Tumor oxygenation correlates with molecular growth determinants in breast cancer

Hypoxic tumor cells may represent a fraction of cells that are not susceptible to radiation or chemotherapy. Intratumoral oxygen partial pressure (pO(2)) is the result of oxygen delivery and consumption. Cell proliferation is one factor to effect oxygen consumption and we therefore studied the correlation between tumor pO(2) and histological parameters. Patients and methods: In 36 women and one man (age range 29-80 years) with suspected breast cancer. Before tumor resection, intralesional pO(2) was determined with a polarographic needle electrode. Under ultrasound control, 200 tumor measurements were obtained; Hb levels, Hk, arterial blood gas parameters, and tissue temperature were determined. The median of pO(2) values and the percentage of hypoxic areas (pO(2) < 10 mmHg) were calculated and correlated with the histological type, grading, ER, PR, and the expression of Ki-67, p53, EGFR, pS2, and c-erb-B2. Results: The overall median pO(2) was 44 mmHg, and 1024 measurements (13.8%) represented hypoxic areas. Ductal and lobular invasive cancers showed median pO(2) of 41 mmHg. The mean pO(2) of G1 tumors was 59 mmHg and the hypoxic fraction 8%, in contrast to G2 tumors with 43 mmHg and 17%, and G3 tumors with 36 mmHg and 20.4% (p < 0.01). We observed a correlation with tumor size and an increased rate of hypoxic areas in T3-4 lesions (p < 0.02). Also tumors with negative nodes or positive ER had significantly higher pO(2) values, as did tumors with an overexpression of c-erb-B2, p53, and cathepsin D. Conclusion: Oxygenation of human breast cancers can safely be measured in patients prior to surgical therapy, pO(2) values correlate both with prognostic markers examined histologically and with molecular growth factors. As the efficacy of preoperative or adjuvant treatment in individuals may depend on oxygen partial pressure, efforts to manipulate tumor pO(2) for therapeutic purpose could be promising.