NEW YORK (GenomeWeb) – A study presented at last week's San Antonio Breast Cancer Symposium has confirmed that women of all races and ethnicities can safely be treated according to the most recent analysis from the TAILORx trial, which were published by the ECOG-ACRIN Cancer Research Group in the New England Journal of Medicine in June 2018 and presented at the American Society for Clinical Oncology annual meeting in Chicago.
Based on the new analysis, the findings from the larger TAILORx trial — that chemotherapy in early-stage breast cancer can be safely avoided if patients Oncotype DX Recurrence Score result is less than 26 — hold true for women of all races or ethnicities, including Black, Hispanic and Asian individuals, a boon for Genomic Health, which sells the test.
However, alongside this positive news, the investigation also reiterated that black women with breast cancer suffer distinctly poorer outcomes than non-black women, adding new evidence that researchers hope will help them narrow down to the genetic and biological bases the reason for this disparity.
In the study, a team led by Kathy Albain, professor of medicine at Loyola University Chicago, examined outcomes among the 9,719 breast cancer patients from the TAILORx trial of whom 693 (7 percent) were black, 405 (4 percent) were Asian, and 889 (9 percent) were Hispanic.
According to Albain and her coauthors, there was no significant difference in the distribution of recurrence scores among black women versus non-black women. Average scores were also largely the same across different racial subgroups.
Similarly, the use of chemotherapy and the type of drugs used were similar for black and white study participants, as well as for Hispanic and non-Hispanic populations. And the same was true for hormone therapy.
Despite this consistency, investigators reported that after nine years of follow-up, 83.1 percent of white women were alive and cancer-free compared to only 78.9 percent of black women.
This represents a 4 percent higher absolute risk of recurrence or death. In addition, when the authors compared outcomes between black and white women, adjusting for multiple factors, they found that black women had a 39 percent higher relative risk of breast cancer recurrence and a 52 percent higher relative risk of death.
The major impact of the TAILORx analysis published in June, was a readout from women with intermediate recurrence scores — between 11 and 25. Prior to the trial, it was not clear whether doctors should use chemotherapy in this subgroup, or if it had no added value, which the new results confirmed.
Albain and colleagues also looked at outcomes for the RS 11-25 group and found that the racial disparity was even more pronounced for these women: an 80 percent higher relative risk of recurrence and a 67 percent higher relative risk of death in black women compared to white women.
Although black women with intermediate scores had such disparate outcomes, this wasn't due to differences in their treatment. In other words, the predictive nature of RS remained intact, with black women treated with chemotherapy seeing no added benefit over hormonal therapy alone.
In other words, even though the study results reveal that black women, especially in the intermediate recurrence score range, are not surviving at the same rate as non-black women, they don't reveal anything about how clinicians should treat black women differently to try to improve their outcomes.
"Not everything that we learn from clinical trials necessarily has a direct implication for clinical care for an individual patient," Joseph Sparano, one of the TAILORx investigators and a professor at the Albert Einstein College of Medicine, said this week. "In this case I think that may be the case. We can't come up with any concrete recommendations to individual patients based on this."
That said, clinicians could take away from the results a motivation to try harder to make sure that black patients with intermediate RS are getting a full benefit from their endocrine therapy, Sparano added. "Adherence is a very important issue in estrogen-receptor positive breast cancer for all women, especially for women who have recurrent scores in the mid-range because a good prognosis for the mid score range is dependent upon [that]."
Although the rates of therapy adherence in the trial weren’t different for different races, the study relied on self-reported adherence measures, "so we can't be 100 percent sure that those patients were taking the therapy," he added.
In terms of research value, the new results add to a growing recognition that there is a distinct biological contribution to racial disparities in breast cancer outcomes, ruling out one more element — the expression of certain genes as measured by OncotypeDx — as a factor in the observed inequity.
"We've ruled out all of the other factors such as lack of access to care, socioeconomic differences, socioeconomic status, more comorbidities, lack of adherence, inadequate therapy, or lack of administration of chemotherapy, or differences in recurrence score. None of those factors can explain what we saw. But this effect is consistent now in three different studies," Sparano said.
The hope is that this added confirmation in the TAILORx cohort will help emphasize the need for more research "to identify what the basis for these disparities is and not to just chalk it up to differences in access to care or treatment delivery," he added.
Some insights into this have emerged in other studies. In data presented earlier this year at the ASCO annual meeting, for example, investigators from Detroit's Henry Ford Health System and the University of California at San Francisco reported on a study of data from The Cancer Genome Atlas that looked for differences in the magnitude of somatic copy number alteration according to individuals' self-reported African-American and European-American race-ethnicity, as well as by regional chromosomal ancestry clues.
The analysis found several gene regions where African-American breast and prostate tumors had higher magnitude alterations, and it uncovered a link between the SCNA data and differential gene expression in 18 genes, including RB1 and PVT1.
In another presentation at the meeting, investigators from the National Institutes of Health, East Carolina University, and Columbia University Medical Center reported on a study of a group of racially diverse breast cancer patients from a catchment area in the northern part of eastern North Carolina.
Exome sequencing of 147 tumors in this cohort revealed differential mutational frequencies in African ancestry versus European ancestry. "Insertion/deletion mutated genes found only in African ancestry included PAX5, CYP2A7, UGT2B17, CYP4A11, ACAA1, KIT and NAT2 with high percentage of cases with mutation account, whereas those genes unique to European ancestry included GSTP1, PRSS53, AURKA, ATF1, BIRC2, PGAP3, and GSTA4," the team wrote.
But Sparano said that the genomic contribution to disparate outcomes remains poorly understood, overall. For their part, the TAILORx group is now planning to do more sophisticated molecular profiling of the tumors from patients enrolled in their trial, and other studies to add to these efforts, he said.