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Published in: Annals of Surgical Oncology 12/2015

01-11-2015 | Breast Oncology

Characterizing Breast Cancer in a Population with Increased Prevalence of Triple-Negative Breast Cancer: Androgen Receptor and ALDH1 Expression in Ghanaian Women

Authors: Erica Proctor, MD, Kelley M. Kidwell, PhD, Evelyn Jiagge, MBChB, Jessica Bensenhaver, MD, Baffour Awuah, MBChB, Kofi Gyan, DVM, MPH, MPA, Kathy Toy, Joseph Kwaku Oppong, MBChB, Ishmael Kyei, MBChB, Francis Aitpillah, MBChB, Ernest Osei-Bonsu, MBChB, Ernest Adjei, MBChB, Michael Ohene-Yeboah, MBChB, Robert Newman Brewer, Linda Ahenkorah Fondjo, PhD, Osei Owusu-Afriyie, MBChB, Max Wicha, MD, Sofia Merajver, MD, PhD, Celina Kleer, MD, Lisa Newman, MD, MPH, FACS, FASCO

Published in: Annals of Surgical Oncology | Issue 12/2015

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Abstract

Background

The androgen receptor (AR) is a commonly-expressed hormone receptor in breast cancer and may be a marker of response to targeted anti-androgen therapy, a particularly attractive option for triple-negative breast cancer (TNBC). Gene expression studies suggest that ARs may distinguish a luminal/AR TNBC subtype from stem cell-like subtypes. TNBC frequency is two to three times higher in African American and African breast cancers compared with White American and European breast cancers, yet little is known regarding TNBC subtypes in high-frequency African-ancestry populations. We evaluated ARs and the mammary stem cell marker aldehyde dehydrogenase 1 (ALDH1) among breast cancers from Ghana, Africa.

Methods

Overall, 147 formalin-fixed, paraffin-embedded invasive breast cancers from the Komfo Anoyke Teaching Hospital in Ghana were studied at the University of Michigan, and analyzed immunohistochemically for estrogen receptor (ER), progesterone receptor (PR), HER2/neu, ALDH1, and AR expression.

Results

The median age of patients was 45 years. Only 31 cases (21 %) were ER-positive, and 14 (10 %) were HER2-positive; 89 (61 %) were TNBCs. For the entire group, 44 % were AR-positive and 45 % were ALDH1-positive. ER/PR-positive tumors were more likely to be AR-positive compared with ER/PR-negative tumors (87 vs. 26 %; p < 0.0001), but there was no association between ALDH1 and AR expression. Among the TNBC cases, 45 % were ALDH1-positive and 24 % were AR-positive. ALDH1 positivity was associated with AR positivity within the subset of TNBC (36 vs. 14 %; p = 0.019).

Conclusion

We confirmed other studies showing a high frequency of TNBC in Africa. Surprisingly, ALDH1 was found to correlate with AR expression among TNBC, suggesting that novel TNBC subtypes may exist among populations with African ancestry.
Literature
1.
go back to reference Brenton JD, Carey LA, Ahmed AA, Caldas C. Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol. 2005;23(29):7350-7360.CrossRefPubMed Brenton JD, Carey LA, Ahmed AA, Caldas C. Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol. 2005;23(29):7350-7360.CrossRefPubMed
2.
go back to reference Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747-752.CrossRefPubMed Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747-752.CrossRefPubMed
3.
go back to reference Alluri P, Newman LA. Basal-like and triple-negative breast cancers: searching for positives among many negatives. Surg Oncol Clin N Am. 2014;23(3):567-577.PubMedCentralCrossRefPubMed Alluri P, Newman LA. Basal-like and triple-negative breast cancers: searching for positives among many negatives. Surg Oncol Clin N Am. 2014;23(3):567-577.PubMedCentralCrossRefPubMed
4.
go back to reference Hudis CA, Gianni L. Triple-negative breast cancer: an unmet medical need. Oncologist. 2011;16 Suppl 1:1-11.CrossRefPubMed Hudis CA, Gianni L. Triple-negative breast cancer: an unmet medical need. Oncologist. 2011;16 Suppl 1:1-11.CrossRefPubMed
5.
go back to reference Lehmann BD, Bauer JA, Chen X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121(7):2750–67.PubMedCentralCrossRefPubMed Lehmann BD, Bauer JA, Chen X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121(7):2750–67.PubMedCentralCrossRefPubMed
7.
go back to reference Masuda H, Baggerly KA, Wang Y, et al. Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes. Clin Cancer Res. 2013;19(19):5533-5540.CrossRefPubMed Masuda H, Baggerly KA, Wang Y, et al. Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes. Clin Cancer Res. 2013;19(19):5533-5540.CrossRefPubMed
8.
go back to reference Shah PD, Gucalp A, Traina TA. The role of the androgen receptor in triple-negative breast cancer. Womens Health (Lond Engl). 2013;9(4):351-360.CrossRefPubMed Shah PD, Gucalp A, Traina TA. The role of the androgen receptor in triple-negative breast cancer. Womens Health (Lond Engl). 2013;9(4):351-360.CrossRefPubMed
9.
go back to reference McNamara KM, Yoda T, Takagi K, Miki Y, Suzuki T, Sasano H. Androgen receptor in triple negative breast cancer. J Steroid Biochem Mol Biol. 2013;133:66-76.CrossRefPubMed McNamara KM, Yoda T, Takagi K, Miki Y, Suzuki T, Sasano H. Androgen receptor in triple negative breast cancer. J Steroid Biochem Mol Biol. 2013;133:66-76.CrossRefPubMed
10.
go back to reference McGhan LJ, McCullough AE, Protheroe CA, et al. Androgen receptor-positive triple negative breast cancer: a unique breast cancer subtype. Ann Surg Oncol. 2014;21(2):361–7.CrossRefPubMed McGhan LJ, McCullough AE, Protheroe CA, et al. Androgen receptor-positive triple negative breast cancer: a unique breast cancer subtype. Ann Surg Oncol. 2014;21(2):361–7.CrossRefPubMed
11.
go back to reference Gucalp A, Tolaney S, Isakoff SJ, et al. Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic Breast Cancer. Clin Cancer Res. 2013;19(19):5505-5512.PubMedCentralCrossRefPubMed Gucalp A, Tolaney S, Isakoff SJ, et al. Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic Breast Cancer. Clin Cancer Res. 2013;19(19):5505-5512.PubMedCentralCrossRefPubMed
12.
go back to reference Gucalp A, Traina TA. Triple-negative breast cancer: role of the androgen receptor. Cancer J. 2010;16(1):62-65.CrossRefPubMed Gucalp A, Traina TA. Triple-negative breast cancer: role of the androgen receptor. Cancer J. 2010;16(1):62-65.CrossRefPubMed
13.
go back to reference Gucalp A, Traina TA. Triple-negative breast cancer: adjuvant therapeutic options. Chemother Res Pract. 2011;2011:696208.PubMedCentralPubMed Gucalp A, Traina TA. Triple-negative breast cancer: adjuvant therapeutic options. Chemother Res Pract. 2011;2011:696208.PubMedCentralPubMed
14.
go back to reference Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31(31):3997-4013.CrossRefPubMed Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31(31):3997-4013.CrossRefPubMed
15.
go back to reference Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28(16):2784-2795.PubMedCentralCrossRefPubMed Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28(16):2784-2795.PubMedCentralCrossRefPubMed
16.
go back to reference von Wahlde MK, Hulsewig C, Ruckert C, Götte M, Kiesel L, Bernemann C. The anti-androgen drug dutasteride renders triple negative breast cancer cells more sensitive to chemotherapy via inhibition of HIF-1alpha-/VEGF-signaling. Gynecol Endocrinol. 2015;31(2):160–4.CrossRef von Wahlde MK, Hulsewig C, Ruckert C, Götte M, Kiesel L, Bernemann C. The anti-androgen drug dutasteride renders triple negative breast cancer cells more sensitive to chemotherapy via inhibition of HIF-1alpha-/VEGF-signaling. Gynecol Endocrinol. 2015;31(2):160–4.CrossRef
17.
go back to reference Ginestier C, Hur MH, Charafe-Jauffret E, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1(5):555-567.PubMedCentralCrossRefPubMed Ginestier C, Hur MH, Charafe-Jauffret E, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1(5):555-567.PubMedCentralCrossRefPubMed
18.
go back to reference McNamara KM, Yoda T, Miki Y, et al. Androgenic pathway in triple negative invasive ductal tumors: its correlation with tumor cell proliferation. Cancer Sci. 2013;104(5):639-646.CrossRefPubMed McNamara KM, Yoda T, Miki Y, et al. Androgenic pathway in triple negative invasive ductal tumors: its correlation with tumor cell proliferation. Cancer Sci. 2013;104(5):639-646.CrossRefPubMed
19.
go back to reference Thike AA, Yong-Zheng Chong L, Cheok PY, et al. Loss of androgen receptor expression predicts early recurrence in triple-negative and basal-like breast cancer. Mod Pathol. 2014;27(3):352–60.PubMed Thike AA, Yong-Zheng Chong L, Cheok PY, et al. Loss of androgen receptor expression predicts early recurrence in triple-negative and basal-like breast cancer. Mod Pathol. 2014;27(3):352–60.PubMed
20.
go back to reference Stark A, Kleer CG, Martin I, et al. African ancestry and higher prevalence of triple-negative breast cancer: findings from an international study. Cancer. 2010;116(21):4926-4932.PubMedCentralCrossRefPubMed Stark A, Kleer CG, Martin I, et al. African ancestry and higher prevalence of triple-negative breast cancer: findings from an international study. Cancer. 2010;116(21):4926-4932.PubMedCentralCrossRefPubMed
21.
go back to reference Schwartz T, Stark A, Pang J, et al. Expression of aldehyde dehydrogenase 1 as a marker of mammary stem cells in benign and malignant breast lesions of Ghanaian women. Cancer. 2013;119(3):488-494.CrossRefPubMed Schwartz T, Stark A, Pang J, et al. Expression of aldehyde dehydrogenase 1 as a marker of mammary stem cells in benign and malignant breast lesions of Ghanaian women. Cancer. 2013;119(3):488-494.CrossRefPubMed
22.
go back to reference Vera-Badillo FE, Templeton AJ, de Gouveia P, et al. Androgen receptor expression and outcomes in early breast cancer: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106(1):djt319.CrossRef Vera-Badillo FE, Templeton AJ, de Gouveia P, et al. Androgen receptor expression and outcomes in early breast cancer: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106(1):djt319.CrossRef
Metadata
Title
Characterizing Breast Cancer in a Population with Increased Prevalence of Triple-Negative Breast Cancer: Androgen Receptor and ALDH1 Expression in Ghanaian Women
Authors
Erica Proctor, MD
Kelley M. Kidwell, PhD
Evelyn Jiagge, MBChB
Jessica Bensenhaver, MD
Baffour Awuah, MBChB
Kofi Gyan, DVM, MPH, MPA
Kathy Toy
Joseph Kwaku Oppong, MBChB
Ishmael Kyei, MBChB
Francis Aitpillah, MBChB
Ernest Osei-Bonsu, MBChB
Ernest Adjei, MBChB
Michael Ohene-Yeboah, MBChB
Robert Newman Brewer
Linda Ahenkorah Fondjo, PhD
Osei Owusu-Afriyie, MBChB
Max Wicha, MD
Sofia Merajver, MD, PhD
Celina Kleer, MD
Lisa Newman, MD, MPH, FACS, FASCO
Publication date
01-11-2015
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 12/2015
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-015-4455-x

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