scholarly journals Personalized Decision Making on Genomic Testing in Early Breast Cancer: Expanding the MINDACT Trial with Decision-Analytic Modeling

2021 ◽  
pp. 0272989X2199117
Author(s):  
Ewout W. Steyerberg ◽  
Liesbeth C. de Wreede ◽  
David van Klaveren ◽  
Patrick M. M. Bossuyt
Keyword(s):  
Breast Cancer ◽  
Decision Making ◽  
Genetic Testing ◽  
Early Stage ◽  
Pragmatic Trial ◽  
Genomic Signature ◽  
Genomic Testing ◽  
Analytic Modeling ◽  
Clinical Risk ◽  
Genomic Test

Background Genomic tests may improve upon clinical risk estimation with traditional prognostic factors. We aimed to explore how evidence on the prognostic strength of a genomic signature (clinical validity) can contribute to individualized decision making on starting chemotherapy for women with breast cancer (clinical utility). Methods The MINDACT trial was a randomized trial that enrolled 6693 women with early-stage breast cancer. A 70-gene signature (Mammaprint) was used to estimate genomic risk, and clinical risk was estimated by a dichotomized version of the Adjuvant!Online risk calculator. Women with discordant risk results were randomized to the use of chemotherapy. We simulated the full risk distribution of these women and estimated individual benefit, assuming a constant relative effect of chemotherapy. Results The trial showed a prognostic effect of the genomic signature (adjusted hazard ratio 2.4). A decision-analytic modeling approach identified far fewer women as candidates for genetic testing (4% rather than 50%) and fewer benefiting from chemotherapy (3% rather than 27%) as compared with the MINDACT trial report. The selection of women benefitting from genetic testing and chemotherapy depended strongly on the required benefit from treatment and the assumed therapeutic effect of chemotherapy. Conclusions A high-quality pragmatic trial was insufficient to directly inform clinical practice on the utility of a genomic test for individual women. The indication for genomic testing may be far more limited than suggested by the MINDACT trial.

scholarly journals Optimizing the Use of Gene Expression Profiling in Early-Stage Breast Cancer

2016 ◽  
Vol 34 (36) ◽  
pp. 4390-4397 ◽  
Author(s):  
Hyun-seok Kim ◽  
Christopher B. Umbricht ◽  
Peter B. Illei ◽  
Ashley Cimino-Mathews ◽  
Soonweng Cho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Decision Making ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Early Stage ◽  
Recurrence Score ◽  
Clinical Samples ◽  
Risk Category ◽  
Clinical Risk

Purpose Gene expression profiling assays are frequently used to guide adjuvant chemotherapy decisions in hormone receptor–positive, lymph node–negative breast cancer. We hypothesized that the clinical value of these new tools would be more fully realized when appropriately integrated with high-quality clinicopathologic data. Hence, we developed a model that uses routine pathologic parameters to estimate Oncotype DX recurrence score (ODX RS) and independently tested its ability to predict ODX RS in clinical samples. Patients and Methods We retrospectively reviewed ordered ODX RS and pathology reports from five institutions (n = 1,113) between 2006 and 2013. We used locally performed histopathologic markers (estrogen receptor, progesterone receptor, Ki-67, human epidermal growth factor receptor 2, and Elston grade) to develop models that predict RS-based risk categories. Ordering patterns at one site were evaluated under an integrated decision-making model incorporating clinical treatment guidelines, immunohistochemistry markers, and ODX. Final locked models were independently tested (n = 472). Results Distribution of RS was similar across sites and to reported clinical practice experience and stable over time. Histopathologic markers alone determined risk category with > 95% confidence in > 55% (616 of 1,113) of cases. Application of the integrated decision model to one site indicated that the frequency of testing would not have changed overall, although ordering patterns would have changed substantially with less testing of estimated clinical risk–high or clinical risk–low cases and more testing of clinical risk–intermediate cases. In the validation set, the model correctly predicted risk category in 52.5% (248 of 472). Conclusion The proposed model accurately predicts high- and low-risk RS categories (> 25 or ≤ 25) in a majority of cases. Integrating histopathologic and molecular information into the decision-making process allows refocusing the use of new molecular tools to cases with uncertain risk.

Exploring and supporting older women's chemotherapy decision-making in early-stage breast cancer

2021 ◽  
Author(s):  
Meghan S. Karuturi ◽  
Sharon H. Giordano ◽  
Diana S. Hoover ◽  
Robert J. Volk ◽  
Ashley J. Housten
Keyword(s):  
Breast Cancer ◽  
Decision Making ◽  
Early Stage ◽  
Early Stage Breast Cancer

scholarly journals Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Focused Update

2017 ◽  
Vol 35 (24) ◽  
pp. 2838-2847 ◽  
Author(s):  
Ian Krop ◽  
Nofisat Ismaila ◽  
Fabrice Andre ◽  
Robert C. Bast ◽  
William Barlow ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systemic Therapy ◽  
Hormone Receptor ◽  
Early Stage ◽  
Adjuvant Systemic Therapy ◽  
Node Negative ◽  
Clinical Risk ◽  
Hormone Receptor Positive ◽  
High Clinical Risk ◽  
Positive Breast Cancer

Purpose This focused update addresses the use of MammaPrint (Agendia, Irvine, CA) to guide decisions on the use of adjuvant systemic therapy. Methods ASCO uses a signals approach to facilitate guideline updates. For this focused update, the publication of the phase III randomized MINDACT (Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy) study to evaluate the MammaPrint assay in 6,693 women with early-stage breast cancer provided a signal. An expert panel reviewed the results of the MINDACT study along with other published literature on the MammaPrint assay to assess for evidence of clinical utility. Recommendations If a patient has hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, node-negative breast cancer, the MammaPrint assay may be used in those with high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy due to its ability to identify a good-prognosis population with potentially limited chemotherapy benefit. Women in the low clinical risk category did not benefit from chemotherapy regardless of genomic MammaPrint risk group. Therefore, the MammaPrint assay does not have clinical utility in such patients. If a patient has hormone receptor–positive, HER2-negative, node-positive breast cancer, the MammaPrint assay may be used in patients with one to three positive nodes and a high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy. However, such patients should be informed that a benefit from chemotherapy cannot be excluded, particularly in patients with greater than one involved lymph node. The clinician should not use the MammaPrint assay to guide decisions on adjuvant systemic therapy in patients with hormone receptor–positive, HER2-negative, node-positive breast cancer at low clinical risk, nor any patient with HER2-positive or triple-negative breast cancer, because of the lack of definitive data in these populations. Additional information can be found at www.asco.org/breast-cancer-guidelines and www.asco.org/guidelineswiki .

Facilitating decision-making in women undergoing genetic testing for hereditary breast cancer: BRECONDA randomized controlled trial results

The Breast ◽  
2017 ◽  
Vol 36 ◽  
pp. 79-85 ◽  
Author(s):  
Kerry A. Sherman ◽  
Christopher J. Kilby ◽  
Laura-Kate Shaw ◽  
Caleb Winch ◽  
Judy Kirk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Decision Making ◽  
Randomized Controlled Trial ◽  
Genetic Testing ◽  
Hereditary Breast Cancer ◽  
Controlled Trial ◽  
Randomized Controlled
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