Ductal Carcinoma in Situ of the Breast
http://www.100md.com
《新英格兰医药杂志》
To the Editor: One take-home message from the review article by Burstein et al. on ductal carcinoma in situ of the breast (April 1 issue)1 is that all women who have undergone breast-conserving surgery should receive routine radiotherapy. This is the impression that I have received from colleagues concerned about a 12 percent recurrence rate in their trial of wide excision alone for ductal carcinoma in situ.2 The pathobiologic events reviewed by Burstein et al. suggest that the treatment of ductal carcinoma in situ can be viewed as a late-stage intervention to prevent invasive breast cancer. The available randomized studies show about a 50 percent reduction in the risk of ipsilateral recurrence with the addition of radiotherapy. Some recurrences will be invasive tumors; the United Kingdom Coordinating Committee on Cancer Research trial estimated that 36 women with ductal carcinoma in situ would need to undergo irradiation to prevent the development of one invasive breast cancer during the first five years of follow-up.3 If radiotherapy were presented to patients as a means of prevention (with a moderate benefit), rather than as a form of treatment for cancer, it seems to me that more women would opt just for mammographic surveillance and that psychological morbidity might be reduced.4
Andrew P. Brown, M.P.H., F.R.C.R.
Payson Center for Cancer Care
Concord, NH 03301
apb16@hotmail.com
References
Burstein HJ, Polyak K, Wong JS, Lester SC, Kaelin CM. Ductal carcinoma in situ of the breast. N Engl J Med 2004;350:1430-1441.
Wong JS, Gadd MA, Gelman R, et al. Wide excision alone for ductal carcinoma in situ (DCIS) of the breast. Breast Cancer Res Treat 2003;82:Suppl 1:S10-S10. abstract.
Houghton J, George WD, Cuzick J, Duggan C, Fentiman IS, Spittle M. Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK, Australia, and New Zealand: randomised controlled trial. Lancet 2003;362:95-102.
Rakovitch E, Franssen E, Kim J, et al. A comparison of risk perception and psychological morbidity in women with ductal carcinoma in situ and early invasive breast cancer. Breast Cancer Res Treat 2003;77:285-293.
To the Editor: Burstein et al. assert that there currently are no prospective methods to identify women with ductal carcinoma in situ who are not likely to benefit from radiotherapy after excision of the tumor. However, Silverstein et al. have developed a prognostic index that stratifies the risk of local recurrence of ductal carcinoma in situ.1 The recently updated and renamed University of Southern California–Van Nuys Prognostic Index scores patients' disease on the basis of four factors and stratifies the risk of local recurrence as low, intermediate, or high.2 In Silverstein's study, patients with low-risk tumors derived no benefit from radiotherapy in terms of local recurrence. Patients with estrogen-receptor–positive, small, low-grade ductal carcinoma in situ who had adequate excision margins could be treated with tamoxifen after excision, although this hypothesis needs validation. If radiotherapy is not used in these patients, a valuable adjunctive treatment could be saved for use in case of a recurrence.
(The views and opinions expressed herein do not necessarily reflect those of the U.S. Army.)
Margarett C. Ellison, M.D.
Women's Cancer Center
Los Angeles, CA 90027
mcellison@pol.net
Patrick J. Kenney, D.O.
Weed Army Community Hospital
Ft. Irwin, CA 96251
References
Silverstein MJ, Lagios M, Craig P, et al. The Van Nuys prognostic index for ductal carcinoma in situ. Breast J 1996;2:38-40.
Silverstein MJ. The University of Southern California/Van Nuys prognostic index for ductal carcinoma in situ of the breast. Am J Surg 2003;186:337-343.
To the Editor: Burstein et al. do not mention an important diagnostic issue. As they state, more than 75 percent of patients with ductal carcinoma in situ present with microcalcifications on mammography. However, their contention that magnified views assist in establishing the extent of ipsilateral disease is not correct in my opinion. In ductal carcinoma in situ, the lesion is invariably larger than the microcalcifications; non–high-grade lesions extend beyond the microcalcifications. In 47 percent of cases, the extension exceeds 2 cm.1
Therapeutic decisions should be made preoperatively. For example, my associates and I recommend vacuum-assisted biopsy, which is not mentioned by Burstein et al.; this procedure is far superior to core biopsy since it minimizes underestimation of the extent and differentiation of the tumor. In my view, vacuum-assisted biopsy is indicated in all patients whose mammograms show microcalcifications. In a recent multicenter study of 2874 patients in whom vacuum-assisted biopsy was performed to evaluate microcalcifications, my associates and I found that 27 percent of the patients had breast cancer, of whom 72 percent had ductal carcinoma in situ or atypical ductal hyperplasia.2 Vacuum-assisted biopsy provided a clear diagnosis and facilitated appropriate preoperative decision making.
Ute Kettritz, M.D.
Helios Klinikum Berlin
13125 Berlin, Germany
ukettritz@berlin.helios-kliniken.de
References
Holland R, Hendriks JHCL, Vebeek ALM, Mravunac M, Schuurmans Stekhoven JH. Extent, distribution, and mammographic/histological correlations of breast ductal carcinoma in situ. Lancet 1990;335:519-522.
Kettritz U, Rotter K, Schreer I, et al. Stereotactic vacuum-assisted breast biopsy in 2874 patients: a multicenter study. Cancer 2004;100:245-251.
To the Editor: If all invasive breast carcinomas arose from in situ lesions, risk factors would be similar for invasive and in situ disease. However, this may not be true for the most important risk factor for breast cancer, advancing age, as we showed in an evaluation of cases of breast carcinoma in the Surveillance, Epidemiology, and End Results (SEER) database.1 Age-specific rates of incidence of invasive tumors rose continuously with advancing age, whereas rates of in situ disease increased until the age of 50 years, after which point they flattened and subsequently fell (Figure 1).
Figure 1. Age-Specific Incidence of Invasive and in Situ Breast Carcinoma in the SEER Database from 1990 to 2000.
The values on the x and y axes are shown on logarithmic scales. Adapted from Anderson and Chu,1 with the permission of the publisher.
In an autopsy series, Nielsen et al. noted the greatest prevalence of preinvasive breast lesions among women between the ages of 40 and 49 years.2 Alpers and Wellings also observed that the prevalence of carcinoma in situ was greater among younger women than among older women.3 Kramer and Rush concluded that carcinoma in situ was infrequent among elderly women.4
In sum, autopsy studies and our observations based on the SEER database suggest that advancing age is a greater risk factor for invasive carcinomas than it is for in situ carcinomas of the breast. In situ lesions may be precursors for some, but not all, invasive breast carcinomas.5
William F. Anderson, M.D., M.P.H.
Kenneth C. Chu, Ph.D.
National Cancer Institute
Bethesda, MD 20892
wanderso@mail.nih.gov
References
Anderson WF, Chu KC. Comparison of preinvasive and invasive breast carcinomas in the Surveillance, Epidemiology, and End Results Program. Breast Cancer Res Treat 2003;82:Suppl 1:S147-S148. abstract.
Nielsen M, Thomsen JL, Primdahl S, Dyreborg U, Andersen JA. Breast cancer and atypia among young and middle-aged women: a study of 110 medicolegal autopsies. Br J Cancer 1987;56:814-819.
Alpers CE, Wellings SR. The prevalence of carcinoma in situ in normal and cancer-associated breasts. Hum Pathol 1985;16:796-807.
Kramer WM, Rush BF Jr. Mammary duct proliferation in the elderly: a histopathologic study. Cancer 1973;31:130-137.
Buerger H, Otterbach F, Simon R, et al. Different genetic pathways in the evolution of invasive breast cancer are associated with distinct morphological subtypes. J Pathol 1999;189:521-526.
The authors reply: Dr. Brown and Drs. Ellison and Kenney highlight the need to identify patients with ductal carcinoma in situ who are unlikely to benefit from radiotherapy after excision. At present, however, such criteria have not been established by prospective studies. A single-center, retrospective analysis that used the Van Nuys Prognostic Index and considered tumor size, margin width, pathological classification, and age, but not estrogen-receptor status, concluded that it was possible to predict a low risk of recurrence and minimal benefit from radiation after excision.1 However, retrospective studies based on other large treatment registries have suggested that the index has mixed value.2,3,4 Subgroup analyses from large, multicenter randomized trials, such as National Surgical Adjuvant Breast and Bowel Project trials B-17 and B-24 and European Organization for Research and Treatment of Cancer trial 10853, suggest that radiotherapy improves outcomes in all patients, irrespective of the baseline risk of recurrent disease. To date, prospective trials conducted in carefully selected, low-risk patients treated with excision alone have not demonstrated adequately low rates of recurrence without radiation. It is not known whether tamoxifen can be substituted for radiotherapy in lowering the risk of recurrence; in the United Kingdom Coordinating Committee on Cancer Research trial, tamoxifen did not lower the risk of recurrence among patients who were receiving radiotherapy.
We agree about the importance of developing criteria to identify low-risk patients and of conducting prospective studies that critically evaluate the need for either radiotherapy or endocrine therapy in these patients. Pending the results of such efforts, radiotherapy should be considered for most patients with ductal carcinoma in situ. Individual patients may decide that the gains are so limited as to obviate the need for such treatment. Realistic appraisals of the risk of recurrence and the benefits of treatment can help patients make better decisions.
Magnified views can help in the evaluation of suspicious mammograms by defining the extent of calcifications and selecting the best areas for biopsy. As Dr. Kettritz notes, vacuum-assisted core biopsy is a widely used, diagnostic biopsy technique. Patients in whom ductal carcinoma in situ is identified by core biopsy should undergo surgical excision.
Ductal carcinoma in situ and invasive breast cancer share epidemiologic risk factors, including age. The data from Drs. Anderson and Chu are provocative, however, and warrant further exploration to clarify why age-specific incidence rates for these two types of tumor differ in postmenopausal women, particularly those older than 70 years of age.
Harold J. Burstein, M.D., Ph.D.
Julia S. Wong, M.D.
Carolyn M. Kaelin, M.D., M.P.H.
Dana–Farber Cancer Institute
Boston, MA 02115
hburstein@partners.org
References
Silverstein MJ. The University of Southern California/Van Nuys prognostic index for ductal carcinoma in situ of the breast. Am J Surg 2003;186:337-343.
de Mascarel I, Bonichon F, MacGrogan G, et al. Application of the Van Nuys prognostic index in a retrospective series of 367 ductal carcinomas in situ of the breast examined by serial macroscopic sectioning: practical considerations. Breast Cancer Res Treat 2000;61:151-159.
Douglas-Jones AG, Logan J, Morgan JM, Johnson R, Williams R. Effect of margins of excision on recurrence after local excision of ductal carcinoma in situ of the breast. J Clin Pathol 2002;55:581-586.
Boland GP, Chan KC, Know WF, Roberts SA, Bundred NJ. Value of the Van Nuys Prognostic Index in prediction of recurrence of ductal carcinoma in situ after breast-conserving surgery. Br J Surg 2003;90:426-432.
Andrew P. Brown, M.P.H., F.R.C.R.
Payson Center for Cancer Care
Concord, NH 03301
apb16@hotmail.com
References
Burstein HJ, Polyak K, Wong JS, Lester SC, Kaelin CM. Ductal carcinoma in situ of the breast. N Engl J Med 2004;350:1430-1441.
Wong JS, Gadd MA, Gelman R, et al. Wide excision alone for ductal carcinoma in situ (DCIS) of the breast. Breast Cancer Res Treat 2003;82:Suppl 1:S10-S10. abstract.
Houghton J, George WD, Cuzick J, Duggan C, Fentiman IS, Spittle M. Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK, Australia, and New Zealand: randomised controlled trial. Lancet 2003;362:95-102.
Rakovitch E, Franssen E, Kim J, et al. A comparison of risk perception and psychological morbidity in women with ductal carcinoma in situ and early invasive breast cancer. Breast Cancer Res Treat 2003;77:285-293.
To the Editor: Burstein et al. assert that there currently are no prospective methods to identify women with ductal carcinoma in situ who are not likely to benefit from radiotherapy after excision of the tumor. However, Silverstein et al. have developed a prognostic index that stratifies the risk of local recurrence of ductal carcinoma in situ.1 The recently updated and renamed University of Southern California–Van Nuys Prognostic Index scores patients' disease on the basis of four factors and stratifies the risk of local recurrence as low, intermediate, or high.2 In Silverstein's study, patients with low-risk tumors derived no benefit from radiotherapy in terms of local recurrence. Patients with estrogen-receptor–positive, small, low-grade ductal carcinoma in situ who had adequate excision margins could be treated with tamoxifen after excision, although this hypothesis needs validation. If radiotherapy is not used in these patients, a valuable adjunctive treatment could be saved for use in case of a recurrence.
(The views and opinions expressed herein do not necessarily reflect those of the U.S. Army.)
Margarett C. Ellison, M.D.
Women's Cancer Center
Los Angeles, CA 90027
mcellison@pol.net
Patrick J. Kenney, D.O.
Weed Army Community Hospital
Ft. Irwin, CA 96251
References
Silverstein MJ, Lagios M, Craig P, et al. The Van Nuys prognostic index for ductal carcinoma in situ. Breast J 1996;2:38-40.
Silverstein MJ. The University of Southern California/Van Nuys prognostic index for ductal carcinoma in situ of the breast. Am J Surg 2003;186:337-343.
To the Editor: Burstein et al. do not mention an important diagnostic issue. As they state, more than 75 percent of patients with ductal carcinoma in situ present with microcalcifications on mammography. However, their contention that magnified views assist in establishing the extent of ipsilateral disease is not correct in my opinion. In ductal carcinoma in situ, the lesion is invariably larger than the microcalcifications; non–high-grade lesions extend beyond the microcalcifications. In 47 percent of cases, the extension exceeds 2 cm.1
Therapeutic decisions should be made preoperatively. For example, my associates and I recommend vacuum-assisted biopsy, which is not mentioned by Burstein et al.; this procedure is far superior to core biopsy since it minimizes underestimation of the extent and differentiation of the tumor. In my view, vacuum-assisted biopsy is indicated in all patients whose mammograms show microcalcifications. In a recent multicenter study of 2874 patients in whom vacuum-assisted biopsy was performed to evaluate microcalcifications, my associates and I found that 27 percent of the patients had breast cancer, of whom 72 percent had ductal carcinoma in situ or atypical ductal hyperplasia.2 Vacuum-assisted biopsy provided a clear diagnosis and facilitated appropriate preoperative decision making.
Ute Kettritz, M.D.
Helios Klinikum Berlin
13125 Berlin, Germany
ukettritz@berlin.helios-kliniken.de
References
Holland R, Hendriks JHCL, Vebeek ALM, Mravunac M, Schuurmans Stekhoven JH. Extent, distribution, and mammographic/histological correlations of breast ductal carcinoma in situ. Lancet 1990;335:519-522.
Kettritz U, Rotter K, Schreer I, et al. Stereotactic vacuum-assisted breast biopsy in 2874 patients: a multicenter study. Cancer 2004;100:245-251.
To the Editor: If all invasive breast carcinomas arose from in situ lesions, risk factors would be similar for invasive and in situ disease. However, this may not be true for the most important risk factor for breast cancer, advancing age, as we showed in an evaluation of cases of breast carcinoma in the Surveillance, Epidemiology, and End Results (SEER) database.1 Age-specific rates of incidence of invasive tumors rose continuously with advancing age, whereas rates of in situ disease increased until the age of 50 years, after which point they flattened and subsequently fell (Figure 1).
Figure 1. Age-Specific Incidence of Invasive and in Situ Breast Carcinoma in the SEER Database from 1990 to 2000.
The values on the x and y axes are shown on logarithmic scales. Adapted from Anderson and Chu,1 with the permission of the publisher.
In an autopsy series, Nielsen et al. noted the greatest prevalence of preinvasive breast lesions among women between the ages of 40 and 49 years.2 Alpers and Wellings also observed that the prevalence of carcinoma in situ was greater among younger women than among older women.3 Kramer and Rush concluded that carcinoma in situ was infrequent among elderly women.4
In sum, autopsy studies and our observations based on the SEER database suggest that advancing age is a greater risk factor for invasive carcinomas than it is for in situ carcinomas of the breast. In situ lesions may be precursors for some, but not all, invasive breast carcinomas.5
William F. Anderson, M.D., M.P.H.
Kenneth C. Chu, Ph.D.
National Cancer Institute
Bethesda, MD 20892
wanderso@mail.nih.gov
References
Anderson WF, Chu KC. Comparison of preinvasive and invasive breast carcinomas in the Surveillance, Epidemiology, and End Results Program. Breast Cancer Res Treat 2003;82:Suppl 1:S147-S148. abstract.
Nielsen M, Thomsen JL, Primdahl S, Dyreborg U, Andersen JA. Breast cancer and atypia among young and middle-aged women: a study of 110 medicolegal autopsies. Br J Cancer 1987;56:814-819.
Alpers CE, Wellings SR. The prevalence of carcinoma in situ in normal and cancer-associated breasts. Hum Pathol 1985;16:796-807.
Kramer WM, Rush BF Jr. Mammary duct proliferation in the elderly: a histopathologic study. Cancer 1973;31:130-137.
Buerger H, Otterbach F, Simon R, et al. Different genetic pathways in the evolution of invasive breast cancer are associated with distinct morphological subtypes. J Pathol 1999;189:521-526.
The authors reply: Dr. Brown and Drs. Ellison and Kenney highlight the need to identify patients with ductal carcinoma in situ who are unlikely to benefit from radiotherapy after excision. At present, however, such criteria have not been established by prospective studies. A single-center, retrospective analysis that used the Van Nuys Prognostic Index and considered tumor size, margin width, pathological classification, and age, but not estrogen-receptor status, concluded that it was possible to predict a low risk of recurrence and minimal benefit from radiation after excision.1 However, retrospective studies based on other large treatment registries have suggested that the index has mixed value.2,3,4 Subgroup analyses from large, multicenter randomized trials, such as National Surgical Adjuvant Breast and Bowel Project trials B-17 and B-24 and European Organization for Research and Treatment of Cancer trial 10853, suggest that radiotherapy improves outcomes in all patients, irrespective of the baseline risk of recurrent disease. To date, prospective trials conducted in carefully selected, low-risk patients treated with excision alone have not demonstrated adequately low rates of recurrence without radiation. It is not known whether tamoxifen can be substituted for radiotherapy in lowering the risk of recurrence; in the United Kingdom Coordinating Committee on Cancer Research trial, tamoxifen did not lower the risk of recurrence among patients who were receiving radiotherapy.
We agree about the importance of developing criteria to identify low-risk patients and of conducting prospective studies that critically evaluate the need for either radiotherapy or endocrine therapy in these patients. Pending the results of such efforts, radiotherapy should be considered for most patients with ductal carcinoma in situ. Individual patients may decide that the gains are so limited as to obviate the need for such treatment. Realistic appraisals of the risk of recurrence and the benefits of treatment can help patients make better decisions.
Magnified views can help in the evaluation of suspicious mammograms by defining the extent of calcifications and selecting the best areas for biopsy. As Dr. Kettritz notes, vacuum-assisted core biopsy is a widely used, diagnostic biopsy technique. Patients in whom ductal carcinoma in situ is identified by core biopsy should undergo surgical excision.
Ductal carcinoma in situ and invasive breast cancer share epidemiologic risk factors, including age. The data from Drs. Anderson and Chu are provocative, however, and warrant further exploration to clarify why age-specific incidence rates for these two types of tumor differ in postmenopausal women, particularly those older than 70 years of age.
Harold J. Burstein, M.D., Ph.D.
Julia S. Wong, M.D.
Carolyn M. Kaelin, M.D., M.P.H.
Dana–Farber Cancer Institute
Boston, MA 02115
hburstein@partners.org
References
Silverstein MJ. The University of Southern California/Van Nuys prognostic index for ductal carcinoma in situ of the breast. Am J Surg 2003;186:337-343.
de Mascarel I, Bonichon F, MacGrogan G, et al. Application of the Van Nuys prognostic index in a retrospective series of 367 ductal carcinomas in situ of the breast examined by serial macroscopic sectioning: practical considerations. Breast Cancer Res Treat 2000;61:151-159.
Douglas-Jones AG, Logan J, Morgan JM, Johnson R, Williams R. Effect of margins of excision on recurrence after local excision of ductal carcinoma in situ of the breast. J Clin Pathol 2002;55:581-586.
Boland GP, Chan KC, Know WF, Roberts SA, Bundred NJ. Value of the Van Nuys Prognostic Index in prediction of recurrence of ductal carcinoma in situ after breast-conserving surgery. Br J Surg 2003;90:426-432.