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Erschienen in: Annals of Surgical Oncology 3/2015

01.12.2015 | Breast Oncology

Back to Basics: Traditional Nottingham Grade Mitotic Counts Alone are Significant in Predicting Survival in Invasive Breast Carcinoma

verfasst von: James M. Chang, MD, Ann E. McCullough, MD, Amylou C. Dueck, PhD, Heidi E. Kosiorek, MS, Idris T. Ocal, MD, Thomas K. Lidner, MD, Richard J. Gray, MD, Nabil Wasif, MD, MPH, Donald W. Northfelt, MD, Karen S. Anderson, MD, PhD, Barbara A. Pockaj, MD

Erschienen in: Annals of Surgical Oncology | Sonderheft 3/2015

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Abstract

Background

Newer multigene molecular profiling assays for breast carcinoma rely heavily on the quantification of genes of proliferation, whereas traditional histological grading reports the mitotic count. The mitotic activity of invasive breast carcinomas may be undervalued; therefore, an evaluation of the prognostic significance of mitotic score in predicting prognosis was performed.

Methods

Retrospective analysis of a single institutional cohort of newly diagnosed estrogen receptor positive (ER+), HER2 negative (HER2−) unilateral invasive breast carcinomas was performed. Mitotic scores from the 3-part Nottingham combined histological grade were compared with clinical parameters. Mitoses were counted on Olympus BX50 microscopes and assigned scores of 1–3 based on observed mitoses.

Results

A total of 1292 ER+, HER2− invasive breast carcinoma patients were identified, with a median follow-up time of 2.6 years (range 0–14 years). Higher mitotic score was significantly associated with younger age, larger tumor size, angiolymphatic invasion, node-positive disease, higher stage, and the use of hormonal and cytotoxic chemotherapy. Mitotic score was significant in modeling time to local/regional recurrence (p = 0.02), recurrence-free survival/RFS (p < 0.001), and overall survival/OS (p = 0.01) with higher mitotic scores associated with worse outcomes. Higher mitotic score correlated significantly with intermediate/high risk Oncotype Dx recurrence scores (p = 0.009).

Conclusions

First-generation molecular profiling assays for estrogen receptor positive invasive breast carcinomas derive much of their predictive power from quantifying genes of proliferation into a single score. Sometimes overlooked in the profusion of molecular data, the time-tested, mitotic count in the Nottingham combined histological grade is a good single-parameter predictor of survival.
Literatur
1.
Zurück zum Zitat Bloom HJ, Richardson WW. Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer. 1957;11:359–77.PubMedPubMedCentralCrossRef Bloom HJ, Richardson WW. Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer. 1957;11:359–77.PubMedPubMedCentralCrossRef
2.
Zurück zum Zitat Elston CW, Ellis IO. 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. 1991;19:403–10.PubMedCrossRef Elston CW, Ellis IO. 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. 1991;19:403–10.PubMedCrossRef
3.
Zurück zum Zitat Elston CW. The assessment of histological differentiation in breast cancer. Aust N Z J Surg. 1984;54:11–5.PubMedCrossRef Elston CW. The assessment of histological differentiation in breast cancer. Aust N Z J Surg. 1984;54:11–5.PubMedCrossRef
4.
Zurück zum Zitat Pereira H, Pinder SE, Sibbering DM, et al. Pathological prognostic factors in breast cancer. IV: should you be a typer or a grader? A comparative study of two histological prognostic features in operable breast carcinoma. Histopathology. 1995;27:219–26.PubMedCrossRef Pereira H, Pinder SE, Sibbering DM, et al. Pathological prognostic factors in breast cancer. IV: should you be a typer or a grader? A comparative study of two histological prognostic features in operable breast carcinoma. Histopathology. 1995;27:219–26.PubMedCrossRef
5.
Zurück zum Zitat Sundquist M, Thorstenson S, Brudin L, Nordenskjold B. Applying the Nottingham prognostic index to a Swedish breast cancer population. South East Swedish Breast Cancer Study Group. Breast Cancer Res Treat. 1999;53:1–8.PubMedCrossRef Sundquist M, Thorstenson S, Brudin L, Nordenskjold B. Applying the Nottingham prognostic index to a Swedish breast cancer population. South East Swedish Breast Cancer Study Group. Breast Cancer Res Treat. 1999;53:1–8.PubMedCrossRef
6.
Zurück zum Zitat Henson DE, Ries L, Freedman LS, Carriaga M. Relationship among outcome, stage of disease, and histologic grade for 22,616 cases of breast cancer. The basis for a prognostic index. Cancer. 1991;68:2142–9.PubMedCrossRef Henson DE, Ries L, Freedman LS, Carriaga M. Relationship among outcome, stage of disease, and histologic grade for 22,616 cases of breast cancer. The basis for a prognostic index. Cancer. 1991;68:2142–9.PubMedCrossRef
7.
Zurück zum Zitat Rakha EA, El-Sayed ME, Lee AH, et al. Prognostic significance of Nottingham histologic grade in invasive breast carcinoma. J Clin Oncol. 2008;26:3153–8.PubMedCrossRef Rakha EA, El-Sayed ME, Lee AH, et al. Prognostic significance of Nottingham histologic grade in invasive breast carcinoma. J Clin Oncol. 2008;26:3153–8.PubMedCrossRef
8.
Zurück zum Zitat Lundin J, Lundin M, Holli K, et al. Omission of histologic grading from clinical decision making may result in overuse of adjuvant therapies in breast cancer: results from a nationwide study. J Clin Oncol. 2001;19:28–36.PubMed Lundin J, Lundin M, Holli K, et al. Omission of histologic grading from clinical decision making may result in overuse of adjuvant therapies in breast cancer: results from a nationwide study. J Clin Oncol. 2001;19:28–36.PubMed
9.
Zurück zum Zitat Simpson JF, Gray R, Dressler LG, et al. Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the Eastern Cooperative Oncology Group Companion Study, EST 4189. J Clin Oncol. 2000;18:2059–69.PubMed Simpson JF, Gray R, Dressler LG, et al. Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the Eastern Cooperative Oncology Group Companion Study, EST 4189. J Clin Oncol. 2000;18:2059–69.PubMed
10.
Zurück zum Zitat World Health Organization Classification of Tumors. Pathology and genetics of tumours of the breast and female genital organs. Lyon: IARC Press; 2003. World Health Organization Classification of Tumors. Pathology and genetics of tumours of the breast and female genital organs. Lyon: IARC Press; 2003.
11.
Zurück zum Zitat Fitzgibbons PL, Page DL, Weaver D, et al. Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med. 2000;124:966–78.PubMed Fitzgibbons PL, Page DL, Weaver D, et al. Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med. 2000;124:966–78.PubMed
12.
Zurück zum Zitat Ellis I, Pinder S, Bobrow L, et al. Pathology reporting of breast disease. Sheffield, London: NHS Cancer Screening Programmes and The Royal College of Pathologists; 2005. Ellis I, Pinder S, Bobrow L, et al. Pathology reporting of breast disease. Sheffield, London: NHS Cancer Screening Programmes and The Royal College of Pathologists; 2005.
13.
Zurück zum Zitat Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24:3726–34.PubMedCrossRef Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24:3726–34.PubMedCrossRef
14.
Zurück zum Zitat van de Vijver MJ, He YD, van’t Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347:1999–2009.PubMedCrossRef van de Vijver MJ, He YD, van’t Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347:1999–2009.PubMedCrossRef
15.
Zurück zum Zitat Habel LA, Shak S, Jacobs MK, et al. A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients. Breast Cancer Res. 2006;8:R25.PubMedPubMedCentralCrossRef Habel LA, Shak S, Jacobs MK, et al. A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients. Breast Cancer Res. 2006;8:R25.PubMedPubMedCentralCrossRef
16.
Zurück zum Zitat van’t Veer LJ, Dai H, van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415:530–6.CrossRef van’t Veer LJ, Dai H, van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415:530–6.CrossRef
17.
Zurück zum Zitat Meyer JS, Alvarez C, Milikowski C, et al. Breast carcinoma malignancy grading by Bloom-Richardson system vs proliferation index: reproducibility of grade and advantages of proliferation index. Mod Pathol. 2005;18:1067–78.PubMedCrossRef Meyer JS, Alvarez C, Milikowski C, et al. Breast carcinoma malignancy grading by Bloom-Richardson system vs proliferation index: reproducibility of grade and advantages of proliferation index. Mod Pathol. 2005;18:1067–78.PubMedCrossRef
18.
Zurück zum Zitat Dalton LW, Page DL, Dupont WD. Histologic grading of breast carcinoma. A reproducibility study. Cancer. 1994;73:2765–70.PubMedCrossRef Dalton LW, Page DL, Dupont WD. Histologic grading of breast carcinoma. A reproducibility study. Cancer. 1994;73:2765–70.PubMedCrossRef
19.
Zurück zum Zitat Lakhani SR, Jacquemier J, Sloane JP, et al. Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. J Natl Cancer Inst. 1998;90:1138–45.PubMedCrossRef Lakhani SR, Jacquemier J, Sloane JP, et al. Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. J Natl Cancer Inst. 1998;90:1138–45.PubMedCrossRef
20.
21.
Zurück zum Zitat Mirza AN, Mirza NQ, Vlastos G, Singletary SE. Prognostic factors in node-negative breast cancer: a review of studies with sample size more than 200 and follow-up more than 5 years. Ann Surg. 2002;235:10–26.PubMedPubMedCentralCrossRef Mirza AN, Mirza NQ, Vlastos G, Singletary SE. Prognostic factors in node-negative breast cancer: a review of studies with sample size more than 200 and follow-up more than 5 years. Ann Surg. 2002;235:10–26.PubMedPubMedCentralCrossRef
22.
Zurück zum Zitat Mandard AM, Denoux Y, Herlin P, et al. Prognostic value of DNA cytometry in 281 premenopausal patients with lymph node negative breast carcinoma randomized in a control trial: multivariate analysis with Ki-67 index, mitotic count, and microvessel density. Cancer. 2000;89:1748–57.PubMedCrossRef Mandard AM, Denoux Y, Herlin P, et al. Prognostic value of DNA cytometry in 281 premenopausal patients with lymph node negative breast carcinoma randomized in a control trial: multivariate analysis with Ki-67 index, mitotic count, and microvessel density. Cancer. 2000;89:1748–57.PubMedCrossRef
23.
Zurück zum Zitat Volpi A, Bacci F, Paradiso A, et al. Prognostic relevance of histological grade and its components in node-negative breast cancer patients. Mod Pathol. 2004;17:1038–44.PubMedCrossRef Volpi A, Bacci F, Paradiso A, et al. Prognostic relevance of histological grade and its components in node-negative breast cancer patients. Mod Pathol. 2004;17:1038–44.PubMedCrossRef
24.
Zurück zum Zitat Thor AD, Liu S, Moore DH, 2nd, Edgerton SM. Comparison of mitotic index, in vitro bromodeoxyuridine labeling, and MIB-1 assays to quantitate proliferation in breast cancer. J Clin Oncol. 1999;17:470–7.PubMed Thor AD, Liu S, Moore DH, 2nd, Edgerton SM. Comparison of mitotic index, in vitro bromodeoxyuridine labeling, and MIB-1 assays to quantitate proliferation in breast cancer. J Clin Oncol. 1999;17:470–7.PubMed
25.
Zurück zum Zitat Lynch J, Pattekar R, Barnes DM, Hanby AM, Camplejohn RS, Ryder K, Gillett CE. Mitotic counts provide additional prognostic information in grade II mammary carcinoma. J Pathol. 2002;196:275–9.PubMedCrossRef Lynch J, Pattekar R, Barnes DM, Hanby AM, Camplejohn RS, Ryder K, Gillett CE. Mitotic counts provide additional prognostic information in grade II mammary carcinoma. J Pathol. 2002;196:275–9.PubMedCrossRef
26.
Zurück zum Zitat Medri L, Volpi A, Nanni O, et al. Prognostic relevance of mitotic activity in patients with node-negative breast cancer. Mod Pathol. 2003;16:1067–75.PubMedCrossRef Medri L, Volpi A, Nanni O, et al. Prognostic relevance of mitotic activity in patients with node-negative breast cancer. Mod Pathol. 2003;16:1067–75.PubMedCrossRef
27.
Zurück zum Zitat Baak JP, van Diest PJ, Voorhorst FJ, van der Wall E, Beex LV, Vermorken JB, Janssen EA. Prospective multicenter validation of the independent prognostic value of the mitotic activity index in lymph node-negative breast cancer patients younger than 55 years. J Clin Oncol. 2005;23:5993–6001.PubMedCrossRef Baak JP, van Diest PJ, Voorhorst FJ, van der Wall E, Beex LV, Vermorken JB, Janssen EA. Prospective multicenter validation of the independent prognostic value of the mitotic activity index in lymph node-negative breast cancer patients younger than 55 years. J Clin Oncol. 2005;23:5993–6001.PubMedCrossRef
28.
Zurück zum Zitat Lende TH, Janssen EA, Gudlaugsson E, et al. In patients younger than age 55 years with lymph node-negative breast cancer, proliferation by mitotic activity index is prognostically superior to adjuvant! J Clin Oncol. 2011;29:852–8.PubMedCrossRef Lende TH, Janssen EA, Gudlaugsson E, et al. In patients younger than age 55 years with lymph node-negative breast cancer, proliferation by mitotic activity index is prognostically superior to adjuvant! J Clin Oncol. 2011;29:852–8.PubMedCrossRef
29.
Zurück zum Zitat Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–26.PubMedCrossRef Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–26.PubMedCrossRef
30.
Zurück zum Zitat Allison KH, Kandalaft PL, Sitlani CM, Dintzis SM, Gown AM. Routine pathologic parameters can predict Oncotype Dx recurrence scores in subsets of ER positive patients: who does not always need testing? Breast Cancer Res Treat. 2012;131:413–24.PubMedCrossRef Allison KH, Kandalaft PL, Sitlani CM, Dintzis SM, Gown AM. Routine pathologic parameters can predict Oncotype Dx recurrence scores in subsets of ER positive patients: who does not always need testing? Breast Cancer Res Treat. 2012;131:413–24.PubMedCrossRef
31.
Zurück zum Zitat Mattes MD, Mann JM, Ashamalla H, Tejwani A. Routine histopathologic characteristics can predict Oncotype DX(TM) recurrence score in subsets of breast cancer patients. Cancer Invest. 2013;31:604–6.PubMedCrossRef Mattes MD, Mann JM, Ashamalla H, Tejwani A. Routine histopathologic characteristics can predict Oncotype DX(TM) recurrence score in subsets of breast cancer patients. Cancer Invest. 2013;31:604–6.PubMedCrossRef
32.
Zurück zum Zitat Klein ME, Dabbs DJ, Shuai Y, Brufsky AM, Jankowitz R, Puhalla SL, Bhargava R. Prediction of the Oncotype Dx recurrence score: use of pathology-generated equations derived by linear regression analysis. Mod Pathol. 2013;26:658–64.PubMedPubMedCentralCrossRef Klein ME, Dabbs DJ, Shuai Y, Brufsky AM, Jankowitz R, Puhalla SL, Bhargava R. Prediction of the Oncotype Dx recurrence score: use of pathology-generated equations derived by linear regression analysis. Mod Pathol. 2013;26:658–64.PubMedPubMedCentralCrossRef
33.
Zurück zum Zitat Auerbach J, Kim M, Fineberg S. Can features evaluated in the routine pathologic assessment of lymph node-negative estrogen receptor-positive stage I or II invasive breast cancer be used to predict the Oncotype Dx recurrence score? Arch Pathol Lab Med. 2010;134:1697–701.PubMed Auerbach J, Kim M, Fineberg S. Can features evaluated in the routine pathologic assessment of lymph node-negative estrogen receptor-positive stage I or II invasive breast cancer be used to predict the Oncotype Dx recurrence score? Arch Pathol Lab Med. 2010;134:1697–701.PubMed
34.
Zurück zum Zitat Zbytek B, Cohen C, Wang J, Page A, Williams DJ, Adams AL. Nottingham-defined mitotic score: comparison with visual and image cytometric phosphohistone H3 labeling indices and correlation with Oncotype Dx recurrence score. Appl Immunohistochem Mol Morphol. 2013;21:48–53.PubMed Zbytek B, Cohen C, Wang J, Page A, Williams DJ, Adams AL. Nottingham-defined mitotic score: comparison with visual and image cytometric phosphohistone H3 labeling indices and correlation with Oncotype Dx recurrence score. Appl Immunohistochem Mol Morphol. 2013;21:48–53.PubMed
Metadaten
Titel
Back to Basics: Traditional Nottingham Grade Mitotic Counts Alone are Significant in Predicting Survival in Invasive Breast Carcinoma
verfasst von
James M. Chang, MD
Ann E. McCullough, MD
Amylou C. Dueck, PhD
Heidi E. Kosiorek, MS
Idris T. Ocal, MD
Thomas K. Lidner, MD
Richard J. Gray, MD
Nabil Wasif, MD, MPH
Donald W. Northfelt, MD
Karen S. Anderson, MD, PhD
Barbara A. Pockaj, MD
Publikationsdatum
01.12.2015
Verlag
Springer US
Erschienen in
Annals of Surgical Oncology / Ausgabe Sonderheft 3/2015
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-015-4616-y

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