Global Breast Cancer Conference 2016 & 5 th International Breast Cancer Symposium April 29 th 2016, 09:40-10:50 How to Use MRI Following Neoadjuvant Chemotherapy (NAC) in Locally Advanced Breast Cancer Nariya Cho, MD, PhD Department of Radiology Seoul National University College of Medicine & Seoul National University Hospital
Contents Background Role of MRI following NAC Ongoing Studies at SNUH Take-Home Message
Contents Background Role of MRI following NAC Ongoing Studies at SNUH Take-Home Message
NAC in Breast Cancer In the early 1980s, to convert inoperable tumors into operable tumors Survival outcomes and locoregional control with NAC are similar to those with adjuvant chemotherapy *Preoperative chemotherapy: updates of NSABP B-18 and B-27. J Clin Oncol 2008;26(5):778 Neoadjuvant chemotherapy for operable breast cancer. Br J of Surg 2007;94:1189
Benefits of NAC in Breast Cancer Patients who show pcr have improved overall survival, disease-free survival and recurrence-free survival outcomes NAC can facilitate BCS *Preoperative chemotherapy: updates of NSABP B-18 and B-27. J Clin Oncol 2008;26(5):778 Neoadjuvant chemotherapy for operable breast cancer. Br J of Surg 2007;94:1189
NAC reduces tumor volume allowing more BCS: mastectomy rate by 17% reduction. Neoadjuvant chemotherapy for operable breast cancer. Br J Surg 2007;94(10):1189
NAC has been increasingly used NAC has been increasingly used with 5% to 14% of breast cancer patients undergoing curative surgery at SNUH
Nomogram Parameters for BCS or Residual Tumor <3cm Following NAC MDACC SNUH Tumor Size (TNM) O O Initial tumor diameter (cm) O O Histologic grade O X Histologic type O X ER status O O Multicentricity O O Distance from nipple X O Calcifications on MG X O DCIS component X O Ki-67 level X O Rouzier R, et al. Cancer. 2006;107:1459-66 Cancer Res Treat 2015;47(2):192
Contents Background Role of MRI following NAC Ongoing Studies at SNUH Take-Home Message
MRI is the most accurate than MG or US. J Natl Cancer Inst 2013;105(5):321-333.
MRI-Model to Guided Surgery after NAC Straver ME, Loo CE, Rutgers EJ, et al. MRI-model to guide the surgical treatment in breast cancer patients after neoadjuvant chemotherapy. Ann Surg 2010;251(4):701-707.:
Underestimation
ER+ Cancer, 43/F, Immediate Re-excision after NAC Initial PET/CT IDC, NG/HG 2/II ER95%, PR 95%, HER2-, Ki67 3% ct2(4cm)n2m0 AC#4, D#4
ER+ Cancer, 43/F, Immediate Re-excision after NAC Breast, left, total mastectomy; DCIS, non-comedo type, intermediate, multifocal -Post-neoadjuvant chemotherapy status -Extent of DCIS: 3.5x3.4x6.0cm Breast, left, BCS; Infiltrating Duct Carcinoma -Post-neoadjuvant chemotherapy status -Invasive tumor size: 1.8x1.8x1.5cm -NG/HG 2/II -DCIS component: present, around the tumor, non-comedo, intermediate grade -Tumor border: infiltrative -Microcalcification; absent -Lymphatic emboli: absent -Surgical margins: Superior involved by DCIS inf/ med/lateral margin: clear Breast, Lt inner excision; DCIS, non-comedo type, intermediate grade, multifocal, scattered - Post-neoadjuvant chemotherapy status - Extent of DCIS: 3.1x1.8x4.0cm - Surgical margins: clear but very close
ER + Cancer, 39/F, Early IBTR after NAC-BCS Initial PET/CT IDC, NG/HG 2/II ER>95%, PR 30%, HER2 FISH-, Ki67 15% ct3n1m0 AC#4, D#4 Breast, right, BCS; IDC, multiple -Post-neoadjuvant chemotherapy status -Invasive tumor size: upto 2.5x1.0x2.5cm -NG/HG 3/II -DCIS component: absent -Surgical margins: Sup/ inf/ med/lateral margin: clear Breast, Rt lower excision; Infiltrating Duct Carcinoma - size:0.8x0.5x0.5cm - Clear but very close to resection margin The patient received RT & tamoxifen
ER + Cancer, 39/F, Early IBTR after NAC-BCS US-guided bx IDC 1cm, NG/HG 2/II ER20% PR- HER2- Ki67 5% Right total mastectomy 23 months later AC#4, D#4
Locoregional recurrence rates was nonsignificantly higher in the downstaged group than preplanned BCS group in the NCT 18.6% (24 of 129) 11.1% (55 of 494) J Natl Cancer Inst 2013;105(5):321-333.
Surgical Extent of Residual Tumor following NAC Although all breast parenchyma initially occupied by the tumor need not be excised, if there are any suspicious findings, they should be excised to prevent early recurrence or immediate re-excision. King TA, Morrow M. Surgical issues in patients with breast cancer receiving neoadjuvant chemotherapy. Nat Rev Clin Oncol 2015;12(6):335-343
Overestimation
Limitation of Evaluation of Residual Disease after NAC With the advent of newer therapeutic agents and targeted therapies, the rates of pcr have increased, however, the rate of BCS has not increased in multiple studies King TA, Morrow M. Surgical issues in patients with breast cancer receiving neoadjuvant chemotherapy. Nat Rev Clin Oncol 2015;12(6):335-343
HER2 + Cancer, 55/F, Total Mastectomy Initial PET/CT IDC, NG/HG 2/II ER- PR- HER2 FISH+, Ki67 15% ct2n3m0 Paclitaxel, Gemcitibine, Herceptin Paclitaxel, Gemcitibine, Herceptin Breast, left, total mastectomy DCIS, noncomedo, high grade, focal, residual with -Post-neoadjuvant chemotherapy status -Extent of tumor: a few scattered -microcalcification in ductal lumen, Clear deep resection margin, No metastasis in 27 lymph nodes
Tumor Subtype
MRI-model to guide the surgical treatment after NAC Ann Surg 2010;251(4):701-707
Molecular Phenotype & MRI-Pathology Correlation Ann Surg 2013;257(1):133-137
Triple Negative Case, 40/F, BCS after NAC-pCR Initial PET/CT IDC, NG/HG 3/III Triple negative, Ki67 70% ct2n1m0 AC#4, D#4 AC#4, D#4 Breast, right conservation surgery No residual tumor -Post-neoadjuvant chemotherapy status -lymphatic emboli absent - Clear resection margins, No metastasis in 5 lymph nodes
ER + Cancer, 43/F, BCS after NAC IDC, NG/HG 3/III ER/PR/HER2 +/+/- Ki67 30% ct2n1m0 DA#6 Breast, right conservation surgery No residual tumor -Post-neoadjuvant chemotherapy status -Microcalcification -Clear resection margins, No metastasis in 5 lymph nodes
ER + Case, 43/F, BCS after NAC Breast, right excision DCIS, comedo and noncomedo, residual with -Post-neoadjuvant chemotherapy, BCS and -Extent of DCIS: 0.5x0.3x0.8cm -Microcalcification: present -Lymphatic emboli: absent -Resection margins: negative 23 months later
MRI interpretation in the context of tumor subtype TNBC: unifocal, concentric shrinkage HER2 (+): multiple ER (+): diffuse non-mass enhancement Mass type > Non-mass type Extent: HER2 or TN accurate, luminal subtype underestimated *King TA, Morrow M. Nat Rev Clin Oncol 2015;12(6):335-343 ** Turnbull LW. NMR Biomed 2009;22(1):28-39
Chemotherapeutic Agents
Taxanes on Assessment with DCE MRI Taxane-containing NCT is associated with an almost complete suppression of contrast enhancement at DCE MRI, irrespective of the type of tissue (benign enhancing lesions and normal fibroglandular tissue) Radiology 2015;277:687-696
HER2-targeted Agents & MRI-Pathology Correlation The accuracy of MRI in predicting the residual tumor extent was significantly lower in patients receiving neoadjuvant HER2-targeted agents Ann Surg 2013;257(1):133-137
Contents Background Role of MRI following NAC Ongoing Studies at SNUH Take-Home Message
Questions Which phase of DCE-MRI is most accurate for the evaluation of lesion extent following NAC? Can we distinguish no residual tumor vs. residual tumor by MRI? Can we distinguish DCIS vs. minimally invasive tumor by MRI?
Phase of DCE-MRI Affects the Accuracy in Residual Tumor Extent Evaluation Initial Phase Delayed Phase 90sec 580sec Enhancement of invasive cancer Enhancement of normal parenchyma, benign tissue, DCIS
Phase of DCE-MRI Affects the Accuracy in Residual Tumor Extent Evaluation Between 2008 and 2012, images from 489 consecutive women who underwent NAC, DCE-MRI, and surgery Pearson Correlation MRI size Invasive Cancer Size Combined Size (In vasive + DCIS) Total (n=489) Initial 0.603 0.630 Delayed 0.588 0.749 Luminal A (n=170) Initial 0.451 0.575 Delayed 0.434 0.626 Luminal B (n=82) Initial 0.582 0.535 Delayed 0.702 0.705 HER2 (n=116) Initial 0.775 0.659 Delayed 0.602 0.881 TNBC (n=121) Initial 0.740 0.771 Delayed 0.753 0.785 Kim SY and Cho N. 2016 RSNA submitted
HER2 (FISH) Positive, ER-PR- Case, 37/F Docetaxel+Epirubicin#3 Initial Phase Delayed Phase Breast, left total mastectomy IDC, multifocal scattered with -Post-neoadjuvant chemotherapy status -Invasive tumor size; up to 1.0x0.8x1.0cm -Extent of tumor including DCIS: 5.7x1.1x5.0cm -NG/HG: 3/III -DCIS component: around the tumor, high grade with microcalcification -no endolymphatic tumor emboli -no involvement of nipple -clear resection margins
IDC, NG/HG 3/III, Triple negative, ct3n1m0 Triple Negative Case, 39/F, BCS DA#6 Initial Phase Delayed Phase Breast, left conservation surgery IDC, residual with -Post-neoadjuvant chemotherapy status -residual tumor size: 1.5x1.3x1.5cm -NG/HG: 3/III -DCIS component: none -endolymphatic tumor emboli -clear resection margins -No metastasis in 9 LNs
Interpretation of DCE-MRI after NAC Initial phase MR images is more accurate for response assessment of NAC while delayed phase MR images is more accurate for planning breast conservation surgery. Kim SY and Cho N. 2016 RSNA submitted
Questions Which phase of DCE-MRI is accurate after NAC? Can we distinguish no residual tumor vs. residual tumor by MRI? Can we distinguish DCIS vs. minimally invasive tumor by MRI?
Definition of pcr Affects Accuracy of MRI J Natl Cancer Inst 2013;105(5):321-333.
Sensitivity MRI negativity threshold: Contrast enhancement similar to normal tissue MRI negativity threshold: complete absence of enhancement Specificity MRI specificity differs according to the definition of radiological CR (enhancement similar to normal tissue vs. complete absence of enhancement) J Natl Cancer Inst 2013;105(5):321-333.
Lesion to Background SER in Distinguishing Residual Tumor vs. No Residual Tumor Mean SER: residual tumor (minimally invasive tumor plus DCIS)>no residual tumor (1.72±0.40 vs. 1.49±0.32, P<0.001). Mean SER: residual DCIS not different that of minimally invasive tumor 0.5cm (1.78±0.36 vs. 1.69±0.41, P=0.181). Cut-off SER value of 1.7 yielded maximum sum of sensitivity and specificity (Az of SER in the prediction of pcr: 0.662 (95% CI: 0.595-0.724). Kim SY and Cho N. 2016 RSNA submitted
Lesion to Background SER in Distinguishing Residual Tumor vs. No Residual Tumor Lesion to background SER on MRI might be useful in distinguishing presence of minimally residual tumor from no residual tumor. It might not be useful in distinguishing residual DCIS from invasive cancer. When an enhancing lesion shows its SER < 1.7 on DCE-MRI, the lesion has high possibility of pathologic complete response. Kim SY and Cho N. 2016 RSNA submitted
Of these HER2 positive tumors, which one would be a pcr? 1 SER 1.6 2 SER 1.0 3 SER 2.6
Contents Background BCS after NCT Role of MRI after NCT Ongoing Studies at SNUH Take-Home Message
Take-Home Message Accuracy of MRI TNBC > HER2 > ER positive tumors Mass type > Non-mass type Initial phase DCE-MRI: response assessment Delayed phase: planning BCS To predict pcr, quantification of SER might be helpful.
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