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Feasibility of obtaining breast epithelial cells from healthy women for studies of cellular proliferation

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Abstract

Increased dietary fat intake and rate of breastepithelial cell proliferation have each been associated withthe development of breast cancer. The goal ofthis study was to measure the effect ofa low fat, high carbohydrate diet on therate of breast epithelial cell proliferation in womenat high risk for breast cancer. Women wererecruited from the intervention and control groups ofa randomized low fat dietary intervention trial, breastepithelial cells were obtained by fine needle aspiration,and cell proliferation was assessed in these samplesusing immunofluorescent detection of Ki-67 and PCNA. Theeffects of needle size and study group oncell yield and cytologic features of the cellswere also examined. Fifty three women (20 inthe intervention group and 33 in the controlgroup) underwent the biopsy procedure. Slides from 38subjects were stained for Ki-67 and from 14subjects for PCNA. No cell proliferation (fluorescence) wasdetected for either Ki-67 or PCNA in anyof the slides. Epithelial cell yield and numberof stromal fragments were greater with a largerneedle size. Numbers of stromal fragments and bipolarnaked nuclei were greater in the low fatas compared to the control group but nodifferences in epithelial cell yield were observed betweenthe two groups. This study confirms that fineneedle aspiration biopsy is a feasible method ofobtaining epithelial cells from women without discrete breastmasses, but suggests that cell proliferation cannot beassessed using Ki-67 and PCNA in such samples.

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References

  1. Welsch CW: Interrelationships between dietary fat and endocrine processes in mammary gland tumorigenesis. In: Ip C, Birt DF, Rogers AE, Mettlin C (eds) Dietary Fat and Cancer. Progress in Clinical and Biological Research. Vol. 222, 1986, pp 623–654

  2. Rogers AE, Lee SY: Chemically induced mammary gland tumors in rats: modulation by dietary fat. In: Ip C, Birt DF, Rogers AE, Mettlin C (eds) Dietary Fat and Cancer. Progress in Clinical and Biological Research. Vol. 222, 1986, pp 255–282

  3. Prentice RL, Kakar F, Hursting S, Sheppard L, Klein R, Kushi LH: Aspects of the rationale for the Women's Health Trial. J Natl Cancer Inst 80: 802–814, 1988

    Google Scholar 

  4. Boyd NF, Martin LJ, Noffel M, Lockwood GA, Tritchler DL: A meta-analysis of studies of dietary fat and breast cancer risk. Br J Cancer 68: 627–636, 1993

    Google Scholar 

  5. Hunter DJ, Spiegelman D, Adami HO, Beeson L, van den Brandt PA, Folsom AR, Fraser GE, Goldbohm A, Graham S, Howe GR, Kushi LH, Marshall JR, McDermott A, Miller AB, Speizer FE, Wolk A, Yaun SS, Willett W: Cohort studies of fat intake and the risk of breast cancer — a pooled analysis. N Engl J Med 334: 356–361, 1996

    Google Scholar 

  6. Wellings SR, Jensen HM, Marcum RG: An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions. J Nat Cancer Inst 55: 231–273, 1975

    Google Scholar 

  7. Jensen HM: Breast pathology, emphasizing precancerous and cancer-associated lesions. Commentaries on Research in Breast Disease 2: 41–86, 1981

    Google Scholar 

  8. Dupont WD, Page DL: Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med 312: 146–151, 1985

    Google Scholar 

  9. Dupont WD, Page DL: Breast cancer risk associated with proliferative disease, age at first birth, and a family history of breast cancer. Am J Epidemiol 125: 769–779, 1987

    Google Scholar 

  10. Goodwin PJ, Boyd NF: Mammographic parenchymal pattern and breast cancer risk: A critical appraisal of the evidence. Am J Epidemiol 127: 1097–1108, 1988

    Google Scholar 

  11. Oza AM, Boyd NF: Mammographic parenchymal patterns: A marker of breast cancer risk. Epidemiol Rev 15: 196–208, 1993

    Google Scholar 

  12. Boyd NF, Byng JW, Jong RA, Fishell EK, Little LE, Miller AB, Lockwood GA, Tritchler DL, Yaffe MJ: Quantitative classification of mammographic densities and breast cancer risk: Results from the Canadian National Breast Screening Study. J Natl Cancer Inst 87: 670–675, 1995

    Google Scholar 

  13. Urbanski S, Jensen HM, Cooke G, McFarlane D, Shannon P, Kruikov V, Boyd NF: The association of histological and radiological indicators of breast cancer risk. Br J Cancer 58: 474–479, 1988

    Google Scholar 

  14. Boyd NF, Jensen H, Cooke G, Lee Han HW: Relationship between mammographic and histological risk factors for breast cancer. J Natl Cancer Inst 84: 1170–1179, 1992

    Google Scholar 

  15. Welsch CW, DeHoog JV, O'Conner DH, Sheffield LG: Influence of dietary fat levels on development and hormone responsiveness of the mouse mammary gland. Cancer Res 45: 6147–6154, 1985

    Google Scholar 

  16. Zhang L, Bird RP, Bruce WR: Proliferative activity of murine mammary epithelium as affected by dietary fat and calcium. Cancer Res 47: 4905–4908, 1987

    Google Scholar 

  17. Hislop TG, Band PR, Deschamps M, NG V, Coldman AJ, Worth AJ, Labo T: Diet and histologic types of benign breast disease defined by subsequent risk of breast cancer. Am J Clin Nutr 131: 263–270, 1990

    Google Scholar 

  18. Lubin F, Was Y, Ron E, Black M, Chetrit A, Rosen N, Alfandary E, Modan B: Nutritional factors associated with benign breast disease etiology: a case-control study. Am J Clin Nutr 50:551–556, 1989

    Google Scholar 

  19. Rohan TE, Cook MG, Potter JD, McMichael AJ: A case-control study of diet and benign proliferative epithelial disorders of the breast. Cancer Res 50: 3176–3181, 1990

    Google Scholar 

  20. Boyd NF, Cousins M, Lockwood G, Tritchler D: Dietary fat and breast cancer risk: the feasibility of a clinical trial of breast cancer prevention. Lipids 27: 821–826, 1992

    Google Scholar 

  21. Boyd NF, Fishell E, Jong R, MacDonald JC, Sparrow RK, Simor IS, Kriukov V, Lockwood G, Tritchler D: Mammographic densities as a criterion for entry to a clinical trial of breast cancer prevention. Br J Cancer 72: 476–479, 1995

    Google Scholar 

  22. Gerdes J, Lemke H, Wacker HH, Schwab J, Stein H: Cell cycle analysis of a cell proliferation associated human nuclear antigen defined by the monoclonal antibody Ki67. J Immunol 133: 1710–1715, 1984

    Google Scholar 

  23. Miyachi K, Fritzler MJ, Tan EM: Autoantibody to a nuclear antigen in proliferating cells. J Immunol 121: 2228–2234, 1978

    Google Scholar 

  24. Santisteban MS, Brugal G: Image analysis of in situ cell cycle related changes of PCNA and Ki-67 proliferating antigen expression. Cell Proliferation 27: 435–453, 1994

    Google Scholar 

  25. Ward JH, Marshall CJ, Berry Schumann G, Hogle H, Cannon-Albright LA, Mcwhorter WP, Eyre HJ, Skolnick MH: Detection of proliferative breast disease by four-quadrant, fine-needle aspiration. J Natl Cancer Inst 82: 964–966, 1990

    Google Scholar 

  26. Marshall CJ, Schumann GB, Ward JH, Riding JM, Cannon-Albright L, Skolnick M: Cytologic identification of clinically occult proliferative breast disease in women with a family history of breast cancer. Am J Clin Pathol 95: 157–165, 1991

    Google Scholar 

  27. Fabian CJ, Zalles C, Kamel S, McKittrick R, Moore WP, Zeiger S, Simon C, Kimler B, Cramer A, Garcia F, Jewell W: Biomarker and cytologic abnormalities in women at high and low risk for breast cancer. J Cell Biochem 17G: 153–160, 1993

    Google Scholar 

  28. Walker RA, Camplejohn RS: Comparison of monoclonal antibody Ki-67 reactivity with grade and DNA flow cytometry of breast carcinomas. Br J Cancer 57: 281, 1988

    Google Scholar 

  29. Gerdes J, Lelle RJ, Pickartz H, Heidenreich W, Schwarting R, Kurtsiefer L, Stauch G, Stein H: Growth fractions in breast cancers determined in situ with monoclonal antibody Ki-67. J Clin Pathol 39: 977–980, 1986

    Google Scholar 

  30. Marchetti E, Querzoli P, Marzola A, Bagni A, Ferretti S, Fabris G, Nenci I: Assessment of proliferative rate of breast cancer by Ki-67 monoclonal antibody. Modern Pathology 3: 31–35, 1990

    Google Scholar 

  31. Pavelic ZP, Pavelic L, Lower EE, Gapany M, Gapany S, Barker EA, Preisler HD: c-myc, c-erb-2, and Ki-67 expression in normal breast tissue and in invasive and noninvasive breast carcinoma. Cancer Res 52: 2597–2602, 1992

    Google Scholar 

  32. Shrestha P, Yamada K, Wada T, Maeda S, Watatani M, Yasutomi M, Takagi H, Mori M: Proliferating cell nuclear antigen in breast lesions: correlation of c-erbB-2 oncoprotein and EGF receptor and its clinicopathological significance in breast cancer. Virchows Arch 421: 193–202, 1992

    Google Scholar 

  33. Pelosi G, Bresaola E, Rodella S, Manfrin E, Piubello Q, Shiavon I, Iannucci A: Expression of proliferating cell nuclear antigen, Ki-67 antigen, estrogen receptor protein, and tumor suppressor p53 gene in cytologic samples of breast cancer: an immunochemical study with clinical, pathobiological, and histologic correlations. Diag Cytopathol 11: 131–140, 1994

    Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, Women's College Hospital, Toronto, Canada

    Naomi A. Miller

  2. Department of Pathology, Interface Cytometry Laboratory, Ontario Cancer Institute, Toronto, Canada

    Michael Thomas & David W. Hedley

  3. Division of Epidemiology and Statistics, Ontario Cancer Institute, Toronto, Canada

    Lisa J. Martin, Stefany Michal & Norman F. Boyd

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  1. Naomi A. Miller
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  2. Michael Thomas
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  6. Norman F. Boyd
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Miller, N.A., Thomas, M., Martin, L.J. et al. Feasibility of obtaining breast epithelial cells from healthy women for studies of cellular proliferation. Breast Cancer Res Treat 43, 201–210 (1997). https://doi.org/10.1023/A:1005784628237

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