Diagnosis of pathological complete response to neoadjuvant chemotherapy in breast cancer by minimal invasive biopsy techniques

Joerg Heil, Sherko Kümmel, Benedikt Schaefgen, Stefan Paepke, Christoph Thomssen, Geraldine Rauch, Beyhan Ataseven, Regina Große, Volker Dreesmann, Thorsten Kühn, Sibylle Loibl, Jens-Uwe Blohmer, Gunter von Minckwitz, Joerg Heil, Sherko Kümmel, Benedikt Schaefgen, Stefan Paepke, Christoph Thomssen, Geraldine Rauch, Beyhan Ataseven, Regina Große, Volker Dreesmann, Thorsten Kühn, Sibylle Loibl, Jens-Uwe Blohmer, Gunter von Minckwitz

Abstract

Background: Neoadjuvant chemotherapy (NACT) is widely used as an efficient breast cancer treatment. Ideally, a pathological complete response (pCR) can be achieved. Up to date, there is no reliable way of predicting a pCR. For the first time, we explore the ability of minimal invasive biopsy (MIB) techniques to diagnose pCR in patients with clinical complete response (cCR) to NACT in this study. This question is of high clinical relevance because a reliable pCR prediction could have direct implications for clinical practice.

Methods: In all, 164 patients were included in this review-board approved, multicenter pooled analysis of prospectively assembled data. Core-cut (CC)-MIB or vacuum-assisted (VAB)-MIB were performed after NACT and before surgery. Negative predictive values (NPV) and false-negative rates (FNR) to predict a pCR in surgical specimen (diagnose pCR through MIB) were the main outcome measures.

Results: Pathological complete response in surgical specimen was diagnosed in 93 (56.7%) cases of the whole cohort. The NPV of the MIB diagnosis of pCR was 71.3% (95% CI: (63.3%; 79.3%)). The FNR was 49.3% (95% CI: (40.4%; 58.2%)). Existence of a clip marker tended to improve the NPV (odds ratio 1.98; 95% CI: (0.81; 4.85)). None of the mammographically guided VABs (n=16) was false-negative (FNR 0%, NPV 100%).

Conclusions: Overall accuracy of MIB diagnosis of pCR was insufficient to suggest changing clinical practice. However, subgroup analyses (mammographically guided VABs) suggest a potential capacity of MIB techniques to precisely diagnose pCR after NACT. Representativity of MIB could be a crucial factor to be focused on in further analyses.

References

    1. ACR Guidelines and Standards Comiittee BL, Berg WA, Birdwell RL (2008) American College of Radiology Practice Guidelines for the Performance of Magnetic Resonance Imaging of the Breast. Available from (cited in 2014).
    1. Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, Brown AM, Robidoux A, Margolese R, Kahlenberg MS, Paik S, Soran A, Wickerham DL, Wolmark N (2006) Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 24(13): 2019–2027.
    1. Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Moher D, Rennie D, de Vet HC, Lijmer JG Standards for Reporting of Diagnostic Accuracy G (2003) The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. The Standards for Reporting of Diagnostic Accuracy Group. Croat Med J 44(5): 639–650.
    1. Chagpar AB, Middleton LP, Sahin AA, Dempsey P, Buzdar AU, Mirza AN, Ames FC, Babiera GV, Feig BW, Hunt KK, Kuerer HM, Meric-Bernstam F, Ross MI, Singletary SE (2006) Accuracy of physical examination, ultrasonography, and mammography in predicting residual pathologic tumor size in patients treated with neoadjuvant chemotherapy. Ann Surg 243(2): 257–264.
    1. 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.
    1. Croshaw R, Shapiro-Wright H, Svensson E, Erb K, Julian T (2011) Accuracy of clinical examination, digital mammogram, ultrasound, and MRI in determining postneoadjuvant pathologic tumor response in operable breast cancer patients. Ann Surg Oncol 18(11): 3160–3163.
    1. Denis F, Desbiez-Bourcier AV, Chapiron C, Arbion F, Body G, Brunereau L (2004) Contrast enhanced magnetic resonance imaging underestimates residual disease following neoadjuvant docetaxel based chemotherapy for breast cancer. Eur J Surg Oncol 30(10): 1069–1076.
    1. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2): 228–247.
    1. Fiorentino C, Berruti A, Bottini A, Bodini M, Brizzi MP, Brunelli A, Marini U, Allevi G, Aguggini S, Tira A, Alquati P, Olivetti L, Dogliotti L (2001) Accuracy of mammography and echography versus clinical palpation in the assessment of response to primary chemotherapy in breast cancer patients with operable disease. Breast Cancer Res Treat 69(2): 143–151.
    1. Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, Cruz AB Jr, Fisher ER, Wickerham DL, Wolmark N, DeCillis A, Hoehn JL, Lees AW, Dimitrov NV (1997) Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol 15(7): 2483–2493.
    1. Gianni L, Zambetti M, Clark K, Baker J, Cronin M, Wu J, Mariani G, Rodriguez J, Carcangiu M, Watson D, Valagussa P, Rouzier R, Symmans WF, Ross JS, Hortobagyi GN, Pusztai L, Shak S (2005) Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol 23(29): 7265–7277.
    1. Goldstein NS, Decker D, Severson D, Schell S, Vicini F, Margolis J, Dekhne NS (2007) Molecular classification system identifies invasive breast carcinoma patients who are most likely and those who are least likely to achieve a complete pathologic response after neoadjuvant chemotherapy. Cancer 110(8): 1687–1696.
    1. Kaufmann M, Hortobagyi GN, Goldhirsch A, Scholl S, Makris A, Valagussa P, Blohmer JU, Eiermann W, Jackesz R, Jonat W, Lebeau A, Loibl S, Miller W, Seeber S, Semiglazov V, Smith R, Souchon R, Stearns V, Untch M, von Minckwitz G (2006) Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol 24(12): 1940–1949.
    1. Kummel S, Holtschmidt J, Loibl S (2014) Surgical treatment of primary breast cancer in the neoadjuvant setting. Br J Surg 101(8): 912–924.
    1. Londero V, Bazzocchi M, Del Frate C, Puglisi F, Di Loreto C, Francescutti G, Zuiani C (2004) Locally advanced breast cancer: comparison of mammography, sonography and MR imaging in evaluation of residual disease in women receiving neoadjuvant chemotherapy. Eur Radiol 14(8): 1371–1379.
    1. Marinovich ML, Houssami N, Macaskill P, Sardanelli F, Irwig L, Mamounas EP, von Minckwitz G, Brennan ME, Ciatto S (2013) Meta-analysis of magnetic resonance imaging in detecting residual breast cancer after neoadjuvant therapy. J Natl Cancer Inst 105(5): 321–333.
    1. Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47(1): 207–214.
    1. NICE (2009) Early and Locally Advanced Breast Cancer: Diagnosis and Treatment; (NICE Clinical Guidelines, No. 80.). Cardiff (UK): National Collaborating Centre for Cancer (UK).
    1. Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortes J (2013) Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 24(9): 2278–2284.
    1. Schott AF, Roubidoux MA, Helvie MA, Hayes DF, Kleer CG, Newman LA, Pierce LJ, Griffith KA, Murray S, Hunt KA, Paramagul C, Baker LH (2005) Clinical and radiologic assessments to predict breast cancer pathologic complete response to neoadjuvant chemotherapy. Breast Cancer Res Treat 92(3): 231–238.
    1. Shin HJ, Kim HH, Ahn JH, Kim SB, Jung KH, Gong G, Son BH, Ahn SH (2011) Comparison of mammography, sonography, MRI and clinical examination in patients with locally advanced or inflammatory breast cancer who underwent neoadjuvant chemotherapy. Br J Radiol 84(1003): 612–620.
    1. Tiezzi DG, Andrade JM, Ribeiro-Silva A, Zola FE, Marana HR, Tiezzi MG (2007) HER-2, p53, p21 and hormonal receptors proteins expression as predictive factors of response and prognosis in locally advanced breast cancer treated with neoadjuvant docetaxel plus epirubicin combination. BMC Cancer 7: 36.
    1. van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L (2001) Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol 19(22): 4224–4237.
    1. von Minckwitz G, Kummel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J, Gerber B, Huober J, Costa SD, Jackisch C, Loibl S, Mehta K, Kaufmann M (2008) Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase III randomized GeparTrio study. J Natl Cancer Inst 100(8): 552–562.
    1. von Minckwitz G, Loibl S, Untch M, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Huober J, Solbach C, Jackisch C, Kunz G, Blohmer JU, Hauschild M, Fehm T, Nekljudova V, Gerber B for the GBGAGOBsg (2014. a) Survival after neoadjuvant chemotherapy with or without bevacizumab or everolimus for HER2-negative primary breast cancer (GBG 44 - GeparQuinto). Ann Oncol 25(12): 2363–2372.
    1. von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, Blohmer JU, Jackisch C, Paepke S, Gerber B, Zahm DM, Kummel S, Eidtmann H, Klare P, Huober J, Costa S, Tesch H, Hanusch C, Hilfrich J, Khandan F, Fasching PA, Sinn BV, Engels K, Mehta K, Nekljudova V, Untch M (2014. b) Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol 15(7): 747–756.
    1. von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, Gerber B, Eiermann W, Hilfrich J, Huober J, Jackisch C, Kaufmann M, Konecny GE, Denkert C, Nekljudova V, Mehta K, Loibl S (2012) Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 30(15): 1796–1804.
    1. Wockel A, Kreienberg R (2008) First Revision of the German S3 Guideline ‘Diagnosis, Therapy, and Follow-Up of Breast Cancer'. Breast Care (Basel) 3(2): 82–86.
    1. Yeh E, Slanetz P, Kopans DB, Rafferty E, Georgian-Smith D, Moy L, Halpern E, Moore R, Kuter I, Taghian A (2005) Prospective comparison of mammography, sonography, and MRI in patients undergoing neoadjuvant chemotherapy for palpable breast cancer. AJR Am J Roentgenol 184(3): 868–877.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren