More Than Meets the Eye: A Case of Breast Cancer Switching from Being Luminal-Androgen-Receptor-Positive to Being Hormone-Receptor-Positive

Overview

Journal Medicina (Kaunas)

Publisher MDPI

Specialty General Medicine

Date 2023 Oct 28

PMID 37893593

Authors

Federica Martorana

Giuseppe Di Grazia

Giovanni Nunzio Rosano

Giada Maria Vecchio

Chiara Conti

Sabrina Nucera

Gaetano Magro

Paolo Vigneri

Affiliations

Soon will be listed here.

Abstract

Triple-negative breast cancer (TNBC) represents about 15% of all breast cancers and is usually characterized by aggressive clinical behavior and a poor prognosis. Four TNBC subgroups have been previously defined with different molecular profiles: (i) luminal androgen receptor (LAR), (ii) mesenchymal (MES), (iii) basal-like immunosuppressed (BLIS) and (iv) basal-like immune-activated (BLIA). Among these, LAR is characterized by the expression of the androgen receptor (AR), and exhibits genomic characteristics that resemble luminal breast cancers, with a still undefined prognosis and clinical behavior. Here, we report a case of a woman affected by recurring LAR TNBC, which underwent phenotypic changes throughout its natural history. After the initial diagnosis of LAR breast cancer, the patient experienced local recurrence with strong expression of the estrogen receptor. Due to this finding, she started treatment with a CDK4/6-inhibitor and an aromatase inhibitor, followed by oral vinorelbine, both with dismal outcomes. Then, she received everolimus and exemestane, which determined temporary disease stabilization. An extensive NGS analysis of tumor tissue showed and mutations. Our case is consistent with previous reports of LAR breast cancer and underlines the potential utility of re-biopsy and molecular testing in breast cancer (BC), especially in rare subtypes.

Citing Articles

Advancements and challenges in triple-negative breast cancer: a comprehensive review of therapeutic and diagnostic strategies.

Xiong N, Wu H, Yu Z Front Oncol. 2024; 14:1405491.

PMID: 38863622 PMC: 11165151. DOI: 10.3389/fonc.2024.1405491.

References

Garrido-Castro A, Lin N, Polyak K . Insights into Molecular Classifications of Triple-Negative Breast Cancer: Improving Patient Selection for Treatment. Cancer Discov. 2019; 9(2):176-198. PMC: 6387871. DOI: 10.1158/2159-8290.CD-18-1177. View

Frampton G, Fichtenholtz A, Otto G, Wang K, Downing S, He J . Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol. 2013; 31(11):1023-31. PMC: 5710001. DOI: 10.1038/nbt.2696. View

He J, Peng R, Yuan Z, Wang S, Peng J, Lin G . Prognostic value of androgen receptor expression in operable triple-negative breast cancer: a retrospective analysis based on a tissue microarray. Med Oncol. 2011; 29(2):406-10. DOI: 10.1007/s12032-011-9832-0. View

Del Re M, Crucitta S, Lorenzini G, De Angelis C, Diodati L, Cavallero D . PI3K mutations detected in liquid biopsy are associated to reduced sensitivity to CDK4/6 inhibitors in metastatic breast cancer patients. Pharmacol Res. 2020; 163:105241. DOI: 10.1016/j.phrs.2020.105241. View

Bauer K, Brown M, Cress R, Parise C, Caggiano V . Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007; 109(9):1721-8. DOI: 10.1002/cncr.22618. View

Nishimura R, Osako T, Okumura Y, Tashima R, Toyozumi Y, Arima N . Changes in the ER, PgR, HER2, p53 and Ki-67 biological markers between primary and recurrent breast cancer: discordance rates and prognosis. World J Surg Oncol. 2011; 9:131. PMC: 3214885. DOI: 10.1186/1477-7819-9-131. View

Zuo T, Wilson P, Cicek A, Harigopal M . Androgen receptor expression is a favorable prognostic factor in triple-negative breast cancers. Hum Pathol. 2018; 80:239-245. DOI: 10.1016/j.humpath.2018.06.003. View

Haffty B, Yang Q, Reiss M, Kearney T, Higgins S, Weidhaas J . Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol. 2006; 24(36):5652-7. DOI: 10.1200/JCO.2006.06.5664. View

Riaz N, Idress R, Habib S, Lalani E . Lack of Androgen Receptor Expression Selects for Basal-Like Phenotype and Is a Predictor of Poor Clinical Outcome in Non-Metastatic Triple Negative Breast Cancer. Front Oncol. 2020; 10:1083. PMC: 7399239. DOI: 10.3389/fonc.2020.01083. View

10.

Turner N, Oliveira M, Howell S, Dalenc F, Cortes J, Gomez Moreno H . Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2023; 388(22):2058-2070. PMC: 11335038. DOI: 10.1056/NEJMoa2214131. View

11.

Aurilio G, Disalvatore D, Pruneri G, Bagnardi V, Viale G, Curigliano G . A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases. Eur J Cancer. 2013; 50(2):277-89. DOI: 10.1016/j.ejca.2013.10.004. View

12.

Sorlie T, Perou C, Tibshirani R, Aas T, Geisler S, Johnsen H . Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001; 98(19):10869-74. PMC: 58566. DOI: 10.1073/pnas.191367098. View

13.

Kao J, Tsai J, Wu T, Wang C, Kuo Y . Receptor discordance and phenotype change in metastatic breast cancer. Asian J Surg. 2020; 44(1):192-198. DOI: 10.1016/j.asjsur.2020.05.032. View

14.

Traina T, Miller K, Yardley D, Eakle J, Schwartzberg L, OShaughnessy J . Enzalutamide for the Treatment of Androgen Receptor-Expressing Triple-Negative Breast Cancer. J Clin Oncol. 2018; 36(9):884-890. PMC: 5858523. DOI: 10.1200/JCO.2016.71.3495. View

15.

Lehmann B, Bauer J, Chen X, Sanders M, Chakravarthy A, Shyr Y . Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011; 121(7):2750-67. PMC: 3127435. DOI: 10.1172/JCI45014. View

16.

. Comprehensive molecular portraits of human breast tumours. Nature. 2012; 490(7418):61-70. PMC: 3465532. DOI: 10.1038/nature11412. View

17.

Burstein M, Tsimelzon A, Poage G, Covington K, Contreras A, Fuqua S . Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res. 2014; 21(7):1688-98. PMC: 4362882. DOI: 10.1158/1078-0432.CCR-14-0432. View

18.

Bonnefoi H, Grellety T, Tredan O, Saghatchian M, Dalenc F, Mailliez A . A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1). Ann Oncol. 2016; 27(5):812-8. DOI: 10.1093/annonc/mdw067. View

19.

Liu Y, Zhu X, Xiao Y, Wu S, Zuo W, Yu Q . Subtyping-based platform guides precision medicine for heavily pretreated metastatic triple-negative breast cancer: The FUTURE phase II umbrella clinical trial. Cell Res. 2023; 33(5):389-402. PMC: 10156707. DOI: 10.1038/s41422-023-00795-2. View

20.

Nik-Zainal S, Davies H, Staaf J, Ramakrishna M, Glodzik D, Zou X . Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature. 2016; 534(7605):47-54. PMC: 4910866. DOI: 10.1038/nature17676. View