Early findings from Phase I and Phase II clinical trials using a new class of drug to treat patients with triple-negative breast cancer are showing promising results. Known as poly (ADP-ribose) polymerase, or PARP inhibitors, these new agents received considerable attention at the American Society of Clinical Oncology meeting in June.
Cheryl Jolly, in the related story, is now enrolled in a Phase III trial, and her tumor is shrinking.
Jennifer Litton, M.D., assistant professor inBreast Medical Oncology, answers questions about this new drug and why it is helping women with this aggressive type of breast cancer.
Exactly what is triple-negative breast cancer?
Triple-negative breast cancer is a subset of breast cancers that are not driven by estrogen or progesterone hormones. They also do not overexpress the HER-2/neu protein. Biologically, they are very aggressive and can grow more rapidly than other types of breast cancer.
Can someone be genetically at high risk for developing it?
Women who have been diagnosed with a BRCA1 deleterious (harmful) mutation as well as younger, premenopausal women and women of African-American descent, appear to have higher rates of developing triple-negative breast cancers, although triple-negative breast cancers can occur at any age and in any race. Women who are diagnosed premenopausally or have a family history of breast and/or ovarian cancers, especially at younger ages, should discuss with their oncologist whether or not they should meet with a genetic counselor.
What makes PARP a different type of treatment?
PARP inhibitors, such as olaparib and BSI-201, belong to a class of drugs that provide targeted therapy. They exploit a specific weakness in tumors stopping them from repairing damage in tumor DNA caused by chemotherapy. In addition, it also takes advantage of a further weakness, especially in tumors whose BRCA genes no longer work -- and causes that cell to die.
In a Phase II study of olaparib presented at the American Society of Clinical Oncology, women with BRCA1 or BRCA2 mutations and advanced breast cancer that persisted despite previous treatment, more than one-third of patients had tumor shrinkage.
BSI-201, in combination with conventional chemotherapy, significantly improved overall and progression-free survival in women with metastatic triple-negative breast cancer, compared with chemotherapy alone.
Why does it seem to work for women with triple-negative breast cancer?
This therapy appears to take advantage of weaknesses commonly seen within a triple-negative breast cancer cell. Also, paired with the right chemotherapy, its activity may not be limited to only triple-negative breast cancers.
What are the side effects of this treatment?
There are several PARP inhibitors currently in development. Some are pills while others are given intravenously. Although side effects differ from drug to drug, overall they are very well tolerated adding little extra toxicity to the accompanying chemotherapy.
What other cancers does it show promise for?
Right now PARP inhibitors are also being considered for other cancers such ovarian, uterine, brain and prostate cancers. As more clinical trial data become available, more tumors may be impacted by this class of drugs.