nach oben

Erschienen in:

02.08.2022 | Clinical trial

Neoadjuvant endocrine therapy for strongly hormone receptor-positive and HER2-negative early breast cancer: results of a prospective multi-center study

verfasst von: Xinguang Wang, Zhaoqing Fan, Xing Wang, Yingjian He, Yiqiang Liu, Xiang Wang, Bailin Zhang, Zefei Jiang, Tao Wang, Zhigang Yu, Fei Wang, Yinhua Liu, Yanping Li, Jianguo Zhang, Bin Luo, Hongchuan Jiang, Tianfeng Wang, Yuntao Xie, Jinfeng Li, Tao Ouyang

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2022

Einloggen, um Zugang zu erhalten

Abstract

Purpose

For estrogen receptor (ER)-positive breast cancer, neoadjuvant endocrine therapy (NET) has been shown to be as effective as neoadjuvant chemotherapy (NACT). We evaluated the prognostic significance of Preoperative Endocrine Prognostic Index (PEPI).

Methods

We conducted a prospective, multi-center, non-randomized, controlled trial that enrolled postmenopausal early-stage strongly ER-positive (≥ 50%) and HER2-negative breast cancer patients. All patients were given 4-month NET before surgery. The primary objective was to investigate the 5-year recurrence-free survival (RFS) in patients who had PEPI 0–1 or pathological complete response (pCR) without chemotherapy. Patients who had PEPI 0–1 or pCR were recommended to receive adjuvant endocrine therapy only and patients had PEPI ≥ 2 may receive adjuvant chemotherapy at the discretion of the treating physician.

Results

A total of 410 patients were included and 352 patients constituted the per-protocol population. Overall, 9 patients (2.5%) had pCR (ypT0/is ypN0), 128 patients (36.4%) had PEPI = 0, and 56 patients (15.9%) had PEPI = 1. After a median follow-up of 60 months (4–104 months), patients who had PEPI 0–1 or pCR showed an improved 5-year RFS [99.5% (95% CI 98.5–99.9%) for PEPI 0–1 or pCR group vs. 93.7% (95% CI 89.6–97.8%) for PEPI ≥ 2 group, P = 0.028]. No survival difference was detected between patients received adjuvant chemotherapy vs. no chemotherapy among PEPI ≥ 2 cases.

Conclusion

PEPI 0–1 or pCR may be used to define a group of ER-positive and HER2-negative postmenopausal early breast cancer patients with low relapse risk for whom adjuvant chemotherapy can be safely withheld. Studies on the identification and alternative treatment options for endocrine-resistant tumors are warranted.

Clinical trial registration

NCT01613560.

Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, Davies S, Fauron C, He X, Hu Z, Quackenbush JF, Stijleman IJ, Palazzo J, Marron JS, Nobel AB, Mardis E, Nielsen TO, Ellis MJ, Perou CM, Bernard PS (2009) Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 27:1160–1167CrossRef

Preece PE, Wood RA, Mackie CR, Cuschieri A (1982) Tamoxifen as initial sole treatment of localised breast cancer in elderly women: a pilot study. Br Med J (Clin Res Ed) 284:869–870CrossRef

Spring LM, Gupta A, Reynolds KL, Gadd MA, Ellisen LW, Isakoff SJ, Moy B, Bardia A (2016) Neoadjuvant endocrine therapy for estrogen receptor-positive breast cancer: a systematic review and meta-analysis. JAMA Oncol 2:1477–1486CrossRef

Ellis MJ, Suman VJ, Hoog J, Lin L, Snider J, Prat A, Parker JS, Luo J, DeSchryver K, Allred DC, Esserman LJ, Unzeitig GW, Margenthaler J, Babiera GV, Marcom PK, Guenther JM, Watson MA, Leitch M, Hunt K, Olson JA (2011) Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype–ACOSOG Z1031. J Clin Oncol 29:2342–2349CrossRef

Eiermann W, Paepke S, Appfelstaedt J, Llombart-Cussac A, Eremin J, Vinholes J, Mauriac L, Ellis M, Lassus M, Chaudri-Ross HA, Dugan M, Borgs M (2001) Preoperative treatment of postmenopausal breast cancer patients with letrozole: a randomized double-blind multicenter study. Ann Oncol 12:1527–1532CrossRef

Smith IE, Dowsett M, Ebbs SR, Dixon JM, Skene A, Blohmer JU, Ashley SE, Francis S, Boeddinghaus I, Walsh G (2005) Neoadjuvant treatment of postmenopausal breast cancer with anastrozole, tamoxifen, or both in combination: the Immediate Preoperative anastrozole, tamoxifen, or combined with tamoxifen (IMPACT) multicenter double-blind randomized trial. J Clin Oncol 23:5108–5116CrossRef

Ellis MJ, Coop A, Singh B, Mauriac L, Llombert-Cussac A, Jänicke F, Miller WR, Evans DB, Dugan M, Brady C, Quebe-Fehling E, Borgs M (2001) Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: Evidence from a phase III randomized trial. J Clin Oncol 19:3808–3816CrossRef

Davey MG, Ryan ÉJ, Boland MR, Barry MK, Lowery AJ, Kerin MJ (2021) Clinical utility of the 21-gene assay in predicting response to neoadjuvant endocrine therapy in breast cancer: a systematic review and meta-analysis. Breast 58:113–120CrossRef

Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, Ollila DW, Sartor CI, Graham ML, Perou CM (2007) The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 13:2329–2334CrossRef

10.

Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, Swain SM, Prowell T, Loibl S, Wickerham DL, Bogaerts J, Baselga J, Perou C, Blumenthal G, Blohmer J, Mamounas EP, Bergh J, Semiglazov V, Justice R, Eidtmann H, Paik S, Piccart M, Sridhara R, Fasching PA, Slaets L, Tang S, Gerber B, Geyer CE Jr, Pazdur R, Ditsch N, Rastogi P, Eiermann W, von Minckwitz G (2014) Pathologic complete response and long-term clinical beneft in breast cancer: the CTNeoBC pooled analysis. Lancet 384:164–172CrossRef

11.

Liedtke C, Mazouni C, Hess KR, André F, Tordai A, Mejia JA, Symmans WF, Gonzalez-Angulo AM, Hennessy B, Green M, Cristofanilli M, Hortobagyi GN, Pusztai L (2008) Response to neoadjuvant therapy and long term survival in patients with triple negative breast cancer. J Clin Oncol 26:1275–1281CrossRef

12.

Ellis MJ, Tao Y, Luo J, A’Hern R, Evans DB, Bhatnagar AS, Chaudri Ross HA, von Kameke A, Miller WR, Smith I, Eiermann W, Dowsett M (2008) Outcome prediction for estrogen receptor-positive breast cancer based on postneoadjuvant endocrine therapy tumor characteristics. J Natl Cancer Inst 100:1380–1388CrossRef

13.

Ellis MJ (2017) Lessons in precision oncology from neoadjuvant endocrine therapy trials in ER+ breast cancer. Breast 34(Suppl 1):S104–S107CrossRef

14.

Pariser AC, Sedghi T, Soulos PR, Killelea B, Gross CP, Mougalian SS (2019) Utilization, duration, and outcomes of neoadjuvant endocrine therapy in the United States. Breast Cancer Res Treat 178:419–426CrossRef

15.

Dowsett M, Nielsen TO, A’Hern R, Bartlett J, Coombes RC, Cuzick J, Ellis M, Henry NL, Hugh JC, Lively T, McShane L, Paik S, Penault-Llorca F, Prudkin L, Regan M, Salter J, Sotiriou C, Smith IE, Viale G, Zujewski JA, Hayes DF (2011) Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. J Natl Cancer Inst 103:1656–1664CrossRef

16.

Nielsen TO, Leung SCY, Rimm DL, Dodson A, Acs B, Badve S, Denkert C, Ellis MJ, Fineberg S, Flowers M, Kreipe HH, Laenkholm AV, Pan H, Penault-Llorca FM, Polley MY, Salgado R, Smith IE, Sugie T, Bartlett JMS, McShane LM, Dowsett M, Hayes DF (2021) Assessment of Ki67 in breast cancer: updated recommendations from the International Ki67 in Breast Cancer Working Group. J Natl Cancer Inst 113:808–819CrossRef

17.

Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47:207–214CrossRef

18.

Ogston KN, Miller ID, Payne S, Hutcheon AW, Sarkar TK, Smith I, Schofield A, Heys SD (2003) A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast 12:320–327CrossRef

19.

Ying M, He Y, Qi M, Dong B, Lu A, Li J, Xie Y, Wang T, Lin B, Ouyang T (2013) Value of pre-treatment biomarkers in prediction of response to neoadjuvant endocrine therapy for hormone receptor-positive postmenopausal breast cancer. Chin J Cancer Res 25:397–404PubMedPubMedCentral

20.

von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, Wolmark N, Rastogi P, Schneeweiss A, Redondo A, Fischer HH, Jacot W, Conlin AK, Arce-Salinas C, Wapnir IL, Jackisch C, DiGiovanna MP, Fasching PA, Crown JP, Wülfing P, Shao Z, Rota Caremoli E, Wu H, Lam LH, Tesarowski D, Smitt M, Douthwaite H, Singel SM, Geyer CE Jr (2019) Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med 380:617–628CrossRef

21.

Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, Kuroi K, Im SA, Park BW, Kim SB, Yanagita Y, Ohno S, Takao S, Aogi K, Iwata H, Jeong J, Kim A, Park KH, Sasano H, Ohashi Y, Toi M (2017) Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med 376:2147–2159CrossRef

22.

Ellis MJ, Suman VJ, Hoog J, Goncalves R, Sanati S, Creighton CJ, DeSchryver K, Crouch E, Brink A, Watson M, Luo J, Tao Y, Barnes M, Dowsett M, Budd GT, Winer E, Silverman P, Esserman L, Carey L, Ma CX, Unzeitig G, Pluard T, Whitworth P, Babiera G, Guenther JM, Dayao Z, Ota D, Leitch M, Olson JA Jr, Allred DC, Hunt K (2017) Ki67 proliferation Index as a tool for chemotherapy decisions during and after neoadjuvant aromatase inhibitor treatment of breast cancer: results From the American College of Surgeons Oncology Group Z1031 Trial (Alliance). J Clin Oncol 35:1061–1069CrossRef

23.

Ueno T, Saji S, Masuda N, Kuroi K, Sato N, Takei H, Yamamoto Y, Ohno S, Yamashita H, Hisamatsu K, Aogi K, Iwata H, Yamanaka T, Sasano H, Toi M (2018) Impact of clinical response to neoadjuvant endocrine therapy on patient outcomes: a follow-up study of JFMC34-0601 multicentre prospective neoadjuvant endocrine trial. ESMO Open 3(2):e000314CrossRef

24.

Kurozumi S, Matsumoto H, Inoue K, Tozuka K, Hayashi Y, Kurosumi M, Oyama T, Fujii T, Horiguchi J, Kuwano H (2018) Impact of combining the progesterone receptor and preoperative endocrine prognostic index (PEPI) as a prognostic factor after neoadjuvant endocrine therapy using aromatase inhibitors in postmenopausal ER positive and HER2 negative breast cancer. PLoS ONE 13:e0201846CrossRef

25.

Suman VJ, Ellis MJ, Ma CX (2015) The ALTERNATE trial: assessing a biomarker driven strategy for the treatment of post-menopausal women with ER+/Her2- invasive breast cancer. Chin Clin Oncol 4:34PubMedPubMedCentral

26.

Fisher B, Jeong JH, Bryant J, Anderson S, Dignam J, Fisher ER, Wolmark N (2004) 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 364:858–868CrossRef

27.

Loibl S, Jackisch C, Lederer B, Untch M, Paepke S, Kümmel S, Schneeweiss A, Huober J, Hilfrich J, Hanusch C, Gerber B, Eidtmann H, Denkert C, Costa SD, Blohmer JU, Nekljudova V, Mehta K, von Minckwitz G (2015) Outcome after neoadjuvant chemotherapy in young breast cancer patients: a pooled analysis of individual patient data from eight prospectively randomized controlled trials. Breast Cancer Res Treat 152:377–387CrossRef

28.

Baxter DE, Kim B, Hanby AM, Verghese ET, Sims AH, Hughes TA (2018) Neoadjuvant endocrine therapy in breast cancer upregulates the cytotoxic drug pump ABCG2/BCRP, and may lead to resistance to subsequent chemotherapy. Clin Breast Cancer 18:481–488CrossRef

29.

Johnston SRD, Harbeck N, Hegg R, Toi M, Martin M, Shao ZM, Zhang QY, Martinez Rodriguez JL, Campone M, Hamilton E, Sohn J, Guarneri V, Okada M, Boyle F, Neven P, Cortés J, Huober J, Wardley A, Tolaney SM, Cicin I, Smith IC, Frenzel M, Headley D, Wei R, San Antonio B, Hulstijn M, Cox J, O’Shaughnessy J, Rastogi P (2020) Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol 38:3987–3998CrossRef

30.

Palmieri C, Cleator S, Kilburn LS, Kim SB, Ahn SH, Beresford M, Gong G, Mansi J, Mallon E, Reed S, Mousa K, Fallowfield L, Cheang M, Morden J, Page K, Guttery DS, Rghebi B, Primrose L, Shaw JA, Thompson AM, Bliss JM, Coombes RC (2014) NEOCENT: a randomised feasibility and translational study comparing neoadjuvant endocrine therapy with chemotherapy in ER-rich postmenopausal primary breast cancer. Breast Cancer Res Treat 148:581–590CrossRef

31.

Fontein DB, Charehbili A, Nortier JW, Meershoek-Klein Kranenbarg E, Kroep JR, Putter H, van Riet Y, Nieuwenhuijzen GA, de Valk B, Terwogt JM, Algie GD, Liefers GJ, Linn S, van de Velde CJ (2014) Efficacy of six month neoadjuvant endocrine therapy in postmenopausal, hormone receptor-positive breast cancer patients–a phase II trial. Eur J Cancer 50:2190–2200CrossRef

32.

Goldhirsch A, Ingle JN, Gelber RD, Coates AS, Thürlimann B, Senn HJ (2009) Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann Oncol 20:1319–1329CrossRef

33.

Korde LA, Somerfield MR, Carey LA, Crews JR, Denduluri N, Hwang ES, Khan SA, Loibl S, Morris EA, Perez A, Regan MM, Spears PA, Sudheendra PK, Symmans WF, Yung RL, Harvey BE, Hershman DL (2021) Neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer: ASCO guideline. J Clin Oncol 39:1485–1505CrossRef

Titel: Neoadjuvant endocrine therapy for strongly hormone receptor-positive and HER2-negative early breast cancer: results of a prospective multi-center study
verfasst von: Xinguang Wang
Zhaoqing Fan
Xing Wang
Yingjian He
Yiqiang Liu
Xiang Wang
Bailin Zhang
Zefei Jiang
Tao Wang
Zhigang Yu
Fei Wang
Yinhua Liu
Yanping Li
Jianguo Zhang
Bin Luo
Hongchuan Jiang
Tianfeng Wang
Yuntao Xie
Jinfeng Li
Tao Ouyang
Publikationsdatum: 02.08.2022
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2022
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-022-06686-1

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Neoadjuvant endocrine therapy for strongly hormone receptor-positive and HER2-negative early breast cancer: results of a prospective multi-center study