This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, J.-H. Articles by Su, M.-Y. Search for Related Content PubMed PubMed Citation Articles by Chen, J.-H. Articles by Su, M.-Y. Related Articles Related Article Social Bookmarking                            What's this?

Magnetic Resonance Imaging in Predicting Pathological Response of Triple Negative Breast Cancer Following Neoadjuvant Chemotherapy

Center for Functional Onco-Imaging, University of California, Irvine, CA; Department of Radiology, China Medical University Hospital, Taichung, Taiwan

Rita S. Mehta

Department of Medicine, University of California, Irvine, CA

Philip M. Carpenter

Department of Pathology and Laboratory Medicine, University of California, Irvine, CA

Orhan Nalcioglu, Min-Ying Su

Center for Functional Onco-Imaging, University of California, Irvine, CA

To the Editor:

Triple-negative (TN) breast cancers account for approximately 12% to 26% of all types of breast cancers.^1-5 TN tumors were aggressive and were usually diagnosed at a later stage.⁵ Independent research data have demonstrated that TN breast cancer carries a poor prognosis. Approximately 85% of TN phenotypic breast cancers are deemed to be basal-like and have a clinical behavior similar to basal-like tumors.² Because of the lack of target receptors, there are still no specific chemotherapeutic agents for TN breast cancer until now. In June 20, 2007, issue of the Journal of Clinical Oncology, we reported on a patient with TN breast cancer, diagnosed during her pregnancy, whose disease showed complete clinical response in magnetic resonance imaging (MRI) and pathological complete response (pCR) after receiving neoadjuvant chemotherapy (NAC) using anthracycline- and taxane-based regimens.⁶ Using MRI, we have recently demonstrated that pCR in human epidermal receptor-2 (HER-2)–positive breast cancer can be predicted with a much higher accuracy rate than for HER-2–negative breast cancer (95% vs 50%).⁷ The role of MRI inpredicting pCR and diagnosing residual tumor for TN breast cancer following NAC is, however, not known.

In a full review of our breast MRI database from 2002 to 2006, 29 patients with pathologically proven TN breast cancer (range, age 25 to 82 years; mean, 50 years) were found. The MRI study was performed on a 1.5 T Phillips Eclipse MR scanner with a standard bilateral breast coil (Philips Medical Systems, Cleveland, OH). The study was approved by the institutional review board and was compliant with the Health Insurance Portability and Accountability Act. All participants gave written informed consent. The diagnosis was made based on core biopsy (n = 27) or excision biopsy (n = 2). Fifteen of the 29 patients received NAC after the diagnosis, including four cycles of dose-dense AC (anthracycline [doxorubicin]-cyclophosphamide) followed by three cycles of paclitaxel (cremophor or albumin-bound paclitaxel) and carboplatin (both 3 weeks on, 1 week off; one cycle) plus or minus six doses of bevacizumab every 2 weeks. All patients had pretreatment baseline breast MRI exams: at least two follow-up exams during the course of therapy, and a final examination after completing the therapy protocol. Following NAC, a definitive surgery and pathologic examination of the breast specimen was performed. The residual disease post-NAC was recorded into one of three categories: (1) no residual malignancy, no sign of cancer cells; (2) no residual invasive cancer, ductal carcinoma in situ present; (3) residual invasive cancer. Defined as no invasive cancer present, pCR includes categories (1) and (2). This definition is used at The University of Texas M.D. Anderson Cancer Center (Houston, TX),⁸ and also at the National Cancer Institute meeting held on March 26 to 27, 2007, entitled, "Preoperative Therapy in Invasive Breast Cancer." In cases with residual invasive cancer, the pathological size was determined as the longest dimension: either the longest dimension on one hematoxylin and eosin–stained slide or from the number of blocks (each 5 mm) where the malignant invasive tumor was detected, whichever was greater.

The tumor size of each patient in all serial MRI studies (pretreatment and all follow-up) was analyzed in one sitting by the radiologist to ensure consistent determination of the tumor boundary. The radiologist was blind to the pathology results. If the one-dimensional size reduction after completing NAC was less than 30% compared with their pretreatment size, the case was classified as a nonresponder (NR). When residual tumor was present with greater than 30% size reduction, the case was classified as a partial response (PR). Cases in which no enhanced tissues were visible were classified as clinical complete response (CCR). When minimal enhancement was found at the previous lesion site with weaker or comparable enhancement relative to normal glandular tissue (ipsilateral or contralateral), the case was classified as probable CCR. Both CCR and probable CCR were considered as CR determined on MRI (noted as MR-CR) and used to evaluate their accuracy in prediction of pCR.

For the 15 patients undergoing NAC, MRI diagnosed nine MR-CR, five PR, and one NR. Overall, the clinical response rate was 93% (14 of 15 patients). Final pathology revealed pCR in nine patients (nine of 15 patients; 60%), PR in five patients, and NR in one patient. MRI accurately predicted eight pCR (eight of nine patients; 89%) with one false-negative diagnosis. For the six non-pCR patients, MRI diagnosed five PR with one false-positive diagnosis. The size correlation between the MR^B and pathology for the five PR patients also showed highly correlated (r² = 0.998).

Rouzier et al⁹ have shown that the TN tumor is more sensitive to paclitaxel and doxorubicin–containing preoperative chemotherapy than the luminal and normal-like cancers. It was shown that a complete pathological response rate was seen in 45% of basal-like cancers and only 6% of luminal cancers. Another NAC study¹⁰ suggested that the clinical response rate to doxorubicin and cyclophosphamide was markedly higher in patients with TN breast cancer than in those with non-TN subtype tumors (85% v 47%; P < .0001). Pathologic complete response to NAC was also higher in patients with TN tumors than in those with non-TN tumors (27% v 7%, P = .01). Using anthracycline and taxane–based regimens, we have demonstrated even higher clinical response and pCR rates than the other two studies previously described.

In our study, the role of MRI in predicting pCR and diagnosing residual tumor for TN breast cancers following NAC was also impressive. With more patients studied in the future, we believe that the definite role of MRI for TN tumors following NAC will be clearer. If MRI can prove its high performance, it will help breast surgeons in planning conserving surgery more reliably. Since the final outcome following NAC was evaluated based on the pathological findings and achieving pCR is considered the ultimate goal for a favorable prognosis,^11-16 predicting pCR preoperatively becomes an important issue and is associated with patient management and follow-up strategy. It was found that despite initial chemosensitivity, patients with the basal-like subtype had worse distant disease-free survival and overall survival than those with the luminal subtype. However, the worse outcome in basal-like subtype breast cancer was due to higher relapse among those patients with residual disease after NAC. Only few patients with pCR had relapsed disease.¹⁰

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Haffty BG, Yang Q, Reiss M, et al: Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol 24:5652-5657, 2006[Abstract/Free Full Text]

2. Rakha EA, El-Sayed ME, Green AR, et al: Prognostic markers in triple-negative breast cancer. Cancer 109:25-32, 2007[CrossRef][Medline]

3. Cleator S, Heller W, Coombes RC: Triple-negative breast cancer: Therapeutic options. Lancet Oncol 8:235-244, 2007[CrossRef][Medline]

4. Carey LA, Perou CM, Livasy CA, et al: Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295:2492-2502, 2006[Abstract/Free Full Text]

5. Bauer KR, Brown M, Cress RD, et al: Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: A population-based study from the California Cancer Registry. Cancer 109:1721-1728, 2007[CrossRef][Medline]

6. Agrawal G, Chen JH, Baick CH, et al: Pathological complete response in triple negative poorly differentiated invasive ductal breast carcinoma detected during pregnancy. J Clin Oncol 25:2618-2620, 2007[Free Full Text]

7. Chen JH, Feig B, Agrawal G, et al: MRI evaluation of pathological complete response and residual tumors in breast cancer following neoadjuvant chemotherapy. Cancer [in press]

8. Jones RL, Lakhani SR, Ring AE, et al: Pathological complete response and residual DCIS following neoadjuvant chemotherapy for breast carcinoma. Br J Cancer 94:358-362, 2006[CrossRef][Medline]

9. Rouzier R, Perou CM, Symmans WF, et al: Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 11:5678-5685, 2005[Abstract/Free Full Text]

10. Carey LA, Dees EC, Sawyer L, et al: The triple negative paradox: Primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 13:2329-2334, 2007[Abstract/Free Full Text]

11. Kuroi K, Toi M, Tsuda H, et al: Un-argued issues on the pathological assessment of response in primary systemic therapy for breast cancer. Biomed Pharmacother 59:S387-392, 2005 (suppl 2)[CrossRef]

12. Chaturvedi S, McLaren C, Schofield AC, 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 93:151-158, 2005[CrossRef][Medline]

13. Ogston KN, Miller ID, Payne S, et al: A new histological grading system to assess response of breast cancers to primary chemotherapy: Prognostic significance and survival. Breast 12:320-327, 2003[CrossRef][Medline]

14. Cleator S, Parton M, Dowsett M: The biology of neoadjuvant chemotherapy for breast cancer. Endocr Relat Cancer 9:183-195, 2002[Abstract]

15. Machiavelli MR, Romero AO, Perez JE, et al: Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma. Cancer J Sci Am 4:125-131, 1998[Medline]

16. Honkoop AH, van Diest PJ, de Jong JS, et al: Prognostic role of clinical, pathological and biological characteristics in patients with locally advanced breast cancer. Br J Cancer 77:621-626, 1998[Medline]

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Article

• Pathological Complete Response in Triple Negative Poorly Differentiated Invasive Ductal Breast Carcinoma Detected During Pregnancy
  Garima Agrawal, Jeon Hor Chen, Choong Hyun Baick, Antony Eugene Chen, Rita S. Mehta, Orhan Nalcioglu, and Min-Ying Su
  JCO 2007 25: 2618-2620 [Full Text]

This article has been cited by other articles:

				G. Frasci, P. Comella, M. Rinaldo, G. Iodice, M. Di Bonito, M. D'Aiuto, A. Petrillo, S. Lastoria, C. Siani, G. Comella, et al. Preoperative weekly cisplatin-epirubicin-paclitaxel with G-CSF support in triple-negative large operable breast cancer Ann. Onc., July 1, 2009; 20(7): 1185 - 1192. [Abstract] [Full Text] [PDF]

				H.-G. Moon, W. Han, J. W. Lee, E. Ko, E.-K. Kim, J.-H. Yu, S. Y. Kang, W. K. Moon, N. Cho, I.-A. Park, et al. Age and HER2 expression status affect MRI accuracy in predicting residual tumor extent after neo-adjuvant systemic treatment Ann. Onc., April 1, 2009; 20(4): 636 - 641. [Abstract] [Full Text] [PDF]

				R. S. Mehta and T. Schubbert Re: HER2 Status and Efficacy of Adjuvant Anthracyclines in Early Breast Cancer: A Pooled Analysis of Randomized Trials J Natl Cancer Inst, May 7, 2008; 100(9): 680 - 680. [Full Text] [PDF]

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, J.-H. Articles by Su, M.-Y. Search for Related Content PubMed PubMed Citation Articles by Chen, J.-H. Articles by Su, M.-Y. Related Articles Related Article Social Bookmarking                            What's this?