9 research outputs found
The 70-gene signature to provide risk stratification and treatment guidance for patients classified as intermediate by the 21-gene assay.
Genomic Impact of Neoadjuvant Therapy on Breast Cancer: Incomplete Response is Associated with Altered Diagnostic Gene Signatures.
PURPOSE: Neoadjuvant therapy (NAT) has been shown to clinically downstage locally advanced breast cancers. This study aimed to determine whether a meaningful change in gene signatures occurs between pre- and post-NAT breast cancers for patients who do not achieve a pathologic complete response.
METHODS: The current analysis included women from the prospective Neoadjuvant Breast Registry Symphony Trial who had breast cancer and awaited NAT. MammaPrint and BluePrint (Agendia, Inc., Irvine, CA) assays were performed on pre- and post-NAT breast tumor samples.
RESULTS: At the completion of NAT, 93 patients with residual disease had their remaining tumor analyzed for MammaPrint and BluePrint. Of 93 patients, 21 switched tumor classification: 16 from high risk (HR) to low risk (LR) and 1 from LR to HR (p \u3c 0.001). Four additional patients switched molecular subtype but remained HR. Although only 17 patients switched in their MammaPrint risk classification, the underlying MPIndex was significantly altered after treatment across all patients (p \u3c 0.001). Additionally, the three BluePrint indices for luminal, human epidermal growth factor receptor 2 (HER2), and basal type also were significantly altered after treatment, in a subtype-dependent manner.
CONCLUSION: This substudy showed that NAT significantly altered the genomic signature of the patient\u27s breast cancer compared with the patient\u27s pretreatment genomic profile. These alterations occurred in a subtype-dependent manner, suggesting that NAT may have either eliminated the most susceptible tumor subclone, leaving the treatment resistant clone with a different genetic signature, or altered molecular characteristics of the original cancer
Pathological complete response in basal subtype tumors to predict improved distant metastasis free survival in the NBRST trial.
Expression of estrogen receptor variants in ER+ basal-type breast cancers that respond to therapy like ER- breast cancers.
Association of 70-gene signature assay findings with physicians\u27 treatment guidance for patients with early breast cancer classified as intermediate risk by the 21-gene assay
Importance: Among patients who undergo the 21-gene assay (21-GA), 39% to 67% receive an intermediate risk result and may receive ambiguous treatment guidance. The 70-gene signature assay (70-GS) may be associated with physicians\u27 treatment decisions in this population with early breast cancer.
Objective: To determine whether 70-GS findings are associated with physicians\u27 decisions about adjuvant treatment and confidence in their recommendations and to evaluate the dichotomous (high- vs low-risk) and continuous distribution of 70-GS indices among this group of patients with intermediate risk.
Design, Setting, and Participants: The Prospective Study of MammaPrint in Breast Cancer Patients With an Intermediate Recurrence Score (PROMIS trial) was an impact study conducted from May 20, 2012, through December 31, 2015, that enrolled 840 patients with early-stage breast cancer and a 21-gene assay recurrence score of 18 to 30. Patients were treated in 58 US institutions.
Interventions: The 70-GS result was given to physicians before adjuvant treatment.
Main Outcomes and Measures: Change in physician treatment decision before vs after receiving the 70-GS result. With a treatment change of greater than 20%, the odds ratio (OR) was applied.
Results: Among the 840 patients who underwent 70-GS classification (mean age, 59 years; range, 27-93 years), 374 (44.5%) had a low-risk and 466 (55.5%) had a high-risk result. The distribution of 70-GS indices did not correlate with recurrence score within the 21-GA intermediate range, with 70-GS low- and high-risk patients observed at every recurrence score. A significant change in adjuvant treatment was associated with receiving the 70-GS classifications with an OR of 0.64 (95% CI, 0.50-0.82; McNemar test, P \u3c .001) for all patients. Among the low-risk patients, 108 of 374 (28.9%) had chemotherapy removed from their treatment recommendation; among the high-risk patients, 171 of 466 (36.7%) had chemotherapy added. Results of the 70-GS were associated with the physician\u27s adjuvant treatment recommendation; 409 high-risk patients (87.8%) were recommended to receive adjuvant chemotherapy, and 339 low-risk patients (90.6%) were recommended no chemotherapy. Physicians reported having greater confidence in their treatment recommendation in 660 cases (78.6%) based on 70-GS results.
Conclusions and Relevance: The 70-GS provides clinically actionable information regarding patients classified as intermediate risk by the 21-GA and was associated with a change in treatment decision in 282 of these patients (33.6%). Chemotherapy was added or withheld by the treating physician based on the results of the 70-GS test. Physicians reported more confidence with their treatment recommendation after receiving 70-GS results
MammaPrint guides treatment decisions in breast cancer: results of the IMPACt trial.
BACKGROUND: Increased usage of genomic risk assessment assays suggests increased reliance on data provided by these assays to guide therapy decisions. The current study aimed to assess the change in treatment decision and physician confidence based on the 70-gene risk of recurrence signature (70-GS, MammaPrint) and the 80-gene molecular subtype signature (80-GS, BluePrint) in early stage breast cancer patients.
METHODS: IMPACt, a prospective, case-only study, enrolled 452 patients between November 2015 and August 2017. The primary objective population included 358 patients with stage I-II, hormone receptor-positive, HER2-negative breast cancer. The recommended treatment plan and physician confidence were captured before and after receiving results for 70-GS and 80-GS. Treatment was started after obtaining results. The distribution of 70-GS High Risk (HR) and Low Risk (LR) patients was evaluated, in addition to the distribution of 80-GS compared to IHC status.
RESULTS: The 70-GS classified 62.5% (n = 224/358) of patients as LR and 37.5% (n = 134/358) as HR. Treatment decisions were changed for 24.0% (n = 86/358) of patients after receiving 70-GS and 80-GS results. Of the LR patients initially prescribed CT, 71.0% (44/62) had CT removed from their treatment recommendation. Of the HR patients not initially prescribed CT, 65.1% (41/63) had CT added. After receiving 70-GS results, CT was included in 83.6% (n = 112/134) of 70-GS HR patient treatment plans, and 91.5% (n = 205/224) of 70-GS LR patient treatment plans did not include CT. For patients who disagreed with the treatment recommended by their physicians, most (94.1%, n = 16/17) elected not to receive CT when it was recommended. For patients whose physician-recommended treatment plan was discordant with 70-GS results, discordance was significantly associated with age and lymph node status.
CONCLUSIONS: The IMPACt trial showed that treatment plans were 88.5% (n = 317/358) in agreement with 70-GS results, indicating that physicians make treatment decisions in clinical practice based on the 70-GS result. In clinically high risk, 70-GS Low Risk patients, there was a 60.0% reduction in treatment recommendations that include CT. Additionally, physicians reported having greater confidence in treatment decisions for their patients in 72% (n = 258/358) of cases after receiving 70-GS results.
TRIAL REGISTRATION: Measuring the Impact of MammaPrint on Adjuvant and Neoadjuvant Treatment in Breast Cancer Patients: A Prospective Registry (NCT02670577) retrospectively registered on Jan 27, 2016