Korean J Radiol.  2015 Oct;16(5):986-995. 10.3348/kjr.2015.16.5.986.

Prognostic Significance of a Complete Response on Breast MRI in Patients Who Received Neoadjuvant Chemotherapy According to the Molecular Subtype

• Ko ES
• Han H
• Han BK
• Kim SM
• Kim RB
• Lee GW
• Park YH
• Nam SJ

• KMID: 2160765
• DOI: http://doi.org/10.3348/kjr.2015.16.5.986

Abstract

OBJECTIVE
To evaluate the relationship between response categories assessed by magnetic resonance imaging (MRI) or pathology and survival outcomes, and to determine whether there are prognostic differences among molecular subtypes.
MATERIALS AND METHODS
We evaluated 174 patients with biopsy-confirmed invasive breast cancer who had undergone MRI before and after neoadjuvant chemotherapy, but before surgery. Pathology findings were classified as a pathologic complete response (pCR) or a non-pCR, and MRI findings were designated as a radiologic CR (rCR) or a non-rCR. We evaluated overall and subtype-specific associations between clinicopathological factors including the assessment categories and recurrence, using the Cox proportional hazards model.
RESULTS
There were 41 recurrences (9 locoregional and 32 distant recurrences). There were statistically significant differences in recurrence outcomes between patients who achieved a radiologic or a pCR and patients who did not achieve a radiologic or a pCR (recurrence hazard ratio, 11.02; p = 0.018 and recurrence hazard ratio, 3.93; p = 0.022, respectively). Kaplan-Meier curves for recurrence-free survival showed that triple-negative breast cancer was the only subtype that showed significantly better outcomes in patients who achieved a CR compared to patients who did not achieve a CR by both radiologic and pathologic assessments (p = 0.004 and 0.001, respectively). A multivariate analysis found that patients who achieved a rCR and a pCR did not display significantly different recurrence outcomes (recurrence hazard ratio, 2.02; p = 0.505 and recurrence hazard ratio, 1.12; p = 0.869, respectively).
CONCLUSION
Outcomes of patients who achieved a rCR were similar to those of patients who achieved a pCR. To evaluate survival difference according to molecular subtypes, a larger study is needed.

Keyword

Breast cancer; Magnetic resonance imaging; Neoadjuvant chemotherapy; Prognosis; Subtype

MeSH Terms

Adult
Aged
Antineoplastic Agents/therapeutic use
Breast Neoplasms/drug therapy/mortality/*pathology
Female
Humans
Kaplan-Meier Estimate
*Magnetic Resonance Imaging
Middle Aged
Neoadjuvant Therapy
Neoplasm Recurrence, Local
Prognosis
Proportional Hazards Models
Receptor, ErbB-2/genetics/metabolism
Receptors, Estrogen/genetics/metabolism
Receptors, Progesterone/genetics/metabolism
Remission Induction
Antineoplastic Agents
Receptor, ErbB-2
Receptors, Estrogen
Receptors, Progesterone

Figure

• 

  Fig. 1 Kaplan-Meier curves for survival based on magnetic resonance imaging assessment category (A) or pathologic assessment category (B). CR = complete response

• 

  Fig. 2 Kaplan-Meier curves for survival in each breast cancer molecular subtype. Radiologic assessment in triple-negative breast cancer (A), HER2-positive breast cancer (B), and ER-positive breast cancer (C). Pathologic assessment in triple-negative breast cancer (D), HER2-positive breast cancer (E), and ER-positive breast cancer (F). CR = complete response, ER = estrogen receptor, HER2 = human epidermal growth factor receptor 2

Reference

1. Gralow JR, Burstein HJ, Wood W, Hortobagyi GN, Gianni L, von Minckwitz G, et al. Preoperative therapy in invasive breast cancer: pathologic assessment and systemic therapy issues in operable disease. J Clin Oncol. 2008; 26:814–819.

2. Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008; 26:778–785.

3. van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001; 19:4224–4237.

4. Buchholz TA, Lehman CD, Harris JR, Pockaj BA, Khouri N, Hylton NF, et al. Statement of the science concerning locoregional treatments after preoperative chemotherapy for breast cancer: a National Cancer Institute conference. J Clin Oncol. 2008; 26:791–797.

5. von Minckwitz G, Blohmer JU, Costa SD, Denkert C, Eidtmann H, Eiermann W, et al. Response-guided neoadjuvant chemotherapy for breast cancer. J Clin Oncol. 2013; 31:3623–3630.

6. Cameron DA, Anderson ED, Levack P, Hawkins RA, Anderson TJ, Leonard RC, et al. Primary systemic therapy for operable breast cancer--10-year survival data after chemotherapy and hormone therapy. Br J Cancer. 1997; 76:1099–1105.

7. Liedtke C, Mazouni C, Hess KR, André F, Tordai A, Mejia JA, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008; 26:1275–1281.

8. Abraham DC, Jones RC, Jones SE, Cheek JH, Peters GN, Knox SM, et al. Evaluation of neoadjuvant chemotherapeutic response of locally advanced breast cancer by magnetic resonance imaging. Cancer. 1996; 78:91–100.

9. Balu-Maestro C, Chapellier C, Bleuse A, Chanalet I, Chauvel C, Largillier R. Imaging in evaluation of response to neoadjuvant breast cancer treatment benefits of MRI. Breast Cancer Res Treat. 2002; 72:145–152.

10. Weatherall PT, Evans GF, Metzger GJ, Saborrian MH, Leitch AM. MRI vs. histologic measurement of breast cancer following chemotherapy: comparison with x-ray mammography and palpation. J Magn Reson Imaging. 2001; 13:868–875.

11. Rieber A, Brambs HJ, Gabelmann A, Heilmann V, Kreienberg R, Kühn T. Breast MRI for monitoring response of primary breast cancer to neo-adjuvant chemotherapy. Eur Radiol. 2002; 12:1711–1719.

12. Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007; 13:2329–2334.

13. Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005; 11:5678–5685.

14. Jones RL, Lakhani SR, Ring AE, Ashley S, Walsh G, Smith IE. Pathological complete response and residual DCIS following neoadjuvant chemotherapy for breast carcinoma. Br J Cancer. 2006; 94:358–362.

15. Park YJ, Youk JH, Son EJ, Gweon HM, Kim JA. Comparison of hormonal receptor and HER2 status between ultrasound-guided 14-gauge core needle biopsy and surgery in breast cancer patients. Ultrasonography. 2014; 33:206–215.

16. Regan MM, Viale G, Mastropasqua MG, Maiorano E, Golouh R, Carbone A, et al. Re-evaluating adjuvant breast cancer trials: assessing hormone receptor status by immunohistochemical versus extraction assays. J Natl Cancer Inst. 2006; 98:1571–1581.

17. Hudis CA, Barlow WE, Costantino JP, Gray RJ, Pritchard KI, Chapman JA, et al. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol. 2007; 25:2127–2132.

18. Chaturvedi S, McLaren C, Schofield AC, Ogston KN, Sarkar TK, Hutcheon AW, et al. Patterns of local and distant disease relapse in patients with breast cancer treated with primary chemotherapy: do patients with a complete pathological response differ from those with residual tumour in the breast? Breast Cancer Res Treat. 2005; 93:151–158.

19. von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012; 30:1796–1804.

20. von Minckwitz G, Untch M, Loibl S. Update on neoadjuvant/preoperative therapy of breast cancer: experiences from the German Breast Group. Curr Opin Obstet Gynecol. 2013; 25:66–73.

21. von Minckwitz G, Untch M, Nüesch E, Loibl S, Kaufmann M, Kümmel S, et al. Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials. Breast Cancer Res Treat. 2011; 125:145–156.

22. Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, et al. 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. 2006; 24:2019–2027.

23. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014; 384:164–172.

24. Yi A, Cho N, Im SA, Chang JM, Kim SJ, Moon HG, et al. Survival outcomes of breast cancer patients who receive neoadjuvant chemotherapy: association with dynamic contrast-enhanced MR imaging with computer-aided evaluation. Radiology. 2013; 268:662–672.

25. Esserman LJ, Berry DA, DeMichele A, Carey L, Davis SE, Buxton M, et al. Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL--CALGB 150007/150012, ACRIN 6657. J Clin Oncol. 2012; 30:3242–3249.

26. Berry DA, Cirrincione C, Henderson IC, Citron ML, Budman DR, Goldstein LJ, et al. Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA. 2006; 295:1658–1667.

27. Hayes DF, Thor AD, Dressler LG, Weaver D, Edgerton S, Cowan D, et al. HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med. 2007; 357:1496–1506.

28. Ko ES, Han BK, Kim RB, Ko EY, Shin JH, Hahn SY, et al. Analysis of factors that influence the accuracy of magnetic resonance imaging for predicting response after neoadjuvant chemotherapy in locally advanced breast cancer. Ann Surg Oncol. 2013; 20:2562–2568.

29. Knauer M, Mook S, Rutgers EJ, Bender RA, Hauptmann M, van de Vijver MJ, et al. The predictive value of the 70-gene signature for adjuvant chemotherapy in early breast cancer. Breast Cancer Res Treat. 2010; 120:655–661.