Long-Term Impact of Various Endocrine Therapy Regimens on Mortality, Local Recurrence, and Metastasis in Breast Cancer: A 25-Year Retrospective Study Long-Term impact of ET on BC

Sadegh Khoddam (1), Mohammad Reza Fattahi (2), Mohammad Esmaeil Akbari (3), Aida Hossein Nezhad (4), Neda Izadi (5), Atieh Akbari (6), Saeed Bakhshi (7), Hojat Dehghanbanadaki (8)
(1) Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Iran, Islamic Republic of,
(2) Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Iran, Islamic Republic of,
(3) Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Iran, Islamic Republic of,
(4) Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Iran, Islamic Republic of,
(5) Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Iran, Islamic Republic of,
(6) Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Iran, Islamic Republic of,
(7) Department of Surgical Oncology, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran, Iran, Islamic Republic of,
(8) Tehran University of Medical Sciences, Tehran, Iran, Iran, Islamic Republic of

Abstract

Background: This retrospective cohort study explores the long-term effects of different endocrine therapy regimens on mortality, local recurrence, and metastasis in breast cancer patients.


Methods: Data from the Referral Cancer Research Center of Shahid Beheshti University of Medical Sciences were analyzed. Records of 2,262 histologically confirmed  breast cancer patients, with 25 years of follow-up were included. We collected patient data, including treatment modalities, and details of the endocrine therapy, and conducted statistical analysis to assess treatment-outcome associations.


Results: Patients had an average age of 49.45 years, and 99.1% were female. The average tumor size was 2.8 cm, with a 12.3% mortality rate. Positive expression of human epidermal growth factor receptor 2, progesterone receptor, and estrogen receptor was found in 17.3%, 71.8%, and 70.6% of patients, respectively. Tamoxifen was administered  to 1,700 patients, letrozole to 715, and exemestane to 540, with an average endocrine therapy duration of 5.2 years. Letrozole treatment duration (P = 0.001) and lymph node involvement (P = 0.028) were independent predictive variables for local recurrence, with longer letrozole therapy associated with lower recurrence.


Conclusion: Estrogen receptor expression and endocrine therapy duration are independent predictive markers for recurrence and mortality. Longer letrozole therapy predicts lower local recurrence. Endocrine therapy duration inversely relates to mortality, recurrence, and local recurrence.

Full text article

Generated from XML file

References

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 May 14-20;365(9472):1687-717. doi: 10.1016/S0140-6736(05)66544-0.

Cardoso F, Loibl S, Pagani O, Graziottin A, Panizza P, Martincich L, et al. The European Society of Breast Cancer Specialists recommendations for the management of young women with breast cancer. Eur J Cancer. 2012 Dec;48(18):3355-77. doi: 10.1016/j.ejca.2012.10.004.

Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. doi: 10.1056/NEJM200103153441101.

Cameron D, Piccart-Gebhart MJ, Gelber RD, Procter M, Goldhirsch A, de Azambuja E, et al; Herceptin Adjuvant (HERA) Trial Study Team. 11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017 Mar 25;389(10075):1195-1205. doi: 10.1016/S0140-6736(16)32616-2.

Dalmau E, Armengol-Alonso A, Muñoz M, Seguí-Palmer MÁ. Current status of hormone therapy in patients with hormone receptor positive (HR+) advanced breast cancer. Breast. 2014 Dec;23(6):710-20. doi: 10.1016/j.breast.2014.09.006.

Cognetti F, Naso G. The clinician's perspective on the 21-gene assay in early breast cancer. Oncotarget. 2021 Dec 21;12(26):2514-2530. doi: 10.18632/oncotarget.28148.

Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF; ATAC/LATTE investigators. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010 Dec;11(12):1135-41. doi: 10.1016/S1470-2045(10)70257-6.

Paik S. Development and clinical utility of a 21-gene recurrence score prognostic assay in patients with early breast cancer treated with tamoxifen. Oncologist. 2007 Jun;12(6):631-5. doi: 10.1634/theoncologist.12-6-631.

Kalli S, Semine A, Cohen S, Naber SP, Makim SS, Bahl M. American Joint Committee on Cancer's Staging System for Breast Cancer, Eighth Edition: What the Radiologist Needs to Know. Radiographics. 2018 Nov-Dec;38(7):1921-1933. doi: 10.1148/rg.2018180056.

Bevers TB, Niell BL, Baker JL, Bennett DL, Bonaccio E, Camp MS, et a. NCCN Guidelines® Insights: Breast Cancer Screening and Diagnosis, Version 1.2023. J Natl Compr Canc Netw. 2023 Sep;21(9):900-909. doi: 10.6004/jnccn.2023.0046.

Barron TI, Cahir C, Sharp L, Bennett K. A nested case-control study of adjuvant hormonal therapy persistence and compliance, and early breast cancer recurrence in women with stage I-III breast cancer. Br J Cancer. 2013 Sep 17;109(6):1513-21. doi: 10.1038/bjc.2013.518.

Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013 Mar 9;381(9869):805-16. doi: 10.1016/S0140-6736(12)61963-1.

Pan H, Gray R, Braybrooke J, Davies C, Taylor C, McGale P, Peto R, Pritchard KI, Bergh J, Dowsett M, Hayes DF; EBCTCG. 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. N Engl J Med. 2017 Nov 9;377(19):1836-1846. doi: 10.1056/NEJMoa1701830.

Petrelli F, Coinu A, Cabiddu M, Ghilardi M, Lonati V, Barni S. Five or more years of adjuvant endocrine therapy in breast cancer: a meta-analysis of published randomised trials. Breast Cancer Res Treat. 2013 Jul;140(2):233-40. doi: 10.1007/s10549-013-2629-4.

Goss PE, Muss HB, Ingle JN, Whelan TJ, Wu M. Extended adjuvant endocrine therapy in breast cancer: current status and future directions. Clin Breast Cancer. 2008 Oct;8(5):411-7. doi: 10.3816/CBC.2008.n.049.

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 Jan 1;110(1). doi: 10.1093/jnci/djx134.

Munzone E, Colleoni M. Optimal management of luminal breast cancer: how much endocrine therapy is long enough? Ther Adv Med Oncol. 2018 Jun 18;10:1758835918777437. doi: 10.1177/1758835918777437.

Bartlett JMS, Sgroi DC, Treuner K, Zhang Y, Ahmed I, Piper T, et al. Breast Cancer Index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the Adjuvant Tamoxifen-To Offer More? (aTTom) trial. Ann Oncol. 2019 Nov 1;30(11):1776-1783. doi: 10.1093/annonc/mdz289.

Akbari M E, Delshad B, Mousavizadeh M . Outcomes of Breast Conservation Surgery and Modified Radical Mastectomy After Neoadjuvant Chemotherapy in Patients with Locally Advanced Breast Cancer. Int J Cancer Manag. 2020;13(2):e14297. doi: 10.5812/ijcm.14297.

Nichol AM, Chan EK, Lucas S, Smith SL, Gondara L, Speers C, et al. The Use of Hormone Therapy Alone Versus Hormone Therapy and Radiation Therapy for Breast Cancer in Elderly Women: A Population-Based Study. Int J Radiat Oncol Biol Phys. 2017 Jul 15;98(4):829-839. doi: 10.1016/j.ijrobp.2017.02.094.

Bense RD, Qiu SQ, de Vries EGE, Schröder CP, Fehrmann RSN. Considering the biology of late recurrences in selecting patients for extended endocrine therapy in breast cancer. Cancer Treat Rev. 2018 Nov;70:118-126. doi: 10.1016/j.ctrv.2018.07.015.

Jinih M, Relihan N, Corrigan MA, O'Reilly S, Redmond HP. Extended Adjuvant Endocrine Therapy in Breast Cancer: Evidence and Update - A Review. Breast J. 2017 Nov;23(6):694-705. doi: 10.1111/tbj.12783.

Cianfrocca M. Overcoming recurrence risk: extended adjuvant endocrine therapy. Clin Breast Cancer. 2008 Dec;8(6):493-500. doi: 10.3816/CBC.2008.n.059.

Neri A, Marrelli D, Rossi S, De Stefano A, Mariani F, De Marco G, et al. Breast cancer local recurrence: risk factors and prognostic relevance of early time to recurrence. World J Surg. 2007 Jan;31(1):36-45. doi: 10.1007/s00268-006-0097-2.

van Maaren MC, de Munck L, Strobbe LJA, Sonke GS, Westenend PJ, Smidt ML, et al. Ten-year recurrence rates for breast cancer subtypes in the Netherlands: A large population-based study. Int J Cancer. 2019 Jan 15;144(2):263-272. doi: 10.1002/ijc.31914.

Chalela P, Munoz E, Inupakutika D, Kaghyan S, Akopian D, Kaklamani V, et al. Improving adherence to endocrine hormonal therapy among breast cancer patients: Study protocol for a randomized controlled trial. Contemp Clin Trials Commun. 2018 Oct 17;12:109-115. doi: 10.1016/j.conctc.2018.10.001.

Krauss K, Stickeler E. Endocrine Therapy in Early Breast Cancer. Breast Care (Basel). 2020 Aug;15(4):337-346. doi: 10.1159/000509362.

Lopez-Tarruella S, Echavarria I, Jerez Y, Herrero B, Gamez S, Martin M. How we treat HR-positive, HER2-negative early breast cancer. Future Oncol. 2022 Mar;18(8):1003-1022. doi: 10.2217/fon-2021-0668.

Authors

Sadegh Khoddam
Mohammad Reza Fattahi
Mohammad Esmaeil Akbari
Aida Hossein Nezhad
aida.hosseinnezhad93@gmail.com (Primary Contact)
Neda Izadi
Atieh Akbari
Saeed Bakhshi
Hojat Dehghanbanadaki
1.
Khoddam S, Fattahi MR, Akbari ME, Hossein Nezhad A, Izadi N, Akbari A, Bakhshi S, Dehghanbanadaki H. Long-Term Impact of Various Endocrine Therapy Regimens on Mortality, Local Recurrence, and Metastasis in Breast Cancer: A 25-Year Retrospective Study: Long-Term impact of ET on BC. Arch Breast Cancer [Internet]. 2024 Jan. 31 [cited 2024 Feb. 21];11(1):40-51. Available from: https://www.archbreastcancer.com/index.php/abc/article/view/799

Article Details

Most read articles by the same author(s)