Ductal carcinoma in situ is a proliferation of malignant epithelial cells confined to the ductolobular system of the breast. It is considered a pre-cursor lesion for invasive breast cancer and when identified patients are treated with some combination of surgery, +/? radiation therapy, and +/adjuvant tamoxifen. However, no good biomarkers exist that can predict with accuracy those cases of DCIS destined to progress to invasive disease or once treated those patients that are likely to suffer a recurrence; thus, in the era of screening mammography it seems likely that many patients with DCIS are overtreated. This paper details the parameters that should be included in a pathology report for a case of DClS with some explanations as to their importance for good clinical decision making. 1. Definition Ductal carcinoma in situ (DCIS) is defined as a proliferation of malignant epithelial cells that has not breached the myoepithelial layer of the ductolobular system. DCIS is a highly heterogeneous disease in terms of presentation, morphology, biomarker expression, underlying genetic alterations, and natural progression. It is considered a precursor lesion with a relative risk (RR) of 8–11 for the subsequent development of invasive carcinoma [1]. In most cases DCIS involves the breast in a unicentric segmental fashion and true multicentric disease is unusual occurring in an estimated 10% of cases. 2. Epidemiology DCIS currently comprises ~20–25% of all newly diagnosed breast cancers in North America up from ~5% of cases in the early 1980’s [2, 3]. This large increase in incidence is largely ascribed to the introduction of screening mammography. Currently 80–85% of DCIS cases are detected by mammography and the remainder are detected as a palpable lump or nipple alteration/discharge [2]. Interestingly the incidence of DCIS in women >50 years of age has been in decline since 2003, a fact that may be related to the declining use of postmenopausal hormonal therapy, whereas the incidence of DCIS continues to rise for women less than age 50 [4]. In addition to the dramatic rise in the incidence of DCIS detection, the introduction of screening mammography has led to a decline in mortality rates from DCIS; the death rate from DCIS diagnosed between 1978 and 1983 (prescreening mammography) was 3.4% at 10 years as compared to 1.9% at 10 years with DCIS diagnosed between 1984 and 1989 (screening era). Additionally, the spectrum of DCIS diagnosed has changed with the use of screening with more low and intermediate grade DCIS being diagnosed while the relative proportion of
References
[1]
W. D. Dupont and D. L. Page, “Risk factors for breast cancer in women with proliferative breast disease,” The New England Journal of Medicine, vol. 312, no. 3, pp. 146–151, 1985.
[2]
V. L. Ernster, R. Ballard-Barbash, W. E. Barlow et al., “Detection of ductal carcinoma in situ in women undergoing screening mammography,” Journal of the National Cancer Institute, vol. 94, no. 20, pp. 1546–1554, 2002.
[3]
D. S. May, N. C. Lee, L. C. Richardson, A. G. Giustozzi, and J. K. Bobo, “Mammography and breast cancer detection by race and Hispanic ethnicity: results from a national program (United States),” Cancer Causes and Control, vol. 11, no. 8, pp. 697–705, 2000.
[4]
K. Kerlikowske, D. L. Miglioretti, D. S. M. Buist, R. Walker, and P. A. Carney, “Declines in invasive breast cancer and use of postmenopausal hormone therapy in a screening mammography population,” Journal of the National Cancer Institute, vol. 99, no. 17, pp. 1335–1339, 2007.
[5]
C. I. Li, J. R. Daling, and K. E. Malone, “Age-specific incidence rates of in situ breast carcinomas by histologic type, 1980 to 2001,” Cancer Epidemiology Biomarkers and Prevention, vol. 14, no. 4, pp. 1008–1011, 2005.
[6]
K. Kerlikowske, R. Walker, D. L. Miglioretti, A. Desai, R. Ballard-Barbash, and D. S. M. Buist, “Obesity, mammography use and accuracy, and advanced breast cancer risk,” Journal of the National Cancer Institute, vol. 100, no. 23, pp. 1724–1733, 2008.
[7]
K. Kerlikowske, D. L. Miglioretti, R. Ballard-Barbash et al., “Prognostic characteristics of breast cancer among postmenopausal hormone users in a screened population,” Journal of Clinical Oncology, vol. 21, no. 23, pp. 4314–4321, 2003.
[8]
“The consensus conference committee. consensus conference on the classification of ductal carcinoma in situ,” Cancer, vol. 80, no. 9, pp. 1798–1802, 1997.
[9]
M. J. Silverstein, D. N. Poller, J. R. Waisman et al., “Prognostic classification of breast ductal carcinoma-in-situ,” The Lancet, vol. 345, no. 8958, pp. 1154–1157, 1995.
[10]
R. Holland, J. L. Peterse, R. R. Millis et al., “Ductal carcinoma in situ: a proposal for a new classification,” Seminars in Diagnostic Pathology, vol. 11, no. 3, pp. 167–180, 1994.
[11]
M. A. Scott, M. D. Lagios, K. Axelsson, L. W. Rogers, T. J. Anderson, and D. L. Page, “Ductal carcinoma in situ of the breast: reproducibility of histological subtype analysis,” Human Pathology, vol. 28, no. 8, pp. 967–973, 1997.
[12]
S. C. Lester, S. Bose, Y. Y. Chen et al., “Protocol for the examination of specimens from patients with ductal carcinoma in situ of the breast,” Archives of Pathology and Laboratory Medicine, vol. 133, no. 1, pp. 15–25, 2009.
[13]
D. C. Allred, Y. Wu, S. Mao et al., “Ductal carcinoma in situ and the emergence of diversity during breast cancer evolution,” Clinical Cancer Research, vol. 14, no. 2, pp. 370–378, 2008.
[14]
T. Tavassoli and P. Devilee, Pathology & Genetics. Tumours of the Breast and Female Genital Organs, IARC Press, Lyon, France, 2003.
[15]
E. A. Rakha, N. Gandhi, F. Climent et al., “Encapsulated papillary carcinoma of the breast: an invasive tumor with excellent prognosis,” American Journal of Surgical Pathology, vol. 35, no. 8, pp. 1093–1103, 2011.
[16]
C. O. C. Bellamy, C. McDonald, D. M. Salter, U. Chetty, and T. J. Anderson, “Noninvasive ductal carcinoma of the breast: the relevance of histologic categorization,” Human Pathology, vol. 24, no. 1, pp. 16–23, 1993.
[17]
F. P. O'Malley and A. Bane, “An update on apocrine lesions of the breast,” Histopathology, vol. 52, no. 1, pp. 3–10, 2008.
[18]
F. P. O'Malley and A. L. Bane, “The spectrum of apocrine lesions of the breast,” Advances in Anatomic Pathology, vol. 11, no. 1, pp. 1–9, 2004.
[19]
C. Leal, R. Henrique, P. Monteiro et al., “Apocrine ductal carcinoma in situ of the breast: histologic classification and expression of biologic markers,” Human Pathology, vol. 32, no. 5, pp. 487–493, 2001.
[20]
P. Guerry, R. A. Erlandson, and P. P. Rosen, “Cystic hypersecretory hyperplasia and cystic hypersecretory duct carcinoma of the breast: pathology, therapy, and follow-up of 39 patients,” Cancer, vol. 61, no. 8, pp. 1611–1620, 1988.
[21]
P. P. Rosen and M. Scott, “Cystic hypersecretory duct carcinoma of the breast,” American Journal of Surgical Pathology, vol. 8, no. 1, pp. 31–41, 1984.
[22]
I. de Mascarel, G. MacGrogan, S. Mathoulin-Pélissier, I. Soubeyran, V. Picot, and J. M. Coindre, “Breast ductal carcinoma in situ with microinvasion: a definition supported by a long-term study of 1248 serially sectioned ductal carcinomas,” Cancer, vol. 94, no. 8, pp. 2134–2142, 2002.
[23]
“Breast,” in AJCC Cancer Staging Manual, F. L. Greene, D. L. Page, I. D. Fleming, et al., Eds., pp. 221–240, 6th edition, 2002.
[24]
T. L. Adamovich and R. M. Simmons, “Ductal carcinoma in situ with microinvasion,” American Journal of Surgery, vol. 186, no. 2, pp. 112–116, 2003.
[25]
D. L. Page, W. D. Dupont, L. W. Rogers, and M. Landenberger, “Intraductal carcinoma of the breast: follow-up after biopsy only,” Cancer, vol. 49, no. 4, pp. 751–758, 1982.
[26]
L. C. Collins, R. M. Tamimi, H. J. Baer, J. L. Connolly, G. A. Colditz, and S. J. Schnitt, “Outcome of patients with ductal carcinoma in situ untreated after diagnostic biopsy: results from the nurses' health study,” Cancer, vol. 103, no. 9, pp. 1778–1784, 2005.
[27]
B. Fisher, S. Land, E. Mamounas, J. Dignam, E. R. Fisher, and N. Wolmark, “Prevention of invasive breast cancer in women with ductal carcinoma in situ: an update of the National Surgical Adjuvant Breast and Bowel Project experience,” Seminars in Oncology, vol. 28, no. 4, pp. 400–418, 2001.
[28]
J. P. Julien, N. Bijker, I. S. Fentiman et al., “Radiotherapy in breast-conserving treatment for ductal carcinoma in situ: first results of the EORTC randomised phase III trial 10853,” The Lancet, vol. 355, no. 9203, pp. 528–533, 2000.
[29]
N. Bijker, P. Meijnen, J. L. Peterse et al., “Breast-conserving treatment with or without radiotherapy in ductal carcinoma-in-situ: ten-year results of european organisation for research and treatment of cancer randomized phase III trial 10853—a study by the EORTC breast cancer cooperative group and EORTC radiotherapy group,” Journal of Clinical Oncology, vol. 24, no. 21, pp. 3381–3387, 2006.
[30]
T. Shamliyan, S. Y. Wang, B. A. Virnig, T. M. Tuttle, and R. L. Kane, “Association between patient and tumor characteristics with clinical outcomes in women with ductal carcinoma in situ,” Journal of the National Cancer Institute Monographs, vol. 2010, no. 41, pp. 121–129, 2010.
[31]
M. J. Silverstein, M. D. Lagios, P. H. Craig, et al., “A prognostic index for ductal carcinoma in situ of the breast,” Cancer, vol. 77, no. 11, pp. 2267–2274, 1996.
[32]
M. J. Silverstein, “The University of Southern California/Van Nuys prognostic index for ductal carcinoma in situ of the breast,” American Journal of Surgery, vol. 186, no. 4, pp. 337–343, 2003.
[33]
M. J. Silverstein and M. D. Lagios, “Choosing treatment for patients with ductal carcinoma in situ: fine tuning the University of Southern California/Van Nuys Prognostic Index,” Journal of the National Cancer Institute, vol. 2010, no. 41, pp. 193–196, 2010.
[34]
R. W. Carlson, D. C. Allred, B. O. Anderson, et al., “Breast cancer: noninvasive and special situations,” Journal of the National Comprehensive Cancer Network, vol. 8, no. 10, pp. 1182–1207, 2010.
[35]
D. C. Allred, S. J. Anderson, S. Paik, et al., “Adjuvant tamoxifen reduces subsequent breast cancer in women with estrogen receptor-positive ductal carcinoma in situ: a study based on NSABP protocol B-24,” Journal of Clinical Oncology, vol. 30, no. 12, pp. 1268–1273, 2012.
[36]
A. Grin, F. P. O'Malley, and A. M. Mulligan, “Cytokeratin 5 and estrogen receptor immunohistochemistry as a useful adjunct in identifying atypical papillary lesions on breast needle core biopsy,” American Journal of Surgical Pathology, vol. 33, no. 11, pp. 1615–1623, 2009.
[37]
F. Otterbach, A. Bànkfalvi, S. Bergner, T. Decker, R. Krech, and W. Boecker, “Cytokeratin 5/6 immunohistochemistry assists the differential diagnosis of atypical proliferations of the breast,” Histopathology, vol. 37, no. 3, pp. 232–240, 2000.
[38]
C. M. Perou, T. S?rlie, M. B. Eisen et al., “Molecular portraits of human breast tumours,” Nature, vol. 406, no. 6797, pp. 747–752, 2000.
[39]
T. S?rlie, C. M. Perou, R. Tibshirani et al., “Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 19, pp. 10869–10874, 2001.
[40]
T. S?rlie, R. Tibshirani, J. Parker et al., “Repeated observation of breast tumor subtypes in independent gene expression data sets,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 14, pp. 8418–8423, 2003.
[41]
A. Vincent-Salomon, C. Lucchesi, N. Gruel et al., “Integrated genomic and transcriptomic analysis of ductal carcinoma in situ of the breast,” Clinical Cancer Research, vol. 14, no. 7, pp. 1956–1965, 2008.
[42]
J. Hannemann, A. Velds, J. B. G. Halfwerk, B. Kreike, J. L. Peterse, and M. J. van de Vijver, “Classification of ductal carcinoma in situ by gene expression profiling,” Breast Cancer Research, vol. 8, no. 5, article R61, 2006.
[43]
S. E. Clark, J. Warwick, R. Carpenter, R. L. Bowen, S. W. Duffy, and J. L. Jones, “Molecular subtyping of DCIS: heterogeneity of breast cancer reflected in pre-invasive disease,” British Journal of Cancer, vol. 104, no. 1, pp. 120–127, 2011.
[44]
R. M. Tamimi, H. J. Baer, J. Marotti et al., “Comparison of molecular phenotypes of ductal carcinoma in situ and invasive breast cancer,” Breast Cancer Research, vol. 10, no. 4, article R67, 2008.
[45]
C. A. Livasy, C. M. Perou, G. Karaca et al., “Identification of a basal-like subtype of breast ductal carcinoma in situ,” Human Pathology, vol. 38, no. 2, pp. 197–204, 2007.
[46]
M. A. Lopez-Garcia, F. C. Geyer, M. Lacroix-Triki, C. Marchió, and J. S. Reis-Filho, “Breast cancer precursors revisited: molecular features and progression pathways,” Histopathology, vol. 57, no. 2, pp. 171–192, 2010.
[47]
S. R. Wellings and H. M. Jensen, “On the origin and progression of ductal carcinoma in the human breast,” Journal of the National Cancer Institute, vol. 50, no. 5, pp. 1111–1116, 1973.
[48]
S. R. Wellings, H. M. Jensen, and R. G. Marcum, “An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions,” Journal of the National Cancer Institute, vol. 55, no. 2, pp. 231–273, 1975.
[49]
T. M. A. Abdel-Fatah, D. G. Powe, Z. Hodi, J. S. Reis-Filho, A. H. S. Lee, and I. O. Ellis, “Morphologic and molecular evolutionary pathways of low nuclear grade invasive breast cancers and their putative precursor lesions: further evidence to support the concept of low nuclear grade breast neoplasia family,” American Journal of Surgical Pathology, vol. 32, no. 4, pp. 513–523, 2008.
[50]
P. T. Simpson, J. S. Reis-Filho, T. Gale, and S. R. Lakhani, “Molecular evolution of breat cancer,” Journal of Pathology, vol. 205, no. 2, pp. 248–254, 2005.