ASCO Breast: Genomic Profiling Multitasks for Breast Cancer Treatment Decisions


SAN FRANCISCO-Oncologists may be able to predict which breast cancer patients need and will respond to systemic therapies with a single genomic profiling assay, researchers said.

SAN FRANCISCO, Sept 12-Oncologists may be able to predict which breast cancer patients need and will respond to systemic therapies with a single genomic profiling assay, researchers said.


Three genomic tests can be done together in a single assay of breast tissue to distinguish breast cancer prognosis and response to endocrine therapy and chemotherapy, according to two studies presented here at the American Society of Clinical Oncology's Breast Cancer Symposium.


“Simultaneous prediction of risk of recurrence and sensitivity to therapies may lead to more appropriate treatment decisions for individuals,” said Lajos Pusztai, MD, PhD, of the University of Texas M.D. Anderson Cancer Center in Houston.


He presented findings of a study using a 76-gene prognostic test along with a 200-gene endocrine sensitivity test and a 30-gene chemotherapy response predictor to simultaneously predict relapse risk and treatment response.

Dr Pusztai and colleagues also reported a study validating the 200-gene test as a predictor of distant relapse-free survival in 2 cohorts of tamoxifen (Nolvadex)-treated patients with hormone receptor–positive breast cancer (P<.001 and P=.0168).


Although other popular genetic tests are already in clinical use, such as Oncotype DX, more are needed, commented Ian E. Krop, MD, PhD, of the Dana-Farber Cancer Institute in Boston, who was a discussant on the 200-gene test validation study.


“The field is still in its infancy and there’s plenty of room for improvement,” he said.


Furthermore, existing genomic tests do not help oncologists determine the likely benefit of each treatment option aside from the overall prognosis if no treatment followed surgery, said W. Fraser Symmans, MD, also of M.D. Anderson.

He presented the results of the validation study assessing the 200-gene index for sensitivity to endocrine therapy (SET). It included 486 women in one cohort and 474 in another who had estrogen receptor–positive breast cancer.


Baseline tissue samples from the women were measured using a microarray to determine expression of the 200 genes and categorize each woman by the SET index as being at high (SET greater than 4.23), intermediate (SET greater than 3.71), or low (SET less than 3.71) risk for relapse if not treated beyond surgery.


When this was correlated with 5-year distant relapse-free survival in the cohorts, the researchers found that a high to intermediate SET score was a significant predictor only among those treated with tamoxifen (P<.001 in one cohort and P=.0168 in the other).


The index was not prognostic among those who received no adjuvant endocrine therapy (P=.611 and P=.818, respectively).

“The study identifies a population of tamoxifen-treated patients with extremely favorable outcome,” Dr Krop said.


But, he cautioned, the analysis did not use a randomized clinical trial, “thus it’s hard to prove it’s a pure predictive marker.” Dr Krop also noted that the test requires frozen tissue rather than the more commonly used formalin fixed, paraffin embedded tissue.


To see whether the 200-gene SET could be applied along with the other two predictors on the same group of patients, Dr Pusztai and colleagues gathered gene expression data measured with a single assay for 2 separate cohorts of women with lymph node–negative stage I or II breast cancer.


In the cohort of 198 patients who received no systemic adjuvant therapy, 143 were predicted by the 76-gene prognostic test to have a high likelihood of recurrence without adjuvant treatment. Among them, the findings were:


  • The 30-gene chemotherapy response test predicted that 79 patients would have pathologic complete response with 8 of these predicted to be responsive to endocrine therapy using the 200-gene SET.
  • The 30-gene test predicted that 64 patients (45%) would have residual cancer after chemotherapy although 26 of them were predicted to benefit from endocrine therapy using the 200-gene SET.



The second cohort of 40 patients received neoadjuvant chemotherapy including paclitaxel (Taxol) and fluorouracil (Adrucil), doxorubicin (Adriamycin), and cyclophosphamide (Cytoxan).


Among them, 26 (65%) were predicted by the 76-gene test to have a poor prognosis with surgery alone.


Four (28%) of these were predicted to have pathologic complete response from chemotherapy using the 30-gene response test. The 200-gene SET predicted 8 (30%) of those likely to have residual disease after chemotherapy would respond to endocrine therapy.

Dr Pusztai said M.D. Anderson will use the set of predictors to triage patients to therapy once they get an investigational device exemption from the FDA.


“Gene expression based classifiers have potential to significantly improve care by removing empiricism from therapeutic decisions,” concluded Dr Krop.




The researchers in both studies reported conflicts of interest for Nuvera Biosciences.


Related Videos
Donna H Ryan, MD Obesity Expert Highlights 2021 Research Success and Looks to 2022 and Beyond
Dapagliflozin slows decline of chronic kidney disease
Primary care physicians should prescribe SGLT2 inhibitors
Related Content
© 2023 MJH Life Sciences

All rights reserved.