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Tumor necrosis by pretreatment breast MRI: association with neoadjuvant systemic therapy (NAST) response in triple-negative breast cancer (TNBC)

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Abstract

Purpose

To determine if tumor necrosis by pretreatment breast MRI and its quantitative imaging characteristics are associated with response to NAST in TNBC.

Methods

This retrospective study included 85 TNBC patients (mean age 51.8 ± 13 years) with MRI before NAST and definitive surgery during 2010–2018. Each MRI included T2-weighted, diffusion-weighted (DWI), and dynamic contrast-enhanced (DCE) imaging. For each index carcinoma, total tumor volume including necrosis (TTV), excluding necrosis (TV), and the necrosis-only volume (NV) were segmented on early-phase DCE subtractions and DWI images. NV and %NV were calculated. Percent enhancement on early and late phases of DCE and apparent diffusion coefficient were extracted from TTV, TV, and NV. Association between necrosis with pathological complete response (pCR) was assessed using odds ratio (OR). Multivariable analysis was used to evaluate the prognostic value of necrosis with T stage and nodal status at staging. Mann–Whitney U tests and area under the curve (AUC) were used to assess performance of imaging metrics for discriminating pCR vs non-pCR.

Results

Of 39 patients (46%) with necrosis, 17 had pCR and 22 did not. Necrosis was not associated with pCR (OR, 0.995; 95% confidence interval [CI] 0.4–2.3) and was not an independent prognostic factor when combined with T stage and nodal status at staging (P = 0.46). None of the imaging metrics differed significantly between pCR and non-pCR in patients with necrosis (AUC < 0.6 and P > 0.40).

Conclusion

No significant association was found between necrosis by pretreatment MRI or the quantitative imaging characteristics of tumor necrosis and response to NAST in TNBC.

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Abbreviations

ADC:

Apparent diffusion coefficient

DCE:

DYNAMIC contrast enhanced

DWI:

Diffusion-weighted imaging

NAST:

Neoadjuvant systemic therapy

NV:

Necrosis volume

pCR:

Pathological complete response

PE:

Percent enhancement

TNBC:

Triple-negative breast cancer

TTV:

Total tumor volume

TV:

Tumor volume without necrosis

References

  1. Bao C, Lu Y, Chen J, Chen D, Lou W, Ding B, Xu L, Fan W (2019) Exploring specific prognostic biomarkers in triple-negative breast cancer. Cell Death Dis 10(11):807

    Article  Google Scholar 

  2. Bae MS, Shin SU, Ryu HS, Han W, Im SA, Park IA, Noh DY, Moon WK (2016) Pretreatment mr imaging features of triple-negative breast cancer: association with response to neoadjuvant chemotherapy and recurrence-free survival. Radiology 281(2):392–400

    Article  Google Scholar 

  3. Maiorano E, Regan MM, Viale G, Mastropasqua MG, Colleoni M, Castiglione-Gertsch M, Price KN, Gelber RD, Goldhirsch A, Coates AS (2010) Prognostic and predictive impact of central necrosis and fibrosis in early breast cancer: Results from two international breast cancer study group randomized trials of chemoendocrine adjuvant therapy. Breast Cancer Res Treat 121(1):211–218

    Article  Google Scholar 

  4. Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V (2007) Descriptive analysis of estrogen receptor (er)-negative, progesterone receptor (pr)-negative, and her2-negative invasive breast cancer, the so-called triple-negative phenotype. Cancer 109(9):1721–1728

    Article  Google Scholar 

  5. Richards CH, Mohammed Z, Qayyum T, Horgan PG, McMillan DC (2011) The prognostic value of histological tumor necrosis in solid organ malignant disease: a systematic review. Future Oncol 7(10):1223–1235

    Article  CAS  Google Scholar 

  6. Vayrynen SA, Vayrynen JP, Klintrup K, Makela J, Karttunen TJ, Tuomisto A, Makinen MJ (2016) Clinical impact and network of determinants of tumour necrosis in colorectal cancer. Br J Cancer 114(12):1334–1342

    Article  CAS  Google Scholar 

  7. Fujisaki A, Aoki T, Kasai T, Kinoshita S, Tomoda Y, Tanaka F, Yatera K, Mukae H, Korogi Y (2016) Pleomorphic carcinoma of the lung: Relationship between ct findings and prognosis. AJR Am J Roentgenol 207(2):289–294

    Article  Google Scholar 

  8. Zhang L, Zha Z, Qu W, Zhao H, Yuan J, Feng Y, Wu B (2018) Tumor necrosis as a prognostic variable for the clinical outcome in patients with renal cell carcinoma: a systematic review and meta-analysis. BMC Cancer 18(1):870

    Article  Google Scholar 

  9. Dietzel M, Baltzer PA, Vag T, Herzog A, Gajda M, Camara O, Kaiser WA (2010) The necrosis sign in magnetic resonance-mammography: diagnostic accuracy in 1,084 histologically verified breast lesions. Breast J 16(6):603–608

    Article  Google Scholar 

  10. Jimenez RE, Wallis T, Visscher DW (2001) Centrally necrotizing carcinomas of the breast: a distinct histologic subtype with aggressive clinical behavior. Am J Surg Pathol 25(3):331–337

    Article  CAS  Google Scholar 

  11. Zhang Y, Ou Y, Yu D, Yong X, Wang X, Zhu B, Zhang Q, Zhou L, Cai Z, Cheng Z (2015) Clinicopathological study of centrally necrotizing carcinoma of the breast. BMC Cancer 15:282

    Article  Google Scholar 

  12. Pu RT, Schott AF, Sturtz DE, Griffith KA, Kleer CG (2005) Pathologic features of breast cancer associated with complete response to neoadjuvant chemotherapy: importance of tumor necrosis. Am J Surg Pathol 29(3):354–358

    Article  Google Scholar 

  13. Masood S (2016) Neoadjuvant chemotherapy in breast cancers. Womens Health (Lond) 12(5):480–491

    Article  Google Scholar 

  14. Lee AH, Gillett CE, Ryder K, Fentiman IS, Miles DW, Millis RR (2006) Different patterns of inflammation and prognosis in invasive carcinoma of the breast. Histopathology 48(6):692–701

    Article  CAS  Google Scholar 

  15. Kato T, Kimura T, Miyakawa R, Tanaka S, Fujii A, Yamamoto K, Kameoka S, Hamano K, Kawakami M, Aiba M (1997) Clinicopathologic study of angiogenesis in japanese patients with breast cancer. World J Surg 21(1):49–56

    Article  CAS  Google Scholar 

  16. Urru SAM, Gallus S, Bosetti C, Moi T, Medda R, Sollai E, Murgia A, Sanges F, Pira G, Manca A, Palmas D, Floris M, Asunis AM, Atzori F, Carru C, D'Incalci M, Ghiani M, Marras V, Onnis D, Santona MC, Sarobba G, Valle E, Canu L, Cossu S, Bulfone A, Rocca PC, De Miglio MR, Orru S (2018) Clinical and pathological factors influencing survival in a large cohort of triple-negative breast cancer patients. BMC Cancer 18(1):56

    Article  Google Scholar 

  17. Uematsu T, Kasami M, Yuen S (2009) Triple-negative breast cancer: correlation between mr imaging and pathologic findings. Radiology 250(3):638–647

    Article  Google Scholar 

  18. Keam B, Im SA, Lee KH, Han SW, Oh DY, Kim JH, Lee SH, Han W, Kim DW, Kim TY, Park IA, Noh DY, Heo DS, Bang YJ (2011) Ki-67 can be used for further classification of triple negative breast cancer into two subtypes with different response and prognosis. Breast Cancer Res 13(2):R22

    Article  Google Scholar 

  19. Walsh EM, Keane MM, Wink DA, Callagy G, Glynn SA (2016) Review of triple negative breast cancer and the impact of inducible nitric oxide synthase on tumor biology and patient outcomes. Crit Rev Oncog 21(5–6):333–351

    Article  Google Scholar 

  20. Fulford LG, Easton DF, Reis-Filho JS, Sofronis A, Gillett CE, Lakhani SR, Hanby A (2006) Specific morphological features predictive for the basal phenotype in grade 3 invasive ductal carcinoma of breast. Histopathology 49(1):22–34

    Article  CAS  Google Scholar 

  21. Ryu DW, Jung MJ, Choi WS, Lee CH (2011) Clinical significance of morphologic characteristics in triple negative breast cancer. J Korean Surg Soc 80(5):301–306

    Article  Google Scholar 

  22. Kawashima H, Inokuchi M, Furukawa H, Kitamura S (2011) Triple-negative breast cancer: are the imaging findings different between responders and nonresponders to neoadjuvant chemotherapy? Acad Radiol 18(8):963–969

    Article  Google Scholar 

  23. Fang P, Musall BC, Son JB, Moreno AC, Hobbs BP, Carter BW, Fellman BM, Mawlawi O, Ma J, Lin SH (2018) Multimodal imaging of pathologic response to chemoradiation in esophageal cancer. Int J Radiat Oncol Biol Phys 102(4):996–1001

    Article  Google Scholar 

  24. Collins J, Epstein JI (2017) Prognostic significance of extensive necrosis in renal cell carcinoma. Hum Pathol 66:108–114

    Article  CAS  Google Scholar 

  25. Rilke F, Colnaghi MI, Cascinelli N, Andreola S, Baldini MT, Bufalino R, Della Porta G, Menard S, Pierotti MA, Testori A (1991) Prognostic significance of her-2/neu expression in breast cancer and its relationship to other prognostic factors. Int J Cancer 49(1):44–49

    Article  CAS  Google Scholar 

  26. Liu YX, Wang KR, Xing H, Zhai XJ, Wang LP, Wang W (2016) Attempt towards a novel classification of triple-negative breast cancer using immunohistochemical markers. Oncol Lett 12(2):1240–1256

    Article  CAS  Google Scholar 

  27. Pistelli M, Pagliacci A, Battelli N, Santinelli A, Biscotti T, Ballatore Z, Berardi R, Cascinu S (2013) Prognostic factors in early-stage triple-negative breast cancer: lessons and limits from clinical practice. Anticancer Res 33(6):2737–2742

    CAS  PubMed  Google Scholar 

  28. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, Swain SM, Prowell T, Loibl S, Wickerham DL, Bogaerts J, Baselga J, Perou C, Blumenthal G, Blohmer J, Mamounas EP, Bergh J, Semiglazov V, Justice R, Eidtmann H, Paik S, Piccart M, Sridhara R, Fasching PA, Slaets L, Tang S, Gerber B, Geyer CE Jr, Pazdur R, Ditsch N, Rastogi P, Eiermann W, von Minckwitz G (2014) Pathological complete response and long-term clinical benefit in breast cancer: the ctneobc pooled analysis. Lancet 384(9938):164–172

    Article  Google Scholar 

  29. Hudis CA, Barlow WE, Costantino JP, Gray RJ, Pritchard KI, Chapman JA, Sparano JA, Hunsberger S, Enos RA, Gelber RD, Zujewski JA (2007) Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the steep system. J Clin Oncol 25(15):2127–2132

    Article  Google Scholar 

  30. Moulder S, Moroney J, Helgason T, Wheler J, Booser D, Albarracin C, Morrow PK, Koenig K, Kurzrock R (2011) Responses to liposomal doxorubicin, bevacizumab, and temsirolimus in metaplastic carcinoma of the breast: biologic rationale and implications for stem-cell research in breast cancer. J Clin Oncol 29(19):e572–575

    Article  Google Scholar 

  31. Houssami N, Macaskill P, von Minckwitz G, Marinovich ML, Mamounas E (2012) Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy. Eur J Cancer 48(18):3342–3354

    Article  CAS  Google Scholar 

  32. Sharma P, Lopez-Tarruella S, Garcia-Saenz JA, Khan QJ, Gomez HL, Prat A, Moreno F, Jerez-Gilarranz Y, Barnadas A, Picornell AC, Monte-Millan MD, Gonzalez-Rivera M, Massarrah T, Pelaez-Lorenzo B, Palomero MI, Gonzalez Del Val R, Cortes J, Fuentes-Rivera H, Morales DB, Marquez-Rodas I, Perou CM, Lehn C, Wang YY, Klemp JR, Mammen JV, Wagner JL, Amin AL, O'Dea AP, Heldstab J, Jensen RA, Kimler BF, Godwin AK, Martin M (2018) Pathological response and survival in triple-negative breast cancer following neoadjuvant carboplatin plus docetaxel. Clin Cancer Res 24(23):5820–5829

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank Stephanie P. Deming from the Department of Scientific Publications, Research Medical Library, at The University of Texas MD Anderson Cancer Center for her assistance in editing and proofreading this document.

Funding

This study has received funding by the National Institutes of Health/National Cancer Institute (Cancer Center Support Grant P30 CA016672); specifically resources from the Biostatistics Resource Group were used.

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    Authors and Affiliations

    1. Department of Breast Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1350, Houston, TX, 77030, USA

      Abeer H. Abdelhafez, Beatriz E. Adrada, Rosalind P. Candelaria, Lumarie Santiago, Gary J. Whitman, Huong T. Le-Petross, Tanya W. Moseley, Elsa Arribas, Deanna L. Lane, Marion E. Scoggins, Jessica W. T. Leung, Hagar S. Mahmoud, Wei T. Yang & Gaiane M. Rauch

    2. Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1472, Houston, TX, 77030, USA

      Benjamin C. Musall, Jong Bum Son, Ken-Pin Hwang, Mark D. Pagel & Jingfei Ma

    3. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1411, Houston, TX, 77030, USA

      KennethR. Hess & Peng Wei

    4. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1354, Houston, TX, 77030, USA

      Jason B. White, Elizabeth E. Ravenberg, Jennifer K. Litton, Vicente Valero & Stacy L. Moulder

    5. Department of Surgery, Baylor College of Medicine, 7200 Cambridge St., Houston, TX, 77030, USA

      Alastair M. Thompson

    6. Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1907, Houston, TX, 77030, USA

      Mark D. Pagel

    7. Division of Diagnostic Imaging, Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1473, Houston, TX, 77030, USA

      Gaiane M. Rauch

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    1. Abeer H. Abdelhafez
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    Correspondence to Gaiane M. Rauch.

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    Conflict of interest

    Dr. Ken-Pin Hwang receives research funding from GE Healthcare; Dr. Tanya W. Moseley is an imaging consultant for Hologic Inc. and Merit Medical Inc.; Dr. Elsa Arribas is a shareholder and serves on the advisory board for Volumetric, Inc.; Dr. Jessica W.T. Leung is an advisor for Subtle Imaging and CureMetrix, and is a speaker for Fujifilm; Dr. Jingfei Ma has ongoing financial relationships with GE Healthcare, Siemens Healthcare, and C4 Imaging; Dr. Mark D. Pagel receives research funding from BioInVision, Inc., and Roche Pharma; receives research benefits from iThera Medical, Inc., Phantech, Inc., and PhotoSound, Inc.; and has a financial relationship with Genentech, Inc.; Dr. Wei T. Yang receives royalties from Elsevier; Dr. Gaiane M. Rauch receives research funding from GE Healthcare.

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    Abeer H. Abdelhafez and Benjamin C. Musall have contributed equally to this work and share co-first authorship.

    Wei T. Yang and Gaiane M. Rauch have contributed equally to this work and share co-last authorship.

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    Abdelhafez, A.H., Musall, B.C., Adrada, B.E. et al. Tumor necrosis by pretreatment breast MRI: association with neoadjuvant systemic therapy (NAST) response in triple-negative breast cancer (TNBC). Breast Cancer Res Treat 185, 1–12 (2021). https://doi.org/10.1007/s10549-020-05917-7

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