Top

Published in:

Open Access 01-02-2016 | Review

Systemic treatment in breast cancer: a primer for radiologists

Authors: Aya Y. Michaels, Abhishek R. Keraliya, Sree Harsha Tirumani, Atul B. Shinagare, Nikhil H. Ramaiya

Published in: Insights into Imaging | Issue 1/2016

Abstract

Cytotoxic chemotherapy, hormonal therapy and molecular targeted therapy are the three major classes of drugs used to treat breast cancer. Imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), ¹⁸F-FDG positron emission tomography (PET)/CT and bone scintigraphy each have a distinct role in monitoring response and detecting drug toxicities associated with these treatments. The purpose of this article is to elucidate the various systemic therapies used in breast cancer, with an emphasis on the role of imaging in assessing treatment response and detecting treatment-related toxicities.

Teaching Points

• Cytotoxic chemotherapy is often used in combination with HER2-targeted and endocrine therapies.

• Endocrine and HER2-targeted therapies are recommended in hormone-receptor- and HER2-positive cases.

• CT is the workhorse for assessment of treatment response in breast cancer metastases.

• Alternate treatment response criteria can help in interpreting pseudoprogression in metastasis.

• Unique toxicities are associated with cytotoxic chemotherapy and with endocrine and HER2-targeted therapies.

(2014) National Clinical Practice Guidelines in Oncology (NCCN guidelines): Breast cancer-version 3.2014. Available via http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#site

Chikarmane SA, Tirumani SH, Howard SA, Jagannathan JP, DiPiro PJ (2015) Metastatic patterns of breast cancer subtypes: what radiologists should know in the era of personalized cancer medicine. Clin Radiol 70:1–10CrossRefPubMed

Jordan VC (2006) Tamoxifen (ici46,474) as a targeted therapy to treat and prevent breast cancer. Br J Pharmacol 147(Suppl 1):S269–S276

Rugo HS (2008) The breast cancer continuum in hormone-receptor-positive breast cancer in postmenopausal women: evolving management options focusing on aromatase inhibitors. Ann Oncol 19:16–27CrossRefPubMed

Semiglazov VF, Semiglazov VV, Dashyan GA et al (2007) Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer. Cancer 110:244–254CrossRefPubMed

Cataliotti L, Buzdar AU, Noguchi S et al (2006) Comparison of anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor-positive breast cancer: the pre-operative “Arimidex” compared to Tamoxifen (PROACT) trial. Cancer 106:2095–2103CrossRefPubMed

Croxtall JD, McKeage K (2011) Fulvestrant: a review of its use in the management of hormone receptor-positive metastatic breast cancer in postmenopausal women. Drugs 71:363–380CrossRefPubMed

Joensuu H, Bono P, Kataja V et al (2009) Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the finher trial. J Clin Oncol 27:5685–5692CrossRefPubMed

Spielmann M, Roche H, Delozier T et al (2009) Trastuzumab for patients with axillary-node-positive breast cancer: results of the FNCLCC-PACS 04 trial. J Clin Oncol 27:6129–6134CrossRefPubMed

10.

Kelly CM, Buzdar AU (2013) Using multiple targeted therapies in oncology: considerations for use, and progress to date in breast cancer. Drugs 73:505–515CrossRefPubMed

11.

Abdel-Razeq H, Marei L (2011) Current neoadjuvant treatment options for HER2-positive breast cancer. Biologics 5:87–94

12.

Lin NU, Dieras V, Paul D et al (2009) Multicenter phase ii study of lapatinib in patients with brain metastases from HER2-positive breast cancer. Clin Cancer Res 15:1452–1459CrossRefPubMed

13.

Swain SM, Kim SB, Cortes J et al (2013) Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (cleopatra study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 14:461–471PubMedCentralCrossRefPubMed

14.

Zimmerman P, Lu DS, Yang LY, Chen S, Sayre J, Kadell B (2000) Hepatic metastases from breast carcinoma: comparison of noncontrast, arterial-dominant, and portal-dominant phase spiral CT. J Comput Assist Tomogr 24:197–203CrossRefPubMed

15.

Sica GT, Ji H, Ros PR (2000) CT and MR imaging of hepatic metastases. AJR Am J Roentgenol 174:691–698CrossRefPubMed

16.

Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. HER2ean Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216CrossRefPubMed

17.

Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247CrossRefPubMed

18.

He H, Cai C, Charnsangavej C et al (2015) Contrast-enhanced computed tomography evaluation of hepatic metastases in breast cancer patients before and after cytotoxic chemotherapy or targeted therapy. Can Assoc Radiol J. doi:10.1016/j.carj.2015.03.005 PubMed

19.

Lee SL, Chang ED, Na SJ et al (2014) Pseudocirrhosis of breast cancer metastases to the liver treated by chemotherapy. Cancer Res Treat 46:98–103PubMedCentralCrossRefPubMed

20.

Shinagare AB, Jagannathan JP, Krajewski KM, Ramaiya NH (2013) Liver metastases in the era of molecular targeted therapy: new faces of treatment response. AJR Am J Roentgenol 201:W15–W28CrossRefPubMed

21.

Tateishi U, Gamez C, Dawood S, Yeung HW, Cristofanilli M, Macapinlac HA (2008) Bone metastases in patients with metastatic breast cancer: morphologic and metabolic monitoring of response to systemic therapy with integrated PET/CT. Radiology 247:189–196CrossRefPubMed

22.

Stattaus J, Hahn S, Gauler T et al (2009) Osteoblastic response as a healing reaction to chemotherapy mimicking progressive disease in patients with small cell lung cancer. Eur Radiol 19:193–200CrossRefPubMed

23.

Jung JI, Kim HH, Park SH et al (2004) Thoracic manifestations of breast cancer and its therapy. Radiographics 24:1269–1285CrossRefPubMed

24.

Tanaka K, Shimizu K, Ohtaki Y et al (2013) Diagnosis and surgical resection of solitary pulmonary nodules in patients with breast cancer. Mol Clin Oncol 1:117–123PubMedCentralPubMed

25.

Nishino M, Jagannathan JP, Ramaiya NH, Van den Abbeele AD (2010) Revised recist guideline version 1.1: what oncologists want to know and what radiologists need to know. AJR Am J Roentgenol 195:281–289CrossRefPubMed

26.

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

27.

Ko ES, Han BK, Kim RB et al (2013) 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 20:2562–2568CrossRefPubMed

28.

McGuire KP, Toro-Burguete J, Dang H et al (2011) MRI staging after neoadjuvant chemotherapy for breast cancer: does tumor biology affect accuracy? Ann Surg Oncol 18:3149–3154CrossRefPubMed

29.

Lobbes M, Prevos R, Smidt M (2012) Response monitoring of breast cancer patients receiving neoadjuvant chemotherapy using breast MRI – a review of current knowledge. J Cancer Ther Res 1:34

30.

Bottcher J, Hansch A, Pfeil A et al (2013) Detection and classification of different liver lesions: comparison of gd-eob-dtpa-enhanced MRI versus multiphasic spiral CT in a clinical single centre investigation. Eur J Radiol 82:1860–1869

31.

Guglielmo FF, Mitchell DG, Gupta S (2014) Gadolinium contrast agent selection and optimal use for body MR imaging. Radiol Clin N Am 52:637–656CrossRefPubMed

32.

Lee KH, Lee JM, Park JH et al (2013) MR imaging in patients with suspected liver metastases: value of liver-specific contrast agent gadoxetic acid. Korean J Radiol 14:894–904PubMedCentralCrossRefPubMed

33.

Shimada K, Isoda H, Hirokawa Y, Arizono S, Shibata T, Togashi K (2010) Comparison of gadolinium-eob-dtpa-enhanced and diffusion-weighted liver MRI for detection of small hepatic metastases. Eur Radiol 20:2690–2698CrossRefPubMed

34.

Ringe KI, Husarik DB, Sirlin CB, Merkle EM (2010) Gadoxetate disodium-enhanced MRI of the liver: part 1, protocol optimization and lesion appearance in the noncirrhotic liver. AJR Am J Roentgenol 195:13–28CrossRefPubMed

35.

Thoeny HC, Ross BD (2010) Predicting and monitoring cancer treatment response with diffusion-weighted MRI. J Magn Reson Imaging 32:2–16PubMedCentralCrossRefPubMed

36.

Shah R, Vattoth S, Jacob R et al (2012) Radiation necrosis in the brain: imaging features and differentiation from tumor recurrence. Radiographics 32:1343–1359CrossRefPubMed

37.

Al-Okaili RN, Krejza J, Wang S, Woo JH, Melhem ER (2006) Advanced MR imaging techniques in the diagnosis of intraaxial brain tumors in adults. Radiographics 26(Suppl 1):S173–S189CrossRefPubMed

38.

Rousseau C, Devillers A, Sagan C et al (2006) Monitoring of early response to neoadjuvant chemotherapy in stage ii and iii breast cancer by [18f]fluorodeoxyglucose positron emission tomography. J Clin Oncol 24:5366–5372CrossRefPubMed

39.

Berriolo-Riedinger A, Touzery C, Riedinger JM et al (2007) [18F]FDG-PET predicts complete pathological response of breast cancer to neoadjuvant chemotherapy. Eur J Nucl Med Mol Imaging 34:1915–1924CrossRefPubMed

40.

Humbert O, Cochet A, Coudert B et al (2015) Role of positron emission tomography for the monitoring of response to therapy in breast cancer. Oncologist 20:94–104CrossRefPubMed

41.

Avril N, Sassen S, Roylance R (2009) Response to therapy in breast cancer. J Nucl Med 50(Suppl 1):55S–63SCrossRefPubMed

42.

Chao ST, Suh JH, Raja S, Lee SY, Barnett G (2001) The sensitivity and specificity of FDG PET in distinguishing recurrent brain tumor from radionecrosis in patients treated with stereotactic radiosurgery. Int J Cancer 96:191–197CrossRefPubMed

43.

Horky LL, Hsiao EM, Weiss SE, Drappatz J, Gerbaudo VH (2011) Dual phase FDG-PET imaging of brain metastases provides superior assessment of recurrence versus post-treatment necrosis. J Neurooncol 103:137–146CrossRefPubMed

44.

Lecouvet FE, Talbot JN, Messiou C et al (2014) Monitoring the response of bone metastases to treatment with magnetic resonance imaging and nuclear medicine techniques: a review and position statement by the HER2ean Organisation for Research and Treatment of Cancer Imaging Group. Eur J Cancer 50:2519–2531CrossRefPubMed

45.

Hamaoka T, Madewell JE, Podoloff DA, Hortobagyi GN, Ueno NT (2004) Bone imaging in metastatic breast cancer. J Clin Oncol 22:2942–2953CrossRefPubMed

46.

Malhotra P, Berman CG (2002) Evaluation of bone metastases in lung cancer. Improved sensitivity and specificity of PET over bone scanning. Cancer Control 9(254):259–260

47.

Wahl RL, Jacene H, Kasamon Y, Lodge MA (2009) From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med 50(Suppl 1):122S–150SPubMedCentralCrossRefPubMed

48.

Torrisi JM, Schwartz LH, Gollub MJ, Ginsberg MS, Bosl GJ, Hricak H (2011) CT findings of chemotherapy-induced toxicity: what radiologists need to know about the clinical and radiologic manifestations of chemotherapy toxicity. Radiology 258:41–56CrossRefPubMed

49.

Cronin CG, O’Connor M, Lohan DG et al (2009) Imaging of the gastrointestinal complications of systemic chemotherapy. Clin Radiol 64:724–733CrossRefPubMed

50.

Park SI, Jeon WH, Jeung HJ, Kim GC, Kim DK, Sim YJ (2014) Clinical features of docetaxel chemotherapy-related lymphedema. Lymphat Res Biol 12:197–202CrossRefPubMed

51.

Shahab N, Haider S, Doll DC (2006) Vascular toxicity of antineoplastic agents. Semin Oncol 33:121–138CrossRefPubMed

52.

Lawson M, Vasilaras A, De Vries A, Mactaggart P, Nicol D (2008) Urological implications of cyclophosphamide and ifosfamide. Scand J Urol Nephrol 42:309–317CrossRefPubMed

53.

Swerdlow AJ, Jones ME (2005) Tamoxifen treatment for breast cancer and risk of endometrial cancer: a case–control study. J Natl Cancer Inst 97:375–384CrossRefPubMed

54.

Fong K, Causer P, Atri M, Lytwyn A, Kung R (2003) Transvaginal US and hysterosonography in postmenopausal women with breast cancer receiving tamoxifen: correlation with hysteroscopy and pathologic study. Radiographics 23:137–150, discussion 151–135 CrossRefPubMed

55.

Ochi J, Hayakawa K, Moriguchi Y, Urata Y, Yamamoto A, Kawai K (2010) Uterine changes during tamoxifen, toremifene, and other therapy for breast cancer: evaluation with magnetic resonance imaging. Jpn J Radiol 28:430–436CrossRefPubMed

56.

Erman M, Abali H, Oran B et al (2004) Tamoxifen-induced tissue factor pathway inhibitor reduction: a clue for an acquired thrombophilic state? Ann Oncol 15:1622–1626CrossRefPubMed

57.

Rodriguez-Frias EA, Lee WM (2007) Cancer chemotherapy II: atypical hepatic injuries. Clin Liver Dis 11:663–676, viiiCrossRefPubMed

58.

Pilleul F, Chave G, Dumortier J, Scoazec JY, Valette PJ (2005) Fatty infiltration of the liver. Detection and grading using dual T1 gradient echo sequences on clinical MR system. Gastroenterol Clin Biol 29:1143–1147CrossRefPubMed

59.

Hadji P, Aapro MS, Body JJ et al (2011) Management of aromatase inhibitor-associated bone loss in postmenopausal women with breast cancer: practical guidance for prevention and treatment. Ann Oncol 22:2546–2555CrossRefPubMed

60.

Lee HE, Jeong NJ, Lee Y et al (2014) Radiation recall dermatitis and pneumonitis induced by trastuzumab (herceptin^®). Int J Dermatol 53:e159–e160

61.

Yeh ET, Bickford CL (2009) Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol 53:2231–2247CrossRefPubMed

62.

Huszno J, Les D, Sarzyczny-Slota D, Nowara E (2013) Cardiac side effects of trastuzumab in breast cancer patients—single center experiences. Contemp Oncol (Pozn) 17:190–195

63.

Guarneri V, Lenihan DJ, Valero V et al (2006) Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience. J Clin Oncol 24:4107–4115CrossRefPubMed

64.

Perez EA, Rodeheffer R (2004) Clinical cardiac tolerability of trastuzumab. J Clin Oncol 22:322–329CrossRefPubMed

65.

Cardinale D, Colombo A, Torrisi R et al (2010) Trastuzumab-induced cardiotoxicity: clinical and prognostic implications of troponin I evaluation. J Clin Oncol 28:3910–3916CrossRefPubMed

66.

Romond EH, Perez EA, Bryant J et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:1673–1684CrossRefPubMed

67.

de Azambuja E, Holmes AP, Piccart-Gebhart M et al (2014) Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol 15:1137–1146CrossRefPubMed

Title: Systemic treatment in breast cancer: a primer for radiologists
Authors: Aya Y. Michaels
Abhishek R. Keraliya
Sree Harsha Tirumani
Atul B. Shinagare
Nikhil H. Ramaiya
Publication date: 01-02-2016
Publisher: Springer Berlin Heidelberg
Published in: Insights into Imaging / Issue 1/2016
Electronic ISSN: 1869-4101
DOI: https://doi.org/10.1007/s13244-015-0447-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Systemic treatment in breast cancer: a primer for radiologists

Abstract

Teaching Points

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Teaching Points

Please log in to get access to this content

Other articles of this Issue 1/2016

The new Interventional Radiology/Diagnostic Radiology dual certificate: “higher standards, better education”

CT imaging features of atrioventricular shunts: what the radiologist must know

Branchial cleft anomalies: a pictorial review of embryological development and spectrum of imaging findings

Lights and shadows of cardiac magnetic resonance imaging in acute myocarditis

Haemangioma, an uncommon cause of an extradural or intradural extramedullary mass: case series with radiological pathological correlation

Ultrasonography of thyroid nodules: a pictorial review