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Atypical Lobular Hyperplasia
Lauren Q. Chang Sen, MDMarion E. Scoggins, MD
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KEY FACTS

  • Terminology

    • Imaging

      • Top Differential Diagnoses

        • Pathology

          • Clinical Issues

            TERMINOLOGY

            • Definitions

              • Lobular (intraepithelial) neoplasia (LN/LIN): Monomorphic dyshesive cells with ↑ nuclear:cytoplasmic ratio, commonly intracytoplasmic vacuoles, fill and distend acini, encompassing spectrum from ALH to LCIS
              • Atypical lobular hyperplasia (ALH): Monomorphic dyshesive cells fill < 50% of acini; overall lobule not distended
              • Lobular carcinoma in situ (LCIS): Filling of ≥ 50% of acini with monomorphic dyshesive cells, expansion of lobule
              • Pagetoid spread: Monomorphic cells of LN extend into ducts, proliferating between native epithelium and basement membrane

            IMAGING

            • General Features

              • Mammographic Findings

                • Ultrasonographic Findings

                  • MR Findings

                    • Image-Guided Biopsy

                      DIFFERENTIAL DIAGNOSIS

                        PATHOLOGY

                        • General Features

                          • Microscopic Features

                            CLINICAL ISSUES

                            • Presentation

                              • Demographics

                                • Natural History & Prognosis

                                  • Treatment

                                    Selected References

                                    1. Calhoun BC: Core needle biopsy of the breast: An evaluation of contemporary data. Surg Pathol Clin. 11(1):1-16, 2018
                                    2. Donaldson AR et al: Breast cancer risk associated with atypical hyperplasia and lobular carcinoma in situ initially diagnosed on core-needle biopsy. Cancer. 124(3):459-465, 2018
                                    3. Linsk A et al: Surgical upgrade rate of breast atypia to malignancy: An academic center's experience and validation of a predictive model. Breast J. 24(2):115-119, 2018
                                    4. Muller KE et al: Isolated atypical lobular hyperplasia diagnosed on breast biopsy: Low upgrade rate on subsequent excision with long-term follow-up. Arch Pathol Lab Med. 142(3):391-395, 2018
                                    5. Schmidt H et al: Observation versus excision of lobular neoplasia on core needle biopsy of the breast. Breast Cancer Res Treat. 168(3):649-654, 2018
                                    6. Mazzola E et al: Reassessing risk models for atypical hyperplasia: age may not matter. Breast Cancer Res Treat. 165(2):285-291, 2017
                                    7. Racz JM et al: Lobular Neoplasia and Atypical Ductal Hyperplasia on Core Biopsy: Current Surgical Management Recommendations. Ann Surg Oncol. 24(10):2848-2854, 2017
                                    8. Calhoun BC et al: Recommendations for excision following core needle biopsy of the breast: a contemporary evaluation of the literature. Histopathology. 68(1):138-51, 2016
                                    9. Clauser P et al: Management of atypical lobular hyperplasia, atypical ductal hyperplasia, and lobular carcinoma in situ. Expert Rev Anticancer Ther. 16(3):335-46, 2016
                                    10. Collins LC et al: Breast cancer risk by extent and type of atypical hyperplasia: An update from the Nurses' Health Studies. Cancer. 122(4):515-20, 2016
                                    11. Degnim AC et al: Extent of atypical hyperplasia stratifies breast cancer risk in 2 independent cohorts of women. Cancer. 122(19):2971-8, 2016
                                    12. Fives C et al: When pathological and radiological correlation is achieved, excision of fibroadenoma with lobular neoplasia on core biopsy is not warranted. Breast. 30:125-129, 2016
                                    13. Nakhlis F et al: Incidence of Adjacent Synchronous Invasive Carcinoma and/or Ductal Carcinoma In-situ in Patients with Lobular Neoplasia on Core Biopsy: Results from a Prospective Multi-Institutional Registry (TBCRC 020). Ann Surg Oncol. 23(3):722-8, 2016
                                    14. Chang Sen LQ et al: Core Breast Biopsies Showing Lobular Carcinoma In Situ Should Be Excised and Surveillance Is Reasonable for Atypical Lobular Hyperplasia. AJR Am J Roentgenol. 207(5):1132-1145, 2016
                                    15. Allen S et al: Is Excisional Biopsy and Chemoprevention Warranted in Patients With Atypical Lobular Hyperplasia on Core Biopsy? Am Surg. 81(9):876-8, 2015
                                    16. Bambhroliya A et al: Barriers to the Use of Breast Cancer Risk Reduction Therapies. J Natl Compr Canc Netw. 13(7):927-35, 2015
                                    17. Schwartz T et al: Screening breast magnetic resonance imaging in women with atypia or lobular carcinoma in situ. J Surg Res. 193(2):519-22, 2015
                                    18. Weinfurtner RJ et al: Magnetic resonance imaging-guided core needle breast biopsies resulting in high-risk histopathologic findings: upstage frequency and lesion characteristics. Clin Breast Cancer. 15(3):234-9, 2015
                                    19. Meroni S et al: Underestimation rate of lobular intraepithelial neoplasia in vacuum-assisted breast biopsy. Eur Radiol. 24(7):1651-8, 2014
                                    20. Chaudhary S et al: Classic lobular neoplasia on core biopsy: a clinical and radio-pathologic correlation study with follow-up excision biopsy. Mod Pathol. 26:762-71, 2013
                                    21. Murray MP et al: Classic lobular carcinoma in situ and atypical lobular hyperplasia at percutaneous breast core biopsy: outcomes of prospective excision. Cancer. 119(5):1073-9, 2013
                                    22. Ibrahim N et al: Surgical outcome of biopsy-proven lobular neoplasia: is there any difference between lobular carcinoma in situ and atypical lobular hyperplasia? AJR Am J Roentgenol. 198(2):288-91, 2012
                                    23. Lewis JL et al: The Significance of Lobular Carcinoma In Situ and Atypical Lobular Hyperplasia of the Breast. Ann Surg Oncol. Epub ahead of print, 2012
                                    24. Linda A et al: Nonsurgical management of high-risk lesions diagnosed at core needle biopsy: can malignancy be ruled out safely with breast MRI? AJR Am J Roentgenol. 198(2):272-80, 2012
                                    25. Niell B et al: Is excisional biopsy required after a breast core biopsy yields lobular neoplasia? AJR Am J Roentgenol. 199(4):929-35, 2012
                                    26. Polat AK et al: Atypical hyperplasia on core biopsy: is further surgery needed? Am J Med Sci. 344(1):28-31, 2012
                                    27. Rendi MH et al: Lobular in-situ neoplasia on breast core needle biopsy: imaging indication and pathologic extent can identify which patients require excisional biopsy. Ann Surg Oncol. 19(3):914-21, 2012
                                    28. Shah-Khan MG et al: Long-term follow-up of lobular neoplasia (atypical lobular hyperplasia/lobular carcinoma in situ) diagnosed on core needle biopsy. Ann Surg Oncol. 19(10):3131-8, 2012
                                    29. Zhao C et al: Pathologic findings of follow-up surgical excision for lobular neoplasia on breast core biopsy performed for calcification. Am J Clin Pathol. 138(1):72-8, 2012
                                    30. Goss PE et al: 3 Study Investigators. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011 Jun 23;364(25):2381-91. Epub 2011 Jun 4. Erratum in: N Engl J Med. 365(14):1361, 2011
                                    31. Hussain M et al: Management of lobular carcinoma in-situ and atypical lobular hyperplasia of the breast--a review. Eur J Surg Oncol. 37(4):279-89, 2011
                                    32. Ansquer Y et al: Risk of invasive breast cancer after lobular intra-epithelial neoplasia: review of the literature. Eur J Surg Oncol. 36(7):604-9, 2010
                                    33. Flegg KM et al: Surgical outcomes of borderline breast lesions detected by needle biopsy in a breast screening program. World J Surg Oncol. 8:78, 2010
                                    34. Graesslin O et al: Histology after lumpectomy in women with epithelial atypia on stereotactic vacuum-assisted breast biopsy. Eur J Surg Oncol. 36(2):170-5, 2010
                                    35. O'Neil M et al: Lobular carcinoma in situ/atypical lobular hyperplasia on breast needle biopsies: does it warrant surgical excisional biopsy? A study of 27 cases. Ann Diagn Pathol. 14(4):251-5, 2010
                                    36. Subhawong AP et al: Incidental minimal atypical lobular hyperplasia on core needle biopsy: correlation with findings on follow-up excision. Am J Surg Pathol. 34(6):822-8, 2010
                                    37. Vogel VG et al: Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing breast cancer. Cancer Prev Res (Phila). 3(6):696-706, 2010
                                    38. Polom K et al: Atypical lobular hyperplasia and lobular carcinoma in situ without other high-risk lesions diagnosed on vacuum-assisted core needle biopsy. The problem of excisional biopsy. Tumori. 95(1):32-5, 2009
                                    39. Brem RF et al: Lobular neoplasia at percutaneous breast biopsy: variables associated with carcinoma at surgical excision. AJR Am J Roentgenol. 190(3):637-41, 2008
                                    40. Cangiarella J et al: Is surgical excision necessary for the management of atypical lobular hyperplasia and lobular carcinoma in situ diagnosed on core needle biopsy?: a report of 38 cases and review of the literature. Arch Pathol Lab Med. 132(6):979-83, 2008
                                    41. Hwang H et al: Atypical lobular hyperplasia and classic lobular carcinoma in situ in core biopsy specimens: routine excision is not necessary. Mod Pathol. 21(10):1208-16, 2008
                                    42. Londero V et al: Lobular neoplasia: core needle breast biopsy underestimation of malignancy in relation to radiologic and pathologic features. Breast. 17(6):623-30, 2008
                                    43. Menon S et al: The significance of lobular neoplasia on needle core biopsy of the breast. Virchows Arch. 452(5):473-9, 2008
                                    44. Sohn VY et al: Lobular neoplasia: is surgical excision warranted? Am Surg. 74(2):172-7, 2008
                                    45. Port ER et al: Results of MRI screening for breast cancer in high-risk patients with LCIS and atypical hyperplasia. Ann Surg Oncol. 14(3):1051-7, 2007
                                    46. Mahoney MC et al: Lobular neoplasia at 11-gauge vacuum-assisted stereotactic biopsy: correlation with surgical excisional biopsy and mammographic follow-up. AJR Am J Roentgenol. 187(4):949-54, 2006
                                    47. Vogel VG et al: Effects of Tamoxifen vs Raloxifene on the Risk of Developing Invasive Breast Cancer and Other Disease Outcomes: The NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 Trial. JAMA. 295:2727-41, 2006
                                    48. Arpino G et al: Lobular neoplasia on core-needle biopsy--clinical significance. Cancer. 101(2):242-50, 2004
                                    49. Foster MC et al: Lobular carcinoma in situ or atypical lobular hyperplasia at core-needle biopsy: is excisional biopsy necessary? Radiology. 231(3):813-9, 2004
                                    50. Dmytrasz K et al: The significance of atypical lobular hyperplasia at percutaneous breast biopsy. Breast J. 9(1):10-2, 2003
                                    51. Page DL et al: Atypical lobular hyperplasia as a unilateral predictor of breast cancer risk: a retrospective cohort study. Lancet. 2003 Jan 11;361(9352):125-9. Erratum in: Lancet. 361(9373):1994, 2003
                                    52. Simpson PT et al: The diagnosis and management of pre-invasive breast disease: pathology of atypical lobular hyperplasia and lobular carcinoma in situ. Breast Cancer Res. 5(5):258-62, 2003
                                    53. Berg WA et al: Atypical lobular hyperplasia or lobular carcinoma in situ at core-needle breast biopsy. Radiology. 218(2):503-9, 2001
                                    54. Fisher B et al: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 90:1371-1388, 1998
                                    Related Anatomy
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                                    Related Differential Diagnoses
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                                    References
                                    Tables

                                    Tables

                                    KEY FACTS

                                    • Terminology

                                      • Imaging

                                        • Top Differential Diagnoses

                                          • Pathology

                                            • Clinical Issues

                                              TERMINOLOGY

                                              • Definitions

                                                • Lobular (intraepithelial) neoplasia (LN/LIN): Monomorphic dyshesive cells with ↑ nuclear:cytoplasmic ratio, commonly intracytoplasmic vacuoles, fill and distend acini, encompassing spectrum from ALH to LCIS
                                                • Atypical lobular hyperplasia (ALH): Monomorphic dyshesive cells fill < 50% of acini; overall lobule not distended
                                                • Lobular carcinoma in situ (LCIS): Filling of ≥ 50% of acini with monomorphic dyshesive cells, expansion of lobule
                                                • Pagetoid spread: Monomorphic cells of LN extend into ducts, proliferating between native epithelium and basement membrane

                                              IMAGING

                                              • General Features

                                                • Mammographic Findings

                                                  • Ultrasonographic Findings

                                                    • MR Findings

                                                      • Image-Guided Biopsy

                                                        DIFFERENTIAL DIAGNOSIS

                                                          PATHOLOGY

                                                          • General Features

                                                            • Microscopic Features

                                                              CLINICAL ISSUES

                                                              • Presentation

                                                                • Demographics

                                                                  • Natural History & Prognosis

                                                                    • Treatment

                                                                      Selected References

                                                                      1. Calhoun BC: Core needle biopsy of the breast: An evaluation of contemporary data. Surg Pathol Clin. 11(1):1-16, 2018
                                                                      2. Donaldson AR et al: Breast cancer risk associated with atypical hyperplasia and lobular carcinoma in situ initially diagnosed on core-needle biopsy. Cancer. 124(3):459-465, 2018
                                                                      3. Linsk A et al: Surgical upgrade rate of breast atypia to malignancy: An academic center's experience and validation of a predictive model. Breast J. 24(2):115-119, 2018
                                                                      4. Muller KE et al: Isolated atypical lobular hyperplasia diagnosed on breast biopsy: Low upgrade rate on subsequent excision with long-term follow-up. Arch Pathol Lab Med. 142(3):391-395, 2018
                                                                      5. Schmidt H et al: Observation versus excision of lobular neoplasia on core needle biopsy of the breast. Breast Cancer Res Treat. 168(3):649-654, 2018
                                                                      6. Mazzola E et al: Reassessing risk models for atypical hyperplasia: age may not matter. Breast Cancer Res Treat. 165(2):285-291, 2017
                                                                      7. Racz JM et al: Lobular Neoplasia and Atypical Ductal Hyperplasia on Core Biopsy: Current Surgical Management Recommendations. Ann Surg Oncol. 24(10):2848-2854, 2017
                                                                      8. Calhoun BC et al: Recommendations for excision following core needle biopsy of the breast: a contemporary evaluation of the literature. Histopathology. 68(1):138-51, 2016
                                                                      9. Clauser P et al: Management of atypical lobular hyperplasia, atypical ductal hyperplasia, and lobular carcinoma in situ. Expert Rev Anticancer Ther. 16(3):335-46, 2016
                                                                      10. Collins LC et al: Breast cancer risk by extent and type of atypical hyperplasia: An update from the Nurses' Health Studies. Cancer. 122(4):515-20, 2016
                                                                      11. Degnim AC et al: Extent of atypical hyperplasia stratifies breast cancer risk in 2 independent cohorts of women. Cancer. 122(19):2971-8, 2016
                                                                      12. Fives C et al: When pathological and radiological correlation is achieved, excision of fibroadenoma with lobular neoplasia on core biopsy is not warranted. Breast. 30:125-129, 2016
                                                                      13. Nakhlis F et al: Incidence of Adjacent Synchronous Invasive Carcinoma and/or Ductal Carcinoma In-situ in Patients with Lobular Neoplasia on Core Biopsy: Results from a Prospective Multi-Institutional Registry (TBCRC 020). Ann Surg Oncol. 23(3):722-8, 2016
                                                                      14. Chang Sen LQ et al: Core Breast Biopsies Showing Lobular Carcinoma In Situ Should Be Excised and Surveillance Is Reasonable for Atypical Lobular Hyperplasia. AJR Am J Roentgenol. 207(5):1132-1145, 2016
                                                                      15. Allen S et al: Is Excisional Biopsy and Chemoprevention Warranted in Patients With Atypical Lobular Hyperplasia on Core Biopsy? Am Surg. 81(9):876-8, 2015
                                                                      16. Bambhroliya A et al: Barriers to the Use of Breast Cancer Risk Reduction Therapies. J Natl Compr Canc Netw. 13(7):927-35, 2015
                                                                      17. Schwartz T et al: Screening breast magnetic resonance imaging in women with atypia or lobular carcinoma in situ. J Surg Res. 193(2):519-22, 2015
                                                                      18. Weinfurtner RJ et al: Magnetic resonance imaging-guided core needle breast biopsies resulting in high-risk histopathologic findings: upstage frequency and lesion characteristics. Clin Breast Cancer. 15(3):234-9, 2015
                                                                      19. Meroni S et al: Underestimation rate of lobular intraepithelial neoplasia in vacuum-assisted breast biopsy. Eur Radiol. 24(7):1651-8, 2014
                                                                      20. Chaudhary S et al: Classic lobular neoplasia on core biopsy: a clinical and radio-pathologic correlation study with follow-up excision biopsy. Mod Pathol. 26:762-71, 2013
                                                                      21. Murray MP et al: Classic lobular carcinoma in situ and atypical lobular hyperplasia at percutaneous breast core biopsy: outcomes of prospective excision. Cancer. 119(5):1073-9, 2013
                                                                      22. Ibrahim N et al: Surgical outcome of biopsy-proven lobular neoplasia: is there any difference between lobular carcinoma in situ and atypical lobular hyperplasia? AJR Am J Roentgenol. 198(2):288-91, 2012
                                                                      23. Lewis JL et al: The Significance of Lobular Carcinoma In Situ and Atypical Lobular Hyperplasia of the Breast. Ann Surg Oncol. Epub ahead of print, 2012
                                                                      24. Linda A et al: Nonsurgical management of high-risk lesions diagnosed at core needle biopsy: can malignancy be ruled out safely with breast MRI? AJR Am J Roentgenol. 198(2):272-80, 2012
                                                                      25. Niell B et al: Is excisional biopsy required after a breast core biopsy yields lobular neoplasia? AJR Am J Roentgenol. 199(4):929-35, 2012
                                                                      26. Polat AK et al: Atypical hyperplasia on core biopsy: is further surgery needed? Am J Med Sci. 344(1):28-31, 2012
                                                                      27. Rendi MH et al: Lobular in-situ neoplasia on breast core needle biopsy: imaging indication and pathologic extent can identify which patients require excisional biopsy. Ann Surg Oncol. 19(3):914-21, 2012
                                                                      28. Shah-Khan MG et al: Long-term follow-up of lobular neoplasia (atypical lobular hyperplasia/lobular carcinoma in situ) diagnosed on core needle biopsy. Ann Surg Oncol. 19(10):3131-8, 2012
                                                                      29. Zhao C et al: Pathologic findings of follow-up surgical excision for lobular neoplasia on breast core biopsy performed for calcification. Am J Clin Pathol. 138(1):72-8, 2012
                                                                      30. Goss PE et al: 3 Study Investigators. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011 Jun 23;364(25):2381-91. Epub 2011 Jun 4. Erratum in: N Engl J Med. 365(14):1361, 2011
                                                                      31. Hussain M et al: Management of lobular carcinoma in-situ and atypical lobular hyperplasia of the breast--a review. Eur J Surg Oncol. 37(4):279-89, 2011
                                                                      32. Ansquer Y et al: Risk of invasive breast cancer after lobular intra-epithelial neoplasia: review of the literature. Eur J Surg Oncol. 36(7):604-9, 2010
                                                                      33. Flegg KM et al: Surgical outcomes of borderline breast lesions detected by needle biopsy in a breast screening program. World J Surg Oncol. 8:78, 2010
                                                                      34. Graesslin O et al: Histology after lumpectomy in women with epithelial atypia on stereotactic vacuum-assisted breast biopsy. Eur J Surg Oncol. 36(2):170-5, 2010
                                                                      35. O'Neil M et al: Lobular carcinoma in situ/atypical lobular hyperplasia on breast needle biopsies: does it warrant surgical excisional biopsy? A study of 27 cases. Ann Diagn Pathol. 14(4):251-5, 2010
                                                                      36. Subhawong AP et al: Incidental minimal atypical lobular hyperplasia on core needle biopsy: correlation with findings on follow-up excision. Am J Surg Pathol. 34(6):822-8, 2010
                                                                      37. Vogel VG et al: Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing breast cancer. Cancer Prev Res (Phila). 3(6):696-706, 2010
                                                                      38. Polom K et al: Atypical lobular hyperplasia and lobular carcinoma in situ without other high-risk lesions diagnosed on vacuum-assisted core needle biopsy. The problem of excisional biopsy. Tumori. 95(1):32-5, 2009
                                                                      39. Brem RF et al: Lobular neoplasia at percutaneous breast biopsy: variables associated with carcinoma at surgical excision. AJR Am J Roentgenol. 190(3):637-41, 2008
                                                                      40. Cangiarella J et al: Is surgical excision necessary for the management of atypical lobular hyperplasia and lobular carcinoma in situ diagnosed on core needle biopsy?: a report of 38 cases and review of the literature. Arch Pathol Lab Med. 132(6):979-83, 2008
                                                                      41. Hwang H et al: Atypical lobular hyperplasia and classic lobular carcinoma in situ in core biopsy specimens: routine excision is not necessary. Mod Pathol. 21(10):1208-16, 2008
                                                                      42. Londero V et al: Lobular neoplasia: core needle breast biopsy underestimation of malignancy in relation to radiologic and pathologic features. Breast. 17(6):623-30, 2008
                                                                      43. Menon S et al: The significance of lobular neoplasia on needle core biopsy of the breast. Virchows Arch. 452(5):473-9, 2008
                                                                      44. Sohn VY et al: Lobular neoplasia: is surgical excision warranted? Am Surg. 74(2):172-7, 2008
                                                                      45. Port ER et al: Results of MRI screening for breast cancer in high-risk patients with LCIS and atypical hyperplasia. Ann Surg Oncol. 14(3):1051-7, 2007
                                                                      46. Mahoney MC et al: Lobular neoplasia at 11-gauge vacuum-assisted stereotactic biopsy: correlation with surgical excisional biopsy and mammographic follow-up. AJR Am J Roentgenol. 187(4):949-54, 2006
                                                                      47. Vogel VG et al: Effects of Tamoxifen vs Raloxifene on the Risk of Developing Invasive Breast Cancer and Other Disease Outcomes: The NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 Trial. JAMA. 295:2727-41, 2006
                                                                      48. Arpino G et al: Lobular neoplasia on core-needle biopsy--clinical significance. Cancer. 101(2):242-50, 2004
                                                                      49. Foster MC et al: Lobular carcinoma in situ or atypical lobular hyperplasia at core-needle biopsy: is excisional biopsy necessary? Radiology. 231(3):813-9, 2004
                                                                      50. Dmytrasz K et al: The significance of atypical lobular hyperplasia at percutaneous breast biopsy. Breast J. 9(1):10-2, 2003
                                                                      51. Page DL et al: Atypical lobular hyperplasia as a unilateral predictor of breast cancer risk: a retrospective cohort study. Lancet. 2003 Jan 11;361(9352):125-9. Erratum in: Lancet. 361(9373):1994, 2003
                                                                      52. Simpson PT et al: The diagnosis and management of pre-invasive breast disease: pathology of atypical lobular hyperplasia and lobular carcinoma in situ. Breast Cancer Res. 5(5):258-62, 2003
                                                                      53. Berg WA et al: Atypical lobular hyperplasia or lobular carcinoma in situ at core-needle breast biopsy. Radiology. 218(2):503-9, 2001
                                                                      54. Fisher B et al: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 90:1371-1388, 1998