Triple negative breast cancer accounts for about 15 percent of all new breast cancer cases in the U.S., but it leads to 25 percent of all breast cancer deaths. A diagnosis of triple negative breast cancer means that the three most common types of receptors known to fuel most breast cancer growth are not present in the cancer tumor. It’s an aggressive cancer that—until now—has only been treated with standard chemo. Now, a new therapy is offering patients hope for the first time.
Brenda Beguin‘s little dog, Cody, is always by her side.
“He takes care of me,” Brenda told Ivanhoe.
She’s needed the support. Eight years ago, she was diagnosed with an aggressive breast cancer. Three years ago, it came back.
“My doctor actually told my daughter and I, ‘instead of doing chemotherapy, you probably should just do the most that you can with the life that you have,’” Brenda said.
However, Brenda didn’t listen. She enrolled in a clinical trial testing new therapies for triple negative cancer.
“Right now, the only treatment we have for triple negative breast cancer is chemotherapy,” Julie R. Gralow, MD, Director, Breast Medical Oncology, Seattle Cancer Care Alliance, told Ivanhoe.
Doctors are now studying PARP inhibitors to prevent cancer cells from becoming resistant to chemo.
“It affects the ability of the tumor cell to heal itself after getting chemotherapy,” Dr. Gralow said.
One other study found triple negative patients with advanced cancer who took the drugs with chemo survived about five months longer than those who received chemo only, with very few side effects.
Today, Brenda only takes the PARP drug.
“I feel it has saved my life,” Brenda said.
Dr. Gralow says one downside of the PARP inhibitors is they are very expensive. While still in clinical trials, she estimates they might cost between 2,000 and 10,000 dollars a month, if they hit the market.
The next step for this research is a larger clinical trial that will test the drug on more patients. During the clinical trial, patients get the drug for free.
BACKGROUND: About 10 to 20 percent of breast cancers—more than one out of every 10—are found to be triple negative. Triple negative breast cancer (TNBC) is a cancer that tests negative for estrogen receptors, HER2, and progesterone receptors. If a woman is to test negative for all three factors, than she has triple-negative breast cancer, meaning that the patient will not respond to hormonal therapy or treatments that target HER2 receptors. Triple negative breast cancer is more often seen in African American women, Hispanic/Latina women, and younger women. Triple negative breast cancer is also more aggressive than most cancers and it is less likely to be seen on a mammogram. This cancer is known to be reoccurring and it is more likely to spread to other parts of the body. (Source: http://www.breastcancer.org/symptoms/diagnosis/trip_neg and http://ww5.komen.org/uploadedFiles/Content_Binaries/KOMEED079100.pdf)
TREATMENT: TNBC is treated with a combination of surgery, radiation, and chemotherapy. Since it tests negative for the three receptors, it isn’t treated with hormone or targeted therapy. If the cancer is caught early enough, it can be treated. Chemotherapy works well in TNBC. It may work even better for TNBC than for other types of breast cancer. (Source: http://ww5.komen.org/uploadedFiles/Content_Binaries/KOMEED079100.pdf
NEW THERAPY: PARP inhibitors, also known as poly ADP-ribose polymerase, are now being studied to treat patients with triple negative breast cancer. One study in 2011 found that the PARP inhibitor boosted overall survival to a median 12.3 months compared with 7.7 months with chemotherapy alone, according to Joyce O’Shaughnessy, MD, of Baylor Sammons Cancer Center in Dallas. Patients on the drug showed similar gains in objective response, clinical benefit, and progression-free survival, with no significant difference in adverse events in the open-label phase II trial. Normal cells favor a BRCA ½-dependant process to repair double-strand breaks in DNA, which are caused by radiation and some chemotherapy. Although patients with BRAC1 or BRCA2 mutations have one functional allele that keeps this mechanism in play for normal cells, cancer cells usually inactivate that allele (allele is one or two more versions of a gene). PARP inhibitors exploit that vulnerability by keeping double-strand breaks from being repaired in cells without the BRCA repair function. Triple negative tumors share characteristics with BRCA1 breast tumors and may have other genetic lesions that impair double-strand repair. However, researchers say to use caution. This trial included only 123 patients with metastatic breast cancer negative for estrogen receptor (ER), progesterone receptor (PR), and HER2 overexpression, which is a small cohort. (Source: http://www.medpagetoday.com/HematologyOncology/BreastCancer/24195)
Julie R. Gralow, MD, Director, Breast Medical Oncology, Seattle Cancer Care Alliance, talks about a new therapy for aggressive breast cancer.
When you’re diagnosed with breast cancer, one more, it’s just not one disease at all?
Dr. Gralow: Well, right now, we are thinking of breast cancer as 4 or 5 different subtypes, but the fact of the matter is the harder you look, the more you find that every single breast cancer is unique if you look at enough genes. It’s an exciting time with all the genomic profiling going on, but it’s actually getting more complicated. Breast cancer is not just one type.
Can you explain what triple negative breast cancer is?
Dr. Gralow: Triple negative is slang for a breast cancer that doesn’t stain positive for estrogen receptor, progesterone receptor and the HER2 receptor. Those are the three main things we look at when we first diagnose a breast cancer in order to help determine treatment options. With that being said, triple negative means it’s negative for all three of those things, but it’s actually really frustrating to define a subset of breast cancer by what it isn’t instead of what it is.
Does that make that harder to treat?
Dr. Gralow: Well, right now, the only treatment we have for triple negative breast cancer is chemotherapy. Estrogen receptor positive breast cancer we can treat with anti-estrogen therapies. HER2 positive breast cancer we can treat with really excellent HER2 targeted therapies, but triple negative because we don’t know what it’s positive for, is just treated with chemo right now.