Clinical Practice Guidelines for Multigene Assays in Early-Stage Breast Cancer 2021

0
0
0

Clinical Practice Guidelines for Multigene Assays in Patients with Early-Stage Breast Cancer: Chinese Society of Breast Surgery (CSBrS) Practice Guidelines 2021

The Chinese Society of Breast Surgery (CSBrS) issued clinical practice guidelines in 2021 to standardize the use of multigene assays in chemotherapy decision-making for early-stage breast cancer patients. These guidelines address the integration of genomic tools into clinical practice, emphasizing their role in risk stratification and treatment personalization. The recommendations are based on high-level evidence and expert consensus, with a focus on assays validated in international trials and their applicability within the Chinese healthcare context.

Role of Multigene Assays in Breast Cancer Prognostication

Multigene assays have transformed the management of early-stage breast cancer by providing genomic insights that complement traditional clinicopathological factors. The 8th edition of the American Joint Committee on Cancer (AJCC) staging system introduced prognostic staging, incorporating non-anatomical biomarkers such as multigene assay results. Notably, assays like Oncotype Dx® and MammaPrint® were integrated into AJCC guidelines due to their validated prognostic and predictive value. In China, the CSBrS guidelines aim to guide clinicians in selecting appropriate assays and interpreting results to optimize adjuvant therapy decisions.

Recommended Multigene Assays

The CSBrS guidelines prioritize two assays based on level I evidence and availability in China:

  1. 70-Gene Signature (MammaPrint®)

    • Technology: Next-generation sequencing (NGS).
    • Level of Evidence: I.
    • Recommendation Strength: A (strong recommendation).
    • Applicable Population: Patients with T1–T2 tumors, 0–3 positive lymph nodes, hormone receptor-positive (HR+), and HER2-negative (HER2–) status.
    • Clinical Utility:
      • Identifies genomic high-risk patients who may derive limited benefit from chemotherapy, despite clinical low-risk categorization.
      • Guides chemotherapy omission in clinical high-risk patients classified as genomic low-risk.

    The MINDACT trial underpins these recommendations, demonstrating that 46% of women classified as clinical high-risk but genomic low-risk could safely avoid chemotherapy without compromising distant metastasis-free survival. The trial enrolled primarily T1–T2 (98.8%), HR+ (88.4%), HER2– (90.3%), and node-negative (79%) patients, with 14.1% having 1–3 positive nodes.

  2. 21-Gene Recurrence Score (Oncotype Dx®)

    • Technology: Reverse transcription-polymerase chain reaction (RT-PCR).
    • Level of Evidence: I.
    • Recommendation Strength: B (moderate recommendation).
    • Applicable Population: Patients with T1–T2 tumors, node-negative (pN0), HR+, HER2– status.
    • Clinical Utility:
      • Recurrence Score (RS) ≤25: Supports chemotherapy omission, particularly for women ≤50 years with RS 16–25, where endocrine therapy alone may suffice.
      • RS 26–30: Insufficient prospective data; clinicians should weigh clinical factors (e.g., age, tumor grade) when considering chemotherapy.
      • RS ≥31: Recommends chemotherapy addition.

    The TAILORx trial validated the 21-gene assay, showing no significant benefit from chemotherapy in patients with RS ≤25 (84.3% of the cohort). For women ≤50 years, a slight benefit in distant recurrence reduction (1.6% at 9 years) was observed in the RS 16–25 subgroup, suggesting individualized decision-making.

Patient Selection Criteria

The guidelines emphasize strict eligibility criteria for multigene testing:

  • Inclusion:
    • Early-stage (T1–T2) invasive breast cancer.
    • HR+ and HER2– subtype.
    • Node-negative (Oncotype Dx®) or 1–3 positive nodes (MammaPrint®).
  • Exclusion:
    • Triple-negative breast cancer (TNBC) or HER2+ patients.
    • Patients with >3 positive lymph nodes.
    • Clinically low-risk HR+/HER2–/node-negative patients (chemotherapy not indicated).

Pre-test requirements include accurate ER, PR, and HER2 status determination using standardized immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH). Tumor tissue samples must meet assay-specific quality standards (e.g., sufficient invasive tumor content, proper fixation).

Treatment Implications Based on Assay Results

  1. MammaPrint®

    • Clinical Low-Risk/Genomic High-Risk: Limited chemotherapy benefit; clinical factors (e.g., patient preference, comorbidities) should guide decisions.
    • Clinical High-Risk/Genomic Low-Risk: Chemotherapy omission is feasible, supported by a 5-year distant metastasis-free survival rate of 94.7% in the MINDACT trial.

  2. Oncotype Dx®

    • RS ≤25: Endocrine therapy alone is sufficient for most patients.
    • RS 26–30: No prospective evidence for chemotherapy omission; consider tumor biology (e.g., Ki-67 index, histological grade).
    • RS ≥31: Clear recommendation for chemotherapy, with trials showing a 13.1% absolute reduction in distant recurrence risk.

Key Considerations and Limitations

  1. Assay Consistency and Availability:

    • Discordance between different multigene assays (e.g., MammaPrint® vs. Oncotype Dx®) is common, with only moderate agreement in risk classification. Clinicians should avoid cross-assay comparisons.
    • EndoPredict®, PAM50®, and Breast Cancer Index (BCI) are recognized internationally but not recommended in China due to limited availability and lack of predictive data for chemotherapy benefit.

  2. Sample Requirements:

    • MammaPrint® requires fresh or formalin-fixed tissue with ≥30% tumor cellularity.
    • Oncotype Dx® mandates fixed paraffin-embedded tissue with ≥0.5 cm³ invasive carcinoma.

  3. Ethnic and Regional Validity:

    • Current evidence derives predominantly from Western populations. The CSBrS advocates multicenter studies in China to validate assay performance in diverse ethnic cohorts.

  4. Cost and Accessibility:

    • High costs and regional disparities in assay availability necessitate individualized decision-making.

Expert Consensus and Future Directions

The CSBrS guidelines reflect unanimous expert agreement on the clinical utility of multigene assays, with 97% endorsing MammaPrint® and 73% supporting Oncotype Dx®. Critical recommendations include:

  • Multidisciplinary team (MDT) discussions for discordant cases (e.g., genomic-clinical risk mismatch).
  • Avoidance of non-validated assays labeled as “similar” to MammaPrint® or Oncotype Dx®.
  • Prioritization of patient-centered decision-making, integrating genomic data with clinicopathological factors.

Future priorities include:

  • Nationwide studies to evaluate assay performance in Chinese populations.
  • Development of cost-effective, region-specific genomic tools.
  • Exploration of extended endocrine therapy guidance using multigene assays.

In summary, the CSBrS guidelines provide a structured framework for multigene assay implementation in China, balancing international evidence with regional practicalities. By aligning testing criteria, result interpretation, and treatment pathways, these recommendations aim to optimize outcomes while minimizing overtreatment in early-stage breast cancer.

doi.org/10.1097/CM9.0000000000001409

Was this helpful?

0 / 0