Role of MRI. When Should an MRI be Ordered? Diagnostic Ability of MRI. Diagnostic Ability of MRI. GOAL improve patient outcomes.

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1 Role of MRI When Should an MRI be Ordered? Jasmine M. Wong, MD March 7, 2015 Screening increased sensitivity in cancer detection Pre-operative staging identifies additional foci of cancer not see by other imaging modalities Surgical planning GOAL improve patient outcomes Diagnostic Ability of MRI Sensitivity 90% Specificity 72% False positives 28% In 16% of cases MRI can find additional ipsilateral focus of cancer 66% of these lesions were malignant Diagnostic Ability of MRI MRI detected suspicious findings occult to conventional imaging 9.3% Incremental cancer detection rate 4.1% Positive predictive value 47.9% MRI is limited in distinguishing between benign and malignant lesions Peters, et al. Meta-analysis of MR imaging in the diagnosis of breast lesions. Radiology 2008;246: Houssami, et al. Accuracy and surgical impact of magnetic resonance imaging in breast cancer staging: Systemic review and meta-analysis in detection of multifocal and multicentric cancer.j Clin Oncol 2008;26: Brennan, et al. Magnetic resonance imaging screening of the contralateral breast in women with newly diagnosed breast cancer: Systemic review and meta-analysis of incremental cancer detection and impact on surgical management. J Clin Oncol 2009;27:

2 MRI and Surgical Outcomes COMICE trial - addition of MRI to triple assessment (clinical exam, mammography, ultrasound) was not significantly associated with a reduced re-operation rate Both groups had 19% of their patients needing reoperation MRI and Surgical Outcomes Monet trial - randomized control trial in patients with non-palpable suspicious breast lesions detected on mammogram or ultrasound Primary breast conserving surgery was similar in both groups Number of conversions to mastectomy did not differ significantly Number of re-excisions for positive margins higher in the MRI group Turnbull, et al. Comparative effectiveness of MRI in breast cancer (COMICE) trial: randomised controlled trial. Lancet 2010;375: Peters, et al. Preoperative MRI and surgical management in patients with nonpalpable breast cancer: The MONET Randomised controlled trial Eur J Cancer 2011;47: Take Away Points MRI has high sensitivity, but low specificity MRI only incrementally increases cancer detection rates both in the ipsilateral and contralateral breast MRI in the pre-operative setting does not affect short term surgical outcomes MRI should not be used for routine screening or routine pre-operative staging Current Clinical Indications High risk patients Invasive lobular carcinoma Neoadjuvant chemotherapy Occult primary 2

3 Women who are BRCA 1 or BRCA 2 gene mutation carriers Untested first degree relatives of BRCA gene mutation carriers Women with greater than 20-25% lifetime risk of developing breast cancer based on family history MRI has higher sensitivity than mammography for detecting breast cancer MRI not affected by breast density MRI has the ability to detect smaller tumors than mammography No data on outcome or survival Saslow, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to Mammography. CA Cancer J Clin 2007;57:75-89 Kriege, et al. Efficacy of MRI and mammography for breast cancer screening in women with familial or genetic predisposition. N Engl J Med2004;351: American Cancer Society Guidelines Women with a history of chest radiation before age 30 Women with TP53 and PTEN gene mutations Sensitivity of MRI in high risk patients ranges from % compared with mammography which ranges from 16 to 40% Saslow, et al. American Cancer Society guidelines for bresat screening with MRI as an adjunct to Mammography. CA Cancer J Clin 2007;57:

4 No consensus on when to start screening in high risk patients 5 years younger than the first relative who presented with breast cancer Starting at age 30 No consensus on when to stop MRI screening American Cancer Society Guidelines Insufficient evidence to recommend or discourage MRI screening of women with 15-20% lifetime risk of breast cancer or women with LCIS, ALH, ADH, dense breasts, or a personal history of cancer Mutation carriers (>50%) Cancer detection rate of 26.5 per 1000 patients High risk (30-49%) Cancer detection rate of 5.4 per 1000 patients Moderate risk (15-29%) Cancer detection rate of 7.8 per 1000 patients Current Clinical Indications High risk patients Invasive lobular carcinoma Neoadjuvant chemotherapy Occult primary Kriege, et al. Efficacy of MRI and mammography for breast cancer screening in women with familial or genetic predisposition. N Engl J Med 2004;351:

5 Invasive lobular carcinoma 2 nd most common breast cancer, but only 5-15% of all breast cancers More likely to be multi-centric, multi-focal and/or bilateral compared to other types Often more difficult to detect Can be difficult to determine extent of disease Invasive Lobular Carcinoma MRI found to more accurately determine tumor size compared to mammography Mammography underestimated the tumor size significantly more frequently than MRI Overestimation of the tumor size happened with equal frequency Usually due to extensive LCIS around the tumor Mann, et al. The value of MRI compared to mammography in the assessment of tumor extent in invasive lobular carcinoma of the breast. Eur J Surg Oncol 2008; 34: Scatter plots of tumor size Invasive Lobular Carcinoma Significantly fewer patients in the MRI group had a re-excision Odds ratio for re-excision 3.29 No significant difference in initial mastectomy rates Mann, et al. The value of MRI compared to mammography in the assessment of tumor extent in invasive lobular carcinoma of the breast. Eur J Surg Oncol 2008; 34: Mann, et al. The impact of preoperative breast MRI on the re-excision rate in invasive lobular carcinoma of the breast. Breast Cancer Res Treat 2010; 119:

6 Current Clinical Indications Invasive lobular carcinoma High risk patients Neoadjuvant chemotherapy Occult primary Neoadjuvant chemotherapy Increased use of neoadjuvant chemotherapy has led to the need for a tool to assess tumor response to treatment MRI offers a non invasive way to assess tumors before, during, and after neoadjuvant treatment to help determine the appropriate surgical therapy for patients MRI Phenotypes 1 well defined, uni-centric mass 2 well defined, multi-lobulated mass 3 area enhancement with nodularity 4 area enhancement without nodularity 5 septal spreading. 6

7 Neoadjuvant Chemotherapy Neoadjuvant Chemotherapy MRI is more accurate than clinical exam, mammography, and ultrasound for determining residual tumor size MRI can predict clinically meaningful tumor reduction Well defined MRI phenotypes have higher rates of tumor reduction than diffuse MRI phenotypes Her2 positive and triple negative tumor have higher rates of tumor reduction than hormone receptor positive and Her2 negative tumors Assessment of tumor volume with MRI has been shown to be a strong predictor of pathologic response to neoadjuvant chemotherapy Multiple studies have shown that the ability of MRI to predict pathologic complete response is related to tumor subtypes Lobbes, et al. The role of magnetic resonance imaging in assessing residual disease and pathologic complete response in breast cancer patients receiving neoadjuvant chemotherapy: a systemic review. Insights Imaging 2013;4: Mukhtar, et al. Clinically Meaningful Tumor Reduction Rates Vary by Prechemotherapy MRI phenotype and Tumor Subtype in the I-SPY 1 TRIAL (CALGB /150012; ACRIN 6657) Ann Surg Oncol 2013;20: Hylton, et al. Locally Advanced Breast Cancer: MR Imaging for Prediction of Response in Neoadjuvant Chemotherapy Results from ACRIN 6657/I-SPY TRIAL Radiology 2012;263: Study N Findings Hayashi et al Sensitivity/Specificity highest in TN tumors PPV decreased in order TN, ER-/Her2+, ER+/Her2+,ER+/Her2- Ko et al Size prediction less accurate in ER+ tumors Cruz et al Better correlation between MRI measured response and pathologic response in TN and Her2+ tumors Loo et al MRI size change associated with path residual disease for TN and Her2+ tumors; not for ER+/Her2- Kuzucan et al Among Her2- tumors, MRI accuracy higher in high-proliferation (high Ki-67) tumors McGuire et al MRI accuracy for predicting pcr lowest in luminal tumors; highest in TN and ER-/Her2+ tumors Current Clinical Indications High risk patients Invasive lobular carcinoma Neoadjuvant chemotherapy Occult primary Greater MRI-pathology agreement and more accurate prediction of pathologic complete response in triple negative and Her2+ hormone receptor negative breast cancers 7

8 Occult Primary MRI recommended in case of axillary nodal metastasis or metastatic disease with unknown primary and negative breast imaging MRI found on average 72% of the tumors with a mean sensitivity of 90% Specificity of 31% Occult Primary MRI found tumors in 70% of the patients with metastatic axillary adenocarcinoma from an unknown primary site Of the patients who underwent surgical excision, cancer was identified by MRI in 95% of the cases de Bresser, et al. Breast MRI in clinically and mammographically occult breast cancer presenting with axillary metastasis: A systemic review. Eur J Surg Oncol 2010;8: Olson, et al. Magnetic resonance imaging facilitates breast conservation for occult breast cancer. Ann Surg Oncol 2000;7(6): Conclusions Screening with MRI should be used only in very specific patient populations MRI has a role in the detection and staging of invasive lobular carcinoma and in cases of occult breast primaries. Interpretation of MRI findings in the setting of neoadjuvant chemotherapy should be done in the context of MRI phenotype and tumor receptor subtypes Thank you! 8