phenotype. CONCLUSIONS: Results suggest that vaccination against HER‐2/neu is safe and well tolerated and induces decline and/or eradication of HER‐2/neu expression. These findings warrant further exploration of HER‐2/neu vaccination in estrogen‐independent breast cancer and highlight the need to target additional tumor‐associated antigens and pathways. Cancer 2012. © 2012 American Cancer Society. Vaccination against HER‐2/neu induces decline and/or eradication of HER‐2/neu expression. These findings warrant further exploration of HER‐2/neu vaccination in estrogen‐independent breast cancer but highlight the need to target additional tumor‐associated antigens and pathways.