In this two-part series presented in conjunction with Triple-Negative Breast Cancer Day (March 3, 2015) we are sharing a conversation with BCRF grantee, Dr. Funmi Olopade, on what we’ve learned about the causes of triple-negative breast cancer (TNBC), how we treat it today and prospects for new therapies in the future. The first part of the Q&A can be found here.
Part II: Treating TNBC
BCRF: What should a woman diagnosed today know about TNBC?
FO: We always hear about how bad TNBC is and a diagnosis of TNBC raises a woman’s anxiety, but I’ve been trying to change how I speak to my patients about this disease. The reason we say it is aggressive is because we don’t have a targeted therapy to treat or prevent it like we do for other types of breast cancers that can be treated with tamoxifen or Herceptin®. While it’s true that TNBC is a very aggressive disease, this type of cancer is also very likely to respond to chemotherapy.
One of the first questions our group asked when we started studying TNBC was who was surviving and who was not. Very early on, we did a retrospective analysis and found that women with TNBC whose cancer responded to chemotherapy, did very well, and for about 50% of patients the cancer never came back. This finding was supported by subsequent studies that have shown that if a woman with TNBC responds to chemotherapy and doesn’t relapse within the first five years, she has a really good chance of being cured.
So while it is daunting to hear that you have TNBC, ongoing research supported by BCRF and others should give hope to patients with TNBC that: 1) if you respond to chemotherapy, your cancer may never come back; and 2) for women with metastatic TNBC, there are clinical trials available testing new drugs that may be effective against their cancer.
So, yes, it is an aggressive disease, but chemotherapy can be very effective and oncologists such as BCRF’s scientific director, Larry Norton, have dedicated their careers to learning how to use chemotherapy most efficiently to achieve the best outcomes for their patients. I think our biggest challenge right now is predicting who will respond and who will not before we treat with chemotherapy.
BCRF: Are we making progress on targeted therapies for TNBC or in identifying biomarkers that will help us to know which women are likely to benefit from chemotherapy?
FO: Yes. For example, since the discovery of BRCA1, we know now that there is something wrong with the DNA repair process in TNBC, and several drugs targeting DNA repair pathways are being tested in clinical trials for women who have a BRCA1-like breast cancer, including TNBC. We’re trying to develop biomarkers to identify women who have a complete response to these drugs so what we know how to treat women with this disease in the future.
In the past we’ve just treated every cancer the same way, but I think in the next few years, especially with our ability to explore not only how the genes and proteins in a tumor may be driving its growth, but also other cellular processes, such as tumor metabolism–we will identify novel biomarkers, so we no longer have to give drugs to women who will not respond to them.
That’s really how we will get to precision medicine. Right now we have an opportunity to develop new drugs and new approaches that will change how we treat TNBC. I’m optimistic about the future for TNBC patients.
There is also increasing emphasis on prevention and I’m really excited about the work BCRF is funding to look for biomarkers of risk so we can identify women before they get cancer.
BCRF: Are there racial differences in incidence and outcomes of TNBC?
FO: We know that Black women are less likely to be diagnosed with early stage breast cancer and are more likely to get TNBC which often has already spread by the time it’s detected through regular screening. Now that we know that BRCA1 mutation causes TNBC, we are developing better treatments and prevention strategies. We can now test for the BRCA1 mutation in all populations to identify women at risk.
The question remains whether there are other gene mutations that we just haven’t discovered yet that increase the risk of TNBC and whether there are population differences. We are only beginning to study other populations, such as Hispanic and Asian groups, to know whether specific mutations are driving TNBC here, too. Through BCRF’s collaborative network of researchers we are accelerating the research globally to better understand the differences in genes and how they may work across populations. It’s the global collaboration working across cultures and ethnicities that will lead to the end of TNBC everywhere.
But addressing disparities in TNBC across ethnicities is more complicated than just understanding genetic risk. Women have to have access to the critical preventive care once they know their risk. In 1997, our group published one of the first studies describing BRCA1 mutations in nine African American families from our high risk clinic. These families all had a high rate of breast and/or ovarian cancer and sometimes other cancers. We discovered three BRCA1 mutations that were unique to African Americans. We thought that study would be a game changer for this community by identifying a genetic link to the high rate of breast cancer. Unfortunately there are significant barriers for many of these women in getting the screening and care they need, be it a lack insurance, limited access to care, cultural barriers or mistrust of the medical community. We’re making progress in addressing these issues, but much work still needs to be done.
BCRF: What’s the biggest challenge that women with TNBC face?
FO: The patients I see fit into two categories and they each face unique challenges.
The first group is the young women who were not expecting to get cancer. Their lives are suddenly fundamentally changed. Many of them were not aware of their risk. They haven’t been thinking about screening or maybe didn’t have access to screening, so when they come into our clinic they already have advanced cancers, and fewer treatment options are available to them. We need to do a better job of identifying this group and, once we identify them, getting them into treatment quickly. These cancers grow very fast and barriers such as denial and concerns about fertility and inadequate care prevent these women from getting the treatment they need. I feel a particular sense of urgency when a young woman is diagnosed with TNBC. We need to mobilize support around her so she can get treatment immediately, and young women in particular need that kind of support. In many cases they are just starting a family or want to have a family in the future, they may be at the height of their careers and they were not expecting to get cancer.
The other group is older women who have been getting regular mammograms and all of a sudden are diagnosed with advanced TNBC. We know that some women with a high risk of breast cancer, including women with BRCA1 mutations, can live cancer-free into their 60s, and for these women mammography is not the best screening.
The conventional view of breast cancer, which is based on studies in white women predominantly of European descent, is that it starts as DCIS, a non-invasive precursor that may or may not become invasive cancer, but that this process will take time. When DCIS is detected in a regular screening mammogram it can be removed to prevent it from becoming an invasive cancer. However, we know that this scenario isn’t true for all breast cancers and that some cancers may have already metastasized (spread) when they are detected, even if the tumors are very small. And this can be the case for women who have a BRCA1 mutation or other high risk factor and don’t know it.
There’s a lot of work being done now to identify markers that can better assess risk. We need to identify women who need more aggressive screening vs. those who will do well with regular mammograms. That research must be done and must be done urgently because right now we rely on age when assessing risk for TNBC, but age is not always predictive. There may be lifestyle or environmental factors that we have not identified yet that help to define individual risk and therefore delay cancer detection. These are questions we should begin asking with the very first mammogram or even earlier.
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