Prognostic significance of in situ carcinoma associated with invasive breast carcinoma. A natural experiment in cancer immunology?

Background: Our previous studies indicate that the in situ phase of mammary carcinogenesis is characteristically associated with cell-mediated immunity (CMI against an immunogen shared by most breast carcinomas. Such reactivity is inversely correlated with stage and appears to impede in situ-to-invasive progression and lethality from invasive breast carcinoma. If in situ carcinomas are indeed associated with ambient, prognostically favorable immunity against such an immunogen, one would expect lethality from invasive breast carcinoma to be reduced in patients with a diagnosis of a prior, simultaneous, or subsequent in situ breast carcinoma. The present study provides a test of such relationships.

Methods: Patient survival was analyzed for 129,394 female patients with invasive breast carcinoma diagnosed in areas covered by the Surveillance, Epidemiology, and End Results (SEER) Program based at the National Cancer Institute (NCI). Patients were classified according to whether they had a prior, simultaneous, or subsequent in situ breast carcinoma and survival was examined for up to 15 years subsequent to diagnosis using life tables and the Cox regression model.

Results: The findings indicate that patients with an invasive breast carcinoma who had a prior, simultaneous, or subsequent in situ breast carcinoma did experience significantly better survival than comparison groups of patients who either did not have an associated cancer of any type, had an associated invasive breast carcinoma, or had an in situ or invasive cancer of non-breast origin.

Conclusions: Our prior and current observations warrant more direct studies of the prognostic, therapeutic, and prophylactic significance of the in situ carcinoma-associated type of specific CMI in breast cancer patients.