The study reviewed here found that breast cancer cells that had high levels of the PARP (polyadenosine diphosphate ADP-ribose polymerase) enzyme were more likely to respond to chemotherapy. These results were presented at the 2010 European Breast Cancer Symposium.
DNA carries genetic information in both healthy and cancer cells. Chemotherapy medicines work against cancer by damaging the DNA or blocking DNA reproduction. But all cells can fix DNA damage caused by chemotherapy medicines; the PARP enzyme helps fix this DNA damage. So while it seems likely that chemotherapy wouldn't be effective on breast cancers with the highest PARP levels, this study found that wasn't true. Breast cancers with the highest PARP levels responded the best to chemotherapy.
The researchers measured PARP levels in cells from breast cancer tissue samples. The samples were put into three groups based on PARP levels: low, medium, and high. About 66% of the tissue samples had medium or high PARP levels.
The researchers looked at how well each cancer responded to chemotherapy. The response was measured as pathologic complete response, which means a biopsy showed no signs of cancer after chemotherapy.
Pathologic complete response was found in:
So it seems that PARP levels might help predict if a breast cancer is likely to respond well to chemotherapy.
More research is needed to better understand if and how to use PARP levels to predict how breast cancer will respond to chemotherapy.
Stay tuned to Breastcancer.org for the latest news on emerging breast cancer treatments.
BARCELONA (MedPage Today) -- A DNA repair enzyme once linked to uncommon forms of breast cancer -- but now identified in all histologic subtypes -- predicted response to chemotherapy in a retrospective analysis of tissue specimens.
The rate of pathologic complete response increased in a linear manner with the level of expression of PARP (polyadenosine diphosphate ADP-ribose polymerase), according to Gunter von Minckwitz, MD, of the German Breast Group Forschungs GmBH in Neu-Isenberg
Analysis of the tissue samples showed that low-level PARP expression was associated with a pathologic complete response rate of 8%, rate of 19.1% with moderate expression, and 26.5% with high-level expression, he reported here at the European Breast Cancer Conference.
In a multivariate analysis, medium- and high-level PARP expression emerged as a significant predictor of pathologic complete response.
"PARP is present in all hormone-receptor and HER2 phenotypes," von Minckwitz said. "High cytoplasmic, but not nuclear, expression of PARP correlates with an aggressive tumor pattern and also predicts a high pathologic complete response to chemotherapy.
"PARP-positive breast cancer might become a new, clinically relevant breast cancer entity," he added.
Prior to von Minckwitz's report, PARP's involvement in breast cancer had centered on uncommon forms of breast cancer, particularly the so-called triple-negative disease: HER2 negative, estrogen-receptor negative, and progesterone-receptor negative.
Last year, investigational PARP inhibitors sparked enthusiasm among breast cancer clinicians and researchers when preliminary studies showed the agents had considerable activity in patients with triple-negative breast cancer.
Laboratory studies suggested potential synergism from the combination of PARP inhibitors and DNA-damaging chemotherapy, and that possibility is the focus of a phase III trial, said von Minckwitz.
To learn more about the nature and activity of PARP, investigators analyzed tissue specimens obtained during a clinical trial of neoadjuvant chemotherapy for patients with T2-T4, nonmetastatic breast cancer.The principal objectives were:
Using an immunoreactive score based on the intensity and extent of tumor-cell staining, investigators rated 638 specimens as having low, medium, or high PARP expression.
Overall, PARP expression was significantly greater in the cytoplasm compared with the nucleus of tumor cells (P=0.012). High expression was associated with nonlobular histology (P<0.0005), higher grade (P<0.0005), and nodal involvement (P=0.030).
Von Minckwitz and colleagues detected PARP expression in phenotypes reflecting all combinations of hormone-receptor and HER2 status. Medium expression accounted for about half of the specimens in each phenotype, and medium and high expression accounted for two-thirds or more of the specimens across phenotypes.
Phenotype, aggressiveness, and pathologic complete response all had correlations with cytoplasmic PARP expression but not nuclear expression.
Although more studies are needed to confirm the findings, "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," von Minckwitz said in a statement distributed by EBCC.
Von Minckwitz had no disclosures.
Primary source: European Breast Cancer Conference Source reference: Von Minckwitz G, et al "PARP is expressed in all subtypes of early breast cancer and is a predictive factor for response to neoadjuvant chemotherapy" EBCC 2010; Abstract 443.
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