Dr. Susan Love Research Foundation | Breast Cancer

"Triple negative" is a term that has only begun to be widely used in the last few years.

In the mid-1980s, when it became apparent that hormone therapies only worked in tumors that were estrogen receptor (ER)-positive or progesterone receptor (PR)-positive, pathologists began to routinely test all breast tumors for their hormone status. As a result, for the past two decades, we've divided women with breast cancer into two categories: those whose could benefit from hormone therapy and those who would not.

This categorization began to change in 1998, when the FDA approved the use of Herceptin for women with metastatic breast cancer that overproduces a protein called HER2. From that point on, all women with metastatic disease also had their tumors tested for their HER2 status. The biggest change, though, occurred in 2006, when the FDA approved the use of Herceptin in the adjuvant setting (after surgery) to reduce the risk of recurrence. With this development, pathologists began to test all tumors for their HER2 status in addition to their ER and PR status.

Gradually, over the past couple of years, instead of describing a tumor as ER negative, PR-negative, and HER2-negative, we began to use the shorthand term "triple negative." This also resulted in a number of news stories about this "new" type of cancer. But it wasn't really new. It's just the use of Herceptin in the adjuvant setting led us to start thinking about these tumors in a new way.

Testing all women with early stage disease for all three receptors allowed us to learn that African-American women appear more likely to develop triple-negative tumors than women of other ethnic backgrounds. We've also found that women who carry a BRCA1 mutation typically develop these types of tumors as well. We don't yet know the biological reasons for this, but scientists are studying African-American women and women with BRCA1 mutations in an attempt to learn why.

Note: Often, the terms "triple negative" and "basal-like" are used interchangeably. But they really shouldn't be. Not all triple-negative tumors have the unique characteristics that define basal-like tumors. (They are called basal-like because these cancers begin in the basal cells that line the breast ducts.) Further, while most basal-like tumors are triple-negative, they aren't always.

Having a tumor that is HER-2 negative means you can't use or benefit from Herceptin. In general, tumors that are HER2-positive are often more aggressive than other tumor types. However, Herceptin's use in the adjuvant setting has somewhat leveled the playing field. So, while being triple-negative means you can't take Herceptin, it's actually not a bad thing in and of itself that your tumor is HER2-negative.

Having a tumor that is ER-negative and PR-negative means that you can't use or benefit from hormone therapy. This means your sole adjuvant treatment option is chemotherapy. However, research indicates that women with early stage ER-negative tumors have benefited more from new chemotherapy regimens than have women with ER-positive tumors. As one recent study published in April 2006 in the Journal of the American Medical Association found, "advances in chemotherapy have lessened the survival differences between ER-positive patients who receive hormonal therapy and ER-negative patients." As a result, women with early stage ER-negative tumors now have a prognosis nearly as good as that of women with ER-positive tumors.

In addition, a study presented at the 2006 San Antonio Breast Cancer Symposium that looked at diet and risk of recurrence, found that women with ER-negative tumors appeared to benefit more from reducing fat in their diet than did women with other types of breast cancer.

In June 2009, researchers presented data the American Society for Clinical Oncology annual meeting about a phase II trial in women investigating a new class of drugs called PARP inhibitors. PARP, or poly (ADP-ribose) polymerase, is an enzyme that repairs damaged DNA. PARP inhibitors keep cancer cells from repairing their own DNA, which can make chemotherapy and radiation more effective. In this trial,chemotherapy was given with or without a PARP inhibitor (given via IV) in women with triple negative tumors who had metastatic disease. The study found that the women who received the PARP inhibitor had a 65% less likely to have a relapse and 60% less likely to die of their disease. Both findings were statistically significant. This study also found few side effects.

The investigators are now conducting a phase III trial in women with metastatic triple negative breast cancer. It is a multi-center randomized trial that will assess the effectiveness of the PARP inhibitor (callsed BSI-201) when combined with gemcitabine and carboplatin (GC). The trial will enroll 420 patients. A randomization process will assign half of the participants to a trial arm that will receive GC and the PARP inhibitor. The other half will receive GC alone. Importantly, the trial will have a crossover provision. This means that patients randomly assiged to receive GC alone will be able to get the PARP inhibitor if their disease progresses. You can learn more about this trial here.

Researchers are also pursuing other new treatments and drug combinations You can find a full list of the clinical trials open to women with triple negative breast cancer here.