A major breast cancer study, recently published in the prestigious New England Journal of Medicine and announced at the world’s leading meeting for oncology professionals, caught the attention of the national news media and, naturally, women, because it found that chemotherapy does not significantly improve disease-free survival rates in some women with early stage breast cancer. IU Simon Cancer Center researcher Sunil Badve, MBBS, was one of the co-authors of the study. The study’s results were announced during the 2018 annual meeting of the American Society of Clinical Oncology (ASCO). Dr. Badve, the Joshua Edwards Professor of Pathology and Laboratory Medicine and professor of medicine at IU School of Medicine, answered questions about this significant research.
Q: The findings of this research study, the Trial Assigning IndividuaLized Options for TReatment (TAILORx), are being hailed as great news for breast cancer patients. What is significant about the findings?
Dr. Badve: The most common type of early-stage breast cancer consists of tumors that express the female hormone receptor (estrogen receptor ER). The prognosis of these women can vary dramatically depending on a variety of factors such as patient age, tumor size and lymph node positivity, meaning the cancer has spread into the adjoining lymph node(s). The current study focuses on women with ER positive (ER+), lymph node negative cancers.
There are a number of tools that have been used to determine the prognosis of these women. Many, if not all, depend on research studies which have been validated using tumors removed decades ago. One of these assays, the 21-gene recurrence score (RS) assay, has been widely used for women with ER+, HER2-negative tumors. The assay categorizes tumors into three classes: those with low-, intermediate- and high-risk RS.
Prior data using this assay had provided some evidence that the major benefit of chemotherapy was observed in high RS with limited benefit in low RS group. Conversely, the major benefit of endocrine therapy was observed in the low RS group. The degree of benefit for patients in the intermediate group was unclear. The TAILORx trial was designed to understand the benefit in the Intermediate (Int-RS) group.
The trial enrolled more than 10,000 patients, of which approximately 7,000 were in the Int-RS group. These patients were randomized to chemotherapy plus endocrine therapy or endocrine therapy alone. The results of the study showed that patients receiving endocrine therapy alone had a similar disease-free and overall survival at median follow-up of nine years from the time of diagnosis. This underlines that many of these women can be spared from getting toxic chemotherapy. Additional analysis of subsets also seemed to suggest that post-menopausal women, even with slightly higher RS, could be spared from chemotherapy.
As breast cancer in the Western world is mainly a disease of post-menopausal women, the results of this trial will mean that a large number of women with breast cancer, approximately 85,000 every year, can now safely avoid chemotherapy. This is indeed a great news for women.
Q: What are some of the side effects of chemotherapy that thousands of women will now be spared, thanks to this research?
Dr. Badve: Chemotherapy is a term applied to the therapeutic use of a combination of drugs that are toxic to the cells. The goal of this type of therapy is to kill the cancer cells. However, the drugs are also toxic to normal cells. The basic hypothesis inherent to this type of therapy is that normal cells will be able to recover from the toxins but the cancer cells, because of their altered genetic structure, will not be able to recover. The toxicity of chemotherapy typically affects rapidly dividing cells. In normal individuals, the locations where these are present in large numbers are the bone marrow, gastrointestinal tract and skin. The toxicity is typically seen in the form of hair loss, diarrhea and low blood counts leading to bleeding and infections. In younger individuals, there is loss of ovarian function leading to premature menopause and infertility. Chemotherapy also affects brain function, often referred to as chemo-brain. Long-term toxicities include increased likelihood of developing blood cancers.
Avoiding chemotherapy is therefore a big deal for our patients not only because of the changes in physical appearance, including the stigma of hair loss, but also because of these other short- and long-term side effects.
Q: What is an Oncotype DX Breast Recurrence Score test? Is it routine for this test to be administered to breast cancer patients?
Dr. Badve: The diagnosis of breast cancer typically starts with the surgeon or imaging radiologists (mammographers) obtaining a needle core biopsy of the tumor. These tissues are then examined by a pathologist, such as myself, who make the diagnosis of cancer. A number of characteristics of the tumor cells are determined using a microscope and these factors are used to predict the behavior of the tumors. Advances in the last few decades have enabled analysis of genetic molecules, DNA and RNA, within the cells using several techniques. The 21-gene assay measures the RNA expression from the biopsied tissue to calculate a recurrence score. This score is a measure of the likelihood of disease-free survival in women taking endocrine therapy for five years.
Q: Were you and your colleagues surprised by the results of this study?
Dr. Badve: Retrospective analysis of patient cohorts had suggested these findings to some extent. However, when one is dealing with the lives of thousands of women every year, one has to be careful and needs hard evidence to change the standard of care.
Q: Help us better understand the significance of the study’s results. How much does this change things for physicians and their patients? It basically changes the standard of care, correct?
Dr. Badve: Absolutely! We have solid evidence now to avoid giving chemotherapy to a large number of women. The trial documented that women with low scores had excellent prognosis and those with intermediate scores do not obtain significant benefit from chemotherapy. This leaves a small group of high RS patients for whom chemotherapy will remain the standard of care. Subgroup analysis of TAILORx also suggested that there might be some benefit for chemotherapy for women 50 years or younger with hormone-receptor positive, HER2-negative, node-negative breast cancer and a Recurrence Score of greater than 15, however, additional studies are needed to confirm this. One would need to carefully weigh the benefits in this subgroup and individualize the use of chemotherapy for these young women.