Skip to main content

Advertisement

Log in

New Developments in Systemic Management for High-Risk Early-Stage Hormone-Receptor-Positive, HER2-Negative Breast Cancer

  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

For high-risk early-stage hormone-receptor-positive, HER2-negative breast cancer (HR + /HER2 − EBC), short- and long-term recurrence risks remain substantial despite local control with surgery and radiation and systemic treatment with chemotherapy and endocrine therapy (ET). Recent trials have provided new strategies for reducing recurrence. The monarchE trial demonstrated that adding 2 years of adjuvant abemaciclib to ET improves invasive disease-free survival (iDFS) and distant recurrence-free survival (DRFS). In the OlympiA trial for high-risk disease in patients with germline BRCA1/BRCA2 mutations, adding 1 year of olaparib to ET improved iDFS, DRFS, and overall survival (OS). In addition, for premenopausal women with high-risk tumors, long-term follow-up of the SOFT, ASTRRA, TEXT, ABCSG-12, and HOBOE trials supports the role of ovarian function suppression (OFS), in combination with adjuvant tamoxifen or aromatase inhibition (AI). For postmenopausal women with high-risk tumors, extended-duration AI for at least 7 years should be used with zoledronic acid. Given the remaining recurrence risk even with these interventions and with the ongoing development of new strategies for HR + disease, patients with high-risk EBC should be encouraged to participate in clinical trials, such as trials of immunotherapy, novel oral estrogen receptor alpha (ERα)-targeting agents, antibody–drug conjugates (ADCs), and trials guided by measurements of minimal residual disease (MRD).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Pan H, Gray R, Braybrooke J, Davies C, Taylor C, McGale P, et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377:1836–46.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Colleoni M, Sun Z, Price KN, Karlsson P, Forbes JF, Thürlimann B, et al. Annual hazard rates of recurrence for breast cancer during 24 years of follow-up: results from the international breast cancer study group trials I to V. J Clin Oncol. 2016;34:927–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. 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;379:111–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Pedersen RN, Esen BÖ, Mellemkjær L, Christiansen P, Ejlertsen B, Lash TL, et al. The incidence of breast cancer recurrence 10–32 years after primary diagnosis. J Natl Cancer Inst. 2022;114:391–9.

    Article  PubMed  Google Scholar 

  5. 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;384:164–72.

    Article  PubMed  Google Scholar 

  6. Salvo EM, Ramirez AO, Cueto J, Law EH, Situ A, Cameron C, et al. Risk of recurrence among patients with HR-positive, HER2-negative, early breast cancer receiving adjuvant endocrine therapy: a systematic review and meta-analysis. Breast. 2021;57:5–17.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Anampa J, Makower D, Sparano JA. Progress in adjuvant chemotherapy for breast cancer: an overview. BMC Med. 2015;13:195.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Burstein HJ. Systemic therapy for estrogen receptor-positive, HER2-negative breast cancer. N Engl J Med. 2020;383:2557–70.

    Article  CAS  PubMed  Google Scholar 

  9. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687–717.

    Article  Google Scholar 

  10. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015;386:1353–61.

    Article  Google Scholar 

  11. Finn RS, Martin M, Rugo HS, Jones S, Im S-A, Gelmon K, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016;375:1925–36.

    Article  CAS  PubMed  Google Scholar 

  12. Tripathy D, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018;19:904–15.

    Article  CAS  PubMed  Google Scholar 

  13. 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;35:3638–46.

    Article  CAS  PubMed  Google Scholar 

  14. Hortobagyi GN, Stemmer SM, Burris HA, Yap Y-S, Sonke GS, Hart L, et al. Overall survival with ribociclib plus letrozole in advanced breast cancer. N Engl J Med. 2022;386:942–50.

    Article  CAS  PubMed  Google Scholar 

  15. Goetz MP, Toi M, Huober J, Sohn J, Tredan O, Park IH, et al. LBA15 MONARCH 3: Interim overall survival (OS) results of abemaciclib plus a nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+, HER2- advanced breast cancer (ABC). Ann Oncol. 2022;33:S1384.

    Article  Google Scholar 

  16. Watt AC, Goel S. Cellular mechanisms underlying response and resistance to CDK4/6 inhibitors in the treatment of hormone receptor-positive breast cancer. Breast Cancer Res. 2022;24:17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. • 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;38:3987–98. This paper reports the preplanned efficacy interim analysis of the monarchE trial of 2 years of abemaciclib added to adjuvant ET for high-risk node-positive HR+/HER2− EBC in which the primary endpoint of iDFS was met at 19 months of follow-up.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. •• 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;32:1571–81. This is an updated analysis of the monarchE trial showing that iDFS improvement with 2 years of abemaciclib added to adjuvant ET for high-risk node-positive HR+/HER2− EBC persists at 27 months of follow-up, leading to FDA approval of abemaciclib use in this setting. This analysis also found that Ki-67 index was prognostic but not predictive of abemaciclib benefit in this population.

    Article  CAS  PubMed  Google Scholar 

  19. Johnston SRD, Toi M, O’Shaughnessy J, Rastogi P, Campone M, Neven P, et al. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023;24:77–90.

    Article  CAS  PubMed  Google Scholar 

  20. Martin M, Hegg R, Kim S-B, Schenker M, Grecea D, Garcia-Saenz JA, et al. Treatment with adjuvant abemaciclib plus endocrine therapy in patients with high-risk early breast cancer who received neoadjuvant chemotherapy: a prespecified analysis of the monarchE randomized clinical trial. JAMA Oncol. 2022;8:1190–4.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 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;33:616–27.

    Article  CAS  PubMed  Google Scholar 

  22. Tarantino P, Jin Q, Mittendorf EA, King TA, Curigliano G, Tolaney SM. Clinical and pathological features of breast cancer patients eligible for adjuvant abemaciclib. Ann Oncol. 2022;33:845–7.

    Article  CAS  PubMed  Google Scholar 

  23. • 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;22:212–22. This paper reports the second interim analysis of the PALLAS trial of 2 years of palbociclib added to adjuvant ET for mixed-risk HR+/HER2− EBC, showing no benefit for iDFS at 24 months of follow-up. At this point, the futility boundary was crossed, and palbociclib was discontinued in patients still receiving it on the trial.

    Article  CAS  PubMed  Google Scholar 

  24. 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;40:282–93.

    Article  CAS  PubMed  Google Scholar 

  25. • Loibl S, Marmé F, Martin M, Untch M, Bonnefoi H, Kim S-B, et al. Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer-the Penelope-B trial. J Clin Oncol. 2021;39:1518–30. This paper reports the PENELOPE-B trial of 1 year of palbociclib added to adjuvant ET for high-risk HR+/HER2− EBC (with residual disease after neoadjuvant chemotherapy), showing no benefit for iDFS at 42.8 months of follow-up. This report also highlights the importance of longer-term follow-up as PENELOPE-B saw transient iDFS curve separation at 6 months that dissipated after a few more years of follow-up.

    Article  CAS  PubMed  Google Scholar 

  26. Spring LM, Wander SA, Andre F, Moy B, Turner NC, Bardia A. Cyclin-dependent kinase 4 and 6 inhibitors for hormone receptor-positive breast cancer: past, present, and future. Lancet. 2020;395:817–27.

    Article  CAS  PubMed  Google Scholar 

  27. Mayer EL, Fesl C, Hlauschek D, Garcia-Estevez L, Burstein HJ, Zdenkowski N, et al. Treatment exposure and discontinuation in the palbociclib collaborative adjuvant study of palbociclib with adjuvant endocrine therapy for hormone receptor-positive/human epidermal growth factor receptor 2-negative early breast cancer (PALLAS/AFT-05/ABCSG-42/BIG-14-03). J Clin Oncol. 2022;40:449–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wander SA, O’Brien N, Litchfield LM, O’Dea D, Morato Guimaraes C, Slamon DJ, et al. Targeting CDK4 and 6 in cancer therapy: emerging preclinical insights related to abemaciclib. Oncologist. 2022;27:811–21.

    Article  PubMed  PubMed Central  Google Scholar 

  29. 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;26:1067-1080.e8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Cousins EM, Goldfarb D, Yan F, Roques J, Darr D, Johnson GL, et al. Competitive kinase enrichment proteomics reveals that abemaciclib inhibits GSK3β and activates WNT signaling. Mol Cancer Res. 2018;16:333–44.

    Article  CAS  PubMed  Google Scholar 

  31. Wander SA, Han HS, Zangardi ML, Niemierko A, Mariotti V, Kim LSL, et al. Clinical outcomes with abemaciclib after prior CDK4/6 inhibitor progression in breast cancer: a multicenter experience. J Natl Compr Canc Netw. 2021;1–8.

  32. Ma CX, Gao F, Luo J, Northfelt DW, Goetz M, Forero A, et al. NeoPalAna: Neoadjuvant palbociclib, a cyclin-dependent kinase 4/6 inhibitor, and anastrozole for clinical stage 2 or 3 estrogen receptor-positive breast cancer. Clin Cancer Res. 2017;23:4055–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. 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;377:523–33.

    Article  CAS  PubMed  Google Scholar 

  34. 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;379:753–63.

    Article  CAS  PubMed  Google Scholar 

  35. Lord CJ, Ashworth A. PARP inhibitors: synthetic lethality in the clinic. Science. 2017;355:1152–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Hu C, Hart SN, Gnanaolivu R, Huang H, Lee KY, Na J, et al. A population-based study of genes previously implicated in breast cancer. N Engl J Med. 2021;384:440–51.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Network CGA. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490:61–70.

    Article  Google Scholar 

  38. Pereira B, Chin S-F, Rueda OM, Vollan H-KM, Provenzano E, Bardwell HA, et al. The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes. Nat Commun. 2016;7:11479.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Vidula N, Dubash T, Lawrence MS, Simoneau A, Niemierko A, Blouch E, et al. Identification of somatically acquired BRCA1/2 mutations by cfDNA analysis in patients with metastatic breast cancer. Clin Cancer Res. 2020;26:4852–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. •• 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;384:2394–405. This paper reports the OlympiA trial of adding 1 year of adjuvant olaparib for high-risk germline BRCA1/BRCA2-mutated HR+/HER2- EBC or TNBC, showing improved iDFS at 2.5 years of follow-up, including in the HR+/HER2− subgroup. This led to the FDA approval of olaparib use in this setting and motivated expanded genetic testing for patients with breast cancer.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. • Geyer CE, Garber JE, Gelber RD, Yothers G, Taboada M, Ross L, et al. Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high risk, early breast cancer. Ann Oncol. 2022;S0923–7534(22):04165–75. This update on the OlympiA trial showed that 1 year of adjuvant olaparib addition for high-risk germline BRCA1/BRCA2-mutated HR+/HER2− EBC or TNBC improves OS.

    Google Scholar 

  42. Tung N, Garber JE. PARP inhibition in breast cancer: progress made and future hopes. NPJ Breast Cancer. 2022;8:47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Tung NM, Robson ME, Ventz S, Santa-Maria CA, Nanda R, Marcom PK, et al. TBCRC 048: Phase II study of olaparib for metastatic breast cancer and mutations in homologous recombination-related genes. J Clin Oncol. 2020;38:4274–82.

    Article  CAS  PubMed  Google Scholar 

  44. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015;386:1341–52.

    Article  Google Scholar 

  45. Tjan-Heijnen VCG, van Hellemond IEG, Peer PGM, Swinkels ACP, Smorenburg CH, van der Sangen MJC, et al. Extended adjuvant aromatase inhibition after sequential endocrine therapy (DATA): a randomised, phase 3 trial. Lancet Oncol. 2017;18:1502–11.

    Article  CAS  PubMed  Google Scholar 

  46. Blok EJ, Kroep JR, Meershoek-Klein Kranenbarg E, Duijm-de Carpentier M, Putter H, van den Bosch J, et al. Optimal duration of extended adjuvant endocrine therapy for early breast cancer; results of the IDEAL trial (BOOG 2006–05). J Natl Cancer Inst. 2018;110:40–48.

  47. Mamounas EP, Bandos H, Lembersky BC, Jeong J-H, Geyer CE, Rastogi P, et al. Use of letrozole after aromatase inhibitor-based therapy in postmenopausal breast cancer (NRG Oncology/NSABP B-42): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20:88–99.

    Article  CAS  PubMed  Google Scholar 

  48. Gnant M, Fitzal F, Rinnerthaler G, Steger GG, Greil-Ressler S, Balic M, et al. Duration of adjuvant aromatase-inhibitor therapy in postmenopausal breast cancer. N Engl J Med. 2021;385:395–405.

    Article  CAS  PubMed  Google Scholar 

  49. • 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;379:122–37. This study reports 8-year outcomes of the SOFT and TEXT trials of intensified ET for premenopausal women with HR+ EBC, using OFS plus AI/tamoxifen in place of tamoxifen alone, showing improved iDFS and OS.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. • Kim H-A, Lee JW, Nam SJ, Park B-W, Im S-A, Lee ES, et al. Adding ovarian suppression to tamoxifen for premenopausal breast cancer: a randomized phase III trial. J Clin Oncol. 2020;38:434–43. This report is of the ASTRRA trial of adding 2 years of OFS to 5 years of tamoxifen for premenopausal women with HR+ EBC, showing improved iDFS and OS at 35 months of follow-up.

    Article  CAS  PubMed  Google Scholar 

  51. Baek SY, Noh WC, Ahn S-H, Kim H-A, Ryu JM, Kim SI, et al. Adding ovarian function suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or resume menstruation after chemotherapy: 8-year follow-up of the randomized ASTRRA trial. JCO. 2022;40:506–506.

    Article  Google Scholar 

  52. • Early Breast CancerTrialists’ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women from four randomised trials. Lancet Oncol. 2022;23:382–92. This meta-analysis of the SOFT, TEXT, ABCSG-12, and HOBOE trials showed that for premenopausal women with HR+ EBC, OFS plus AI is superior to OFS plus tamoxifen for breast cancer recurrence.

  53. Gnant M, Mlineritsch B, Stoeger H, Luschin-Ebengreuth G, Heck D, Menzel C, et al. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial. Lancet Oncol. 2011;12:631–41.

    Article  CAS  PubMed  Google Scholar 

  54. Regan MM, Walley BA, Fleming GF, Francis PA, Colleoni MA, Láng I, et al. Abstract GS2–05: Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): update of the combined TEXT and SOFT trials. Cancer Research. 2022;82:GS2–05-GS2–05.

  55. Sukumar JS, Quiroga D, Kassem M, Grimm M, Shinde NV, Appiah L, et al. Patient preferences and adherence to adjuvant GnRH analogs among premenopausal women with hormone receptor positive breast cancer. Breast Cancer Res Treat. 2021;190:183–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Partridge AH, LaFountain A, Mayer E, Taylor BS, Winer E, Asnis-Alibozek A. Adherence to initial adjuvant anastrozole therapy among women with early-stage breast cancer. J Clin Oncol. 2008;26:556–62.

    Article  CAS  PubMed  Google Scholar 

  57. Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Láng I, et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014;371:107–18.

    Article  PubMed  PubMed Central  Google Scholar 

  58. 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;385:2336–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. 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;380:2395–405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Lloyd MR, Wander SA, Hamilton E, Razavi P, Bardia A. Next-generation selective estrogen receptor degraders and other novel endocrine therapies for management of metastatic hormone receptor-positive breast cancer: current and emerging role. Ther Adv Med Oncol. 2022;14:17588359221113694.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Brett JO, Spring LM, Bardia A, Wander SA. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res. 2021;23:85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bidard FC, Callens C, Dalenc F, Pistilli B, De La Motte RT, Clatot F, et al. Prognostic impact of ESR1 mutations in ER+ HER2- MBC patients prior treated with first line AI and palbociclib: an exploratory analysis of the PADA-1 trial. JCO. 2020;38:1010–1010.

    Article  Google Scholar 

  63. Coombes RC, Page K, Salari R, Hastings RK, Armstrong A, Ahmed S, et al. Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence. Clin Cancer Res. 2019;25:4255–63.

    Article  CAS  PubMed  Google Scholar 

  64. Garcia-Murillas I, Schiavon G, Weigelt B, Ng C, Hrebien S, Cutts RJ, et al. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med. 2015;7:302ra133.

    Article  PubMed  Google Scholar 

  65. Magbanua MJM, Swigart LB, Wu H-T, Hirst GL, Yau C, Wolf DM, et al. Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival. Ann Oncol. 2021;32:229–39.

    Article  CAS  PubMed  Google Scholar 

  66. Lipsyc-Sharf M, de Bruin EC, Santos K, McEwen R, Stetson D, Patel A, et al. Circulating tumor DNA and late recurrence in high-risk hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. J Clin Oncol. 2022;40:2408–19.

    Article  CAS  PubMed  Google Scholar 

  67. Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC, et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med. 2005;353:793–802.

    Article  CAS  PubMed  Google Scholar 

  68. Tjensvoll K, Nordgård O, Skjæveland M, Oltedal S, Janssen EAM, Gilje B. Detection of disseminated tumor cells in bone marrow predict late recurrences in operable breast cancer patients. BMC Cancer. 2019;19:1131.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Bachelot T, Cottu P, Chabaud S, Dalenc F, Allouache D, Delaloge S, et al. Everolimus added to adjuvant endocrine therapy in patients with high-risk hormone receptor-positive, human epidermal growth factor receptor 2-negative primary breast cancer. J Clin Oncol. 2022;40:3699–708.

    Article  CAS  PubMed  Google Scholar 

  70. 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;6:676–84.

    Article  PubMed  Google Scholar 

  71. Tolaney SM, Barroso-Sousa R, Keenan T, Li T, Trippa L, Vaz-Luis I, et al. Effect of eribulin with or without pembrolizumab on progression-free survival for patients with hormone receptor-positive, ERBB2-negative metastatic breast cancer: a randomized clinical trial. JAMA Oncol. 2020;6:1598–605.

    Article  PubMed  Google Scholar 

  72. Rugo HS, Delord J-P, Im S-A, Ott PA, Piha-Paul SA, Bedard PL, et al. Safety and antitumor activity of pembrolizumab in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. Clin Cancer Res. 2018;24:2804–11.

    Article  CAS  PubMed  Google Scholar 

  73. Dirix LY, Takacs I, Jerusalem G, Nikolinakos P, Arkenau H-T, Forero-Torres A, et al. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN solid tumor study. Breast Cancer Res Treat. 2018;167:671–86.

    Article  CAS  PubMed  Google Scholar 

  74. Patel S, Othus M, Prieto V, Lowe M, Buchbinder E, Chen Y, et al. LBA6 Neoadjvuant versus adjuvant pembrolizumab for resected stage III-IV melanoma (SWOG S1801). Ann Oncol. 2022;33:S1408.

    Article  Google Scholar 

  75. Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. 2022;386:1973–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Shen Y-C, Ghasemzadeh A, Kochel CM, Nirschl TR, Francica BJ, Lopez-Bujanda ZA, et al. Combining intratumoral Treg depletion with androgen deprivation therapy (ADT): preclinical activity in the Myc-CaP model. Prostate Cancer Prostatic Dis. 2018;21:113–25.

    Article  CAS  PubMed  Google Scholar 

  77. Perera M, Beech BB, De Jesus EM, Gmelich C, Yip W, Boorjian SA, et al. Neoadjuvant systemic therapy prior to radical prostatectomy for clinically localized high-risk prostate cancer. Front Urol. 2022;2: 864646.

    Article  Google Scholar 

  78. Schmid P, Cortes J, Dent R, Pusztai L, McArthur H, Kümmel S, et al. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556–67.

    Article  CAS  PubMed  Google Scholar 

  79. Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387:9–20.

    Article  CAS  PubMed  Google Scholar 

  80. Rugo HS, Bardia A, Marmé F, Cortes J, Schmid P, Loirat D, et al. Primary results from TROPiCS-02: a randomized phase 3 study of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) in patients (Pts) with hormone receptor–positive/HER2-negative (HR+/HER2-) advanced breast cancer. JCO. 2022;40:LBA1001–LBA1001.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Erica L. Mayer MD, MPH.

Ethics declarations

Conflict of interest

Erica L. Mayer reports consulting for Novartis, Eli Lilly, Gilead, AstraZeneca, and Diaccurate. Jamie O. Brett has nothing to disclose.

Human and animal rights and informed consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Brett, J.O., Mayer , E.L. New Developments in Systemic Management for High-Risk Early-Stage Hormone-Receptor-Positive, HER2-Negative Breast Cancer. Curr. Treat. Options in Oncol. 24, 594–610 (2023). https://doi.org/10.1007/s11864-023-01082-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11864-023-01082-3

Keywords

Navigation