In an interview with Targeted Oncology, Ann H. Partridge, MD, MPH, discussed the response to neoadjuvant chemotherapy among patients with ER-positive, HER2-negative breast cancer and how the 21-gene Breast Recurrence Score aids in the prediction of response for this treatment.
Neoadjuvant chemotherapy is vital for young patients with estrogen receptor (ER)-positive, HER2-negative breast cancer as their characteristics usually include large tumors and more lymph node involvement, according to a poster presentation. A 21-gene assay, Breast Recurrence Score, has previously demonstrated the ability to predict the benefit of adjuvant chemotherapy in this patient population. A group of researchers, therefore, set out to explore the assay’s ability to predict benefit to neoadjuvant chemotherapy.
Results from the analysis were recently presented during the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program showing low to intermediate risk in young patients with high-risk ER-positive, HER2-negative disease, and pathological complete responses (PCRs) among patients with high Recurrence Score results.
Of the 76 women enrolled in the cohort, specimens for 71 patients were retrospectively assessed for genomic expression. The mean recurrence score observed was 51.9% for patients who achieved a PCR compared with 26.6% for those who did not achieve a PCR (P =.0005). The PCR rate among patients who had a Recurrence Score of greater than 25 was 21% compared with 5% among patients with a Recurrence Score of less than 25.
In an interview with Targeted Oncology, Ann H. Partridge, MD, MPH, vice chair of Medical Oncology, founder and director of the Program for Young women with Breast Cancer, and senior physician at Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, discussed the response to neoadjuvant chemotherapy among patients with ER-positive, HER2-negative breast cancer and how the 21-gene Breast Recurrence Score aids in the prediction of response for this treatment.
TARGETED ONCOLOGY: How was the 21-gene Breast Recurrence Score was previously utilized in this space?
Partridge: Historically, we've increasingly used genomic expression prediction assays, such as the 21-gene Breast Recurrence Score test, to help us to decide their value or the lack thereof. What we're learning is that these tests can be very predictive of the benefits of chemotherapy or lack thereof. Now, there are good perspective data for use of these assays in the setting, particularly for women who have node-negative hormone receptor (HR)-positive breast cancer. [It’s helpful for oncologists treating] patients with lower-risk, hormone-sensitive cancer and trying to decide if chemotherapy is worth it.
Nowadays, though, we recognize that tests like this can help us to predict the value of chemotherapy.
TARGETED ONCOLOGY: Are there any other data investigation recurrence score prior to the study you presented at ASCO?
Partridge: There have been a handful of other studies that have looked at the relationship between genomic expression, prediction tests and preoperative therapy and response. They're kind of a mixed bag but tend to lean in the direction of the genomic expression prediction assays, including Oncotype, predicting response to neoadjuvant therapy, particularly chemotherapy.
TARGETED ONCOLOGY: What was the rationale for the study that you presented at ASCO?
Partridge: The rationale for our work was to look at women aged 40 and under
who received neoadjuvant therapy for hormone-sensitive breast cancer. Women were only selected by the fact that they were in a study of ours from which data were collected prospectively.
We were able to get a pretreatment specimen from most patients, and then we were able to look at their response to that neoadjuvant therapy. Not surprisingly, it was consistent with all of the other data that we have from the recurrence. That suggests that the Oncotype score can help us to predict response to therapy. At a lower score, patients are less likely to have a response to chemotherapy, and at a higher score, they more likely to get a very robust response.
TARGETED ONCOLOGY: Can you discuss the methods used to perform this analysis, as wells as the patients population?
Partridge: The compelling thing about this patient population is that most of the data include all patients with breast cancer, patients with ER-positive disease, and the vast majority of patients are in their fifties, sixties, and seventies.
We've been reluctant to adopt these tests in a robust way in our young patients. In a young patient who is at risk of recurrence, you’re going to have a higher bar to not give them everything you've got, if you're worried about them having a cancer and a threat to their life. It makes sense, and on the flip side, they have the longest time to live with the repercussions of chemotherapy. If we could have a test that can tell us that neoadjuvant chemotherapy is not likely to help, then why would we not do that test and help give those women something else rather than give them chemotherapy? That’s what's unique about this data set.
For this dataset, we used our young women’s cohort, which a population of patients aged 40 and underwho we've been following over the last decade or so, and we were able to collect a large proportion of those women who had ER-positive disease for whom had tumor specimens. In the ones who got neoadjuvant therapy, we were able to look at their pretreatment tumor specimens in order to show that while half of them did indeed have higher risk recurrence scores and likely benefited from the chemotherapy, for the other half with lower risk recurring scores, they didn’t benefit at all, and that’s why this is not practice-changing data. However, we can say that the tumors appear not to shrink or have as much of a response if they had lower risk scores. This suggests that maybe we need to use a different strategy to get a response in the preoperative setting for those patients and maybe a hormone-based strategy with the targeted therapy, might be a better approach to test.
TARGETED ONCOLOGY: What were the findings from this study?
Partridge: The findings from the study showed us that women with a lower risk oncotype on pre-neoadjuvant treatment biopsy seemed to have less response to neoadjuvant chemotherapy.
In women with a higher risk oncotype, it appeared to be on a continuum of the higher the oncotype, the higher the benefit from chemotherapy in terms of response rates.
TARGETED ONCOLOGY: How do genomic profiling assays play a role in decision-making for patients who are in need of neoadjuvant therapy in the future?
Partridge: We do routinely use genetic expression assays to help us to determine whether or not chemotherapy would be valuable. In the preoperative setting, we’re increasingly using them because we know that at least in postmenopausal women, hormonal therapy is as good as chemotherapy in ER-positive disease, and it's probably more so the right thing to do in women with lower risk genomic expression.
In premenopausal women, we haven’t had quick adoption of this strategy, but I think these data suggest that maybe we should be adopting it more. It's hard to forgo chemotherapy, though, when you don't have a great alternative besides the hormones.
TARGETED ONCOLOGY: Are there any other unanswered questions that you hope research in this area will address in the future?
Partridge: I hope that in future research were able to study the ability to shrink tumors and affect long term outcomes in our patients with hormone-sensitive breast cancer, using alternative strategies to standard chemotherapy, particularly when those treatment like chemotherapy are not likely to get us exactly where we want to be. Genomic expression predictor test can help us to separate out tumors that might have a great response to the neoadjuvant chemotherapy and those that might do better with another approach.