HRD assay platform mismatch in breast or ovarian cancer: HRD-positive call by Myriad myCh...

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ID	`RF-BREAST-OVARIAN-HRD-ASSAY-DISTINCTION`
Тип	Тривожна ознака
Статус	переглянуто 2026-04-29 \| очікує клінічного підпису
Хвороби	`DIS-BREAST` `DIS-OVARIAN`
Джерела	`SRC-CIVIC` `SRC-ESMO-OVARIAN-2024` `SRC-NCCN-BREAST-2025` `SRC-NCCN-OVARIAN-2025` `SRC-PRIMA-GONZALEZ-MARTIN-2019`

Походження тривожної ознаки

Визначення	HRD assay platform mismatch in breast or ovarian cancer: HRD-positive call by Myriad myChoice CDx (composite Genomic Instability Score GIS = LOH + TAI + LST, threshold ≥42) is NOT interchangeable with HRD-positive by FoundationOne CDx HRD (LOH-high ≥16% genomic LOH + BRCA1/2 status, no TAI / LST). The two FDA-approved companion diagnostics use different scoring systems and have ~10-15% discordance in head-to-head series; clinical-trial regimen approvals are platform-locked: olaparib + bevacizumab maintenance in advanced ovarian (PAOLA-1, Ray-Coquard NEJM 2019) is FDA-indicated only on Myriad GIS-based HRD; niraparib monotherapy maintenance (PRIMA, González-Martín NEJM 2019) is also Myriad-validated. F1CDx HRD-high has no companion-diagnostic indication in ovarian PARPi maintenance — using F1CDx LOH-high to indicate olaparib + bev or niraparib is off-label / extrapolated. Action: when an...
Клінічний напрям	investigate
Категорія	high-risk-biology

Логіка спрацьовування

{
  "all_of": [
    {
      "any_of": [
        {
          "finding": "hrd_status",
          "value": "positive"
        },
        {
          "finding": "hrd_call",
          "value": "positive"
        }
      ]
    },
    {
      "any_of": [
        {
          "finding": "hrd_assay_platform",
          "value": "foundationone_cdx"
        },
        {
          "finding": "hrd_assay_platform",
          "value": "f1cdx"
        },
        {
          "finding": "hrd_assay_platform",
          "value": "loh_only"
        },
        {
          "finding": "hrd_score_source",
          "value": "f1cdx_loh_high"
        }
      ]
    }
  ],
  "type": "biomarker"
}

Нотатки

**Why platform-locked matters clinically:** PARPi-maintenance ovarian regimen | HRD CDx in pivotal trial | FDA indication wording ----------------------------------------------------------------- - olaparib + bev (PAOLA-1) | Myriad myChoice GIS ≥42 | "HRD-positive by an FDA-approved test" → in practice Myriad - niraparib mono (PRIMA) | Myriad myChoice GIS ≥42 | "regardless of HRD" but HRD-positive subgroup HR 0.43 vs HRD-neg HR 0.68 - olaparib mono (SOLO-1) | gBRCA / sBRCA only | not HRD-score-based - rucaparib (ARIEL3) | LOH-high (Foundation Medicine LOH only) | EU only, US withdrawn 2022 — narrow precedent for F1CDx-LOH **Discordance mechanism:** Myriad GIS captures three independent genome-scarring footprints (LOH, telomeric allelic imbalance TAI, large-scale state transitions LST). F1CDx HRD aggregates only LOH + BRCA. A tumor with high TAI but moderate LOH may be Myriad- positive and F1CDx-negative; a tumor with widespread LOH from non-HRR causes (chromothripsis, CDK12-loss) may be F1CDx-positive but Myriad-negative on the composite cut-point. Empirical concordance ~85-90%; the disagreement zone is clinically consequential when PARPi-maintenance benefit is being decided. **Ac...

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