An immunotherapy schedule in endocrine-dependent metastatic breast cancer: correlation between clinical course and immunologic parameters.
The authors reported important benefits and survival with an immunotherapy schedule in patients with endocrine-dependent breast cancer with distant metastases. Here they update clinical outcome and correlate it with immunologic data. Twenty-nine consecutive patients with metastatic disease stable or responsive to first-line antiestrogens were recruited and treated with cyclic administration of beta-interferon and interleukin-2 combined with continuous conventional anti-estrogen therapy. Eosinophils and the total number of lymphocytes and CD4+, CD8+, and CD16+56+ cells were determined in the peripheral blood during first-line hormone immunotherapy before and 24 to 72 hours after the administration of interleukin-2. At the last observation (June 30, 2004), 10 patients had died. After a mean follow-up of 59 +/- 37 months (range 9-163), definite median time had not yet been reached either for clinical benefit or for overall survivals; estimated values were 38, 103, and 106 months for clinical benefit and overall survival from first-line anti-estrogen treatment and from diagnosis of distant metastases, respectively. Two patients maintained complete remission 108 and 163 months after the beginning of first-line anti-estrogen therapy. In patients with clinical benefit, eosinophils, total lymphocytes, and CD4+, CD8+, and CD16+56+ cells significantly increased after interleukin-2 administration (from P < 0.012 to P < 0.000). In the patients with progressive disease, only a slight increase in eosinophils occurred (P = 0.038). No further adverse events other than the minimal ones described occurred. The estimated median benefit and survivals are more than three times longer than previously shown in similar populations. The differing response to interleukin-2 can be explained by the hypothesis that resting cancer cells during clinical benefit do not inhibit the immune system, while at the onset of resistance they recover the constitutive ability to inhibit it.
Nicolini
Andrea
A
Department of Internal Medicine, University of Pisa, 56126 Pisa Italy. a.nicolini@int.med.unipi.it
Carpi
Angelo
A
Rossi
Giuseppe
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D016516:CD4-CD8 Ratio; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D007962:Leukocytes / Q000276:immunology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D007376:Interleukin-2; D013629:Tamoxifen; D016899:Interferon-beta