Addition of anti-estrogen therapy to anti-HER2 dendritic cell vaccination improves regional nodal immune response and pathologic complete response rate in patients with ERpos/HER2pos early breast cancer

OncoImmunology

卷:6

Gary K. Koski¹  Crystal Oechsle¹  Angela DeMichele²  Paul J. Zhang²  Carla S. Fisher²  Salman Zaheer²  Shuwen Xu²  Robert E. Roses²  Brian J. Czerniecki²  Elizabeth S. McDonald²  Elizabeth Fitzpatrick²  Lea Lowenfeld²  Jashodeep Datta²  Megan Fracol²  Rosemarie Mick³ 

[1] Kent State University;

[2] University of Pennsylvania Perelman School of Medicine;

[3] University of Pennsylvania;

关键词: breast cancer;    estrogen;    her2;    immunotherapy;    sentinel lymph nodes;   

DOI  :  10.1080/2162402X.2016.1207032

来源: DOAJ

【 摘 要 】

HER2-directed therapies are less effective in patients with ERpos compared to ERneg breast cancer, possibly reflecting bidirectional activation between HER2 and estrogen signaling pathways. We investigated dual blockade using anti-HER2 vaccination and anti-estrogen therapy in HER2pos/ERpos early breast cancer patients. In pre-clinical studies of HER2pos breast cancer cell lines, ERpos cells were partially resistant to CD4+ Th1 cytokine-induced metabolic suppression compared with ERneg cells. The addition of anti-estrogen treatment significantly enhanced cytokine sensitivity in ERpos, but not ERneg, cell lines. In two pooled phase-I clinical trials, patients with HER2pos early breast cancer were treated with neoadjuvant anti-HER2 dendritic cell vaccination; HER2pos/ERpos patients were treated with or without concurrent anti-estrogen therapy. The anti-HER2 Th1 immune response measured in the peripheral blood significantly increased following vaccination, but was similar across the three treatment groups (ERneg vaccination alone, ERpos vaccination alone, ERpos vaccination + anti-estrogen therapy). In the sentinel lymph nodes, however, the anti-HER2 Th1 immune response was significantly higher in ERpos patients treated with combination anti-HER2 vaccination plus anti-estrogen therapy compared to those treated with anti-HER2 vaccination alone. Similar rates of pathologic complete response (pCR) were observed in vaccinated ERneg patients and vaccinated ERpos patients treated with concurrent anti-estrogen therapy (31.4% vs. 28.6%); both were significantly higher than the pCR rate in vaccinated ERpos patients who did not receive anti-estrogen therapy (4.0%, p = 0.03). Since pCR portends long-term favorable outcomes, these results support additional clinical investigations using HER2-directed vaccines in combination with anti-estrogen treatments for ERpos/HER2pos DCIS and invasive breast cancer.

【 授权许可】

Unknown