Barcelona—A protein previously thought to exist only in a limited number of tumors in fact exists across all breast cancer subtypes, a finding that can help predict the tumor’s response to chemotherapy and guide treatment decisions.
These results are from a study, led by first author Gunter von Minckwitz, MD, of the German Breast Group Forschungs GmbH, Neu-Isenburg, Germany, which looked at the protein polyadenosine diphosphate [ADP]-ribose polymerase (PARP), its expression in various hormone and HER2 receptor subtypes of early breast cancer, and its predictive value for pathological complete response. With PARP inhibited, cell death occurs, meaning that chemotherapy can be targeted precisely at cancer cells, while leaving normal, healthy cells relatively untouched. The research team examined tissue from 582 patients who received neoadjuvant chemotherapy, staining the samples immunohistochemically for PARP, ER, PgR, and HER2 expression. PARP expression was scored as low, medium, or high.
High expression was found in 19.9% of 286 HR+/HER2- tumors, 20.2% of 129 HR+/HER2+ tumors, 36.0% of 50 HR-/HER2+ tumors, and 35.6% of 101 HR-/HER2- tumors. Patients with high PARP expression showed a pathological complete response rate of 25.7% compared to 18.8% and 6.1% in patients with medium or low expression (P < .001).
“The relationship to total response was remarkable,” Professor von Minckwitz said in a press release announcing the findings. “Tumors with a high level of PARP expression had a total response in 26% of cases, whereas those tumors which did not express PARP had a total response in only 9%. Additionally, we found that the presence of PARP can provide more accurate prognostic information than the grade of differentiation or degree of abnormality of tumors. We believe that this is the first study to describe a broad expression of PARP in untreated breast tumors together with a correlation of sensitivity to chemotherapy.”
The authors conclude that because PARP expression can be detected by immunohistochemistry in all subtypes of early breast cancers and it predicts pathological complete re sponse to neoadjuvant taxane anthracycline–based chemotherapy, clinical investigation of PARP inhibitors should not be limited to triple-negative tumors alone.
However, the question of whether immunohistochemical detection of PARP is the best method of predicting PARP inhibitor efficacy remains, the scientists said. “We need more prospective trials to be sure that there is no better way of making sure that the right people are getting the right therapy,” said Professor von Minckwitz. “However, it would be fair to say that we believe that we may be on the verge of a major change in the way breast cancer is treated.”
