Basal-Like Subgroup is Associated with Younger Age, Increased Expression of Androgen Receptor, and Worse Prognosis, while Non-basal-like Subtype is Associated with Higher BMI in Triple-Negative Breast Cancer Patients

Ibnu Purwanto, Didik Setyo Heiyanto, Ahmad Ghozali, Irianiwati Widodo, Iwan Dwiprahasto, Teguh Aryandono, Sofia Mubarika Haryana

Abstract


BACKGROUND: Triple-negative breast cancer (TNBC) represents a heterogenous disease which differ in characteristic, treatment response and prognosis. We aim to perform in-depth analysis on the clinicopathologic feature and the prognostic value of basal-like and non-basal-like TNBC patients in an Indonesian tertiary hospital.

METHODS: We retrospectively included patients diagnosed with TNBC between 2014-2017. Clinical variables were collected from medical record. Expression of epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6), p53 mutant and androgen receptor (AR) were examined by using immunohistochemistry (IHC).

RESULTS: We included 67 subjects, 67.1% were basal-like and the remaining 32.9% were non-basal-like, with mean age of 51 years old, 59.7% subjects had BMI <25 and 40.3% subjects had BMI ≥25; 16.4%, 65.7%, and 17.9% subjects presented with early stage, locally advanced stage, and distant metastasis respectively; T<5 cm was found in 29.9% subjects, while 70.1% subjects had T≥5; 67.2% subjects presented with N-, while 32.8% subjects were N+. The most common histological type was infiltrating ductal (82% of subjects). P53 mutant and AR expressions were positive in 44.8% and 15% subjects, respectively. Basal-like subtype presented with younger age at and had higher expression of AR, while non-basal-like subtype is associated with BMI ≥25 (p<0.05). Basal-like subjects had shorter overall survival (23.9 months (95% CI: 21.9-25.9) vs. 26.1 months (95% CI: 23-29.2).

CONCLUSION: Basal-like subtype is associated with worse prognosis, younger age at diagnosis and increased expression of AR, while non-basal-like subtype is associated with higher BMI in Indonesian TNBC.

KEYWORDS: TNBC, subtype; basal-like, young age, Indonesia


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References


Wahidin M, Noviani R, Hermawan S, Andriani V, Ardian A, Djarir H. Population-based cancer registration in Indonesia. Asian Pacific J Cancer Prev. 2012; 13: 1709-10, CrossRef.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68: 394-424, CrossRef.

Carey L, Winer E, Viale G, Cameron D, Gianni L. Triple-negative breast cancer: disease entity or title of convenience? Nat Rev Clin Oncol. 2010; 7: 683-92, CrossRef.

Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000; 406: 747-52, CrossRef.

Purwanto I, Dwiprahasto I, Aryandono T, Haryana SM. Treatment options for Indonesian triple negative breast cancer patients: a literature review of current state and potentials for future improvement. J Med Sci. 2020; 52: 81-101, CrossRef.

Giovannelli P, Di Donato M, Auricchio F, Castoria G, Migliaccio A. Androgens induce invasiveness of triple negative breast cancer cells through AR/Src/PI3-K complex assembly. Sci Rep. 2019; 9: 4490, CrossRef.

Coradini D, Biganzoli E, Ardoino I, Ambrogi F, Boracchi P, Demicheli R, et al. p53 status identifies triple-negative breast cancer patients who do not respond to adjuvant chemotherapy. Breast. 2015; 24: 294-7, CrossRef.

Dieci MV, Tsvetkova V, Griguolo G, Miglietta F, Mantiero M, Tasca G, et al. Androgen receptor expression and association with distant disease-free survival in triple negative breast cancer: analysis of 263 patients treated with standard therapy for stage I-III disease. Front Oncol. 2019; 9: 452, CrossRef.

Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 2006; 295: 2492-502, CrossRef.

Abdelrahman AE, Rashed HE, Abdelgawad M, Abdelhamid MI. Prognostic impact of EGFR and cytokeratin 5/6 immunohistochemical expression in triple-negative breast cancer. Ann Diagn Pathol. 2017; 28: 43-53, CrossRef.

Chottanapund S, Van Duursen MBM, Ratchaworapong K, Navasumrit P, Ruchirawat M, Van den Berg M. Androgen receptor expression in Thai breast cancer patients. Med Sci (Basel). 2016; 4: 15, CrossRef.

Thike AA, Chong LYZ, Cheok PY, Li HH, Yip GWC, Bay BH, et al. Loss of androgen receptor expression predicts early recurrence in triple-negative and basal-like breast cancer. Mod Pathol. 2014; 27: 352-60, CrossRef.

Qi JP, Yang YL, Zhu H, Wang J, Jia Y,1 Liu N, et al. Expression of the androgen receptor and its correlation with molecular subtypes in 980 chinese breast cancer patients. Breast Cancer (Auckl). 2012; 6: 1-8, CrossRef.

Gucalp A, Tolaney S, Isakoff SJ, Ingle JN, Liu MC, Carey LA, et al. Phase II trial of bicalutamide in patients with androgen receptor–positive, estrogen receptor–negative metastatic breast cancer. Clin Cancer Res. 2013; 19: 5505-12, CrossRef.

Xu M, Yuan Y, Yan P, Jiang J, Ma P, Nio X, et al. Prognostic significance of androgen receptor expression in triple negative breast cancer: a systematic review and meta-analysis. Clin Breast Cancer. 2020; 20: e385-96, CrossRef.

Astvatsaturyan K, Yue Y, Walts AE, Bose S. Androgen receptor positive triple negative breast cancer: clinicopathologic, prognostic, and predictive features. PLoS One. 2018; 13(6): e0197827, CrossRef.

Choi JE, Kang SH, Lee SJ, Bae YK. Androgen receptor expression predicts decreased survival in early stage triple-negative breast cancer. Ann Surg Oncol. 2015; 22: 82-9, CrossRef.

Masuda H, Baggerly KA, Wang Y, Zhang Y, Gonzalez-Angulo AM, Meric-Bernstam F, et al. Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes. Clin Cancer Res. 2013; 19: 5533-40, CrossRef.

Bonnefoi H, Grellety T, Tredan O, Saghatchian M, Dalenc F, Mailliez A, et al. 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: 812-8, CrossRef.

Traina TA, Miller K, Yardley DA, Eakle J, Schwartzberg LS, O'Shaughnessy J, et al. Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer. J Clin Oncol. 2018; 36: 884-90, CrossRef.

Abubakar M, Guo C, Koka H, Sung H, Shao N, Guida J, et al. Clinicopathological and epidemiological significance of breast cancer subtype reclassification based on p53 immunohistochemical expression. NPJ Breast Cancer. 2019; 5: 20, CrossRef.

The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumors. Nature. 2012; 490: 61-70, CrossRef.

Biganzoli E, Coradini D, Ambrogi F, Garibaldi JM, Lisboa P, Soria D, et al. p53 status identifies two subgroups of triple-negative breast cancers with distinct biological features. Jpn J Clin Oncol. 2011; 41: 172-9, CrossRef.

Walerych D, Napoli M, Collavin L, Del Sal G. The rebel angel: mutant p53 as the driving oncogene in breast cancer. Carcinogenesis. 2012; 33: 2007-17, CrossRef.

Millis SZ, Gatalica Z, Winkler J, Vranic S, Kimbrough J, Reddy S, et al. Predictive biomarker profiling of > 6000 breast cancer patients shows heterogeneity in TNBC, with treatment implications. Clin Breast Cancer. 2015; 15: 473-481.e3, CrossRef.

Lee DS, Yoon SY, Looi LM, Kang P, Kang IN, Sivanandan K, et al. Comparable frequency of BRCA1, BRCA2 and TP53 germline mutations in a multi-ethnic Asian cohort suggests TP53 screening should be offered together with BRCA1/2 screening to early-onset breast cancer patients. Breast Cancer Res. 2012; 14: R66, CrossRef.

Dookeran KA, Dignam JJ, Holloway N, Ferrer K, Sekosan M, McCaskill-Stevens W, et al. Race and the prognostic influence of p53 in women with breast cancer. Ann Surg Oncol. 2012; 19: 2334-44, CrossRef.

Babu KG, Anand A, Laksmaiah KC, Lokanatha D, Jacob LA, Babu MS, et al. Correlation of BMI with breast cancer subtype and tumour size. Ecancermedicalscience. 2018; 12: 845, CrossRef.

Dietze EC, Chavez TA, Seewaldt VL. Obesity and triple-negative breast cancer. Am J Pathol. 2018; 188: 280-90, CrossRef.

Sun X, Wang M, Wang M, Yu X, Guo J, Sun T, et al. Metabolic reprogramming in triple-negative breast cancer. Front Oncol. 2020; 10: 428, CrossRef.




DOI: https://doi.org/10.18585/inabj.v12i4.1289

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