The use of chemotherapy to treat women with early-stage breast cancer “declined markedly over time,” according to analysis of data from 2,926 women between the ages of 20 and 79. The trends documented “are remarkable for their steepness of decline, independent of clinical factors and despite no major change in the evidence base over the study period,” 2013 to 2015, the study authors reported in the Journal of the National Cancer Institute.1
It is interesting to see the picture of how doctors use both objective and genomic evidence—but also what patients want—to make a decision [about recommending chemotherapy].— Allison W. Kurian, MD, MSc
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The overall decline in the use of chemotherapy was more than 13 percentage points, from 34.5% to 21.3% (P < .001). “As a practicing breast oncologist, I had the sense there has been this trend, but it really was a significant drop within 2 years, going from more than one-third to about one-fifth. That is a pretty big change over that relatively short period,” the study’s lead author, Allison W. Kurian, MD, MSc, said in an interview with The ASCO Post. Dr. Kurian is Associate Professor of Medicine and Health Research and
Policy at Stanford University School of Medicine, California. The study was co-led by Steven J. Katz, MD, MPH (the senior author), at the University of Michigan, and included co-investigators at -Emory University and the University of Southern California.
Optional Chemotherapy
The study was limited to patients with stage I or II estrogen receptor–positive, HER2-negative breast cancer. “Patients with stage 0 disease were excluded because they were not eligible for treatment with chemotherapy,” the authors explained.
“For this study, we were interested in patients for whom chemotherapy may well be optional,” Dr. Kurian added. “With HER2-positive or triple-negative breast cancer, that is usually not the case. It is in the group with estrogen receptor–positive, HER2-negative disease where there is uncertainty about whether chemo is needed.”
Surveillance, Epidemiology, and End Results (SEER) data from Georgia and Los Angeles County in California were used for the study. “We wanted it to be population-based, so it would represent people across all different types of health-care systems and economic gradients,” Dr. Kurian revealed. Those two areas “are ethnically diverse and in slightly different ways, so we thought we could get a representative population-based picture.” The SEER data were merged with responses to surveys sent to patients approximately 3 months after surgery.
Similar Trends
More than 85% of the patients had node-negative cancer or micrometastases. Among these women, the decline in the proportion receiving chemotherapy was 12.5%, just slightly less than the overall decline, with 14.1% reporting receiving chemotherapy by the end of the study period in 2015.
The decline in the use of chemotherapy was greater for node-positive patients, 16.9%, although the overall percentage expectedly remains high, at 64.2%. “The shape of the curve is very similar. The trends were very similar,” Dr. Kurian said. “It is just that they started at a higher level because more often they should get chemotherapy.”
Recurrence Scores
Previous studies had documented a decline in use of chemotherapy for early-stage breast cancer with an increasing use of the 21-gene recurrence score. The authors noted, “Guidelines stipulate recurrence score as the only assay validated to predict chemotherapy response.”
Steven J. Katz, MD, MPH
Slightly more than half of the patients in the study with node-negative/micrometastatic disease received genomic testing with the 21-gene recurrence score, with a slow increase over time from 52.1% to 54.3%. “By contrast, during the same time period, recurrence score testing in patients with node-positive disease increased from 26.1% to 42.7%,” the authors stated. They estimated that the changing rate of recurrence score use accounted for about one-third of the decline in chemotherapy use among node-positive patients.
“We were surprised. We thought more of it might be due to the increasing use of the recurrence score, but a full two-thirds was not explained by that,” Dr. Kurian acknowledged.
“We weren’t able to drill down on exactly why. But we were able to do some work looking at how doctors make decisions. We gave them some scenarios, saying, if you had this patient, what would you do?”
Oncologists’ Recommendations
The scenarios were outlined in surveys completed by 304 oncologists. Responses showed that although few would recommend chemotherapy for patients with a favorable prognosis scenario, more than two-thirds of the oncologists would order a genomic test before making the decision, and virtually all would recommend chemotherapy if the genomic profiling predicted a high risk of distant recurrence.
Presented with a less favorable prognosis scenario, almost all the oncologists would recommend chemotherapy, although they were somewhat less likely to recommend chemotherapy and much more likely to order a genomic test for patients who wanted to avoid chemotherapy. The oncologists were much less likely to recommend chemotherapy if the recurrence score predicted a low risk of recurrence.
“Our results suggest that oncologists use tumor genomic profiling to adjudicate mismatch between patient preference and practice guidelines,” the authors wrote. “Oncologists were much more likely to order [a genomic test] if patient preferences were discordant with their recommendations” and to adjust their recommendations based on patient preferences and the recurrence score. Oncologists’ perspectives on chemotherapy recommendations elicited independently “generally adhered to practice guidelines yet also reflect a willingness to be responsive to patient desires.”
No Evidence of Disconnect
“It is interesting to see the picture of how doctors use both objective and genomic evidence—but also what patients want—to make a decision. If the patient said, I don’t want chemotherapy, that would push them more toward ordering a genetic test and reduce their recommendation strength. And if both the test and the patient were against chemotherapy, they were much less likely to recommend chemotherapy,” Dr. Kurian commented.
“When you look at the trends of what actually happened in terms of chemotherapy receipt, and then you look at what patients say their oncologists told them, the trends are very similar,” Dr. Kurian said. According to patients’ reports, oncologists’ recommendations declined by 13.3 percentage points (from 44.9% to 3l.6%) during the study period. “The recommendations for chemotherapy are going along with the trend” for actual use of chemotherapy, Dr. Kurian observed. “So maybe the oncologists are recommending it and the patients are agreeing. Or, the patients come in and say, this is what I want, and the oncologists say, I agree with you. But we aren’t seeing evidence of a disconnect.”
“It really is a change in the way doctors are interpreting data. I think they interpreted the same data differently in 2013 than in 2015 in terms of, should I treat this person with chemotherapy? I suspect this likely also could be driven by or contributed to by patient preferences. There has been kind of a cultural shift in the way people think about treatment and overtreatment.”
‘Overshooting the Mark’
“The trends we document are remarkable for their steepness of decline, independent of clinical factors and despite no major change in the evidence base over the study period. This result represents an evolution of clinical oncology culture driven by oncologists’ appropriate concerns about overtreatment in this generally favorable-prognosis population,” the authors concluded. “However, a lingering concern is oncologists may be overshooting the mark in patients with a less-favorable prognosis, especially if pending trials do not support that genomic testing algorithms are equally predictive in node-positive vs node-negative disease. Thus, the results of pending clinical trials will be essential to confirm the rationale of this approach to treatment.”
Most of the data supporting the use of the 21-gene recurrence score comes from node-negative patients, Dr. Kurian explained, with only limited data on node-positive patients. “The ongoing RxPONDER trial is going to give us data on node-positive patients, and it is possible it won’t be as predictive.” That would impact the use of genomic testing, she added, “because doctors are motivated by the science and want to do what is proven to work.”
“It is both understandable and easier for most oncologists to err on the side of overtreatment than undertreatment,” Philip D. Poorvu, MD, and Eric P. Winer, MD, FASCO, of the Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, wrote in an accompanying editorial.2 “As clinicians, we fear omitting a therapy that could be lifesaving, but benefits and toxicities must be balanced. Clinical trials such as TAILORx and RxPONDER will likely identify patient populations that can safely forgo chemotherapy. For those who do still receive chemotherapy, recent data support limiting anthracyclines to women with higher-risk features, thus reducing long-term complications.” ■
DISCLOSURE: Drs. Kurian and Winer reported no conflicts of interest.
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