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Emerging Targeted Therapies for Early Breast Cancer

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Abstract

Breast cancer is the most common malignancy and the second leading cause of cancer-related mortality in the United States (US). Most patients are diagnosed with early-stage disease; however, there is still a need to prevent recurrences that often present as incurable metastatic disease. The treatment landscape of early-stage breast cancer is evolving rapidly. The immune checkpoint inhibitor pembrolizumab is approved in combination with neoadjuvant chemotherapy for the treatment of high-risk triple-negative breast cancer (TNBC). The cyclin-dependent kinase (CDK) 4 and 6 inhibitor abemaciclib is approved for adjuvant treatment of patients with high-risk hormone receptor (HR)-positive disease. While adjuvant olaparib has shown significant improvement in outcomes for patients with pathogenic/likely pathogenic BRCA1/2 mutations and high-risk human epidermal growth factor receptor 2 (HER2)-negative breast cancer, and is approved in this setting. For the HER2-positive subtype, the post-neoadjuvant therapy can be tailored based on the response to neoadjuvant chemotherapy and HER2-targeted agents. In this narrative review, we summarize the most recent approvals for early-stage breast cancer as well as frequently encountered clinical challenges utilizing these medications.

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References

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7–33.

    PubMed  Google Scholar 

  2. Ahmad A. Breast cancer statistics: recent trends. Adv Exp Med Biol. 2019;1152:1–7.

    CAS  PubMed  Google Scholar 

  3. program S. SEER cancer statistics review (CSR) 1975–2012. 2012. Available at: https://seer.cancer.gov/archive/csr/1975_2012/browse_csr.php?sectionSEL=4&pageSEL=sect_04_table.13.html.

  4. Division of Cancer Prevention and Control, Centers for Disease Control and Prevention. https://www.cdc.gov/cancer/dcpc/about/CDC 2022.

  5. Schmid P CJ, Dent R, Pusztai L, McArthur H, Kummel S, et al. KEYNOTE-522: Phase 3 study of neoadjuvant pembrolizumab + chemotherapy versus placebo + chemotherapy, followed by adjuvant pembrolizumab versus placebo in early stage trile negative breast cancer. In: ESMO Virtual Plenary Virtual, 2021.

  6. von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019;380(7):617–28.

    Google Scholar 

  7. Yu NY, Iftimi A, Yau C, Tobin NP, van’t Veer L, Hoadley KA, et al. Assessment of long-term distant recurrence-free survival associated with tamoxifen therapy in postmenopausal patients with luminal A or luminal B breast cancer. JAMA Oncol. 2019;5(9):1304–9.

    PubMed  PubMed Central  Google Scholar 

  8. Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001;30:96–102.

    Google Scholar 

  9. Early Breast Cancer Trialists’ Collaborative G. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol. 2018;19(1):27–39.

    Google Scholar 

  10. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–72.

    PubMed  Google Scholar 

  11. Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017;376(22):2147–59.

    CAS  PubMed  Google Scholar 

  12. Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020;382(9):810–21.

    CAS  PubMed  Google Scholar 

  13. Brown M, Tsodikov A, Bauer KR, Parise CA, Caggiano V. The role of human epidermal growth factor receptor 2 in the survival of women with estrogen and progesterone receptor-negative, invasive breast cancer: the California Cancer Registry, 1999–2004. Cancer. 2008;112(4):737–47.

    PubMed  Google Scholar 

  14. Blum JL, Flynn PJ, Yothers G, Asmar L, Geyer CE Jr, Jacobs SA, et al. Anthracyclines in early breast cancer: the ABC trials-USOR 06–090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J Clin Oncol. 2017;35(23):2647–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. US FDA. FDA approves pembrolizumab for high-risk early-stage triple-negative breast cancer. FDA; 2021.

  16. Pusztai L, Denkert C, O’Shaughnessy J, Cortes J, Dent RA, McArthur HL, et al. Event-free survival by residual cancer burden after neoadjuvant pembrolizumab + chemotherapy versus placebo + chemotherapy for early TNBC: Exploratory analysis from KEYNOTE-522. J Clin Oncol. 2022;40(16 suppl):503.

    Google Scholar 

  17. Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im SA, Yusof MM, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817–28.

    PubMed  Google Scholar 

  18. Schmid P, Rugo HS, Adams S, Schneeweiss A, Barrios CH, Iwata H, et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21(1):44–59.

    CAS  PubMed  Google Scholar 

  19. Gianni L, Huang CS, Egle D, Bermejo B, Zamagni C, Thill M, et al. Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple-negative, early high-risk and locally advanced breast cancer: NeoTRIP Michelangelo randomized study. Ann Oncol. 2022;33(5):534–43.

    CAS  PubMed  Google Scholar 

  20. Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, et al. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020;396(10257):1090–100.

    CAS  PubMed  Google Scholar 

  21. Loi S, Schmid P, Aktan G, Karantza V, Salgado R. Relationship between tumor infiltrating lymphocytes (TILs) and response to pembrolizumab (pembro)+chemotherapy (CT) as neoadjuvant treatment (NAT) for triple-negative breast cancer (TNBC): phase Ib KEYNOTE-173 trial. Ann Oncol. 2019;30:iii2.

    Google Scholar 

  22. Rugo HS, Loi S, Adams S, et al. PD-l1 immunohistochemistry assay comparison in atezolizumab plus nab-paclitaxel-treated advanced triple-negative breast cancer. J Natl Cancer Inst. 2021;113(12):1733–43.

    PubMed Central  Google Scholar 

  23. Bianchini G, Huang C, Egle D, Bermejo B, Zamagni C, et al. LBA13 - Tumour infiltrating lymphocytes (TILs), PD-L1 expression and their dynamics in the NeoTRIPaPDL1 trial. ESMO Virtual Congress 2020. Ann Oncol. 2020;31(Suppl 4):S1142–215. https://doi.org/10.1016/annonc/annonc3252020.

    Article  Google Scholar 

  24. Asano Y, Kashiwagi S, Goto W, Takada K, Takahashi K, Hatano T, et al. Prediction of treatment response to neoadjuvant chemotherapy in breast cancer by subtype using tumor-infiltrating lymphocytes. Anticancer Res. 2018;38(4):2311–21.

    PubMed  Google Scholar 

  25. Burstein MD, Tsimelzon A, Poage GM, Covington KR, Contreras A, Fuqua SAW, et al. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res. 2015;21(7):1688–98.

    CAS  PubMed  Google Scholar 

  26. Emens LA, Goldstein LD, Schmid P, Rugo HS, Adams S, Barrios CH, et al. The tumor microenvironment (TME) and atezolizumab + nab-paclitaxel (A+nP) activity in metastatic triple-negative breast cancer (mTNBC): IMpassion130. J Clin Oncol. 2021;39(15 Suppl):1006.

    Google Scholar 

  27. Hutchinson KE, Yost SE, Chang CW, Johnson RM, Carr AR, McAdam PR, et al. Comprehensive profiling of poor-risk paired primary and recurrent triple-negative breast cancers reveals immune phenotype shifts. Clin Cancer Res. 2020;26(3):657–68.

    CAS  PubMed  Google Scholar 

  28. Szekely B, Bossuyt V, Li X, Wali VB, Patwardhan GA, Frederick C, et al. Immunological differences between primary and metastatic breast cancer. Ann Oncol. 2018;29(11):2232–9.

    CAS  PubMed  Google Scholar 

  29. Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378(22):2078–92.

    CAS  PubMed  Google Scholar 

  30. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–32.

    CAS  PubMed  Google Scholar 

  31. Liu J, Blake SJ, Yong MCR, Harjunpää H, Ngiow SF, Takeda K, et al. Improved efficacy of neoadjuvant compared to adjuvant immunotherapy to eradicate metastatic disease. Cancer Discov. 2016;6(12):1382–99.

    CAS  PubMed  Google Scholar 

  32. Nanda R, Liu MC, Yau C, Shatsky R, Pusztai L, Wallace A, et al. Effect of pembrolizumab plus neoadjuvant chemotherapy on pathologic complete response in women with early-stage breast cancer: an analysis of the ongoing phase 2 adaptively randomized I-SPY2 trial. JAMA Oncol. 2020;6(5):676–84.

    PubMed  Google Scholar 

  33. Schmid P, Salgado R, Park YH, Muñoz-Couselo E, Kim SB, Sohn J, et al. Pembrolizumab plus chemotherapy as neoadjuvant treatment of high-risk, early-stage triple-negative breast cancer: results from the phase 1b open-label, multicohort KEYNOTE-173 study. Ann Oncol. 2020;31(5):569–81.

    CAS  PubMed  Google Scholar 

  34. Loibl S, Schneeweiss A, Huober JB, Braun M, Rey J, Blohmer JU, et al. Durvalumab improves long-term outcome in TNBC: results from the phase II randomized GeparNUEVO study investigating neodjuvant durvalumab in addition to an anthracycline/taxane based neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC). J Clin Oncol. 2021;39(15 Suppl):506.

    Google Scholar 

  35. Geyer CE, Jr., Loibl S, Rastogi P, Seiler S, Costantino JP, Nekljudova V, et al. Abstract OT2-04-08: a randomized double-blind phase III clinical trial of neoadjuvant chemotherapy (NAC) with atezolizumab or placebo in patients (pts) with triple negative breast cancer (TNBC) followed by adjuvant atezolizumab or placebo: NSABP B-59/GBG 96-GeparDouze. Cancer Res. 2020;80(4 Suppl):OT2-04-8-OT2-8.

  36. Saji S, McArthur HL, Ignatiadis M, Bailey A, El-Abed S, Brandao M, et al. ALEXANDRA/IMpassion030: a phase 3 study of standard adjuvant chemotherapy with or without atezolizumab in patients with early-stage triple-negative breast cancer. J Clin Oncol. 2021;39(15 Suppl):TPS597-TPS.

  37. Pusztai L, Barlow W, Ganz P, Henry N, White J, Jagsi R, et al. Abstract OT1-02-04: SWOG S1418/NRG -BR006: A randomized, phase III trial to evaluate the efficacy and safety of MK-3475 as adjuvant therapy for triple receptor-negative breast cancer with ≥1 cm residual invasive cancer or positive lymph nodes (>pN1mic) after neoadjuvant chemotherapy. Cancer Res. 2018;78(4 Suppl):OT1-02-4-OT1-4.

  38. Conte PF, Dieci MV, Bisagni G, Laurentiis MD, Tondini CA, Schmid P, et al. Phase III randomized study of adjuvant treatment with the ANTI-PD-L1 antibody avelumab for high-risk triple negative breast cancer patients: the A-BRAVE trial. J Clin Oncol. 2020;38(15 Suppl):TPS598-TPS.

  39. Voorwerk L, Slagter M, Horlings HM, Sikorska K, van de Vijver KK, de Maaker M, et al. Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial. Nat Med. 2019;25(6):920–8.

    CAS  PubMed  Google Scholar 

  40. Shah AN, Flaum LE, Rademaker A, Santa-Maria CA, Jain S, Helenowski IB, et al. A phase II study of pembrolizumab and capecitabine for triple-negative (TN) and hormone receptor-positive, HER2-negative endocrine-refractory metastatic breast cancer (MBC). J Clin Oncol. 2019;37(15 Suppl):1096.

    Google Scholar 

  41. Robson M, Im S-A, Senkus E, Xu B, Domchek SM, Masuda N, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017;377(6):523–33.

    CAS  PubMed  Google Scholar 

  42. Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee K-H, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018;379(8):753–63.

    CAS  PubMed  Google Scholar 

  43. Tutt ANJ, Garber JE, Kaufman B, Viale G, Fumagalli D, Rastogi P, et al. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer. N Engl J Med. 2021;384(25):2394–405.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Tutt ANJ, Graber J, Gelber K-A Phillips, A Eisen, OT, et al. VP1-2022: pre-specified event-driven analysis of overall survival (OS) in the OlympiA phase III trial of adjuvant olaparib (OL) in germline BRCA1/2 mutation (gBRCAm) associated breast cancer. In: Esmo Virtual Plennary, 2022.

  45. Marmé F, Solbach C, Michel L, Schneeweiss A, Blohmer JU, Huober J, et al. Utility of the CPS + EG scoring system in triple-negative breast cancer treated with neoadjuvant chemotherapy. Eur J Cancer. 2021;153:203–12.

    PubMed  Google Scholar 

  46. von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017;377(2):122–31.

    Google Scholar 

  47. Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25–32.

    CAS  PubMed  Google Scholar 

  48. Ganz PA BH, Spanic T, et al. Quality of life results from OlympiA: A phase III, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)-adjuvant chemotherapy in patients with germline BRCA1/2 mutations and high-risk HER-2 negative early breast cancer. In: Presented at: 2021 San Antonio Breast Cancer Symposium; December 7.

  49. Matulonis UA, Monk BJ. PARP inhibitor and chemotherapy combination trials for the treatment of advanced malignancies: does a development pathway forward exist? Ann Oncol. 2017;28(3):443–7.

    CAS  PubMed  Google Scholar 

  50. Domchek SM, Postel-Vinay S, Im SA, Park YH, Delord JP, Italiano A, et al. Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. Lancet Oncol. 2020;21(9):1155–64.

    CAS  PubMed  Google Scholar 

  51. Konstantinopoulos PA, Waggoner SE, Vidal GA, Mita MM, Fleming GF, Holloway RW, et al. TOPACIO/Keynote-162 (NCT02657889): a phase 1/2 study of niraparib + pembrolizumab in patients (pts) with advanced triple-negative breast cancer or recurrent ovarian cancer (ROC)—results from ROC cohort. J Clin Oncol. 2018;36(15 Suppl):106.

    Google Scholar 

  52. Jiao S, Xia W, Yamaguchi H, Wei Y, Chen M-K, Hsu J-M, et al. PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression. Clin Cancer Res. 2017;23(14):3711–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Mehta AK, Cheney EM, Hartl CA, Pantelidou C, Oliwa M, Castrillon JA, et al. Targeting immunosuppressive macrophages overcomes PARP inhibitor resistance in BRCA1-associated triple-negative breast cancer. Nat Cancer. 2021;2(1):66–82.

    CAS  PubMed  Google Scholar 

  54. Paakkola NM, Karakatsanis A, Mauri D, Foukakis T, Valachis A. The prognostic and predictive impact of low estrogen receptor expression in early breast cancer: a systematic review and meta-analysis. ESMO Open. 2021;6(6): 100289.

    PubMed  PubMed Central  Google Scholar 

  55. Howlader N, Altekruse SF, Li CI, Chen VW, Clarke CA, Ries LA, Cronin KA. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014;106(5):dju055. https://doi.org/10.1093/jnci/dju055.

  56. Fisher B, Jeong JH, Bryant J, Anderson S, Dignam J, Fisher ER, et al. Treatment of lymph-node-negative, oestrogen-receptor-positive breast cancer: long-term findings from National Surgical Adjuvant Breast and Bowel Project randomised clinical trials. Lancet. 2004;364(9437):858–68.

    CAS  PubMed  Google Scholar 

  57. Francis PA, Pagani O, Fleming GF, Walley BA, Colleoni M, Láng I, et al. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018;379(2):122–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Regan MM, Walley BA, Fleming GF, et al: Randomized comparisons of adjuvant aromatase inhibitor exemestane plus ovarian function suppression vs tamoxifen in premenopausal women with hormone receptor–positive early breast cancer: update of the TEXT and SOFT trials. In: 2021 San Antonio Breast Cancer Symposium. Abstract GS2-05. Presented 8 Dec 2021.

  59. Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379(2):111–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Sparano JA, Gray RJ, Ravdin PM, Makower DF, Pritchard KI, Albain KS, et al. Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer. N Engl J Med. 2019;380(25):2395–405.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Kalinsky K, Barlow WE, Gralow JR, Meric-Bernstam F, Albain KS, Hayes DF, et al. 21-gene assay to inform chemotherapy benefit in node-positive breast cancer. N Engl J Med. 2021;385(25):2336–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016;17(4):425–39.

    CAS  PubMed  Google Scholar 

  63. Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017;35(32):3638–46.

    CAS  PubMed  Google Scholar 

  64. Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol. 2018;29(7):1541–7.

    CAS  PubMed  Google Scholar 

  65. Mayer EL, Dueck AC, Martin M, Rubovszky G, Burstein HJ, Bellet-Ezquerra M, et al. Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2021;22(2):212–22.

    CAS  PubMed  Google Scholar 

  66. Gnant M, Dueck AC, Frantal S, Martin M, Burstein HJ, Greil R, et al. Adjuvant palbociclib for early breast cancer: the PALLAS trial results (ABCSG-42/AFT-05/BIG-14-03). J Clin Oncol. 2022;40(3):282–93.

    CAS  PubMed  Google Scholar 

  67. Loibl S, Marmé F, Martin M, Untch M, Bonnefoi H, Kim SB, et al. Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer—the Penelope-B trial. J Clin Oncol. 2021;39(14):1518–30.

    CAS  PubMed  Google Scholar 

  68. Slamon DJ, Fasching PA, Patel R, Verma S, Hurvitz SA, Chia SKL, et al. NATALEE: phase III study of ribociclib (RIBO) + endocrine therapy (ET) as adjuvant treatment in hormone receptor–positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer (EBC). J Clin Oncol. 2019;37(15 Suppl):TPS597-TPS.

  69. Johnston SRD, Harbeck N, Hegg R, Toi M, Martin M, Shao ZM, et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2−, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol. 2020;38(34):3987–98.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Harbeck N, Rastogi P, Martin M, Tolaney SM, Shao ZM, Fasching PA, et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32(12):1571–81.

    CAS  PubMed  Google Scholar 

  71. Toi M BF, Im YH, Reinisch M, Molthrop D. Adjuvant abemaciclib combined with endocrine therapy: efficacy results in monarchE cohort 1. In: ESMO Breast 2022, Berlin, 2022.

  72. Freedman RA, Graff SL, Somerfield MR, Telli ML, Wolff AC, Giordano SH. Adjuvant abemaciclib plus endocrine therapy in the treatment of high-risk early breast cancer: ASCO guideline rapid recommendation update Q and A. JCO Oncol Pract. 2022:Op2200140.

  73. Rugo HS, O’Shaughnessy J, Boyle F, Toi M, Broom R, Blancas I, et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: safety and patient-reported outcomes from the monarchE study. Ann Oncol. 2022;33(6):616–27.

    CAS  PubMed  Google Scholar 

  74. Navarro-Yepes J, Chen X, Bui T, Kettner NM, Hunt KK, Keyomarsi K. Abstract PD2-05: differential mechanisms of acquired resistance to abemaciclib versus palbociclib reveal novel therapeutic strategies for CDK4/6 therapy-resistant breast cancers. Cancer Res. 2020;80(4 Supplement):PD2-05-PD2.

  75. Hafner M, Mills CE, Subramanian K, Chen C, Chung M, Boswell SA, et al. Multiomics profiling establishes the polypharmacology of FDA-approved CDK4/6 inhibitors and the potential for differential clinical activity. Cell Chem Biol. 2019;26(8):1067-80.e8.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–82.

    CAS  PubMed  Google Scholar 

  77. Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244(4905):707–12.

    CAS  PubMed  Google Scholar 

  78. von Minckwitz G, Huang C-S, Mano MS, Loibl S, Mamounas EP, Untch M, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2018;380(7):617–28.

    Google Scholar 

  79. Tolaney SM, Guo H, Pernas S, Barry WT, Dillon DA, Ritterhouse L, et al. Seven-year follow-up analysis of adjuvant paclitaxel and trastuzumab trial for node-negative, human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2019;37(22):1868–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Tolaney SM, Tayob N, Dang C, Yardley DA, Isakoff SJ, Valero V, et al. Adjuvant trastuzumab emtansine versus paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer (ATEMPT): a randomized clinical trial. J Clin Oncol. 2021;39(21):2375–85.

    CAS  PubMed  Google Scholar 

  81. Liobl SJJ, Sonnenblock A, Parlier D, Winer E, et al. VP6-2022: Adjuvant pertuzumab and trastuzumab in patients with early HER-2 positive breast cancer in APHINITY: 8.4 years’ follow-up. Ann Oncol. 2022;33(9):P986–7.

    Google Scholar 

  82. Chan A, Moy B, Mansi J, Ejlertsen B, Holmes FA, Chia S, et al. Final efficacy results of neratinib in HER2-positive hormone receptor-positive early-stage breast cancer from the phase III ExteNET trial. Clin Breast Cancer. 2021;21(1):80-91.e7.

    CAS  PubMed  Google Scholar 

  83. Barcenas CH, Hurvitz SA, Di Palma JA, Bose R, Chien AJ, Iannotti N, et al. Improved tolerability of neratinib in patients with HER2-positive early-stage breast cancer: the CONTROL trial. Ann Oncol. 2020;31(9):1223–30.

    CAS  PubMed  Google Scholar 

  84. Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382(7):597–609.

    CAS  PubMed  Google Scholar 

  85. Cortés J, Kim S-B, Chung W-P, Im S-A, Park YH, Hegg R, et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022;386(12):1143–54.

    PubMed  Google Scholar 

  86. Hassett MJ, Li H, Burstein HJ, Punglia RS. Neoadjuvant treatment strategies for HER2-positive breast cancer: cost-effectiveness and quality of life outcomes. Breast Cancer Res Treat. 2020;181(1):43–51.

    CAS  PubMed  Google Scholar 

  87. Fundytus A, Sengar M, Lombe D, Hopman W, Jalink M, Gyawali B, et al. Access to cancer medicines deemed essential by oncologists in 82 countries: an international, cross-sectional survey. Lancet Oncol. 2021;22(10):1367–77.

    PubMed  PubMed Central  Google Scholar 

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Correspondence to Sara M. Tolaney.

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Paolo Tarantino: Consulting fees from AstraZeneca. Filipa Lynce: Consulting or advisory role for Bristol Myers Squibb, Pfizer/EMD Serono, ASCO, and AstraZeneca; institutional research funding from Pfizer, Bristol Myers Squibb, Inivata, AstraZeneca, Zentalis, Merck and CytomX. Erica L. Mayer: Consulting for Lilly, Novartis, Gilead, AstraZeneca. Ana C. Garrido-Castro: Research funding (paid to the institution) from AstraZeneca, Gilead Sciences/Immunomedics and Merck. Ada Waks: Institutional research funding from Genentech, Merck, and MacroGenics. Sara M. Tolaney: Consulting or advisory role for Novartis, Pfizer, Merck, Lilly, Nektar, NanoString Technologies, AstraZeneca, Puma Biotechnology, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, Seattle Genetics, Odonate Therapeutics, OncoPep, Kyowa Hakko Kirin, Samsung Bioepis, CytomX Therapeutics, Daiichi Sankyo, Athenex, Gilead, Mersana, Certara, Chugai Pharma, Ellipses Pharma, Infinity, 4D Pharma, OncoSec Medical Inc., BeyondSpring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, and ARC Therapeutics; and institutional research funding from Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol Myers Squibb, Eisai, AstraZeneca, NanoString Technologies, Cyclacel, Nektar, Gilead, Odonate Therapeutics, Sanofi, and Seattle Genetics. Ilana Schlam, Stefania Morganti, and Dario Trapani declare they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Authors' contributions

The authors confirm contributions to the paper as follows: data collection: Ilana Schlam, Paolo Tarantino, Sara M. Tolaney; draft manuscript preparation: Ilana Schlam, Paolo Tarantino, Stefania Morganti, Filipa Lynce, Dario Trapani, Erica L. Mayer, Ana C. Garrido-Castro, Ada Waks, Sara M. Tolaney. All authors reviewed and approved the final version of the manuscript.

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Schlam, I., Tarantino, P., Morganti, S. et al. Emerging Targeted Therapies for Early Breast Cancer. Drugs 82, 1437–1451 (2022). https://doi.org/10.1007/s40265-022-01781-5

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