Looking for the basics on Triple Negative Breast Cancer and other types of breast cancer? Start here.
A breast cancer diagnosis of "triple negative" can leave you—as it did me—feeling helpless and clueless. The received wisdom is that Triple Negative breast cancer (TNBC) is a particularly threatening cancer type for which there is seldom a good outcome. But as usual, received wisdom is not the whole truth.
The following basic facts about TNBC are selected to help you or a loved-one banish the helpless-clueless feeling and deal effectively with your doctors.
WHAT DOES TRIPLE NEGATIVE BREAST CANCER MEAN?
"Triple Negative" refers to the genetic make-up of a breast tumor. TNBC has few genes relating to estrogen receptors (ER), few genes relating to progesterone receptors (PR), and few genes relating to human epidermal growth factor receptor-2 (HER2). Only about 10-15% of breast cancers are Triple Negative.
Triple Negative tumors are defined by molecular biology: a tumor tissue sample is examined using a special fluorescent laboratory technique called an assay, and its entire gene structure is arrayed. The assay shows which of several types of breast cancer the particular tumor belongs to.
Some TNBC is basal-like. Basal-like tumors are aggressive and are thought by scientists to be "source" cells for cancers. But not all basal-like breast cancers are TN, and not all TNBC are basal-like. Fifteen to forty percent of basal-like breast cancers are not TN, and about ten percent of TNBC are not basal-like. Still, you may find your doctor using these terms interchangeably, so it's a good idea to ask for clarification. Cancers that are both TN and basal-like are most likely to be highly aggressive.
TNBC tumors are also classified into four stages on the basis of size and lymph-node involvement. Stage I means that the tumor is less than 2 cm in size and there is no lymph node involvement. Stages II and III indicate larger size and degrees of lymph node involvement. Stage IV means that metastasis has already occurred.
Microscopic examination of tissue (histology) yields information on rate of cancer growth. Most TNBC tumors are Grade III, relatively fast growing. TNBC generally reveals high levels of factors that regulate tumor cell growth and spread, e.g. Ki-67 antigen and p53 oncoprotein.
See the strategies one woman used to get herself through her diagnosis of triple negative breast cancer.
IS TNBC A "WORSE" TYPE OF BREAST CANCER?
TNBC has a high and rapidly rising risk of relapse within two years of diagnosis—a "worse" short-term prognosis compared to other, hormone-positive cancers.
On the other hand, two years after diagnosis, the risk of relapse falls rapidly, and continues to fall—a "good" longer-term prognosis. In fact, after year 5 the risk of recurrence begins to approach that of other breast cancers and after year 7 the risk of recurrence actually falls below that of other breast cancers.
Differences in prognosis depend on response to treatments. Chemotherapy is more effective with TNBC than with breast cancers that are estrogen receptor positive. TNBC patients benefit particularly from adjuvant chemotherapy (given after surgery).
Many doctors recommend radiation after chemotherapy and surgery, in hopes of killing any cancer cells developing in the diagnosed breast.
For locally recurrent or metastatic TNBC, current treatments are more limited than treatments for estrogen-dependent breast cancer. TNBC does not respond to hormonal therapies, such as may be given for many years to manage hormone-dependent breast cancers.
In some instances, neo-adjuvant (pre-surgery) chemotherapy is also effective against TNBC.
WHO GETS TNBC?
TNBC clusters in certain population groups. Research on large populations has shown that young women are more likely to have TNBC than older women. African American Women are much more likely to have TNBC than non-African Americans in the same age group. Concentrations of TNBC have also been found among Ashkenazi Jews.
One cause of clustering among certain ethnic groups is an inherited genetic mutation called BRCA1. This mutation is often found in basal-like TNBC. Its presence has been most thoroughly studied in relation to African-American women.*
Many patients diagnosed with TNBC fear they carry the BRCA1 mutation, but in fact, most do not. Women with particular disease and history profiles, such as early age of diagnosis, and many breast cancers in the family, are most likely to have BRCA1.
Such women are likely candidates for BRCA1 testing. Having the BRCA1 genetic test means having to make choices about what to do if BRCA1 is found. For example, the patient may choose double mastectomy and/or removal of her ovaries to help prevent contralateral breast cancer and/or metastasis to the ovaries.
If a patient tests positive for BRCA1, her sisters and daughters are generally tested for the mutation as well. They too must consider preventive measures such as mastectomy or removal of ovaries. Genetic counselors can help each individual make this decision, and your doctor can help you find a counselor.
WHAT SPECIFIC CHEMOTHERAPIES WILL BE OFFERED?
The three most common standard chemotherapies used today after surgery for TNBC are
- anthracycline and taxane in combination.
In simplest terms, CMF (a combination of three drugs: cyclophosphamide, methotrexate and fluorouracil) and taxanes (paclitaxel and docetaxel) are aimed directly at the cell division process.
Taxanes have been shown to be more effective in combination with anthracycline than when used alone. Anthracyline is an antibiotic that causes cells to die by damaging DNA in the cell. Statistically, the efficacy of anthracyline combined with taxane is about 4 percentage points higher than the efficacy of CMF. However, this regime is also more toxic than CMF. Most importantly, anthracycline has potential heart toxicity; CMF does not. Most clinicians regularly include anthracyclines in their tool kit. But some patient advocates question whether anthracycline improves overall survival enough to justify its toxic threats.
Each patient should choose her chemotherapy after full discussion, with her doctor, of efficacy, future risk reduction, and toxicity. Everyone should always bear in mind that statistics describe occurrence in a large group of patients and do not necessarily apply to a particular individual.
Watch the webinar "Developments in the Treatment of Metastatic Triple Negative Breast Cancer"
WHAT DOES RECURRENT TNBC LOOK LIKE?
One of the reasons for difficulty in treating recurrent TNBC is that new tumors may not be molecularly identical to original tumors. Should this happen, a person should not jump to the conclusion that her original diagnosis was wrong. She should make sure that her doctor knows about her first, TNBC diagnosis and understands its significance for treatment of the recurrent breast cancer.
WHAT NEW TREATMENTS ARE ON THE HORIZON?
Recently new drugs have been introduced to treat locally recurrent or metastatic TNBC. Some agents are in Phase III clinical trials that test on patients randomly assigned to different treatment groups the efficacy for progression free survival and/or overall survival. Phase III trials also evaluate toxicity of treatment combinations. Different drugs are targeted to different processes in the growth and spread of cancer.
Bevacizumab is one widely tested drug. Bevacizumab (e.g. Avastin) targets angiogenesis, the process by which external blood cells are recruited to spread cancers. Among several Phase III trials are:
- Beatrice Trial. This trial is underway. It tests bevacizumab in combination with standard adjuvant chemotherapy.
- ECOG E5103 Trial. This trial is underway. It studies adjuvant chemotherapy with or without bevacizumab.
Many other trials are targeted to TNBC, but most of them are relatively small. CALGB 40603 is a large, nationwide Trial for TNBC only, using multiple drugs including taxanes, platinum, and bevacizumab, for neoadjuvant (pre-surgery) chemotherapy on large tumors. +
Academic and pharmaceutical researchers are in early stage exploration of many additional treatment options relating to TNBC. The numerous targets chosen for research may be cell division and growth behavior processes; changes in the area surrounding the tumor (stroma); the vascular system; damage or repair of DNA; pathways that signal changes in cancer cell behavior; proteins, kinases or enzymes, and more. Some studies test new agents, some test new treatments for known agents. Such research is only newly focused on TNBC. While the research is of interest, the likelihood that it will lead to generally accepted radical changes in clinical practice in the near future is not high.
Nevertheless one avenue of exploration that may have a clinical pay-off in the mid-term is PARP inhibitors for patients having BRCA1. PARP is an acronym for a nuclear enzyme within cells that directs repair of certain types of damaged DNA. PARP is a broad target for many diseases, including ovarian cancer.#
WHAT POST-TREATMENT FOLLOW-UPS ARE NEEDED?
Follow-up mammograms, MRIs and sonograms are recommended if TNBC is not metastatic. These scans are usually performed twice a year for the first few years, then once a year. Radiation oncologists and medical oncologists advise on these choices and combinations of image types.
Metastatic survivors should discuss emerging treatment protocols and clinical trials with a breast oncologist.
*For more detail on population studies, and treatment too, search out the work of Lisa Carey M.D., Ass. Prof. Hematology-oncology, University of North Carolin
+Information on Phase III Clinical trials can be found on the website http://clinicaltrials.gov, or from your doctor.
By Gail Garfield Schwartz