A type of breast cancer known as triple-negative breast cancer, more common among younger, African American women, is the focus of a new Detroit center. It builds on 10 years of research in Michigan and Africa and now expanding to Haiti, China and India.
Dr. Lisa Newman, a beast surgeon, directs the International Center for the Study of Breast Cancer Subtypes at the Henry Ford Health System, announced earlier this year. In an interview with medical writer Patricia Anstett, author of “Breast Cancer Surgery and Reconstruction: What’s Right for You,” by Rowman & Littlefield, Newman describes the international program, its research and the promise its work holds.
Q. Tell us about the center. Is there anything like it?
A. There is nothing quite like this. When I joined the Henry Ford Health System, the Ford system agreed to set up this center to continue and expand research I’ve been doing over the last 10 years. It looks globally at patterns of breast cancer among women with diverse backgrounds. The work started because of my interest in breast cancer disparities and the fact that there are higher mortality rates in African American women. One reason for this survival disparity is related to the fact that African American women are more likely to get cancers that are biologically aggressive, such as the triple-negative breast cancers. This issue motivated my interest in looking at women in the continent of Africa to determine whether there are some genetic or hereditary factors associated with African ancestry that might explain these patterns.
Initially these international studies were based upon a partnership with a single hospital in Ghana, but we have since expanded and collaborate with colleagues in three different Ghanaian facilities as well as a hospital in Ethiopia. We are currently in the process of bringing other colleagues on board from hospitals in Haiti, China, and India. As a center, we now are fully resourced to do this work. It’s very exciting. Our mission statement is “To reduce the global breast cancer burden through advances in research and delivery of care to diverse populations worldwide.”
Q. Is Henry Ford the sole funder?
A.The Henry Ford Health System is the primary and dominant funder but some of the research we do is sponsored by others. Because our work involves extensive investment into the breast health care needs of socioeconomically disadvantaged patients here in Michigan as well as in other parts of the country and abroad, we are constantly in need of additional funding sources and we are also dependent upon the generosity of philanthropic donors.
By looking at the breast cancer subtypes of women around the world we hope to generate a comprehensive picture of triple-negative breast cancer as well other breast cancer subtypes. This global library of information in an era of precision medicine should lead to novel therapies and improved insights regarding screening and prevention. One of our most recent grants is from the Susan G. Komen Race for the Cure, specifically for a study performing gene expression profiling and sub-typing of triple-negative breast cancers in women of all different backgrounds. So we will be studying triple-negative breast cancer sub-types in White/Caucasian American, African American, Ethiopian (representing east Africa) and Ghanaian (representing west Africa) women. We invite White/Caucasian American and African American women throughout the area to participate.
Q. Are you involved with the Susan G. Komen project in Detroit and other U.S. cities this fall to collect breast tissue samples from women?
A. The national Komen project, aimed at developing a breast tissue repository for women with diverse backgrounds and based at Indiana University, is a very exciting program. I absolutely support the participation and contributions of women to that database. This particular body of work is separate from the research that I’ve been pursuing through the International Center, and the Komen tissue bank seeks to recruit women who have not been diagnosed with breast cancer.
Q. Take me back 20 years. What did we know then about breast cancer subtypes?
A. A few decades ago, we assumed breast cancer was just one disease. We did not have insights into the separate categories of breast cancer, nor did we have treatments to target specific subtypes of breast cancer to improve survival rates.
Q. Why is that information important?
A. In clinical practice, we look for three important markers to determine treatment needs of a breast cancer patient: the estrogen receptor, the progesterone receptor and the HER2/neu marker. The tumors that are negative (lacking) for those three markers are the cancers we label as triple-negative breast cancers.
Breast cancers that are positive for either the estrogen or progesterone marker are what we call hormone-receptor-positive cancers and we have special, hormonally-active cancer-fighting pills that are very powerful in treating these types of cancers. For cancers that are positive for the HER2/neu marker, we also have effective, targeted treatments. The therapies that target these markers are all medical treatments. The vast majority of breast cancer patients will still require surgery to control the disease in the breast itself and also to address the lymph nodes or glands of the underarm area. However, many breast cancer patients, even those with early-stage disease, are at risk for having microscopic disease hidden in other parts of the body such as the liver or the lungs. Our medical treatments for breast cancer are therefore extremely important because they can get into these body organs either directly through the bloodstream or after being absorbed from the stomach and they can eliminate the threat of distant, metastatic disease. Having special targeted medical therapies for breast cancers that express one of the three basic markers has led to many more long-term survivors with these cancers.
For the triple-negative breast cancers, we can use general chemotherapy, which is non-targeted treatment that will kill any rapidly dividing cells but we really need to develop targeted treatments. We need to find specific markers that are expressed by these triple-negative breast cancers. By studying the breast cancer burden of women in Africa (where triple-negative breast cancers are much more common), we have a wonderful opportunity to improve medical care in a tragically under-resourced environment while we look for tumor markers that might be useful in treatment, and we also have exciting prospects for learning more about the genetic causes of triple-negative breast cancer as well as explanations for breast cancer disparities in the United States.
Q. How would you describe where medicine is at finding markers for triple-negative cancers?
A. We are beyond the beginning stages. We have gene expression profiling studies that can characterize triple-negative cancers. There are at least six different subtypes. There may, however, be additional subtypes and that’s why it is important to study more African American women and African women with triple-negative breast cancers. We don’t know enough about breast cancers in these women. That’s the goal of the Komen research that my group has been pursuing. Accurate subtyping of triple-negative breast cancers may help to identify patients that should be treated with anti-androgen therapy or with novel neoadjuvant/preoperative chemotherapy regimens.
Q. That’s where the story gets interesting. Women may fear triple-negative breast cancer if they are diagnosed with it. They may think, oh my gosh, I got the worse kind. But not all triple-negative breast cancers are the same, right? Some are deadlier than others?
A. Exactly. You hit the nail on the head; triple-negative breast cancers are not one single tumor type. It indeed remains essential for women to understand that early detection is extremely important for triple-negative breast cancers. If we catch a triple-negative breast cancer early, when the tumors are small and the lymph nodes are negative, then our patient is much more likely to have a good outcome with effective treatment.
Q. That brings me to a related question. I heard you speak and know you have very strong concerns that new recommendations from some national organizations to change the age during which it’s advised to get a mammogram may be particularly detrimental to women of color. Tell me more about that.
A. I personally feel, as does the entire Henry Ford Breast Oncology Program, as well as many other academic societies, that women should start getting their yearly mammograms at age 40 if they have an average risk of getting breast cancer. Women with a family history of breast or ovarian cancer, or any other indices of high risk, may need to start their mammograms at even a younger age, or they may need additional screening studies such as breast MRI.
For the average American women with average risk, she should start getting those yearly mammograms at age 40. However, mammograms are not perfect and so if a woman has any danger signs or symptoms such as a bloody nipple discharge or a new breast lump, then she should seek medical attention promptly, regardless of when she had her most recent mammogram and regardless of its result. Those of us who advocate beginning mammograms at age 40 are very fearful that recommendations where women are advised to start mammograms at later ages will be detrimental to women’s health.
Q. Are big centers like Ford saying no to these new national mammography recommendations?
A. Absolutely. The Breast Oncology Program at Henry Ford has endorsed a position statement supporting yearly mammograms beginning at age forty. We care for a large and diverse patient populations, where approximately one-third of our breast cancer patients are African American and so we see many cases of triple-negative breast cancer; we also see many women with premenopausal breast cancer, since African American women are also more likely to be diagnosed with breast cancer at young ages. We feel that it is imperative to protect our patient population with an aggressive approach to screening mammography. Prior to assuming my current position with the Henry Ford Health System in December 2015, I served as Director of the Breast Care Center for the University of Michigan for thirteen years, and the U-M Cancer Center also advocated in favor of yearly mammograms for women beginning at age 40. The National Comprehensive Cancer Network continues to say women should have mammograms starting at age 40. The American Cancer Society says mammography is a must by the time a woman reaches age 45 but they also say that women should have access to yearly mammograms beginning at age 40.
Q. If you have been told you have a triple-negative breast tumor, what do you need to do next? Are there tests you want to ask for? What are the steps you would recommend for a woman with that diagnosis?
A. A woman needs to be sure she is being cared for by a good, multidisciplinary breast oncology team and program because management of triple-negative breast cancer will often involve multiple modalities, almost always including surgery. The extent of the surgery depends on the size of the patient’s cancer, her breast size, her body habitus, and very importantly, the surgical plan should also account for the patient’s personal preferences regarding the choice of mastectomy versus lumpectomy. Successful treatment of triple negative breast cancer will often involve chemotherapy and radiation. Radiation is almost always necessary for the lumpectomy patients. The multi-disciplinary team includes doctors in surgical oncology, medical breast oncology and radiation breast oncology. A radiology breast specialist or imager is key so that the tumor and both breasts can be carefully characterized. An experienced breast pathologist also is essential so that the tumor biopsy material and surgical specimens can be comprehensively evaluated. The entire team is critical, and this team should work together in real-time, so that each patient’s treatment is coordinated with a standardized approach throughout the continuum of her care.
Having a triple-negative breast cancer is also a red flag that a woman might have inherited predisposition for breast cancer. Most triple-negative breast cancer patients will be referred to undergo genetic counseling and testing, regardless of whether there is any family history of breast or ovarian cancer.
Q. Do many of these women end up finding out they have a BRCA mutation?
Q. You have found there are populations in different countries within Africa that have different rates of women with triple-negative breast cancers. Why is that? You have said migration patterns are one of the reasons. What would rates differ among African women within one continent?
A. There are fascinating patterns. Most of our work has focused on West Africa in hospitals where we found that more than half of the breast cancer patients have triple-negative tumors. More recently we have been looking at breast cancer in Ethiopia, representing East Africa. It turns out that in the work we’ve done so far, the frequency of triple-negative breast cancers in Ethiopia is similar to the frequency of triple-negative cancers seen in White/Caucasian American women and in Europe, where only about 15% of tumors are triple-negative breast cancers.
Our theory is that forced population migration patterns through the slave trade, genetics, and shared ancestry provide an explanation for these various triple-negative breast cancer patterns. The colonial era trans-Atlantic slave trade largely brought sub-Saharan west Africans to the United States, and consequently there is a substantial degree of shared ancestry between African American women and western sub-Saharan African women (including Ghanaians). For east Africa (including Ethiopia), however, the slave trade more commonly resulted in forced migration eastward, toward Asian countries. African American women therefore tend to have less shared ancestry with east African women compared to west African women. We speculate that this explains the similarities in the breast cancer burden of western sub-Saharan African women and African American women, but differences compared to east African breast cancer patients.
Q. Are there special issues for women in countries who don’t have good access to genetic testing, as well as breast cancer treatments like radiation?
A. Yes. We see horrendously heart-breaking cases of breast cancer in Africa. The majority of women present with very advanced stages of disease. The ability to test for the various markers that we use routinely in the United States (the estrogen and progesterone receptors and the HER2/neu marker) is largely unavailable in most of the hospitals in Africa where these women are receiving care. This is an example of the importance of programs such as our international center. By pursuing this research, we’ve actually been able to establish programs in the hospitals where we work so that physicians can obtain this molecular marker information. This testing improves their ability to treat breast cancers more appropriately and more effectively. So it’s been very exciting work, and very, very gratifying.
Q. Is there tremendous stigma in these countries because too often cancer is diagnosed late when it’s more deadly?
A. Yes. There are marital issues where women are concerned about being ostracized by their families because of a breast cancer diagnosis. Many women earn their living and support their families by being traders and selling their goods in public markets or on the roadsides. They often fear that being disfigured or having arm mobility problems following breast cancer surgery will place them at a disadvantage in being able to work and earn a living.
Q. So what haven’t I asked? What else do you want to add?
A. I am so excited that Henry Ford leadership invested in creating this international breast cancer research center. It promises to be incredibly powerful in terms of adding to our breast cancer research base; it will be valuable in improving health care in many low and middle-income countries. And it’s incredibly gratifying in terms of the academic exchange process_ being able to bring our colleagues from Africa here to Michigan to learn about advances in patterns of breast cancer diagnosis as well as treatment, and being able to take our trainees to Africa to see how medicine is practiced in different cultures and environments with extremely limited resources. These experiences improve our perspective and make all of us better physicians.
Q. And hopefully it will improve treatment everywhere for women with triple-negative disease.
A. I have no doubt that this will be part of the promise.