Early response by MR imaging and ultrasound as predictor of pathologic complete response to 12-week neoadjuvant therapy for different early breast cancer subtypes: Combined analysis from the WSG ADAPT subtrials

Monika Graeser^{1

2

3}, Simone Schrading⁴, Oleg Gluz^{1

2

5}, Kevin Strobel⁴, Rachel Würstlein^{1

6}, Sherko Kümmel^{1

7

8}, Claudia Schumacher⁹, Eva-Maria Grischke¹⁰, Helmut Forstbauer¹¹, Michael Braun¹², Matthias Christgen¹³, Jascha Adams¹⁴, Henrik Nitzsche², Marianne Just¹⁵, Hans Holger Fischer¹⁶, Bahriye Aktas^{17

18}, Jochem Potenberg¹⁹, Raquel von Schumann², Cornelia Kolberg-Liedtke^{8

17}, Nadia Harbeck^{1

6}, Christiane K Kuhl⁴, Ulrike Nitz^{1

2}

Affiliations

¹ West German Study Group, Moenchengladbach, Germany.
² Ev. Hospital Bethesda, Breast Center Niederrhein, Moenchengladbach, Germany.
³ Department of Gynecology, University Medical Center Hamburg, Hamburg, Germany.
⁴ Department of Diagnostic and Interventional Radiology, Hospital of the University of Aachen, RWTH, Aachen, Germany.
⁵ University Hospital Cologne, Cologne, Germany.
⁶ Breast Center, Department of Gynecology and Obstetrics and CCCLMU, LMU University Hospital, Munich, Germany.
⁷ Breast Unit, Kliniken Essen-Mitte, Essen, Germany.
⁸ University Hospital Charité, Humboldt University Berlin, Berlin, Germany.
⁹ St. Elisabeth Hospital Cologne, Breast Center, Cologne, Germany.
¹⁰ University Clinic Tuebingen, Women's Clinic, Tuebingen, Germany.
¹¹ Practice Network Troisdorf, Troisdorf, Germany.
¹² Department of Gynecology, Breast Center, Red Cross Hospital Munich, Munich, Germany.
¹³ Institute of Pathology, Medical School Hannover, Hannover, Germany.
¹⁴ Alcedis GmbH, Giessen, Germany.
¹⁵ Oncological Practice, Bielefeld, Germany.
¹⁶ Protestant Clinics Gelsenkirchen, Gelsenkirchen, Germany.
¹⁷ Department of Gynecology and Obstetrics, University Clinics Essen, Essen, Germany.
¹⁸ Department of Gynecology, University Hospital Leipzig, Leipzig, Germany.
¹⁹ Ev. Waldkrankenhaus Berlin, Berlin, Germany.

PMID: 33533487
PMCID: PMC8048810
DOI: 10.1002/ijc.33495

Early response by MR imaging and ultrasound as predictor of pathologic complete response to 12-week neoadjuvant therapy for different early breast cancer subtypes: Combined analysis from the WSG ADAPT subtrials

Monika Graeser et al. Int J Cancer. 2021.

. 2021 May 15;148(10):2614-2627.

doi: 10.1002/ijc.33495. Epub 2021 Feb 11.

Authors

Affiliations

¹ West German Study Group, Moenchengladbach, Germany.
² Ev. Hospital Bethesda, Breast Center Niederrhein, Moenchengladbach, Germany.
³ Department of Gynecology, University Medical Center Hamburg, Hamburg, Germany.
⁴ Department of Diagnostic and Interventional Radiology, Hospital of the University of Aachen, RWTH, Aachen, Germany.
⁵ University Hospital Cologne, Cologne, Germany.
⁶ Breast Center, Department of Gynecology and Obstetrics and CCCLMU, LMU University Hospital, Munich, Germany.
⁷ Breast Unit, Kliniken Essen-Mitte, Essen, Germany.
⁸ University Hospital Charité, Humboldt University Berlin, Berlin, Germany.
⁹ St. Elisabeth Hospital Cologne, Breast Center, Cologne, Germany.
¹⁰ University Clinic Tuebingen, Women's Clinic, Tuebingen, Germany.
¹¹ Practice Network Troisdorf, Troisdorf, Germany.
¹² Department of Gynecology, Breast Center, Red Cross Hospital Munich, Munich, Germany.
¹³ Institute of Pathology, Medical School Hannover, Hannover, Germany.
¹⁴ Alcedis GmbH, Giessen, Germany.
¹⁵ Oncological Practice, Bielefeld, Germany.
¹⁶ Protestant Clinics Gelsenkirchen, Gelsenkirchen, Germany.
¹⁷ Department of Gynecology and Obstetrics, University Clinics Essen, Essen, Germany.
¹⁸ Department of Gynecology, University Hospital Leipzig, Leipzig, Germany.
¹⁹ Ev. Waldkrankenhaus Berlin, Berlin, Germany.

PMID: 33533487
PMCID: PMC8048810
DOI: 10.1002/ijc.33495

Abstract

We evaluated the role of early response after 3 weeks of neoadjuvant treatment (NAT) assessed by ultrasound (US), magnetic resonance imaging (MRI) and Ki-67 dynamics for prediction of pathologic complete response (pCR) in different early breast cancer subtypes. Patients with HR+/HER2+, HR-/HER2- and HR-/HER2+ tumors enrolled into three neoadjuvant WSG ADAPT subtrials underwent US, MRI and Ki-67 assessment at diagnosis and after 3 weeks of NAT. Early response was defined as complete or partial response (US, MRI) and ≥30% proliferation decrease or <500 invasive tumor cells (Ki-67). Predictive values and area under the receiver operating characteristic (AUC) curves for prediction of pCR (ypT0/is ypN0) after 12-week NAT were calculated. Two hundred twenty-six had MRI and 401 US; 107 underwent both MRI and US. All three methods yielded a similar AUC in HR+/HER2+ (0.66-0.67) and HR-/HER2- tumors (0.53-0.63), while MRI and Ki-67 performed better than US in HR-/HER2+ tumors (0.83 and 0.79 vs 0.56). Adding MRI+/-Ki-67 increased AUC of US in HR-/HER2+ tumors to 0.64 to 0.75. MRI and Ki-67 demonstrated highest sensitivity in HR-/HER2- (0.8-1) and HR-/HER2+ tumors (1, both). Negative predictive value was similar for all methods in HR+/HER2+ (0.71-0.74) and HR-/HER2- tumors (0.85-1), while it was higher for MRI and Ki-67 compared to US in HR-/HER2+ subtype (1 vs 0.5). Early response assessed by US, MRI and Ki-67 is a strong predictor for pCR after 12-week NAT. Strength of pCR prediction varies according to tumor subtype. Adding MRI+/-Ki-67 to US did not improve pCR prediction in majority of our patients.

Keywords: breast cancer; magnetic resonance imaging; neoadjuvant therapy; pathologic complete response; ultrasound.

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Conflict of interest statement

Oleg Gluz acts as Co‐Director West German Study Group (WSG), received honoraria from Genomic Health/Exact Sciences, Roche, Celgene, Pfizer, Novartis, NanoString Technologies, AstraZeneca, served in consulting/advisory role for Celgene, Genomic Health/Exact Sciences, Lilly, MSD, Novartis, Pfizer, Roche, and received travel support from Roche. Rachel Würstlein served in consulting/advisory role as well as on speakers' bureau for and received travel support from Agendia, Amgen, Aristo, AstraZeneca, Boeringer Ingelheim, Carl Zeiss, Celgene, Clinsol, Daiichi‐Sankyo, Eisai, Genomic Health, Glaxo Smith Kline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Nanostring, Novartis, Odonate, Onkowissen, Paxman, Palleos, Pfizer, Pierre Fabre, PumaBiotechnolgogy, Riemser, Roche, Sandoz/Hexal, Seattle Genetics, Tesaro Bio, Teva, Viatris. Sherko Kümmel acts as Co‐Director West German Study Group (WSG), received personal fees from Lilly, Roche, Genomic Health, Novartis, Amgen, Celgene, Daiichi Sankyo, AstraZeneca, SOMATEX Medical Technologies, MSD, Pfizer, Puma Biotechnology, PFM medical, and nonfinancial support from Roche, Daiichi Sankyo, Sonoscope. Michael Braun received honoraria from AstraZeneca, Exact Sciences, Novartis, Pfizer, Roche, Teva, travel support from AstraZeneca, Celgene, Medac, Novartis, Roche and served in consulting/advisory role for AstraZeneca, Exact Sciences, Novartis, Puma, Roche. Bahriye Aktas reports a potential financial conflict of interest as follows: Pfizer Pharma GmbH, Roche Pharma AG, Novartis Pharma GmbH, AstraZeneca GmbH, PharmaMar GmbH, MSD Merck Sharp & Dohme GmbH, Onkowissen.de GmbH, Lilly Deutschland GmbH, Promedicis GmbH. Cornelia Kolberg‐Liedtke has ownership interest in Theraklion, Phaon Scientific (both applicable for immediate family member), received honoraria from Roche, AstraZeneca, Celgene, Novartis, Pfizer, Lilly, Hexal, Amgen, SonoScape, and an immediate family member received honoraria from Pfizer, Novartis, Roche, Genomic Health, Amgen, AstraZeneca, Riemser, Carl Zeiss MediTec, TEVA Pharmaceuticals Industries, Theraklion, Janssen‐Cilag, GlaxoSmithKline, LIV Pharma, served in consulting/advisory role for Roche, Novartis, Pfizer, Celgene, Phaon Scientific, and an immediate family member served in consulting/advisory role for Pfizer, Novartis, SurgVision, CarlZeissMeditec, Amgen, Onkowissen, received research funding from Roche, Novartis, Pfizer, and received travel support from Roche, Daiichi Sankyo, Novartis, and an immediate family member received research funding from Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo. Nadia Harbeck acts as Co‐Director West German Study Group (WSG) and reports a potential financial conflict of interest as follows: AstraZeneca, Lilly, Novartis, Pfizer, Pierre Fabre, Roche/Genentech, Merck Sharp & Dohme, Seattle Genetics. Ulrike Nitz acts as Co‐Director West German Study Group (WSG), received honoraria from Agendia, Amgen, Celgene, Genomic Health, NanoString Technologies, Novartis pharma, Pfizer Pharmaceuticals, Roche/Genentech, Teva, served in consulting/advisory role for Genomic Health, Roche, provided expert testimony for Genomic Health, received travel support from Genomic Health, Pfizer Pharmaceuticals, Roche, and her institution received research funding from Agendia, Amgen, Celgene, Genomic Health, NanoString Technologies, Roche, Sanofi.

Figures

**FIGURE 2**
ROC curves for detecting pCR by US, by MRI and by Ki‐67. Data are shown for all patients with MRI and US (A) and for patients with HR+/HER2+ (B), HR−/HER2− (C) and HR−/HER2+ (D) tumors. MRI and US data were available for 107 patients and Ki‐67 data were available for 86 patients. HER2, human epidermal growth factor receptor 2; HR, hormone receptor; MRI, magnetic resonance imaging; pCR, pathological complete response; ROC, receiver operating characteristic; US, ultrasound

See this image and copyright information in PMC

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Early response by MR imaging and ultrasound as predictor of pathologic complete response to 12-week neoadjuvant therapy for different early breast cancer subtypes: Combined analysis from the WSG ADAPT subtrials

Affiliations

Early response by MR imaging and ultrasound as predictor of pathologic complete response to 12-week neoadjuvant therapy for different early breast cancer subtypes: Combined analysis from the WSG ADAPT subtrials

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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