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01-05-2020 | Cytostatic Therapy | Preclinical study

Mitotic score and pleomorphic histology in invasive lobular carcinoma of the breast: impact on disease-free survival

Authors: Rita A. Mukhtar, Gregor Krings, Yunn-Yi Chen, Matina E. Mamounas, Kelly Fahrner-Scott, Jasmine Wong, Michael Alvarado, Cheryl Ewing, Laura J. Esserman, Hope Rugo

Published in: Breast Cancer Research and Treatment | Issue 1/2020

Abstract

Purpose

Pleomorphic invasive lobular carcinoma (ILC) has long been thought to have worse outcomes than classic ILC and is therefore often treated with chemotherapy. However, recent data question the utility of the pleomorphic designation, as the poor outcomes seen may be related to other associated high-risk features. Importantly, mitotic count may better define a subset of ILC with high risk of recurrence. We sought to determine the impact of pleomorphic histology versus mitotic count on disease-free survival (DFS) in pure ILC. Additionally, we evaluated whether pleomorphic histology was associated with receipt of chemotherapy when adjusting for other factors.

Methods

We analyzed a cohort of 475 patients with stage I–III pure ILC. We used Kaplan–Meier estimates, and Cox proportional hazards and logistic regression for multivariate analyses. Pleomorphic histology was confirmed by central pathology review.

Results

In a multivariate model, pleomorphic histology was not associated with reduced DFS. Only mitotic score, receptor subtype, and pathologic stage were independently and significantly associated with DFS. Patients with pleomorphic ILC were significantly more likely to receive chemotherapy than patients with classic ILC (adjusted odds ratio 2.96, p = 0.026).

Conclusions

The pleomorphic designation in ILC does not have clinical utility and should not be used to determine therapy. Rather, mitotic count identified clear prognostic groups in this cohort of pure ILC.

Felts JL, Zhu J, Han B, Smith SJ, Truica CI (2017) An analysis of oncotype DX recurrence scores and clinicopathologic characteristics in invasive lobular breast cancer. Breast J. https://doi.org/10.1111/tbj.12751 CrossRefPubMed

Wenzel J, Zeisig R, Haider W, Habedank S, Fichtner I (2010) Inhibition of pulmonary metastasis in a human MT3 breast cancer xenograft model by dual liposomes preventing intravasal fibrin clot formation. Breast Cancer Res Treat 121(1):13–22. https://doi.org/10.1007/s10549-009-0448-4 CrossRefPubMed

Lips EH, Mukhtar RA, Yau C, de Ronde JJ, Livasy C, Carey LA, Loo CE, Vrancken-Peeters MJ, Sonke GS, Berry DA, Van't Veer LJ, Esserman LJ, Wesseling J, Rodenhuis S, Shelley Hwang E, Investigators IST (2012) Lobular histology and response to neoadjuvant chemotherapy in invasive breast cancer. Breast Cancer Res Treat 136(1):35–43. https://doi.org/10.1007/s10549-012-2233-z CrossRefPubMedPubMedCentral

Loibl S, Volz C, Mau C, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, Gerber B, Hanusch C, Jackisch C, Kummel S, Huober J, Denkert C, Hilfrich J, Konecny GE, Fett W, Stickeler E, Harbeck N, Mehta KM, Nekljudova V, von Minckwitz G, Untch M (2014) Response and prognosis after neoadjuvant chemotherapy in 1,051 patients with infiltrating lobular breast carcinoma. Breast Cancer Res Treat 144(1):153–162. https://doi.org/10.1007/s10549-014-2861-6 CrossRefPubMed

Stein RG, Wollschlager D, Kreienberg R, Janni W, Wischnewsky M, Diessner J, Stuber T, Bartmann C, Krockenberger M, Wischhusen J, Wockel A, Blettner M, Schwentner L, Group BS (2016) The impact of breast cancer biological subtyping on tumor size assessment by ultrasound and mammography—a retrospective multicenter cohort study of 6543 primary breast cancer patients. BMC Cancer 16:459. https://doi.org/10.1186/s12885-016-2426-7 CrossRefPubMedPubMedCentral

Wanis ML, Wong JA, Rodriguez S, Wong JM, Jabo B, Ashok A, Lum SS, Solomon NL, Reeves ME, Garberoglio CA, Senthil M (2013) Rate of re-excision after breast-conserving surgery for invasive lobular carcinoma. Am Surg 79(10):1119–1122PubMed

Weidner N, Semple JP (1992) Pleomorphic variant of invasive lobular carcinoma of the breast. Hum Pathol 23(10):1167–1171CrossRef

Al-Baimani K, Bazzarelli A, Clemons M, Robertson SJ, Addison C, Arnaout A (2015) Invasive pleomorphic lobular carcinoma of the breast: pathologic, clinical, and therapeutic considerations. Clin Breast Cancer 15(6):421–425. https://doi.org/10.1016/j.clbc.2015.06.010 CrossRefPubMed

Middleton LP, Palacios DM, Bryant BR, Krebs P, Otis CN, Merino MJ (2000) Pleomorphic lobular carcinoma: morphology, immunohistochemistry, and molecular analysis. Am J Surg Pathol 24(12):1650–1656CrossRef

10.

Narendra S, Jenkins SM, Khoor A, Nassar A (2015) Clinical outcome in pleomorphic lobular carcinoma: a case-control study with comparison to classic invasive lobular carcinoma. Ann Diagn Pathol 19(2):64–69. https://doi.org/10.1016/j.anndiagpath.2015.01.005 CrossRefPubMedPubMedCentral

11.

Rakha EA, van Deurzen CH, Paish EC, Macmillan RD, Ellis IO, Lee AH (2013) Pleomorphic lobular carcinoma of the breast: is it a prognostically significant pathological subtype independent of histological grade? Mod Pathol 26(4):496–501. https://doi.org/10.1038/modpathol.2012.197 CrossRefPubMed

12.

Elston CW, Ellis IO (1991) Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19(5):403–410CrossRef

13.

McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM, Statistics Subcommittee of the NCIEWGoCD (2005) REporting recommendations for tumour MARKer prognostic studies (REMARK). Br J Cancer 93(4):387–391. https://doi.org/10.1038/sj.bjc.6602678 CrossRefPubMedPubMedCentral

14.

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

15.

Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC, American Society of Clinical O, College of American P (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med 134(7):e48–72. https://doi.org/10.1043/1543-2165-134.7.e48 CrossRefPubMed

16.

Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF, American Society of Clinical O, College of American P (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. J Clin Oncol 31(31):3997–4013. https://doi.org/10.1200/JCO.2013.50.9984 CrossRef

17.

Dixon JM, Anderson TJ, Page DL, Lee D, Duffy SW (1982) Infiltrating lobular carcinoma of the breast. Histopathology 6(2):149–161CrossRef

18.

Abdelkader A, Jorns JM (2018) Pleomorphic lobular carcinoma: a controversially aggressive variant of invasive lobular carcinoma of the breast. Int J Surg Pathol 26(5):434–436. https://doi.org/10.1177/1066896917744878 CrossRefPubMed

19.

Reis-Filho JS, Simpson PT, Jones C, Steele D, Mackay A, Iravani M, Fenwick K, Valgeirsson H, Lambros M, Ashworth A, Palacios J, Schmitt F, Lakhani SR (2005) Pleomorphic lobular carcinoma of the breast: role of comprehensive molecular pathology in characterization of an entity. J Pathol 207(1):1–13. https://doi.org/10.1002/path.1806 CrossRefPubMed

20.

Simpson PT, Reis-Filho JS, Lambros MB, Jones C, Steele D, Mackay A, Iravani M, Fenwick K, Dexter T, Jones A, Reid L, Da Silva L, Shin SJ, Hardisson D, Ashworth A, Schmitt FC, Palacios J, Lakhani SR (2008) Molecular profiling pleomorphic lobular carcinomas of the breast: evidence for a common molecular genetic pathway with classic lobular carcinomas. J Pathol 215(3):231–244. https://doi.org/10.1002/path.2358 CrossRefPubMed

21.

Zhu S, Ward BM, Yu J, Matthew-Onabanjo AN, Janusis J, Hsieh CC, Tomaszewicz K, Hutchinson L, Zhu LJ, Kandil D, Shaw LM (2018) IRS2 mutations linked to invasion in pleomorphic invasive lobular carcinoma. JCI Insight. https://doi.org/10.1172/jci.insight.97398 CrossRefPubMedPubMedCentral

22.

Eusebi V, Magalhaes F, Azzopardi JG (1992) Pleomorphic lobular carcinoma of the breast: an aggressive tumor showing apocrine differentiation. Hum Pathol 23(6):655–662CrossRef

23.

Buchanan CL, Flynn LW, Murray MP, Darvishian F, Cranor ML, Fey JV, King TA, Tan LK, Sclafani LM (2008) Is pleomorphic lobular carcinoma really a distinct clinical entity? J Surg Oncol 98(5):314–317. https://doi.org/10.1002/jso.21121 CrossRefPubMed

24.

Ohashi R, Matsubara M, Watarai Y, Yanagihara K, Yamashita K, Tsuchiya SI, Takei H, Naito Z (2017) Pleomorphic lobular carcinoma of the breast: a comparison of cytopathological features with other lobular carcinoma variants. Cytopathology 28(2):122–130. https://doi.org/10.1111/cyt.12362 CrossRefPubMed

25.

Yang LP, Sun HF, Zhao Y, Chen MT, Zhang N, Jin W (2017) Clinicopathological characteristics and survival outcomes in pleomorphic lobular breast carcinoma of the breast: a SEER population-based study. Cancer Med 6(12):2867–2875. https://doi.org/10.1002/cam4.1244 CrossRefPubMedPubMedCentral

26.

Groenendijk FH, Jager A, Cardoso F, van Deurzen CHM (2018) A nationwide registry-based cohort study of the MammaPrint genomic risk classifier in invasive breast cancer. Breast 38:125–131. https://doi.org/10.1016/j.breast.2017.12.015 CrossRefPubMed

Title: Mitotic score and pleomorphic histology in invasive lobular carcinoma of the breast: impact on disease-free survival
Authors: Rita A. Mukhtar
Gregor Krings
Yunn-Yi Chen
Matina E. Mamounas
Kelly Fahrner-Scott
Jasmine Wong
Michael Alvarado
Cheryl Ewing
Laura J. Esserman
Hope Rugo
Publication date: 01-05-2020
Publisher: Springer US
Keyword: Cytostatic Therapy
Published in: Breast Cancer Research and Treatment / Issue 1/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-020-05606-5

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