Update Breast Cancer 2022 Part 1 – Early Stage Breast Cancer

Abstract

Evidence relating to the treatment of breast cancer patients with early-stage disease has increased significantly in the past year. Abemaciclib, olaparib, and pembrolizumab are new drugs with good efficacy in the relevant patient groups. However, some questions remain unanswered. In particular, it remains unclear which premenopausal patients with hormone receptor-positive breast cancer should be spared unnecessary treatment. The question of the degree to which chemotherapy exerts a direct cytotoxic effect on the tumor or reduces ovarian function through chemotherapy could be of key importance. This group of patients could potentially be spared chemotherapy. New, previously experimental biomarker analysis methods, such as spatial analysis of gene expression (spatial transcriptomics) are gradually finding their way into large randomized phase III trials, such as the NeoTRIP trial. This in turn leads to a better understanding of the predictive factors of new therapies, for example immunotherapy. This review summarizes the scientific innovations from recent congresses such as the San Antonio Breast Cancer Symposium 2021 but also from recent publications.

Key words

BRCA (breast cancer antigen) - breast cancer - estrogen receptor - oral therapy

Publikationsverlauf

Eingereicht: 21. März 2022

Angenommen nach Revision: 26. März 2022

Artikel online veröffentlicht:
03. Juni 2022

• References/Literatur

• 1 Tutt ANJ, Garber JE, Kaufman B. et al. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. N Engl J Med 2021; 384: 2394-2405
• 2 Litton JK, Rugo HS, Ettl J. et al. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl J Med 2018; 379: 753-763
• 3 Robson M, Im S-A, Senkus E. et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med 2017; 377: 523-533
• 4 Turner NC, Telli ML, Rugo HS. et al. A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO). Clin Cancer Res 2019; 25: 2717-2724
• 5 Tutt ANJ, Garber J, Gelber RD. et al. 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. Ann Oncol 2022; ESMO Virtual Plenary VP1 – 2022.
• 6 Ditsch N, Kolberg-Liedtke C, Friedrich M. et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2021. Breast Care (Basel) 2021; 16: 214-227
• 7 Ditsch N, Untch M, Kolberg-Liedtke C. et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2020. Breast Care (Basel) 2020; 15: 294-309
• 8 Ditsch N, Untch M, Thill M. et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2019. Breast Care (Basel) 2019; 14: 224-245
• 9 Fasching PA, Yadav S, Hu C. et al. Mutations in BRCA1/2 and Other Panel Genes in Patients With Metastatic Breast Cancer-Association With Patient and Disease Characteristics and Effect on Prognosis. J Clin Oncol 2021; 39: 1619-1630
• 10 Couch FJ, Hart SN, Sharma P. et al. Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. J Clin Oncol 2015; 33: 304-311
• 11 Shimelis H, LaDuca H, Hu C. et al. Triple-Negative Breast Cancer Risk Genes Identified by Multigene Hereditary Cancer Panel Testing. J Natl Cancer Inst 2018;
• 12 Foulkes WD. The ten genes for breast (and ovarian) cancer susceptibility. Nat Rev Clin Oncol 2021; 18: 259-260
• 13 Müller V, Welslau M, Lüftner D. et al. Update Breast Cancer 2022 Part 2 – Advanced Stage Breast Cancer. Geburtshilfe Frauenheilkd 2022; 82: 590-600
• 14 Kraus C, Hoyer J, Vasileiou G. et al. Gene panel sequencing in familial breast/ovarian cancer patients identifies multiple novel mutations also in genes others than BRCA1/2. Int J Cancer 2017; 140: 95-102
• 15 Tung NM, Robson ME, Ventz S. et al. TBCRC048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes. J Clin Oncol 2020; 38: 4274-4282
• 16 Kar SP, Beesley J, Amin Al Olama A. et al. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types. Cancer Discov 2016; 6: 1052-1067
• 17 Stevens KN, Vachon CM, Lee AM. et al. Common breast cancer susceptibility loci are associated with triple-negative breast cancer. Cancer Res 2011; 71: 6240-6249
• 18 Schmidt MK, Hogervorst F, van Hien R. et al. Age- and Tumor Subtype-Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers. J Clin Oncol 2016; 34: 2750-2760
• 19 Breast Cancer Association Consortium. Dorling L, Carvalho S. et al. Breast Cancer Risk Genes – Association Analysis in More than 113,000 Women. N Engl J Med 2021;
• 20 Dunning AM, Michailidou K, Kuchenbaecker KB. et al. Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170. Nat Genet 2016; 48: 374-386
• 21 Wu L, Shi W, Long J. et al. A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer. Nat Genet 2018;
• 22 Couch FJ, Kuchenbaecker KB, Michailidou K. et al. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer. Nat Commun 2016; 7: 11375
• 23 Wunderle M, Olmes G, Nabieva N. et al. Risk, Prediction and Prevention of Hereditary Breast Cancer – Large-Scale Genomic Studies in Times of Big and Smart Data. Geburtshilfe Frauenheilkd 2018; 78: 481-492
• 24 Chlebowski RT, Aragaki AK, Pan K. Breast Cancer Prevention: Time for Change. JCO Oncol Pract 2021; 17: 709-716
• 25 Nangia JR, Rimawi MF. Breast Cancer Prevention: Where Are We?. JCO Oncol Pract 2021; 17: 720-722
• 26 Chlebowski RT, Anderson GL, Aragaki AK. et al. Association of Menopausal Hormone Therapy With Breast Cancer Incidence and Mortality During Long-term Follow-up of the Womenʼs Health Initiative Randomized Clinical Trials. JAMA 2020; 324: 369-380
• 27 Rossouw JE, Anderson GL, Prentice RL. et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Womenʼs Health Initiative randomized controlled trial. JAMA 2002; 288: 321-333
• 28 Denkert C, von Minckwitz G, Darb-Esfahani S. et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol 2018; 19: 40-50
• 29 Ingold Heppner B, Untch M, Denkert C. et al. Tumor-Infiltrating Lymphocytes: A Predictive and Prognostic Biomarker in Neoadjuvant-Treated HER2-Positive Breast Cancer. Clin Cancer Res 2016; 22: 5747-5754
• 30 Wurfel F, Erber R, Huebner H. et al. TILGen: A Program to Investigate Immune Targets in Breast Cancer Patients – First Results on the Influence of Tumor-Infiltrating Lymphocytes. Breast Care (Basel) 2018; 13: 8-14
• 31 Hollingsworth RE, Jansen K. Turning the corner on therapeutic cancer vaccines. NPJ Vaccines 2019; 4: 7
• 32 Antonarelli G, Corti C, Tarantino P. et al. Therapeutic cancer vaccines revamping: technology advancements and pitfalls. Ann Oncol 2021; 32: 1537-1551
• 33 Corti C, Giachetti P, Eggermont AMM. et al. Therapeutic vaccines for breast cancer: Has the time finally come?. Eur J Cancer 2022; 160: 150-174
• 34 Van Hoecke L, Verbeke R, Dewitte H. et al. mRNA in cancer immunotherapy: beyond a source of antigen. Mol Cancer 2021; 20: 48
• 35 Hashimoto S, Noguchi E, Bando H. et al. Neoantigen prediction in human breast cancer using RNA sequencing data. Cancer Sci 2021; 112: 465-475
• 36 Li W, Amei A, Bui F. et al. Impact of Neoantigen Expression and T-Cell Activation on Breast Cancer Survival. Cancers (Basel) 2021;
• 37 Reimann H, Nguyen A, Sanborn JZ. et al. Identification and validation of expressed HLA-binding breast cancer neoepitopes for potential use in individualized cancer therapy. J Immunother Cancer 2021;
• 38 Gerber B, Heintze K, Stubert J. et al. Axillary lymph node dissection in early-stage invasive breast cancer: is it still standard today?. Breast Cancer Res Treat 2011; 128: 613-624
• 39 Mittendorf EA, Bellon JR, King TA. Regional Nodal Management in Patients With Clinically Node-Negative Breast Cancer Undergoing Upfront Surgery. J Clin Oncol 2020; 38: 2273-2280
• 40 Bradley R, Braybrooke J, Gray R. et al. Aromatase inhibitors versus tamoxifen in pre-menopausal women with estrogen receptor positive early stage breast cancer treated with ovarian suppression: A patient level meta-analysis of 7,030 women in four randomised trials. San Antonio Breast Cancer Symposium 2021; 2021: GS2-04
• 41 Regan MM, Walley BA, Fleming GF. et al. 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. San Antonio Breast Cancer Symposium 2021; 2021: GS2-05
• 42 Kalinsky K, Barlow WE, Gralow JR. et al. 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer. N Engl J Med 2021; 385: 2336-2347
• 43 Piccart M, vanʼt Veer LJ, Poncet C. et al. 70-gene signature as an aid for treatment decisions in early breast cancer: updated results of the phase 3 randomised MINDACT trial with an exploratory analysis by age. Lancet Oncol 2021; 22: 476-488
• 44 Sparano JA, Gray RJ, Makower DF. et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N Engl J Med 2018; 379: 111-121
• 45 Nitz UA, Gluz O, Kümmel S. et al. Endocrine therapy response and 21-Gene Expression Assay for therapy guidance in HR+/HER2- early breast cancer. J Clin Oncol 2022; in press
• 46 Ruddy KJ, Schaid DJ, Partridge AH. et al. Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer. Fertil Steril 2019; 112: 731-739.e1
• 47 Kalinsky KM, Barlow WE, Gralow JR. et al. Distant-disease free interval in participants (pts) with 1–3 positive lymph nodes (LN), hormone receptor-positive (HR+) and her2-negative (HER2-) breast cancer (BC) with recurrence score (RS) < or = 25 randomized to endocrine therapy (ET) ± chemotherapy (CT): SWOG s1007 (RxPONDER). San Antonio Breast Cancer Symposium 2021; 2021: GS2-07
• 48 Mayer EL, Dueck AC, Martin 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: 212-222
• 49 Gnant M, Dueck AC, Frantal S. et al. Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03). J Clin Oncol 2022; 40: 282-293
• 50 Harbeck N, Rastogi P, Martin M. 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: 1571-1581
• 51 Precisiononcologynews.com. Novartis Anticipating Radioligands, New Precision Therapies to Continue Oncology Segment Growth. 2022 Accessed February 02, 2022 at: https://www.precisiononcologynews.com/cancer/novartis-anticipating-radioligands-new-precision-therapies-continue-oncology-segment-growth%23Yf6ALvgxkuU
• 52 European Medicines Agency. Verzenios. 2022 Accessed May 19, 2022 at: https://www.ema.europa.eu/en/documents/product-information/verzenios-epar-product-information_en.pdf
• 53 Rugo HS, OʼShaughnessy J, Boyle F. 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;
• 54 Nabieva N, Kellner S, Fehm T. et al. Influence of patient and tumor characteristics on early therapy persistence with letrozole in postmenopausal women with early breast cancer: results of the prospective Evaluate-TM study with 3941 patients. Ann Oncol 2018; 29: 186-192
• 55 Lüftner D, Schütz F, Stickeler E. et al. Update Breast Cancer 2021 Part 5 – Advanced Breast Cancer. Geburtshilfe Frauenheilkd 2022;
• 56 Thomssen C, Fehm TN, Stickeler E. et al. Update Breast Cancer 2021 Part 4 – Prevention and Early Stages. Geburtshilfe Frauenheilkd 2022;
• 57 Ruiz-Borrego M, Guerrero-Zotano A, Bermejo B. et al. Phase III evaluating the addition of fulvestrant (F) to anastrozole (A) as adjuvant therapy in postmenopausal women with hormone receptor-positive HER2-negative (HR+/HER2-) early breast cancer (EBC): results from the GEICAM/2006–10 study. Breast Cancer Res Treat 2019; 177: 115-125
• 58 Hurvitz SA, Quiroga V, Park YH. et al. Neoadjuvant giredestrant (GDC-9545) + palbociclib versus anastrozole + palbociclib in postmenopausal women with estrogen receptor-positive, HER2-negative, untreated early breast cancer: Primary analysis of the randomized, open-label, phase II coopERA breast cancer study. San Antonio Breast Cancer Symposium 2021; 2021: GS1-07
• 59 Bardia A, Neven P, Streich G. et al. Elacestrant, an oral selective estrogen receptor degrader (SERD), vs. investigatorʼs choice of endocrine monotherapy for ER+/HER2- advanced/metastatic breast cancer (mBC) following progression on prior endocrine and CDK4/6 inhibitor therapy: Results of EMERALD phase 3 trial. San Antonio Breast Cancer Symposium 2021; 2021: GS2-02
• 60 Wang N, Li X, Wang R. et al. Spatial transcriptomics and proteomics technologies for deconvoluting the tumor microenvironment. Biotechnol J 2021; 16: e2100041
• 61 Longo SK, Guo MG, Ji AL. et al. Integrating single-cell and spatial transcriptomics to elucidate intercellular tissue dynamics. Nat Rev Genet 2021; 22: 627-644
• 62 Bianchini G, Wang XQ, Danenberg E. et al. Single-cell spatial analysis by imaging mass cytometry and immunotherapy response in triple-negative breast cancer (TNBC) in the NeoTRIPaPDL1 trial. San Antonio Breast Cancer Symposium 2021; 2021: GS1-00
• 63 Keating SM, Taylor DL, Plant AL. et al. Opportunities and Challenges in Implementation of Multiparameter Single Cell Analysis Platforms for Clinical Translation. Clin Transl Sci 2018; 11: 267-276
• 64 Schmid P, Cortes J, Dent R. et al. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. N Engl J Med 2022;
• 65 Schmid P, Cortes J, Dent R. et al. KEYNOTE-522: Phase III study of neoadjuvant pembrolizumab + chemotherapy vs. placebo + chemotherapy, followed by adjuvant pembrolizumab vs. placebo for early-stage TNBC. Ann Oncol 2021; 32: VP7-2021
• 66 Schmid P, Cortes J, Dent R. et al. KEYNOTE-522: Phase 3 study of pembrolizumab + chemotherapy vs. placebo + chemotherapy as neoadjuvant treatment, followed by pembrolizumab vs. placebo as adjuvant treatment for early-stage high-risk triple-negative breast cancer (TNBC). San Antonio Breast Cancer Symposium 2021; 2021: GS1-01
• 67 Fisher B, Costantino JP, Wickerham DL. et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 2005; 97: 1652-1662
• 68 Powles TJ, Ashley S, Tidy A. et al. Twenty-year follow-up of the Royal Marsden randomized, double-blinded tamoxifen breast cancer prevention trial. J Natl Cancer Inst 2007; 99: 283-290
• 69 Cuzick J, Sestak I, Cawthorn S. et al. Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol 2015; 16: 67-75
• 70 Cuzick J, Sestak I, Forbes JF. et al. Use of anastrozole for breast cancer prevention (IBIS-II): long-term results of a randomised controlled trial. Lancet 2020; 395: 117-122
• 71 Goss PE, Ingle JN, Ales-Martinez JE. et al. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med 2011; 364: 2381-2391