Efficacy of neoadjuvant endocrine therapy compared with neoadjuvant chemotherapy in pre-menopausal patients with oestrogen receptor-positive and HER2-negative, lymph node-positive breast cancer

Hee Jeong Kim, Woo Chul Noh, Eun Sook Lee, Yong Sik Jung, Lee Su Kim, Wonshik Han, Seok Jin Nam, Gyung -Yub Gong, Hwa Jung Kim, Sei Hyun Ahn, Hee Jeong Kim, Woo Chul Noh, Eun Sook Lee, Yong Sik Jung, Lee Su Kim, Wonshik Han, Seok Jin Nam, Gyung -Yub Gong, Hwa Jung Kim, Sei Hyun Ahn

Abstract

Introduction: Neoadjuvant endocrine therapy (NET) has demonstrated efficacy in post-menopausal patients with hormone-responsive breast cancer. This trial was designed to compare the efficacy of neoadjuvant chemotherapy (NCT) with NET in pre-menopausal breast cancer.

Patients and methods: In this prospective, randomised, phase III study, oestrogen receptor (ER)-positive, HER2-negative, and lymph node-positive pre-menopausal breast cancer patients were recruited from 7 hospitals in South Korea. Enrolled patients were randomly assigned (1:1) to receive 24 weeks of either NCT or NET with goserelin and tamoxifen. The primary purpose was to evaluate the non-inferiority of NET compared to NCT using clinical response, assessed by MRI. Besides, pathological complete response rate (pCR), changes in Ki-67 expression, breast conservation surgery (BCS) rate, and quality of life were included as secondary endpoints.

Results: A total of 187 patients were assigned to receive NCT (n = 95) or NET (n = 92), and 87 patients in each group completed treatments. More NCT patients had complete response or partial response than NET patients using MRI (NCT 83.7% vs. NET 52.9%, 95% CI 17.6-44.0, p < 0.001) and callipers (NCT 83.9% vs. NET 71.3%, 95% CI 0.4-24.9, p = 0.046). Three NCT patients (3.4%) and one NET patient (1.2%) showed pCR (p < 0.005). No difference existed in the conversion rate of BCS (13.8% for NCT vs. 11.5% for NET, p = 0.531) and Ki-67 change (p = 0.114) between the two groups. Nineteen NCT patients had treatment-related grade 3 or worse events compared with none in the NET group.

Conclusions: Better clinical responses were observed in pre-menopausal patients after 24 weeks of NCT compared to those observed after NET.

Trial registration: Clinicaltrials.gov, NCT01622361. Registration June 19, 2012.

Keywords: Breast cancer; Clinical response; Neoadjuvant chemotherapy; Neoadjuvant endocrine therapy; Pre-menopausal women.

Conflict of interest statement

All authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Trial profile
Fig. 2
Fig. 2
Response rate according to treatments. a Clinical response measure by calliper. b Clinical response measure by MRI. c Detailed clinical response measure by calliper. d Detailed clinical response measure by MRI

References

    1. Ahn SH, Son BH, Kim SW, Kim SI, Jeong J, Ko S-S, Han W. Poor outcome of hormone receptor–positive breast Cancer at very young age is due to tamoxifen resistance: nationwide survival data in Korea—a report from the Korean Breast Cancer Society. J Clin Oncol. 2007;25(17):2360–2368. doi: 10.1200/JCO.2006.10.3754.
    1. Swain SM, Jeong J-H, Wolmark N. Amenorrhea from breast cancer therapy — not a matter of dose. N Engl J Med. 2010;363(23):2268–2270. doi: 10.1056/NEJMc1009616.
    1. Swain SM, Jeong J-H, Geyer CEJ, Costantino JP, Pajon ER, Fehrenbacher L, Atkins JN, Polikoff J, Vogel VG, Erban JK, et al. Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med. 2010;362(22):2053–2065. doi: 10.1056/NEJMoa0909638.
    1. Jung M, Shin HJ, Rha SY, Jeung HC, Hong S, Moon YW, Kim HS, Oh KJ, Yang WI, Roh JK, et al. The clinical outcome of chemotherapy-induced amenorrhea in premenopausal young patients with breast cancer with long-term follow-up. Ann Surg Oncol. 2010;17(12):3259–3268. doi: 10.1245/s10434-010-1172-3.
    1. Goncalves R, Bose R. Using multigene tests to select treatment for early-stage breast cancer. J Natl Compr Cancer Netw. 2013;11(2):174–182. doi: 10.6004/jnccn.2013.0025.
    1. Harbeck N, Schmitt M, Meisner C, Friedel C, Untch M, Schmidt M, Sweep CGJ, Lisboa BW, Lux MP, Beck T, et al. Ten-year analysis of the prospective multicentre Chemo-N0 trial validates American Society of Clinical Oncology (ASCO)-recommended biomarkers uPA and PAI-1 for therapy decision making in node-negative breast cancer patients. Eur J Cancer. 2013;49(8):1825–1835. doi: 10.1016/j.ejca.2013.01.007.
    1. Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE, Jr, Dees EC, Goetz MP, Olson JA, Jr, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379(2):111–121. doi: 10.1056/NEJMoa1804710.
    1. Cardoso F, van't Veer LJ, Bogaerts J, Slaets L, Viale G, Delaloge S, Pierga JY, Brain E, Causeret S, DeLorenzi M, et al. 70-gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med. 2016;375(8):717–729. doi: 10.1056/NEJMoa1602253.
    1. Albain KS, Barlow WE, Shak S, Hortobagyi GN, Livingston RB, Yeh IT, Ravdin P, Bugarini R, Baehner FL, Davidson NE, et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol. 2010;11(1):55–65. doi: 10.1016/S1470-2045(09)70314-6.
    1. Lim E, Winer EP. Adjuvant chemotherapy in luminal breast cancers. Breast. 2011;20(Supplement 3):S128–S131. doi: 10.1016/S0960-9776(11)70309-5.
    1. Chang J, Lee A, Lee J, Lim W, Sung SH, Moon B-I. Correlation between the molecular subtype of breast cancer and the in vitro adenosine triphosphate-based chemosensitivity assay. J Korean Surg Soc. 2013;84(6):313–320. doi: 10.4174/jkss.2013.84.6.313.
    1. Gv M, Blohmer JU, Costa SD, Denkert C, Eidtmann H, Eiermann W, Gerber B, Hanusch C, Hilfrich J, Huober J, et al. Response-guided neoadjuvant chemotherapy for breast cancer. J Clin Oncol. 2013;31(29):3623–3630. doi: 10.1200/JCO.2012.45.0940.
    1. Ellis MJ, Coop A, Singh B, Tao Y, Llombart-Cussac A, Jänicke F, Mauriac L, Quebe-Fehling E, Chaudri-Ross HA, Evans DB, et al. Letrozole inhibits tumor proliferation more effectively than tamoxifen independent of HER1/2 expression status. Cancer Res. 2003;63(19):6523–6531.
    1. Smith IE, Dowsett M, Ebbs SR, Dixon JM, Skene A, Blohmer J-U, Ashley SE, Francis S, Boeddinghaus I, Walsh G. 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. 2005;23(22):5108–5116. doi: 10.1200/JCO.2005.04.005.
    1. Cataliotti L, Buzdar AU, Noguchi S, Bines J, Takatsuka Y, Petrakova K, Dube P, Tosello de Oliveira C. Comparison of anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor-positive breast cancer. Cancer. 2006;106(10):2095–2103. doi: 10.1002/cncr.21872.
    1. Semiglazov VF, Semiglazov VV, Dashyan GA, Ziltsova EK, Ivanov VG, Bozhok AA, Melnikova OA, Paltuev RM, Kletzel A, Berstein LM. Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer. Cancer. 2007;110(2):244–254. doi: 10.1002/cncr.22789.
    1. Masuda N, Sagara Y, Kinoshita T, Iwata H, Nakamura S, Yanagita Y, Nishimura R, Iwase H, Kamigaki S, Takei H, et al. Neoadjuvant anastrozole versus tamoxifen in patients receiving goserelin for premenopausal breast cancer (STAGE): a double-blind, randomised phase 3 trial. Lancet Oncol. 2012;13(4):345–352. doi: 10.1016/S1470-2045(11)70373-4.
    1. Hage AN, Capriccioso C, Brennan J, Heiden B, Zheutlin A, Sabel MS. Impact of neoadjuvant chemotherapy on surgical outcomes among patients with hormone receptor positive breast cancer. J Surg Oncol. 2017;116(6):665–670. doi: 10.1002/jso.24721.
    1. Kuerer HM, Sahin AA, Hunt KK, Newman LA, Breslin TM, Ames FC, Ross MI, Buzdar AU, Hortobagyi GN, Singletary SE. Incidence and Impact of documented eradication of breast cancer axillary lymph node metastases before surgery in patients treated with neoadjuvant chemotherapy. Ann Surg. 1999;230(1):72. doi: 10.1097/00000658-199907000-00011.
    1. Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012;379(9816):633–640. doi: 10.1016/S0140-6736(11)61847-3.
    1. Kim HS, Shin MS, Kim CJ, Yoo SH, Yoo TK, Eom YH, Chae BJ, Song BJ. Improved model for predicting axillary response to neoadjuvant chemotherapy in patients with clinically node-positive breast cancer. J Breast Cancer. 2017;20(4):378–385. doi: 10.4048/jbc.2017.20.4.378.
    1. Boughey JC, Suman VJ, Mittendorf EA, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the acosog z1071 (alliance) clinical trial. JAMA. 2013;310(14):1455–1461. doi: 10.1001/jama.2013.278932.
    1. Kuehn T, Bauerfeind I, Fehm T, Fleige B, Hausschild M, Helms G, Lebeau A, Liedtke C, Gv M, Nekljudova V, et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol. 2013;14(7):609–618. doi: 10.1016/S1470-2045(13)70166-9.
    1. Kang Y-J, Han W, Park S, You JY, Yi HW, Park S, Nam S, Kim JH, Yun KW, Kim HJ, et al. Outcome following sentinel lymph node biopsy-guided decisions in breast cancer patients with conversion from positive to negative axillary lymph nodes after neoadjuvant chemotherapy. Breast Cancer Res Treat. 2017;166(2):473–480. doi: 10.1007/s10549-017-4423-1.
    1. Palmieri C, Cleator S, Kilburn LS, Kim SB, Ahn S-H, Beresford M, Gong G, Mansi J, Mallon E, Reed S, et al. NEOCENT: a randomised feasibility and translational study comparing neoadjuvant endocrine therapy with chemotherapy in ER-rich postmenopausal primary breast cancer. Breast Cancer Res Treat. 2014;148(3):581–590. doi: 10.1007/s10549-014-3183-4.
    1. Llombart-Cussac A, Guerrero Á, Galán A, Carañana V, Buch E, Rodríguez-Lescure Á, Ruiz A, Fuster Diana C, Guillem Porta V. Phase II trial with letrozole to maximum response as primary systemic therapy in postmenopausal patients with ER/PgR[+] operable breast cancer. Clin Transl Oncol. 2012;14(2):125–131. doi: 10.1007/s12094-012-0771-9.
    1. Barbie TU, Ma C, Margenthaler JA. Management of premenopausal women with neoadjuvant endocrine therapy: a single-institution experience. Ann Surg Oncol. 2015;22(12):3861–3865. doi: 10.1245/s10434-015-4487-2.
    1. Alba E, Calvo L, Albanell J, De la Haba JR, Arcusa Lanza A, Chacon JI, Sanchez-Rovira P, Plazaola A, Lopez Garcia-Asenjo JA, Bermejo B, et al. Chemotherapy (CT) and hormonotherapy (HT) as neoadjuvant treatment in luminal breast cancer patients: results from the GEICAM/2006-03, a multicenter, randomized, phase-II study. Ann Oncol. 2012;23(12):3069–3074. doi: 10.1093/annonc/mds132.
    1. Carpenter R, Doughty JC, Cordiner C, Moss N, Gandhi A, Wilson C, Andrews C, Ellis G, Gui G, Skene AI. Optimum duration of neoadjuvant letrozole to permit breast conserving surgery. Breast Cancer Res Treat. 2014;144(3):569–576. doi: 10.1007/s10549-014-2835-8.
    1. Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B, Senn HJ, Albain KS, André F, Bergh J, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol. 2013;24(9):2206–2223. doi: 10.1093/annonc/mdt303.
    1. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–172. doi: 10.1016/S0140-6736(13)62422-8.
    1. Moon H-G, Han W, Ahn SK, Cho N, Moon WK, Im S-A, Park IA, Noh D-Y. Breast cancer molecular phenotype and the use of HER2-targeted agents influence the accuracy of breast MRI after neoadjuvant chemotherapy. Ann Surg. 2013;257(1):133–137. doi: 10.1097/SLA.0b013e3182686bd9.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다