Immuno-hormonal phenotypes associated with tumor proliferation and metastasis in breast cancer patients

Previously, the associations were described between tumor proliferation rates (levels of Ki67 positive cells), and levels of IgA and IgG antibodies against estradiol (E2) and progesterone (Pg) (IgA₁-E2 and IgA₁-Pg, IgG₁-E2 and IgG₁-Pg) as well as corresponding antiidiotypic antibodies (IgG₂-E2 and IgG₂-Pg) in breast cancer patients (BCP). The purpose of the present work was to look for a combined influence of E2 and Pg, antibodies against benzo[a]pyrene (Bp), E2 and Pg, and antiidiotypic antibodies to E2 and Pg, searching for relations with Ki67 positive cells in tumors and metastatic disease in BCP. We performed studies in blood serum of 1245 BC patients before anticancer treatment (620 women with stage I BCP; 475, stage II; 150, with stages III+IV). Antibodies and antiantibodies were studied using ELISA technique with adsorbed haptens-BSA conjugates and monoclonal antibodies to E2 and Pg, respectively. The patients were divided into several groups with different individual levels of the studied factors. Low-proliferating tumors (Ki67≤20%) combined with metastases (Met+) were less frequent whereas tumors with Ki67>20% + Met- were more common among 143 BCP with IgG₂-Pg ≤1.95 conventional units (c.u.) than in 332 BCP with IgG₂-Pg>1.95 c.u. (10.0% vs 21.1% and 42.0% vs 26.2%, p<0.01). Tumors with Ki67>20% were revealed in 94 BCP with IgG₂-Pg>1.95 c.u. + IgG₁-Bp>14.3 c.u., more frequently than in 238 BCP with IgG₂-Pg >1.95 c.u. + IgG₁-Bp≤ 4.3 c.u. (69.2% vs 50.1%, p<0.01). Tumors with Ki67≤20% + Met- were diagnosed more frequently, and Ki67>20% + Met+ were less common in 102 BCP with IgG₂-Pg>2.1 c.u. + IgG₂-E2>3.3 c.u. than in 42 BCP with IgG2-Pg>2.1 c.u. + IgG₂-E2≤3.3 c.u. (33.3% and 16.7% vs 7.1% and 31.0%, p<0.01). 43 BCP had high levels of E2 (>166 pmol/L) combined with IgG₂-Pg>2.1 c.u. + IgG₁-Bp≤14.3 c.u. + Pg>869 pmol/L, and the most aggressive tumors (Ki67>20% + Met+) more frequent than 33 BCP with low levels of E2≤166 pmol/L combined with the same factors (55.8% vs 21.2%, p<0.01). Each of these immuno-hormonal phenotypes has been found equally common in BCP with I, II, and III+IV stages. In conclusion, individual features on the tumor proliferation and metastasis in II stage BCP were dependent on individual combinations of IgG₂-Pg, IgG₂-E2, IgG₁-Bp, E2, and Pg serum levels. Immuno-hormonal phenotypes during tumor growth did not change upon tumor progression.

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