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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2018

Open Access 01-12-2018 | Review

Overcoming endocrine resistance in metastatic hormone receptor-positive breast cancer

Authors: Anishka D’Souza, Darcy Spicer, Janice Lu

Published in: Journal of Hematology & Oncology | Issue 1/2018

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Abstract

Endocrine therapy has historically formed the basis of treatment of metastatic hormone receptor-positive breast cancer. The development of endocrine resistance has led to the development of newer endocrine drug combinations. Use of the CDK4/6 inhibitors has significantly improved progression-free survival in this group of patients. There are multiple studies of the use of P13K inhibitors and mTOR inhibitors for use as subsequent lines of therapy, particularly for endocrine resistance. The optimal sequencing of therapy should be based on medical comorbidities, prior adjuvant therapies, quality of life, side-effect profile, and disease-free interval.
Literature
1.
2.
Sini V, Cinieri S, Conte P, De Laurentiis M, Leo AD, Tondini C, Marchetti P. Endocrine therapy in post-menopausal women with metastatic breast cancer: from literature and guidelines to clinical practice. Crit Rev Oncol Hematol. 2016;100:57–68.CrossRefPubMed
3.
Di Leo A, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, Verhoeven D, Pedrini JL, Smirnova I, Lichinitser MR, Pendergrass K, Garnett S, Lindemann JP, Sapunar F, Martin M. Results of the CONFIRM phase III trial comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with estrogen receptor-positive advanced breast cancer. J Clin Oncol. 2010;28(30):4594–600.CrossRefPubMed
4.
Robertson JF, Lindemann JP, Llombart-Cussac A, Rolski J, Feltl D, Dewar J, Emerson L, Dean A, Ellis MJ. Fulvestrant 500 mg versus anastrozole 1 mg for the FIRST-line treatment of advanced breast cancer: follow-up analysis from the randomized 'FIRST' study. Breast Cancer Res Treat. 2012;136(2):503–11.CrossRefPubMed
5.
Ellis MJ, Llombart-Cussac A, Feltl D, Dewar JA, Jasiówka M, Hewson N, Rukazenkov Y, Robertson JF. Fulvestrant 500 mg versus anastrozole 1 mg for the First-line treatment of advanced breast cancer: overall survival analysis from the phase II FIRST study. J Clin Oncol. 2015;33(32):3781–7.CrossRefPubMedPubMedCentral
6.
Robertson JFR, Bondarenko IM, Trishkina E, Dvorkin M, Panasci L, Manikhas A, Shparyk Y, Cardona-Huerta S, Cheung KL, Philco-Salas MJ, Ruiz-Borrego M, Shao Z, Noguchi S, Rowbottom J, Stuart M, Grinsted LM, Fazal M, Ellis MJ. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet. 2016;388(10063):2997–3005.CrossRefPubMed
7.
Cardoso F, Costa A, Senkus E, Aapro M, André F, Barrios CH, Bergh J, Bhattacharyya G, Biganzoli L, Cardoso MJ, Carey L, Corneliussen-James D, Curigliano G, Dieras V, El Saghir N, Eniu A, Fallowfield L, Fenech D, Francis P, Gelmon K, Gennari A, Harbeck N, Hudis C, Kaufman B, Krop I, Mayer M, Meijer H, Mertz S, Ohno S, Pagani O, et al. 3rd ESO-ESMO international consensus guidelines for advanced breast Cancer (ABC 3). Ann Oncol. 2017;28(1):16–33.PubMed
8.
Bedard PL, Freedman OC, Howell A, Clemons M. Overcoming endocrine resistance in breast cancer: are signal transduction inhibitors the answer? Breast Cancer Res Treat. 2008;108(3):307–17.CrossRefPubMed
9.
10.
Augereau P, Patsouris A, Bourbouloux E, Gourmelon C, Abadie Lacourtoisie S, Berton Rigaud D, Soulié P, Frenel JS, Campone M. Hormonoresistance in advanced breast cancer: a new revolution in endocrine therapy. Ther Adv Med Oncol. 2017;9(5):335–46.CrossRefPubMedPubMedCentral
11.
Turner NC, Huang Bartlett C, Cristofanilli M. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med. 2015;373(17):1672–3.CrossRefPubMed
12.
Barroso-Sousa R, Shapiro GI, Tolaney SM. Clinical development of the CDK4/6 inhibitors ribociclib and abemaciclib in breast cancer. Breast Care (Basel). 2016;11(3):167–73.CrossRef
13.
Vidula N, Rugo HS. Cyclin-dependent kinase 4/6 inhibitors for the treatment of breast cancer: a review of preclinical and clinical data. Clin Breast Cancer. 2016;16(1):8–17.CrossRefPubMed
14.
Xu H, Yu S, Liu Q, Yuan X, Mani S, Pestell R, Wu K. Recent advances of highly selective CDK4/6 inhibitors in breast cancer. J Hematol Oncol. 2017;10:97.
15.
Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, Gauthier E, Lu DR, Randolph S, Diéras V, Slamon DJ. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016;375(20):1925–36.CrossRefPubMed
16.
Rugo H, Finn R, Dieras V, Ettl J, Lipatov O, Joy A, Harbeck N, Castrellon A, Lu D, Mori A, Gauthier E, Huang C, Gelmon K, Slamon D. Palbociclib (PAL) + letrozole (LET) as first-line therapy in estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (ABC): Efficacy and safety updates with longer follow-up across patient subgroups. In: 2017 San Antonio breast Cancer symposium. San Antonio; 2017.
17.
Martín M, Hoffman J, Ruiz-Borrego M, Muñoz M, Calvo L, Crownover P, García-Sáenz J, Alba E, Wang D, Thallinger C, Stradella A, Montaño Á, Adamo B, Antolín S, Moreno-Antón F, Falo C, Ruiz V, Martín N, Caballero R, Carrasco E, Gil-Gil M. Evaluation of the drug interaction potential of palbociclib and exemestane—results from the PEARL pharmacokinetic sub-Study. In: 2017 San Antonio Breast Cancer Symposium. San Antonio; 2017.
18.
Tripathy D, Bardia A, Blum J, Rocque G, Wilks S, Lakhanpal S, Migas J, Cappelleri J, Perkins J, Comstock G, Wang Y. POLARIS: Palbociclib (P) in hormone receptor-positive (HR+) advanced breast cancer: a prospective multicenter noninterventional study. In: 2017 San Antonio Breast Cancer Symposium. San Antonio; 2017.
19.
Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Blackwell KL, André F, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Petrakova K, Hart LL, Villanueva C, Chan A, Jakobsen E, Nusch A, Burdaeva O, Grischke EM, Alba E, Wist E, Marschner N, Favret AM, Yardley D, Bachelot T, Tseng LM, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375(18):1738–48.CrossRefPubMed
20.
Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee K, Campos-Gomez S, Villanueva Vazquez R, Jung K, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. In: 2017 San Antonio Breast Cancer Symposium. San Antonio; 2017.
21.
Patnaik A, Rosen Le S, Tolaney SM, Tolcher AW, Goldman JW, Gandhi L, Papadopoulos KP, Beeram M, Rasco DW, Myrand SP, Kulanthaivel P, Li L, Frenzel M, Cronier DM, Chan EM, Flaherty KT, Wen PY, Shapiro GI. Clinical activity of LY2835219, a novel cell cycle inhibitor selective for CDK4 and CDK6, in patients with metastatic breast cancer. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research. San Diego: American Association for Cancer Research; 2014.
22.
Dickler MN, Tolaney SM, Rugo HS, Cortés J, Diéras V, Patt D, Wildiers H, Hudis CA, O'Shaughnessy J, Zamora E, Yardley DA, Frenzel M, Koustenis A, Baselga J. MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR+/HER2- metastatic breast cancer. Clin Cancer Res. 2017;23(17):5218–24.CrossRefPubMedPubMedCentral
23.
Sledge GW, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Frenzel M, Lin Y, Barriga S, Smith IC, Bourayou N, Llombart-Cussac A. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017;35(25):2875–84.CrossRefPubMed
24.
Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017;35(32):3638–46.CrossRefPubMed
25.
Steelman LS, Martelli AM, Cocco L, Libra M, Nicoletti F, Abrams SL, McCubrey JA. The therapeutic potential of mTOR inhibitors in breast cancer. Br J Clin Pharmacol. 2016;82(5):1189–212.CrossRefPubMedPubMedCentral
26.
27.
Bachelot T, Bourgier C, Cropet C, Ray-Coquard I, Ferrero JM, Freyer G, Abadie-Lacourtoisie S, Eymard JC, Debled M, Spaëth D, Legouffe E, Allouache D, El Kouri C, Pujade-Lauraine E. Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study. J Clin Oncol. 2012;30(22):2718–24.CrossRefPubMed
28.
Baselga J, Campone M, Piccart M, Burris HA, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012;366(6):520–9.CrossRefPubMed
29.
Piccart M, Hortobagyi GN, Campone M, Pritchard KI, Lebrun F, Ito Y, Noguchi S, Perez A, Rugo HS, Deleu I, Burris HA, Provencher L, Neven P, Gnant M, Shtivelband M, Wu C, Fan J, Feng W, Taran T, Baselga J. Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2†. Ann Oncol. 2014;25(12):2357–62.CrossRefPubMed
30.
Jerusalem G, Mariani G, Ciruelos EM, Martin M, Tjan-Heijnen VC, Neven P, Gavila JG, Michelotti A, Montemurro F, Generali D, Simoncini E, Lang I, Mardiak J, Naume B, Camozzi M, Lorizzo K, Bianchetti S, Conte P. Safety of everolimus plus exemestane in patients with hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer progressing on prior non-steroidal aromatase inhibitors: primary results of a phase IIIb, open-label, single-arm, expanded-access multicenter trial (BALLET). Ann Oncol. 2016;27(9):1719–25.CrossRefPubMed
31.
Schmid P, Zaiss M, Harper-Wynne C. MANTA - a randomized phase II study of fulvestrant in combination with the dual mTOR inhibitor AZD2014 or everolimus or fulvestrant alone in estrogen receptor-positive advanced or metastatic breast cancer. In: San Antonio Breast Cancer Symposium 2017. San Antonio; 2017.
32.
Juric D, Argiles G, Burris H, Gonzalez-Angulo A, Saura C, Quadt C, Douglas M, Demanse D, De Buck S, Baselga J. Phase I study of BYL719, an alpha-specific PI3K inhibitor, in patients with PIK3CA mutant advanced solid tumors: preliminary efficacy and safety in patients with PIK3CA mutant ER-positive (ER+) metastatic breast cancer (MBC). In: Thirty-Fifth Annual CTRC-AACR San Antonio Breast Cancer Symposium. San Antonio: American Association for Cancer Research; 2012.
33.
Juric D, Gonzalez-Angulo A, Burris H, Schuler M, Schellens J, Berlin J, Gupta A, Seggewiss-Bernhardt R, Adamo B, Gil-Martin M, Bootle D, Boehm M, De Buck S, Demanse D, Quadt C, Baselga J. Preliminary safety, pharmacokinetics and anti-tumor activity of BYL719, an alpha-specific PI3K inhibitor in combination with fulvestrant: Results from a phase I study. In: Thirty-Sixth Annual CTRC-AACR San Antonio Breast Cancer Symposium. San Antonio: American Association for Cancer Research; 2013.
34.
Juric D, Andra F, Rugo H. Combined alpelisib (BYL719) and Fulvestrant in PIK3CA-altered or wild-type estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. In: 2016 Miami Breast Cancer Conference; 2016.
35.
Massacesi C, Di Tomaso E, Urban P, Germa C, Quadt C, Trandafir L, Aimone P, Fretault N, Dharan B, Tavorath R, Hirawat S. PI3K inhibitors as new cancer therapeutics : implications for clinical trial design. OncoTargets Ther. 2016;9:203–10.CrossRef
36.
Baselga J, Im SA, Iwata H, Cortés J, De Laurentiis M, Jiang Z, Arteaga CL, Jonat W, Clemons M, Ito Y, Awada A, Chia S, Jagiełło-Gruszfeld A, Pistilli B, Tseng LM, Hurvitz S, Masuda N, Takahashi M, Vuylsteke P, Hachemi S, Dharan B, Di Tomaso E, Urban P, Massacesi C, Campone M. Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(7):904–16.CrossRefPubMedPubMedCentral
37.
Di Leo A, Seok Lee K, Ciruelos E, Lønning P, Janni W, O'Regan R, Mouret Reynier M, Kalev D, Egle D, Csoszi T, Bordonaro R, Decker T, Tjan-Heijnen V, Blau S, Schirone A, Weber D, El-Hashimy M, Dharan B, Sellami D, Bachelot T. BELLE-3: A phase III study of buparlisib + fulvestrant in postmenopausal women with HR+, HER2–, aromatase inhibitor-treated, locally advanced or metastatic breast cancer, who progressed on or after mTOR inhibitor-based treatment. In: 2016 San Antonio Breast Cancer Symposium. San Antonio: Cancer Research; 2016.
38.
Krop IE, Mayer IA, Ganju V, Dickler M, Johnston S, Morales S, Yardley DA, Melichar B, Forero-Torres A, Lee SC, de Boer R, Petrakova K, Vallentin S, Perez EA, Piccart M, Ellis M, Winer E, Gendreau S, Derynck M, Lackner M, Levy G, Qiu J, He J, Schmid P. Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016;17(6):811–21.CrossRefPubMedPubMedCentral
39.
Juric D, Ismail-Khan R, Campone M, García-Estévez L, Becerra C, De Boer R, Hamilton E, Mayer I, Hui R, Lathrop K, Pagani O, Asano S, Bhansali S, Zhang V, Hewes B, Munster P. Phase Ib/II study of ribociclib and alpelisib and letrozole in ER+, HER2– breast cancer: Safety, preliminary efficacy and molecular analysis. In: Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium. San Antonio: Cancer Research; 2015.
40.
Forero A, Han H, Dees E, Wesolowski R, Bardia A, Kabos P, Kern K, Perea R, Pierce K, Houk B, Rugo H. Phase Ib study to assess the safety, tolerability, and clinical activity of gedatolisib in combination with palbociclib and either letrozole or fulvestrant in women with metastatic or locally advanced/recurrent breast cancer (B2151009). In: 2017 San Antonio Breast Cancer Symposium. San Antonio; 2017.
41.
Willemse PH, van der Ploeg E, Sleijfer DT, Tjabbes T, van Veelen H. A randomized comparison of megestrol acetate (MA) and medroxyprogesterone acetate (MPA) in patients with advanced breast cancer. Eur J Cancer. 1990;26(3):337–43.CrossRefPubMed
42.
Abrams J, Aisner J, Cirrincione C, Berry DA, Muss HB, Cooper MR, Henderson IC, Panasci L, Kirshner J, Ellerton J, Norton L. Dose-response trial of megestrol acetate in advanced breast cancer: cancer and leukemia group B phase III study 8741. J Clin Oncol. 1999;17(1):64–73.CrossRefPubMed
43.
Lonning PE, Taylor PD, Gun A, Iddon J. High-dose estrogen treatment in post-menopausal breast patients heavily exposed to endocrine therapy. Breast Cancer Res Treat. 2001;67(2):111–6.CrossRefPubMed
44.
Cardoso F, Bischoff J, Brain E, Zotano Á, Lück HJ, Tjan-Heijnen VC, Tanner M, Aapro M. A review of the treatment of endocrine responsive metastatic breast cancer in postmenopausal women. Cancer Treat Rev. 2013;39(5):457–65.CrossRefPubMed
45.
Liu B, Song Y, Liu D. Recent development in clinical applications of PD-1 and PD-L1 antibodies for cancer immunotherapy. J Hematol Oncol. 2017;10(1):174.CrossRefPubMedPubMedCentral
46.
47.
48.
Yu S, Li A, Liu Q, Yuan X, Xu H, Jiao D, Pestell R, Han X, Wu K. Recent advances of bispecific antibodies in solid tumors. J Hematol Oncol. 2017;10(1):155.CrossRefPubMedPubMedCentral
49.
Tolcher AW, Sznol M, Hu-Lieskovan S, Papadopoulos KP, Patnaik A, Rasco DW, Di Gravio D, Huang B, Gambhire D, Chen Y, Thall AD, Pathan N, Schmidt EV, Chow LQM. Phase Ib study of utomilumab (PF-05082566), a 4-1BB/CD137 agonist, in combination with pembrolizumab (MK-3475) in patients with advanced solid tumors. Clin Cancer Res. 2017;23:5349–57.CrossRefPubMed
50.
Wang J, Yuan R, Song W, et al. PD-1, PD-L1 (B7-H1) and tumor-site immune modulation therapy: the historical perspective. J Hematol Oncol. 2017;10(1):34.CrossRefPubMedPubMedCentral
51.
Sri Lakshmi HY, Zhao F, Miller KD, Tevaarwerk AJ, Wagner LI, Gray RJ, Sparano JA, Connolly RM. E2112: randomized phase iii trial of endocrine therapy plus entinostat/placebo in patients with hormone receptor-positive advanced breast cancer. NPJ Breast Cancer. 2018;4(1):1–5.CrossRef
Metadata
Title
Overcoming endocrine resistance in metastatic hormone receptor-positive breast cancer
Authors
Anishka D’Souza
Darcy Spicer
Janice Lu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2018
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-018-0620-6

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