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01-06-2014 | Preclinical study

Two histopathologically different diseases: hormone receptor-positive and hormone receptor-negative tumors in HER2-positive breast cancer

Authors: Hee Jin Lee, In Ah Park, So Yeon Park, An Na Seo, Bora Lim, Yun Chai, In Hye Song, Na Eun Kim, Joo Young Kim, Jong Han Yu, Jin-Hee Ahn, Gyungyub Gong

Published in: Breast Cancer Research and Treatment | Issue 3/2014

Abstract

The clinical behavior of human epidermal growth factor 2 (HER2)-positive breast cancer, including pathologic complete response rate and pattern of relapse and metastasis, differs substantially according to hormone receptor (HR) status. We investigated various histopathologic features of HER2-positive breast cancer and their correlation with HR status. We retrospectively analyzed tumors of 450 HER2-positive breast cancer patients treated with chemotherapy and 1 year of trastuzumab. HR−/HER2+ tumors showed higher nuclear grade, less tubule formation, higher histologic grade, frequent apocrine features, diffuse and abundant lymphocytic infiltration, strong HER2 immunohistochemical staining (3+), higher average HER2 copy number and HER2/CEP17 ratio, the absence of HER2 genetic heterogeneity, and greater p53 expression than HR+/HER2+ tumors. An inverse correlation was observed between estrogen receptor or progesterone receptor Allred score and average HER2 copy number or HER2/CEP17 ratio. The percentage of ductal carcinoma in situ (DCIS) within the tumor was negatively correlated with ER Allred score, but positively correlated with average HER2 copy number and HER2/CEP17 ratio. Pathologic tumor size and DCIS percentage also showed a significant inverse correlation. Ratio of metastatic to total examined lymph node number was significantly correlated with average HER2 copy number and HER2/CEP17 ratio. High pT stage (hazard ratio, 2.370; p = 0.027), the presence of lymphovascular invasion (hazard ratio, 2.806; p = 0.005), and HR negativity (hazard ratio, 2.202; 1.074–4.513; p = 0.031) were found to be independent prognostic indicators of poor disease-free survival. In conclusion, HR+/HER2+ and HR−/HER2+ breast cancer showed distinct histopathologic features that may be relevant to their distinct clinical behavior.

Perou CM, Sorlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752PubMedCrossRef

Cancer Genome Atlas N (2012) Comprehensive molecular portraits of human breast tumours. Nature 490:61–70CrossRef

Harvey JM, Clark GM, Osborne CK, Allred DC (1999) Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 17:1474–1481PubMed

Morrow M (2013) Personalizing extent of breast cancer surgery according to molecular subtypes. Breast 22(Suppl 2):S106–S109PubMedCrossRef

Park YH, Lee S, Cho EY et al (2010) Patterns of relapse and metastatic spread in HER2-overexpressing breast cancer according to estrogen receptor status. Cancer Chemother Pharmacol 66:507–516PubMedCrossRef

Sihto H, Lundin J, Lundin M et al (2011) Breast cancer biological subtypes and protein expression predict for the preferential distant metastasis sites: a nationwide cohort study. Breast Cancer Res 13:R87–R97PubMedCentralPubMedCrossRef

Konecny G, Pauletti G, Pegram M et al (2003) Quantitative association between HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer. J Natl Cancer Inst 95:142–153PubMedCrossRef

Hammond ME, Hayes DF, Wolff AC, Mangu PB, Temin S (2010) American society of clinical oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Oncol Pract 6:195–197PubMedCentralPubMedCrossRef

Wolff AC, Hammond ME, Hicks DG et al (2013) 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. Arch Pathol Lab Med 138(2):241–256. doi:10.5858/arpa.2013-0953-SA PubMedCrossRef

10.

Seol H, Lee HJ, Choi Y et al (2012) Intratumoral heterogeneity of HER2 gene amplification in breast cancer: its clinicopathological significance. Mod Pathol 25:938–948PubMedCrossRef

11.

Pekar G, Hofmeyer S, Tabar L et al (2013) Multifocal breast cancer documented in large-format histology sections: long-term follow-up results by molecular phenotypes. Cancer 119:1132–1139PubMedCrossRef

12.

Lakhani SR, Eliis IO, Schnitt SJ, Tan PH, van de Vijver MJ (eds) (2012) WHO classification of tumours of the breast, 4th edn. International Agency for Research on Cancer, Lyon

13.

Bhargava R, Beriwal S, Striebel JM, Dabbs DJ (2010) Breast cancer molecular class ERBB2: preponderance of tumors with apocrine differentiation and expression of basal phenotype markers CK5, CK5/6, and EGFR. Appl Immunohistochem Mol Morphol 18:113–118PubMedCrossRef

14.

Nitta H, Hauss-Wegrzyniak B, Lehrkamp M et al (2008) Development of automated brightfield double in situ hybridization (BDISH) application for HER2 gene and chromosome 17 centromere (CEN 17) for breast carcinomas and an assay performance comparison to manual dual color HER2 fluorescence in situ hybridization (FISH). Diagn Pathol 3:41PubMedCentralPubMedCrossRef

15.

Ma Y, Lespagnard L, Durbecq V et al (2005) Polysomy 17 in HER-2/neu status elaboration in breast cancer: effect on daily practice. Clin Cancer Res 11:4393–4399PubMedCrossRef

16.

Vance GH, Barry TS, Bloom KJ et al (2009) Genetic heterogeneity in HER2 testing in breast cancer: panel summary and guidelines. Arch Pathol Lab Med 133:611–612PubMed

17.

Lewis JT, Ketterling RP, Halling KC et al (2005) Analysis of intratumoral heterogeneity and amplification status in breast carcinomas with equivocal (2+) HER-2 immunostaining. Am J Clin Pathol 124:273–281PubMedCrossRef

18.

Striebel JM, Bhargava R, Horbinski C, Surti U, Dabbs DJ (2008) The equivocally amplified HER2 FISH result on breast core biopsy: indications for further sampling do affect patient management. Am J Clin Pathol 129:383–390PubMedCrossRef

19.

Brunelli M, Manfrin E, Martignoni G et al (2009) Genotypic intratumoral heterogeneity in breast carcinoma with HER2/neu amplification: evaluation according to ASCO/CAP criteria. Am J Clin Pathol 131:678–682PubMedCrossRef

20.

Paik S, Kim C, Wolmark N (2008) HER2 status and benefit from adjuvant trastuzumab in breast cancer. N Engl J Med 358:1409–1411PubMedCrossRef

21.

Dowsett M, Procter M, McCaskill-Stevens W et al (2009) Disease-free survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the HERA Trial. J Clin Oncol 27:2962–2969PubMedCentralPubMedCrossRef

22.

Wiechmann L, Sampson M, Stempel M et al (2009) Presenting features of breast cancer differ by molecular subtype. Ann Surg Oncol 16:2705–2710PubMedCrossRef

23.

Viani GA, Afonso SL, Stefano EJ, De Fendi LI, Soares FV (2007) Adjuvant trastuzumab in the treatment of her-2-positive early breast cancer: a meta-analysis of published randomized trials. BMC Cancer 7:153PubMedCentralPubMedCrossRef

24.

Yamashita H, Nishio M, Toyama T et al (2004) Coexistence of HER2 over-expression and p53 protein accumulation is a strong prognostic molecular marker in breast cancer. Breast Cancer Res 6:R24–R30PubMedCentralPubMedCrossRef

25.

Sek P, Zawrocki A, Biernat W, Piekarski JH (2010) HER2 molecular subtype is a dominant subtype of mammary Paget’s cells. An immunohistochemical study. Histopathology 57:564–571PubMedCrossRef

26.

Denkert C, Loibl S, Noske A et al (2010) Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol 28:105–113PubMedCrossRef

27.

Mahmoud SM, Paish EC, Powe DG et al (2011) Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol 29:1949–1955PubMedCrossRef

28.

Loi S, Sirtaine N, Piette F et al (2013) Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98. J Clin Oncol 31:860–867PubMedCrossRef

29.

Seo AN, Lee HJ, Kim EJ et al (2013) Tumour-infiltrating CD8+ lymphocytes as an independent predictive factor for pathological complete response to primary systemic therapy in breast cancer. Br J Cancer 109:2705–2713PubMedCrossRef

30.

Lee HJ, Seo JY, Ahn JH, Ahn SH, Gong G (2013) Tumor-associated lymphocytes predict response to neoadjuvant chemotherapy in breast cancer patients. J Breast Cancer 16:32–39PubMedCentralPubMedCrossRef

Title: Two histopathologically different diseases: hormone receptor-positive and hormone receptor-negative tumors in HER2-positive breast cancer
Authors: Hee Jin Lee
In Ah Park
So Yeon Park
An Na Seo
Bora Lim
Yun Chai
In Hye Song
Na Eun Kim
Joo Young Kim
Jong Han Yu
Jin-Hee Ahn
Gyungyub Gong
Publication date: 01-06-2014
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2014
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-014-2983-x

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