Targeted therapies against HER2 (trastuzumab, lapatinib) have improved the efficacy of treatment and the outcome of patients with HER2-positive breast cancer. Lapatinib is a tyrosine kinase inhibitor targeting EGFR1 and HER2: it binds the intracellular domain of these receptors and blocks their downstream signaling pathways. In combination with capecitabine, it is the standard of care for patients with trastuzumab-resistant advanced breast cancer. We present the case of a patient exhibiting a complete and prolonged clinical response to second-line treatment with lapatinib and capecitabine after failure of trastuzumab-based therapy. 18FDG-PET allowed the detection of disease remission several months before computed tomography. Molecular imaging with 18FDG seems the most powerful way to measure the pharmacodynamic effects of targeted anticancer drugs. This case report confirms that18FDG-PET plays a key role not only in detecting metastatic disease but also in evaluating the response to HER2-directed therapy.
SlamonD.J., GodolphinW., JonesL.A., HoltJ.A., WongS.G., KeithD.E., LevinW.J., StuartS.G., UdoveJ., UllrichA., PressM.F.Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science, 244: 702–712, 1989.
2.
RossJ.S., FletcherJ.A., BloomK.J., LinetteG.P., StecJ., SymmansW.F., PusztaiL., HortobagyiG.N.: Targeted therapy in breast cancer: the HER-2/neu gene and protein. Mol Cell Proteomics, 3: 379–398, 2004.
3.
SlamonD.J., ClarkG.M., WongS.G., LevinW.J., UllrichA., McGuireW.L.: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science, 235: 177–182, 1987.
4.
SlamonD.J., Leyland-JonesB., ShakS., FuchsH., PatonV., BajamondeA., FlemingT., EiermannW., WolterJ., PegramM., BaselgaJ., NortonL.: Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med, 344: 783–792, 2001.
5.
PuglisiF., PiccartM.: Trastuzumab and breast cancer. Are we just beyond the prologue of a fascinating story? Onkologie, 28: 547–549, 2005.
6.
NahtaR., YuD., HungM.C., HortobagyiG.N., EstevaF.J.: Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol, 3: 269–280, 2006.
7.
MontemurroF., RedanaS., VialeG., SannaG., DonadioM., ValabregaG., del CurtoB., BottiniA., BottiG., dei TosA.P., JacomuzziM.E., Di BonitoM., DaneseS., ClavarezzaM., KulkaJ., Di PalmaS., DurandoA., SapinoA., AgliettaM.: Retrospective evaluation of clinical outcomes in patients with HER2-positive advanced breast cancer progressing on trastuzumab-based therapy in the pre-lapatinib era. Clin Breast Cancer, 8: 436–442, 2008.
8.
KonecnyG.E., PegramM.D., VenkatesanN., FinnR., YangG., RahmehM., UntchM., RusnakD.W., SpeharG., MullinR.J., KeithB.R., GilmerT.M., BergerM., PodratzK.C., SlamonD.J.: Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res, 66: 1630–1639, 2006.
9.
CameronD.A., SteinS.: Drug Insight: intracellular inhibitors of HER2-clinical development of lapatinib in breast cancer. Nat Clin Pract Oncol, 5: 512–520, 2008.
10.
ScaltritiM., VermaC., GuzmanM., JimenezJ., ParraJ.L., PedersenK., SmithD.J., LandolfiS., Ramon y CajalS., ArribasJ., BaselgaJ.: Lapatinib, a HER2 tyrosine kinase inhibitor, induces stabilization and accumulation of HER2 and potentiates trastuzumab-dependent cell cytotoxicity. Oncogene, 28: 803–814, 2009.
11.
CameronD., CaseyM., PressM., LindquistD., PienkowskiT., RomieuC.G., ChanS., Jagiello-GruszfeldA., KaufmanB., CrownJ., ChanA., CamponeM., ViensP., DavidsonN., GorbounovaV., RaatsJ.I., SkarlosD., NewstatB., RoychowdhuryD., PaolettiP., OlivaC., RubinS., SteinS., GeyerC.E.: A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat, 112: 533–543, 2008.
12.
GeyerC.E., ForsterJ., LindquistD., ChanS., RomieuC.G., PienkowskiT., Jagiello-GruszfeldA., CrownJ., ChanA., KaufmanB., SkarlosD., CamponeM., DavidsonN., BergerM., OlivaC., RubinS.D., SteinS., CameronD.: Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med, 35: 2733–2743, 2006. Erratum in: N Engl J Med, 356: 1487, 2007.
13.
ErbB2 over-expressing metastatic breast cancer study using paclitaxel, trastuzumab, and lapatinib. Available at: http://clinicaltrials.gov/show/NCT00272987. Accessed December 21, 2012.
14.
A study of AC followed by a combination of paclitaxel plus trastuzumab or lapatinib or both given before surgery to patients with operable HER2 positive invasive breast cancer. Available at: http://clinicaltrials.gov/show/NCT00486668. Accessed December 21, 2012.
Paclitaxel and trastuzumab with or without lapatinib in treating patients with stage II or stage III breast cancer that can be removed by surgery. Available at: http://clinicaltrials.gov/show/NCT00770809. Accessed December 21, 2012.
17.
TomaselloG., de AzambujaE., DinhP., SnojN., Piccart-GebhartM.: Jumping higher: is it still possible? The ALTTO trial challenge. Expert Rev Anticancer Ther, 8: 1883–1890, 2008.
18.
ConstantinidouA., MartinA., SharmaB., JohnstonS.R.: Positron emission tomography/computed tomography in the management of recurrent/metastatic breast cancer: a large retrospective study from the Royal Marsden Hospital. Ann Oncol, 22: 307–314, 2011.
19.
KrakN.C., BoellaardR., HoekstraO.S., TwiskJ.W., HoekstraC.J., LammertsmaA.A.: Effects of ROI definition and reconstruction method on quantitative outcome and applicability in a response monitoring trial. Eur J Nucl Med Mol Imaging, 32: 294–301, 2005.
20.
Dose SchwarzJ., BaderM., JenickeL., HemmingerG., JänickeF., AvrilN.: Early prediction of response to chemotherapy in metastatic breast cancer using sequential 18F-FDG PET. J Nucl Med, 46: 1144–1150, 2005.
21.
DuchJ., FusterD., MuñozM., FernándezP.L., ParedesP., FontanillasM., GuzmánF., RubíS., LomeñaF.J., PonsF.: 18F-FDG PET/CT for early prediction of response to neoadjuvant chemotherapy in breast cancer. Eur J Nucl Med Mol Imaging, 36: 1551–1557, 2009.
22.
KawadaK., MurakamiK., SatoT., KojimaY., EbiH., MukaiH., TaharaM., ShimokataK., MinamiH.: Prospective study of positron emission tomography for evaluation of the activity of lapatinib, a dual inhibitor of the ErbB1 and ErbB2 tyrosine kinases, in patients with advanced tumors. Jpn J Clin Oncol, 37: 44–48, 2007.
