Integrated MRI-Derived, Pathologic, and Molecular Biomarkers for Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer

Abstract

Aim: To investigate the predictive value of pretreatment breast magnetic resonance imaging (MRI) findings, clinicopathological characteristics, and molecular tumor features for pathological response to neoadjuvant chemotherapy (NACT).

Method: This retrospective study included 194 patients with invasive breast cancer who underwent pretreatment breast MRI, received NACT, and subsequently underwent surgery between 2015 and 2020. Pathological response was assessed using the Miller–Payne grading system and categorized as complete/near-complete response (grades 4–5), partial response (grade 3), or limited response (grades 1–2). Quantitative and morphological MRI parameters, together with clinicopathological and molecular characteristics, were analyzed. Independent predictors of pathological response were identified using multinomial logistic regression analysis.

Results: According to the Miller–Payne classification, 80 patients (41.2%) achieved complete/near-complete response, 98 (50.5%) partial response, and 16 (8.2%) limited response. Histologic subtype, tumor grade, HER2 status, Ki-67 index, molecular subtype, ADC, BPE, tumor margins, enhancement pattern, and MSI were significantly associated with pathological response. In multivariable analysis, non-ductal histology and minimal BPE independently predicted limited versus complete/near-complete response, whereas non-luminal molecular subtype, minimal BPE, and MSI ≥429 independently predicted limited versus partial response. Lower ADC independently distinguished partial from complete/near-complete response. However, substantial overlap in biological and imaging features remained across response groups.

Conclusion: Pretreatment MRI biomarkers may provide complementary information for predicting NACT response when interpreted with clinicopathologic and molecular features. Lower ADC was not an independent predictor of limited response. The occurrence of similar biological and imaging features in both highly responsive and limited-response tumors highlights substantial treatment-response heterogeneity and supports an integrated multiparametric assessment rather than reliance on any single biomarker.

Keywords

• Breast cancer
• neoadjuvant chemotherapy
• breast MRI
• imaging biomarkers
• pathological treatment response.

Supporting Institution

The authors received no financial support for the research, authorship, and/or publication of this article.

Ethical Statement

The study was approved by the Clinical Research Ethics Committee of Istanbul Training and Research Hospital (Decision No: 3, Approval Date: January 14, 2022). The study was conducted in accordance with the ethical principles of the Declaration of Helsinki

Meme Kanserinde Neoadjuvan Kemoterapi Yanıtının Öngörülmesinde MRG Tabanlı, Patolojik ve Moleküler Biyobelirteçler

Abstract

Amaç: Bu çalışmanın amacı, meme kanserli hastalarda neoadjuvan kemoterapiye (NAKT) patolojik yanıtın öngörülmesinde tedavi öncesi meme manyetik rezonans görüntüleme (MRG) bulguları ile klinikopatolojik ve moleküler tümör özelliklerinin prediktif değerini araştırmaktır.

Yöntem: Bu retrospektif çalışmaya, 2015–2020 yılları arasında tedavi öncesi meme MRG incelemesi yapılan, NAKT uygulanan ve ardından cerrahi tedavi gerçekleştirilen 194 invaziv meme kanseri hastası dahil edildi. Patolojik yanıt Miller–Payne derecelendirme sistemine göre değerlendirildi ve tam/tama yakın yanıt (derece 4–5), parsiyel yanıt (derece 3) ve sınırlı yanıt (derece 1–2) olarak sınıflandırıldı. Kantitatif ve morfolojik MRG parametreleri ile klinikopatolojik ve moleküler özellikler analiz edildi. Patolojik yanıtın bağımsız belirleyicileri multinomiyal lojistik regresyon analizi ile değerlendirildi.

Bulgular: Miller–Payne sınıflamasına göre hastaların 80'i (%41,2) tam/tama yakın, 98'i (%50,5) parsiyel ve 16'sı (%8,2) sınırlı yanıt gösterdi. Histolojik alt tip, tümör derecesi, HER2 durumu, Ki-67 indeksi, moleküler alt tip, ADC, BPE, tümör kenar özellikleri, kontrastlanma paterni ve MSI patolojik yanıt ile anlamlı ilişkiliydi. Çok değişkenli analizde non-duktal histoloji ve minimal BPE, tam/tama yakın yanıta göre sınırlı yanıtı; non-luminal moleküler alt tip, minimal BPE ve MSI ≥429 ise parsiyel yanıta göre sınırlı yanıtı bağımsız olarak öngördü. Düşük ADC değerleri parsiyel yanıtı tam/tama yakın yanıttan bağımsız olarak ayırt etti. Bununla birlikte, yanıt grupları arasında biyolojik ve görüntüleme özellikleri açısından belirgin örtüşme gözlendi.

Sonuç: Tedavi öncesi MRG biyobelirteçleri, klinikopatolojik ve moleküler özelliklerle birlikte değerlendirildiğinde NAKT yanıtının öngörülmesine tamamlayıcı bilgi sağlayabilir. Düşük ADC sınırlı yanıtın bağımsız belirleyicisi değildir. Aynı biyolojik ve görüntüleme özelliklerinin hem yüksek hem de sınırlı yanıt gösteren tümörlerde bulunabilmesi, tedavi yanıtındaki belirgin heterojenliği ortaya koymakta ve tek bir belirteç yerine bütünleşik, multiparametrik değerlendirmeyi desteklemektedir.

Keywords

• Meme kanseri
• neoadjuvan kemoterapi
• meme MRG
• görüntüleme biyobelirteçleri
• patolojik tedavi yanıtı

Supporting Institution

The authors received no financial support for the research, authorship, and/or publication of this article.

Ethical Statement

Bu çalışma, İstanbul Eğitim ve Araştırma Hastanesi Klinik Araştırmalar Etik Kurulu tarafından onaylanmıştır (Karar No: 3, Onay Tarihi: 14 Ocak 2022). Çalışma, Helsinki Bildirgesi'nin güncel etik ilkelerine uygun olarak gerçekleştirilmiştir.

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