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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 13/2019

Open Access 01-12-2019 | Breast Cancer | Breast Oncology

Validation of Residual Cancer Burden as Prognostic Factor for Breast Cancer Patients After Neoadjuvant Therapy

Authors: Hannah Deborah Müller, MD, Florian Posch, MD, Christoph Suppan, MD, Ute Bargfrieder, MD, Melanie Gumpoldsberger, MD, Robert Hammer, MD, Hubert Hauser, MD, Nadia Dandachi, PhD, Kurt Prein, MD, Herbert Stoeger, MD, Sigurd Lax, MD, Marija Balic, MD, PhD

Published in: Annals of Surgical Oncology | Issue 13/2019

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Abstract

Background

Assessing the residual cancer burden (RCB) predictive performance, the potential subgroup effects, and time-dependent impact on breast cancer patients who underwent neoadjuvant therapy in a developer’s independent cohort is essential for its usage in clinical routine.

Methods

Between 2011 and 2016, the RCB scores of 184 female breast cancer patients were prospectively collected, and subsequent clinicopathological and follow-up data were obtained retrospectively. Recurrence-free survival (RFS), overall survival (OS), as well as subgroup analysis, and time-dependent variables were calculated with multivariate, complex, or linear statistical models.

Results

A total of 184 patients (HER2 33%, TNBC 27%), with a mean follow-up time of 4 years, treated with neoadjuvant systemic therapy (92% anthracycline-taxane based) were analyzed revealing 43 events (38 recurrences, 28 deaths). High RCB scores were associated with recurrence (median index: 2.34 vs. 1.39 points, rank-sum p < 0.0001), decreased RFS (hazard ratio [HR] = 1.80, 95% confidence interval [CI] 1.44–2.24, p < 0.0001) and reduced OS (HR 1.96, 95% CI 1.49–2.59, p < 0.0001). The RCB score showed proportionality of hazards (interaction HR with linear follow-up time = 1.00, p = 0.896) and good discriminating power (Harrell’s c index 0.7).

Conclusions

Our results confirm the RCB score as externally valid prognostic marker and being independent of molecular subtype for RFS and OS in a clinical setting.
Appendix
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Literature
1.
2.
Ferlay J, Colombet M, Soerjomataram I, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer. 2018;103:356–387.CrossRefPubMed
3.
DeSantis CE, Ma J, Goding Sauer A, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 2017;67(6):439–48.CrossRefPubMed
4.
DeSantis C, Ma J, Bryan L, Jemal A. Breast cancer statistics, 2013. CA Cancer J Clin. 2014;64(1):52–62.CrossRefPubMed
5.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.CrossRefPubMed
6.
7.
Berruti A, Amoroso V, Gallo F, et al. Pathologic complete response as a potential surrogate for the clinical outcome in patients with breast cancer after neoadjuvant therapy: a meta-regression of 29 randomized prospective studies. J Clin Oncol. 2014;32(34):3883–91.CrossRefPubMed
8.
Von Minckwitz G, Untch M, Blohmer J-U, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30(15):1796–804.CrossRef
9.
Chen JH, Bahri S, Mehta RS, et al. Impact of factors affecting the residual tumor size diagnosed by MRI following neoadjuvant chemotherapy in comparison to pathology. J Surg Oncol. 2014;109(2):158–67.CrossRefPubMed
10.
Cardoso F, Harbeck N, Fallowfield L, Kyriakides S, Senkus E, ESMO Guidelines Working Group. Locally recurrent or metastatic breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(suppl_7):vii11–19.PubMed
11.
Schott AF, Roubidoux MA, Helvie MA, et al. Clinical and radiologic assessments to predict breast cancer pathologic complete response to neoadjuvant chemotherapy. Breast Cancer Res Treat. 2005;92(3):231–8.CrossRefPubMed
12.
Schott AF, Hayes DF. Defining the benefits of neoadjuvant chemotherapy for breast cancer. J Clin Oncol. 2012;30(15):1747.CrossRefPubMed
13.
Mazouni C, Peintinger F, Wan-Kau S, et al. Residual ductal carcinoma in situ in patients with complete eradication of invasive breast cancer after neoadjuvant chemotherapy does not adversely affect patient outcome. J Clin Oncol. 2007;25(19):2650–5.CrossRefPubMed
14.
Honkoop A, Van Diest P, De Jong J, et al. Prognostic role of clinical, pathological and biological characteristics in patients with locally advanced breast cancer. Br J Cancer. 1998;77(4):621.CrossRefPubMedPubMedCentral
15.
Cockburn A, Yan J, Rahardja D, et al. Modulatory effect of neoadjuvant chemotherapy on biomarkers expression; assessment by digital image analysis and relationship to residual cancer burden in patients with invasive breast cancer. Hum Pathol. 2014;45(2):249–58.CrossRefPubMed
16.
Fisher B, Bryant J, Wolmark N, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998;16(8):2672–85.CrossRefPubMed
17.
Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007;25(28):4414–22.CrossRefPubMed
18.
Rouzier R, Extra J-M, Klijanienko J, et al. Incidence and prognostic significance of complete axillary downstaging after primary chemotherapy in breast cancer patients with T1 to T3 tumors and cytologically proven axillary metastatic lymph nodes. J Clin Oncol. 2002;20(5):1304–10.CrossRefPubMed
19.
Earl H, Provenzano E, Abraham J, et al. Neoadjuvant trials in early breast cancer: pathological response at surgery and correlation to longer term outcomes–what does it all mean? BMC Med. 2015;13(1):234.CrossRefPubMedPubMedCentral
20.
Romero A, Garcia-Saenz J, Fuentes-Ferrer M, et al. Correlation between response to neoadjuvant chemotherapy and survival in locally advanced breast cancer patients. Ann Oncol. 2012;24(3):655–61.CrossRefPubMed
21.
Hennessy BT, Hortobagyi GN, Rouzier R, et al. Outcome after pathologic complete eradication of cytologically proven breast cancer axillary node metastases following primary chemotherapy. J Clin Oncol. 2005;23(36):9304–11.CrossRefPubMed
22.
Guarneri V, Broglio K, Kau S-W, et al. Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol. 2006;24(7):1037–44.CrossRefPubMed
23.
Abrial SC, Penault-Llorca F, Delva R, et al. High prognostic significance of residual disease after neoadjuvant chemotherapy: a retrospective study in 710 patients with operable breast cancer. Breast Ccancer Res Treat. 2005;94(3):255–63.CrossRef
24.
Provenzano E, Bossuyt V, Viale G, et al. Standardization of pathologic evaluation and reporting of postneoadjuvant specimens in clinical trials of breast cancer: recommendations from an international working group. Mod Pathol. 2015;28(9):1185.CrossRefPubMed
25.
Kaufmann M, Hortobagyi GN, Goldhirsch A, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol. 2006;24(12):1940–9.CrossRefPubMed
26.
Bossuyt V, Provenzano E, Symmans W, et al. Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration. Ann Oncol. 2015;26(7):1280–91.CrossRefPubMedPubMedCentral
27.
Symmans WF, Wei C, Gould R, et al. Long-term prognostic risk after neoadjuvant chemotherapy associated with residual cancer burden and breast cancer subtype. J Clin Oncol. 2017;35(10):1049–60.CrossRefPubMedPubMedCentral
28.
Naidoo K, Parham DM, Pinder SE. An audit of residual cancer burden reproducibility in a UK context. Histopathology. 2017;70(2):217–22.CrossRefPubMed
29.
Choi M, Park YH, Ahn JS, et al. Assessment of pathologic response and long-term outcome in locally advanced breast cancers after neoadjuvant chemotherapy: comparison of pathologic classification systems. Breast Cancer Res Treat. 2016;160(3):475–89.CrossRefPubMed
30.
Corben AD, Abi-Raad R, Popa I, et al. Pathologic response and long-term follow-up in breast cancer patients treated with neoadjuvant chemotherapy: a comparison between classifications and their practical application. Arch Pathol Lab Med. 2013;137(8):1074–82.CrossRefPubMed
31.
Campbell JI, Yau C, Krass P, et al. Comparison of residual cancer burden, American Joint Committee on Cancer staging and pathologic complete response in breast cancer after neoadjuvant chemotherapy: results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657). Breast Cancer Res Treat. 2017;165(1):181–91.CrossRefPubMedPubMedCentral
32.
Peintinger F, Sinn B, Hatzis C, et al. Reproducibility of residual cancer burden for prognostic assessment of breast cancer after neoadjuvant chemotherapy. Mod Pathol. 2015;28(7):913.CrossRefPubMedPubMedCentral
33.
Sharma P, López-Tarruella S, García-Saenz JA, et al. Pathological response and survival in triple-negative breast cancer following neoadjuvant carboplatin plus docetaxel. Clin Cancer Res. 2018;24:5820–5829.CrossRefPubMedPubMedCentral
34.
Quintela-Fandino M, Lluch A, Manso L, et al. 18F-fluoromisonidazole PET and activity of neoadjuvant nintedanib in early HER2-negative breast cancer: a window-of-opportunity randomized trial. Clin Cancer Res. 2017;23(6):1432–41.CrossRefPubMed
35.
Cottu P, D’hondt V, Dureau S, et al. Letrozole and palbociclib versus chemotherapy as neoadjuvant therapy of high-risk luminal breast cancer. Ann Oncol. 2018;29:2334–2340.CrossRefPubMed
36.
Martín M, Chacón JI, Antón A, et al. Neoadjuvant therapy with weekly nanoparticle albumin-bound paclitaxel for luminal early breast cancer patients: results from the NABRAX Study (GEICAM/2011-02), a multicenter, non-randomized, phase II Trial, with a companion biomarker analysis. Oncologist. 2017;22(11):1301–8.CrossRefPubMedPubMedCentral
37.
Hammond MEH, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med. 2010;134(7):e48–72.PubMed
38.
Kosa C, Kardos L, Kovacs J, Szollosi Z. Comparison of dual-color dual-hapten brightfield in situ hybridization (DDISH) and fluorescence in situ hybridization in breast cancer HER2 assessment. Pathol Res Pract. 2013;209(3):147–50.CrossRefPubMed
39.
40.
Wolff AC, Hammond MEH, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007;131(1):18–43.PubMed
41.
Wolff AC, Hammond MEH, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med. 2013;138(2):241–56.CrossRefPubMedPubMedCentral
42.
43.
Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Contemporary Clin Trials. 1996;17(4):343–6.CrossRef
44.
Pencina MJ, D’Agostino RB. Overall C as a measure of discrimination in survival analysis: model specific population value and confidence interval estimation. Stat Med. 2004;23(13):2109–23.CrossRefPubMed
45.
Prat A, Pineda E, Adamo B, et al. Clinical implications of the intrinsic molecular subtypes of breast cancer. Breast. 2015;24:S26–35.CrossRefPubMed
46.
Sueta A, Yamamoto Y, Hayashi M, et al. Clinical significance of pretherapeutic Ki67 as a predictive parameter for response to neoadjuvant chemotherapy in breast cancer: is it equally useful across tumor subtypes? Surgery. 2014;155(5):927–35.CrossRefPubMed
47.
Sheri A, Smith I, Johnston S, et al. Residual proliferative cancer burden to predict long-term outcome following neoadjuvant chemotherapy. Ann Oncol. 2014;26(1):75–80.CrossRefPubMed
48.
Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008;26(8):1275–81.CrossRefPubMed
49.
Buzdar AU, Ibrahim NK, Francis D, et al. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2–positive operable breast cancer. J Clin Oncol. 2005;23(16):3676–85.CrossRefPubMed
Metadata
Title
Validation of Residual Cancer Burden as Prognostic Factor for Breast Cancer Patients After Neoadjuvant Therapy
Authors
Hannah Deborah Müller, MD
Florian Posch, MD
Christoph Suppan, MD
Ute Bargfrieder, MD
Melanie Gumpoldsberger, MD
Robert Hammer, MD
Hubert Hauser, MD
Nadia Dandachi, PhD
Kurt Prein, MD
Herbert Stoeger, MD
Sigurd Lax, MD
Marija Balic, MD, PhD
Publication date
01-12-2019
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 13/2019
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-019-07741-w

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