Norwalk Hospital clinical trials offer new approaches to breast cancer

Norwalk Hospital, part of the Western Connecticut Health Network, has recently opened two important clinical research trials for women with advanced (stage IV) breast cancer. The first trial will test whether an anti-PDL1 antibody can improve the effects of chemotherapy for women with triple-negative breast cancer (TNBC). The anti-PDL1 antibody targets a patient’s immune system so it can recognize cancer cells and attack them.
There are three most common types of receptors that fuel most breast cancers: estrogen, progesterone and the HER-2/neu gene. None of these is present in triple-negative breast cancer tumors, which means common treatments like hormone therapy and drugs that target estrogen, progesterone and HER-2 are ineffective.
According to Richard Zelkowitz, MD, medical director of the Smilow Family Breast Health Center at Norwalk Hospital, “Women with triple-negative breast cancer cannot be treated with hormonal therapies or anti-Her2 directed therapies such as the drug Herceptin. The only treatment available to them is chemotherapy. That is until now. The anti-PDL1 antibody unlocks the brakes on a patient’s immune system and has been very effective in a number of other cancers. We certainly hope it improves the treatment of women with TNBC.”
Triple-negative breast cancer occurs in about 10% to 20% of diagnosed breast cancers, according to, and most often affects younger people, African Americans, Hispanics or those with the BRCA1 gene mutation.
That gene mutation is the focus of the second trial at Norwalk Hospital. It is aimed at women who have inherited the BRCA genetic mutation (that predisposes to breast and ovarian cancer) and have developed stage IV breast cancer.
The trial will test if a new “PARP inhibitor” drug can improve the effectiveness of chemotherapy treatment. A mutation in the BRCA1 or 2 genes leads to defects in DNA repair, which predisposes carriers to breast, ovarian and other cancers.
PARP, which stands for poly (ADP-ribose) polymerase, is a family of enzymes found throughout the body. The DNA within cells often breaks and PARP is needed to help a cell repair certain types of damage, including tumor cells.
According to an article published by the Dana Farber Cancer Institute, studies have shown that cells lacking PARP activity switch over to another repair mechanism that can fix breaks in both strands of DNA. This is known as homologous recombination.
“It so happens that the BRCA1 and BRCA2 genes are linchpins for this repair activity,” the article says. “If both copies of one BRCA gene are mutated in a tumor cell, the cell loses the ability to fix itself by homologous recombination. BRCA-related tumors thus must fall back on other ways to repair their DNA. But, in theory, if both BRCA and PARP mechanisms are broken, the cell dies.”
Normal cells would not be as damaged because they are not defective in the same way, the article says.
“PARP inhibitors have been approved for patients with the BRCA mutation who develop ovarian cancer, so we hope they will also be effective against breast cancer caused by the same genetic defect,” said Dr. George Zahrah, director of genetics at Norwalk Hospital,
To find out more about these and other cancer research studies at the Western Connecticut Health Network, contact Jennifer Long, APRN, at 203-852-2996.