Amy M. Fowler, MD, PhD; Wei Tse Yang, MBBS; Amal Melhem-Bertrandt, MD
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KEY FACTS
Terminology
Imaging
Pathology
Clinical Issues
TERMINOLOGY
Definitions
Primary systemic neoadjuvant chemotherapy (NAC) or endocrine therapy (NET) prior to breast surgery
↓ tumor burden to convert inoperable to operable; mastectomy to breast-conserving therapy (BCT); &/or downstage axilla
Assessment of response: Physical exam, imaging, pathology
Imaging Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Complete response: Resolution of imaging finding(s)
Progressive disease: 20% ↑ in lesion diameter &/or appearance of new lesions
Partial response: ≥ 30% ↓ in lesion diameter
Stable disease: Residual tumor, neither partial response nor progressive disease
Adjuvant therapy: Chemotherapy &/or endocrine therapy after definitive breast surgery
IMAGING
Mammographic Findings
Ultrasonographic Findings
MR Findings
Nuclear Medicine Findings
Image-Guided Biopsy
Imaging Recommendations
DIFFERENTIAL DIAGNOSIS
PATHOLOGY
Staging, Grading, & Classification
Gross Pathologic & Surgical Features
Microscopic Features
CLINICAL ISSUES
Presentation
Natural History & Prognosis
Treatment
DIAGNOSTIC CHECKLIST
Consider
Image Interpretation Pearls
Reporting Tips
Selected References
The University of Texas MD Anderson Cancer Center: Residual Cancer Burden Calculator. Accessed January 16, 2019.
Fukada I et al: Pattern of tumor shrinkage during neoadjuvant chemotherapy is associated with prognosis in low-grade luminal early breast cancer. Radiology. 286(1):49-57, 2018
Mazari FAK et al: Human epidermal growth factor 2-positive breast cancer with mammographic microcalcification: relationship to pathologic complete response after neoadjuvant chemotherapy. Radiology. 170960, 2018
Moy L: Do tumor shrinkage patterns at breast MR imaging predict survival? Radiology. 286(1):58-9, 2018
Chen L et al: Direct comparison of PET/CT and MRI to predict the pathological response to neoadjuvant chemotherapy in breast cancer: a meta-analysis. Sci Rep. 7(1):8479, 2017
Expert Panel on Breast Imaging et al: ACR Appropriateness Criteria® monitoring response to neoadjuvant systemic therapy for breast cancer. J Am Coll Radiol. 14(11S):S462-S475, 2017
Fowler AM et al: Imaging neoadjuvant therapy response in breast cancer. Radiology. 285(2):358-375, 2017
Symmans WF et al: Long-term prognostic risk after neoadjuvant chemotherapy associated with residual cancer burden and breast cancer subtype. J Clin Oncol. 35(10):1049-60, 2017
Leddy R et al: Effects of neoadjuvant chemotherapy on benign breast lesions compared to cancers: should an additional lesion on magnetic resonance imaging responding similar to cancer after neoadjuvant chemotherapy be viewed with suspicion? J Clin Imaging Sci. 6:39, 2016
De Los Santos JF et al: Magnetic resonance imaging as a predictor of pathologic response in patients treated with neoadjuvant systemic treatment for operable breast cancer. Translational Breast Cancer Research Consortium trial 017. Cancer. 119(10):1776-83, 2013
Hylton N: MR imaging for the prediction of breast cancer response to neoadjuvant chemotherapy. Radiology. 266(1):367, 2013
Luparia A et al: Accuracy of tumour size assessment in the preoperative staging of breast cancer: comparison of digital mammography, tomosynthesis, ultrasound and MRI. Radiol Med. 118(7):1119-36, 2013
O'Sullivan TD et al: Optical imaging correlates with magnetic resonance imaging breast density and reveals composition changes during neoadjuvant chemotherapy. Breast Cancer Res. 15(1):R14, 2013
Baselga J et al: Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 379(9816):616, 2012
Esserman LJ 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. 30(26):3242-9, 2012
Houssami N et al: Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy. Eur J Cancer. 48(18):3342-54, 2012
Hylton NM et al: Locally advanced breast cancer: MR imaging for prediction of response to neoadjuvant chemotherapy--results from ACRIN 6657/I-SPY TRIAL. Radiology. 263(3):663-72, 2012
Kuzucan A et al: Diagnostic performance of magnetic resonance imaging for assessing tumor response in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy is associated with molecular biomarker profile. Clin Breast Cancer. 12(2):110-8, 2012
Shin HJ et al: Prediction of pathologic response to neoadjuvant chemotherapy in patients with breast cancer using diffusion-weighted imaging and MRS. NMR Biomed. 25(12):1349-59, 2012
Tateishi U et al: Neoadjuvant chemotherapy in breast cancer: prediction of pathologic response with PET/CT and dynamic contrast-enhanced MR imaging--prospective assessment. Radiology. 263(1):53-63, 2012
Untch M et al: Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol. 13(2):135-44, 2012
Wahner-Roedler DL et al: The use of molecular breast imaging to assess response in women undergoing neoadjuvant therapy for breast cancer: a pilot study. Clin Nucl Med. 37(4):344-50, 2012
Chen JH et al: Breast cancer: evaluation of response to neoadjuvant chemotherapy with 3.0-T MR imaging. Radiology. 261(3):735-43, 2011
Loo CE et al: Magnetic resonance imaging response monitoring of breast cancer during neoadjuvant chemotherapy: relevance of breast cancer subtype. J Clin Oncol. 29(6):660-6, 2011
Martoni AA et al: Prospective study on the FDG-PET/CT predictive and prognostic values in patients treated with neoadjuvant chemoradiation therapy and radical surgery for locally advanced rectal cancer. Ann Oncol. 22(3):650-6, 2011
McGuire KP et al: MRI staging after neoadjuvant chemotherapy for breast cancer: does tumor biology affect accuracy? Ann Surg Oncol. 18(11):3149-54, 2011
Gianni L et al: Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 375(9712):377-84, 2010
Park SH et al: Diffusion-weighted MR imaging: pretreatment prediction of response to neoadjuvant chemotherapy in patients with breast cancer. Radiology. 257(1):56-63, 2010
Straver ME et al: MRI-model to guide the surgical treatment in breast cancer patients after neoadjuvant chemotherapy. Ann Surg. 251(4):701-7, 2010
Woodhams R et al: Identification of residual breast carcinoma following neoadjuvant chemotherapy: diffusion-weighted imaging--comparison with contrast-enhanced MR imaging and pathologic findings. Radiology. 254(2):357-66, 2010
Yuan Y et al: Accuracy of MRI in prediction of pathologic complete remission in breast cancer after preoperative therapy: a meta-analysis. AJR Am J Roentgenol. 195(1):260-8, 2010
Kelly AM et al: Breast cancer sentinel node identification and classification after neoadjuvant chemotherapy-systematic review and meta analysis. Acad Radiol. 16(5):551-63, 2009
Lee JH et al: The role of radiotracer imaging in the diagnosis and management of patients with breast cancer: part 1--overview, detection, and staging. J Nucl Med. 50(4):569-81, 2009
Pons F et al: Breast cancer therapy: the role of PET-CT in decision making. Q J Nucl Med Mol Imaging. 53(2):210-23, 2009
Seo JH et al: Meta-analysis of pre-operative aromatase inhibitor versus tamoxifen in postmenopausal woman with hormone receptor-positive breast cancer. Cancer Chemother Pharmacol. 63(2):261-6, 2009
Wahl RL et al: From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 50 Suppl 1:122S-50S, 2009
Chen JH et al: Inflammatory breast cancer after neoadjuvant chemotherapy: can magnetic resonance imaging precisely diagnose the final pathological response? Ann Surg Oncol. 15(12):3609-13, 2008
Chen JH et al: MRI evaluation of pathologically complete response and residual tumors in breast cancer after neoadjuvant chemotherapy. Cancer. 2008 Jan 1;112(1):17-26. Erratum in: Cancer. 112(7):1642, 2008
Emmering J et al: Preoperative [18F] FDG-PET after chemotherapy in locally advanced breast cancer: prognostic value as compared with histopathology. Ann Oncol. 19(9):1573-7, 2008
Padhani AR et al: Prediction of clinicopathologic response of breast cancer to primary chemotherapy at contrast-enhanced MR imaging: initial clinical results. Radiology. 239(2):361-74, 2006
Peintinger F et al: Accuracy of the combination of mammography and sonography in predicting tumor response in breast cancer patients after neoadjuvant chemotherapy. Ann Surg Oncol. 13(11):1443-9, 2006
Partridge SC et al: MRI measurements of breast tumor volume predict response to neoadjuvant chemotherapy and recurrence-free survival. AJR Am J Roentgenol. 184(6):1774-81, 2005
Yeh E et al: Prospective comparison of mammography, sonography, and MRI in patients undergoing neoadjuvant chemotherapy for palpable breast cancer. AJR Am J Roentgenol. 184(3):868-77, 2005
Londero V et al: 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):1371-9, 2004
Tseng J et al: 18F-FDG kinetics in locally advanced breast cancer: correlation with tumor blood flow and changes in response to neoadjuvant chemotherapy. J Nucl Med. 45(11):1829-37, 2004
Rosen EL et al: Accuracy of MRI in the detection of residual breast cancer after neoadjuvant chemotherapy. AJR Am J Roentgenol. 181(5):1275-82, 2003
Burcombe RJ et al: Evaluation of good clinical response to neoadjuvant chemotherapy in primary breast cancer using [18F]-fluorodeoxyglucose positron emission tomography. Eur J Cancer. 38(3):375-9, 2002
Partridge SC et al: Accuracy of MR imaging for revealing residual breast cancer in patients who have undergone neoadjuvant chemotherapy. AJR Am J Roentgenol. 179(5):1193-9, 2002
Rouzier R et al: Primary chemotherapy for operable breast cancer: incidence and prognostic significance of ipsilateral breast tumor recurrence after breast-conserving surgery. J Clin Oncol. 19(18):3828-35, 2001
Schelling M et al: Positron emission tomography using [(18)F]Fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer. J Clin Oncol. 18(8):1689-95, 2000
Young H et al: Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 35(13):1773-82, 1999
Bassa P et al: Evaluation of preoperative chemotherapy using PET with fluorine-18-fluorodeoxyglucose in breast cancer. J Nucl Med. 37(6):931-8, 1996
Helvie MA et al: Locally advanced breast carcinoma: accuracy of mammography versus clinical examination in the prediction of residual disease after chemotherapy. Radiology. 198(2):327-32, 1996
Vinnicombe SJ et al: Primary breast cancer: mammographic changes after neoadjuvant chemotherapy, with pathologic correlation. Radiology. 198(2):333-40, 1996
Dershaw DD et al: Assessment of response to therapy of primary breast cancer by mammography and physical examination. Cancer. 75(8):2093-8, 1995
Moskovic EC et al: Mammography in the assessment of response to medical treatment of large primary breast cancer. Clin Radiol. 47(5):339-44, 1993
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References
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Tables
KEY FACTS
Terminology
Imaging
Pathology
Clinical Issues
TERMINOLOGY
Definitions
Primary systemic neoadjuvant chemotherapy (NAC) or endocrine therapy (NET) prior to breast surgery
↓ tumor burden to convert inoperable to operable; mastectomy to breast-conserving therapy (BCT); &/or downstage axilla
Assessment of response: Physical exam, imaging, pathology
Imaging Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Complete response: Resolution of imaging finding(s)
Progressive disease: 20% ↑ in lesion diameter &/or appearance of new lesions
Partial response: ≥ 30% ↓ in lesion diameter
Stable disease: Residual tumor, neither partial response nor progressive disease
Adjuvant therapy: Chemotherapy &/or endocrine therapy after definitive breast surgery
IMAGING
Mammographic Findings
Ultrasonographic Findings
MR Findings
Nuclear Medicine Findings
Image-Guided Biopsy
Imaging Recommendations
DIFFERENTIAL DIAGNOSIS
PATHOLOGY
Staging, Grading, & Classification
Gross Pathologic & Surgical Features
Microscopic Features
CLINICAL ISSUES
Presentation
Natural History & Prognosis
Treatment
DIAGNOSTIC CHECKLIST
Consider
Image Interpretation Pearls
Reporting Tips
Selected References
The University of Texas MD Anderson Cancer Center: Residual Cancer Burden Calculator. Accessed January 16, 2019.
Fukada I et al: Pattern of tumor shrinkage during neoadjuvant chemotherapy is associated with prognosis in low-grade luminal early breast cancer. Radiology. 286(1):49-57, 2018
Mazari FAK et al: Human epidermal growth factor 2-positive breast cancer with mammographic microcalcification: relationship to pathologic complete response after neoadjuvant chemotherapy. Radiology. 170960, 2018
Moy L: Do tumor shrinkage patterns at breast MR imaging predict survival? Radiology. 286(1):58-9, 2018
Chen L et al: Direct comparison of PET/CT and MRI to predict the pathological response to neoadjuvant chemotherapy in breast cancer: a meta-analysis. Sci Rep. 7(1):8479, 2017
Expert Panel on Breast Imaging et al: ACR Appropriateness Criteria® monitoring response to neoadjuvant systemic therapy for breast cancer. J Am Coll Radiol. 14(11S):S462-S475, 2017
Fowler AM et al: Imaging neoadjuvant therapy response in breast cancer. Radiology. 285(2):358-375, 2017
Symmans WF et al: Long-term prognostic risk after neoadjuvant chemotherapy associated with residual cancer burden and breast cancer subtype. J Clin Oncol. 35(10):1049-60, 2017
Leddy R et al: Effects of neoadjuvant chemotherapy on benign breast lesions compared to cancers: should an additional lesion on magnetic resonance imaging responding similar to cancer after neoadjuvant chemotherapy be viewed with suspicion? J Clin Imaging Sci. 6:39, 2016
De Los Santos JF et al: Magnetic resonance imaging as a predictor of pathologic response in patients treated with neoadjuvant systemic treatment for operable breast cancer. Translational Breast Cancer Research Consortium trial 017. Cancer. 119(10):1776-83, 2013
Hylton N: MR imaging for the prediction of breast cancer response to neoadjuvant chemotherapy. Radiology. 266(1):367, 2013
Luparia A et al: Accuracy of tumour size assessment in the preoperative staging of breast cancer: comparison of digital mammography, tomosynthesis, ultrasound and MRI. Radiol Med. 118(7):1119-36, 2013
O'Sullivan TD et al: Optical imaging correlates with magnetic resonance imaging breast density and reveals composition changes during neoadjuvant chemotherapy. Breast Cancer Res. 15(1):R14, 2013
Baselga J et al: Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 379(9816):616, 2012
Esserman LJ 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. 30(26):3242-9, 2012
Houssami N et al: Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy. Eur J Cancer. 48(18):3342-54, 2012
Hylton NM et al: Locally advanced breast cancer: MR imaging for prediction of response to neoadjuvant chemotherapy--results from ACRIN 6657/I-SPY TRIAL. Radiology. 263(3):663-72, 2012
Kuzucan A et al: Diagnostic performance of magnetic resonance imaging for assessing tumor response in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy is associated with molecular biomarker profile. Clin Breast Cancer. 12(2):110-8, 2012
Shin HJ et al: Prediction of pathologic response to neoadjuvant chemotherapy in patients with breast cancer using diffusion-weighted imaging and MRS. NMR Biomed. 25(12):1349-59, 2012
Tateishi U et al: Neoadjuvant chemotherapy in breast cancer: prediction of pathologic response with PET/CT and dynamic contrast-enhanced MR imaging--prospective assessment. Radiology. 263(1):53-63, 2012
Untch M et al: Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol. 13(2):135-44, 2012
Wahner-Roedler DL et al: The use of molecular breast imaging to assess response in women undergoing neoadjuvant therapy for breast cancer: a pilot study. Clin Nucl Med. 37(4):344-50, 2012
Chen JH et al: Breast cancer: evaluation of response to neoadjuvant chemotherapy with 3.0-T MR imaging. Radiology. 261(3):735-43, 2011
Loo CE et al: Magnetic resonance imaging response monitoring of breast cancer during neoadjuvant chemotherapy: relevance of breast cancer subtype. J Clin Oncol. 29(6):660-6, 2011
Martoni AA et al: Prospective study on the FDG-PET/CT predictive and prognostic values in patients treated with neoadjuvant chemoradiation therapy and radical surgery for locally advanced rectal cancer. Ann Oncol. 22(3):650-6, 2011
McGuire KP et al: MRI staging after neoadjuvant chemotherapy for breast cancer: does tumor biology affect accuracy? Ann Surg Oncol. 18(11):3149-54, 2011
Gianni L et al: Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 375(9712):377-84, 2010
Park SH et al: Diffusion-weighted MR imaging: pretreatment prediction of response to neoadjuvant chemotherapy in patients with breast cancer. Radiology. 257(1):56-63, 2010
Straver ME et al: MRI-model to guide the surgical treatment in breast cancer patients after neoadjuvant chemotherapy. Ann Surg. 251(4):701-7, 2010
Woodhams R et al: Identification of residual breast carcinoma following neoadjuvant chemotherapy: diffusion-weighted imaging--comparison with contrast-enhanced MR imaging and pathologic findings. Radiology. 254(2):357-66, 2010
Yuan Y et al: Accuracy of MRI in prediction of pathologic complete remission in breast cancer after preoperative therapy: a meta-analysis. AJR Am J Roentgenol. 195(1):260-8, 2010
Kelly AM et al: Breast cancer sentinel node identification and classification after neoadjuvant chemotherapy-systematic review and meta analysis. Acad Radiol. 16(5):551-63, 2009
Lee JH et al: The role of radiotracer imaging in the diagnosis and management of patients with breast cancer: part 1--overview, detection, and staging. J Nucl Med. 50(4):569-81, 2009
Pons F et al: Breast cancer therapy: the role of PET-CT in decision making. Q J Nucl Med Mol Imaging. 53(2):210-23, 2009
Seo JH et al: Meta-analysis of pre-operative aromatase inhibitor versus tamoxifen in postmenopausal woman with hormone receptor-positive breast cancer. Cancer Chemother Pharmacol. 63(2):261-6, 2009
Wahl RL et al: From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 50 Suppl 1:122S-50S, 2009
Chen JH et al: Inflammatory breast cancer after neoadjuvant chemotherapy: can magnetic resonance imaging precisely diagnose the final pathological response? Ann Surg Oncol. 15(12):3609-13, 2008
Chen JH et al: MRI evaluation of pathologically complete response and residual tumors in breast cancer after neoadjuvant chemotherapy. Cancer. 2008 Jan 1;112(1):17-26. Erratum in: Cancer. 112(7):1642, 2008
Emmering J et al: Preoperative [18F] FDG-PET after chemotherapy in locally advanced breast cancer: prognostic value as compared with histopathology. Ann Oncol. 19(9):1573-7, 2008
Padhani AR et al: Prediction of clinicopathologic response of breast cancer to primary chemotherapy at contrast-enhanced MR imaging: initial clinical results. Radiology. 239(2):361-74, 2006
Peintinger F et al: Accuracy of the combination of mammography and sonography in predicting tumor response in breast cancer patients after neoadjuvant chemotherapy. Ann Surg Oncol. 13(11):1443-9, 2006
Partridge SC et al: MRI measurements of breast tumor volume predict response to neoadjuvant chemotherapy and recurrence-free survival. AJR Am J Roentgenol. 184(6):1774-81, 2005
Yeh E et al: Prospective comparison of mammography, sonography, and MRI in patients undergoing neoadjuvant chemotherapy for palpable breast cancer. AJR Am J Roentgenol. 184(3):868-77, 2005
Londero V et al: 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):1371-9, 2004
Tseng J et al: 18F-FDG kinetics in locally advanced breast cancer: correlation with tumor blood flow and changes in response to neoadjuvant chemotherapy. J Nucl Med. 45(11):1829-37, 2004
Rosen EL et al: Accuracy of MRI in the detection of residual breast cancer after neoadjuvant chemotherapy. AJR Am J Roentgenol. 181(5):1275-82, 2003
Burcombe RJ et al: Evaluation of good clinical response to neoadjuvant chemotherapy in primary breast cancer using [18F]-fluorodeoxyglucose positron emission tomography. Eur J Cancer. 38(3):375-9, 2002
Partridge SC et al: Accuracy of MR imaging for revealing residual breast cancer in patients who have undergone neoadjuvant chemotherapy. AJR Am J Roentgenol. 179(5):1193-9, 2002
Rouzier R et al: Primary chemotherapy for operable breast cancer: incidence and prognostic significance of ipsilateral breast tumor recurrence after breast-conserving surgery. J Clin Oncol. 19(18):3828-35, 2001
Schelling M et al: Positron emission tomography using [(18)F]Fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer. J Clin Oncol. 18(8):1689-95, 2000
Young H et al: Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 35(13):1773-82, 1999
Bassa P et al: Evaluation of preoperative chemotherapy using PET with fluorine-18-fluorodeoxyglucose in breast cancer. J Nucl Med. 37(6):931-8, 1996
Helvie MA et al: Locally advanced breast carcinoma: accuracy of mammography versus clinical examination in the prediction of residual disease after chemotherapy. Radiology. 198(2):327-32, 1996
Vinnicombe SJ et al: Primary breast cancer: mammographic changes after neoadjuvant chemotherapy, with pathologic correlation. Radiology. 198(2):333-40, 1996
Dershaw DD et al: Assessment of response to therapy of primary breast cancer by mammography and physical examination. Cancer. 75(8):2093-8, 1995
Moskovic EC et al: Mammography in the assessment of response to medical treatment of large primary breast cancer. Clin Radiol. 47(5):339-44, 1993
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