Author: Lei Wan
Editors: Whit Froehlich and Shweta Ramdas
My mom was diagnosed with cancer two years ago. She had early-stage breast cancer: tumor size of less than five centimeters, fewer than three cancer-positive lymph nodes in the armpit region, and no cancer-positive lymph nodes nearby. But hers was also an aggressive type of cancer. At the time, I was a graduate student in the States and my parents lived in China, so we talked on the phone every two days about the progress of her treatment. She received surgery, radiation, a tailored drug treatment, and chemotherapy. My mom is tough and stubborn. Most of the time she just mentioned the good news that the cancer had been eliminated. Occasionally, she would say that her life was changed by the cancer treatment: for example, she had to quit her job.
I was shocked by my mom’s diagnosis. She is always physically active and mostly eats vegetables. I barely recognized her after the chemotherapy. She had lost 30 pounds and all of her hair, her skin was pale, and her nails were purple. Her face was unrecognizable because of the weight and hair loss, and she looked almost 20 years older.
My mom is cancer-free now, but she is not the same person that she was. Her appetite is half of what it was before, and she cannot lift heavy things. As a graduate student studying cancer biology, I had learned that chemotherapy would cause side effects like the ones I saw in my mom, including hair loss, vomiting, and nail loss. However, until my mom’s physical appearance and life were transformed by chemotherapy, I didn’t realize the magnitude of its impact on patients. Looking at my mom, I wish that we had better options for patients with early-stage breast cancer so they don’t have to suffer these devastating side effects.
Does Every Breast Cancer Patient Need Chemotherapy?
According to Cancer Statistics, around 200,000 women are diagnosed with breast cancer in the US each year. 80% have an early-stage breast cancer. Early-stage breast patients undergo surgery to remove cancerous tissue and radiation therapy to prevent the cancer from spreading. Depending on whether three proteins that drive cancer growth—estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)—are present, patients are treated with different post-surgery therapies. If ER or PR is present, hormone therapy is used to block the function of these receptors; tamoxifen is the most widely used hormone for treatment. On the other hand, if the cancer cells are HER2-positive (meaning that HER2 protein is present), patients receive anti-HER2 treatment: trastuzumab, pertuzumab, lapatinib, or trastuzumab-emtansine.
Patients who are more likely to have recurrent cancer based on their genetics and clinicopathologic biomarkers receive chemotherapy to prevent cancer from coming back. Chemotherapy eliminates some cancer cells and reduces their spread. The common chemotherapy treatments used in breast cancer block the multiplication of rapidly dividing cells, such as cancer cells. But chemotherapy does not only kill cancer cells but also other fast-growing cells—which causes a myriad of side effects.
Among patients who receive chemotherapy, as many as 96% experience fatigue, 80% experience nausea and vomiting, and 65% experience alopecia (cancer-associated hair loss). Neutropenia (low number of neutrophils, a type of white blood cells), cardiotoxicity (toxicity that affects the heart), and cognitive dysfunction are other common side effects. As a result, quality of life of patients who receive chemotherapy can be severely affected.
Identifying Patients Who Need Chemotherapy with Biomarkers
Clearly, chemotherapy is a double-edged sword. For patients with incurable metastatic breast cancer (in which cancer cells spread to other organs) and patients who have a high risk of getting cancer again, chemotherapy significantly improves survival rate. However, in early-stage breast cancer, it’s not clear whether the benefits outweigh the risks. Surveys show that most patients are hesitant to receive chemotherapy and try to avoid it completely. Realizing this, physicians are evaluating additional tests to guide the use of chemotherapy in patients with early-stage breast cancer. Much of the focus is on tumor biomarker assays, which employ biological fingerprints to identify patients who will benefit from chemotherapy.
Breast cancer biomarker assays measure the expression of genes that are associated with breast cancer recurrence. The expression levels of these genes are then used to categorize patients into three groups: high-, medium-, and low-disease recurrence risk, which can guide physicians to identify patients who will benefit from receiving chemotherapy.
Three of the currently available biomarker assays are listed in the table below.
|Number of Genes in Test||Breast Cancer Type||Prognosis||Chemotherapy Prediction|
Lymph node negative
|Differentiate 10-year recurrence and survival rate||Guide decision on chemotherapy|
Lymph node negative
|Differentiate 10-year recurrence and survival rate||In conjunction with other factors such as age and tumor size to guide decision on chemotherapy|
|MammaPrint||70||All early-stage breast cancer||Differentiate 5-year recurrence and survival rate|
In theory, tumor biomarker assays are promising in individualizing patient treatments in clinical trials. For example, Oncotype DX is used by clinicians to guide the selection of chemotherapy in patients with ER/PR-positive, HER2-negative, and node-negative breast cancer. And recent research studies seem to support the reliability of the test in guiding the physicians’ decisions on chemotherapy—if patient’s recurrence score is low (low risk of recurrence), most of the patients do not need chemotherapy to prevent recurrence.
A Work in Progress
But Oncotype DX does not work for all breast cancer patients. And unfortunately, the reliability of the other two tests is not yet clear. Although PAM-50 and MammaPrint are approved by the Food and Drug Administration for predicting whether the cancer will come back, the two tests are yet not recommended to guide the use of chemotherapy.
According to Dr. Jacqueline Jeruss, the Director of the Michigan Medicine Breast Care Center, and Dr. Aki Morikawa, an oncologist at the University of Michigan, there is not enough clinical evidence supporting the ability of these tests to predict whether patients will benefit from chemotherapy. Because of this, patients like my mom with HER2-positive breast cancer still have to receive the traditional treatment: a combination of chemo and anti-HER2 treatment.
When asked whether PAM-50 and MammaPrint will be used to guide patient treatments in the near future, Jeruss and Morikawa said that “[It] will depend on the sufficiency of clinical evidence.” They further explained: “Studies of PAM50 and MammaPrint have to show that in early-stage breast cancer, under the guidance of these assays, patients without chemotherapy would have greater or equal survival benefits compared with chemotherapy. Moreover, physicians and patients should decide together if a biomarker assay should be conducted and if a chemotherapy is worthwhile considering the cost, benefits, and harms.”
Nevertheless, tumor biomarker assays have revolutionized our understanding of cancer biology and patient prognosis. Patient care will continue to be improved by integrating these assays with cancer prognosis and treatment, and in the future, more breast cancer patients can take advantage of the tests and avoid unnecessary side effects from chemotherapy.
About the author
Lei is a postdoctoral fellow in the Translational Oncology Program at the University of Michigan. Her research focuses on targeted therapy development and drug resistance in aggressive breast cancer. She received her PhD in Nutritional Sciences at The Ohio State University. Besides sciences, she enjoys doing ballet and yoga.
Read more by Lei here.