Introduction. About half of all new ipsilateral events after a primary ductal carcinoma in situ (DCIS) are invasive carcinoma. We studied tumor markers in the primary DCIS in relation to type of event (invasive versus in situ). Methods. Two hundred and sixty-six women with a primary DCIS from two source populations, all with a known ipsilateral event, were included. All new events were regarded as recurrences. Patient and primary tumor characteristics (estrogen receptor (ER), progesterone receptor (PR), HER2, EGFR, and Ki67) were evaluated. Logistic regression was used to calculate odd ratios and 95% confidence intervals in univariate and multivariate analyses. Results. One hundred and thirty-six of the recurrences were invasive carcinoma and 130 were in situ. The recurrence was more often invasive if the primary DCIS was ER+ (OR 2.5, 95% CI 1.2–5.1). Primary DCIS being HER2+ (OR 0.5, 95% CI 0.3–0.9), EGFR+ (OR 0.4, 95% CI 0.2–0.9), and ER95？/HER2+ (OR 0.2, 95% CI 0.1–0.6) had a lower risk of a recurrence being invasive. Conclusions. In this study, comparing type of recurrence after a DCIS showed that the ER？/HER2+ tumors were related to a recurrence being a new DCIS. And surprisingly, tumors being ER+, HER2？, and EGFR？ were related to a recurrence being invasive cancer. 1. Introduction Ductal carcinoma in situ (DCIS) of the breast is a clinically and molecularly heterogeneous disease with different malignant potentials [1, 2]. The risk of local recurrence after breast-conserving surgery only (BCS) is rather high and even higher than after surgery for invasive breast cancer [3, 4]. In DCIS, adding radiotherapy after BCS lowered the relative risk with approximately 50%, from 28.1% to 12.9% after ten years in a meta-analyses including four randomized studies [5, 6]. About half of the women with a local recurrence develop a new DCIS and the other half an invasive carcinoma [7–10]. Although women with a primary DCIS have a very good prognosis [6], those with a subsequent invasive carcinoma have an increased risk of dying from breast cancer. In a recently published study the 15-year breast cancer specific survival was just over 60% among those with an invasive recurrence after a primary DCIS [11, 12]. One of the major goals of the treatment of DCIS is to prevent invasive disease. There are surgical and biological risk factors for local recurrence, for example, young age, mode of detection (clinically detected as compared to screening detected), margins, and grade [13, 14]. Also, a recently published study using the Oncotype DX DCIS score showed that
References
[1]
D. Porter, J. Lahti-Domenici, A. Keshaviah et al., “Molecular markers in ductal carcinoma in situ of the breast,” Molecular Cancer Research, vol. 1, no. 5, pp. 362–375, 2003.
[2]
E. S. Wai, M. L. Lesperance, C. S. Alexander et al., “Predictors of local recurrence in a population-based cohort of women with ductal carcinoma in situ treated with breast conserving surgery alone,” Annals of Surgical Oncology, vol. 18, no. 1, pp. 119–124, 2011.
[3]
S. Darby, P. McGale, C. Correa et al., “Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10 801 women in 17 randomised trials,” The Lancet, vol. 378, no. 9804, pp. 1707–1716, 2011.
[4]
E. T. Siponen, H. Joensuu, and M. H. Leidenius, “Local recurrence of breast cancer after mastectomy and modern multidisciplinary treatment,” Acta Oncologica, vol. 52, no. 1, pp. 66–72, 2013.
[5]
C. Correa, P. McGale, C. Taylor et al., “Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast,” Journal of the National Cancer Institute Monographs, vol. 2010, no. 41, pp. 162–177, 2010.
[6]
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.
[7]
C. Correa, P. McGale, C. Taylor et al., “Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast,” Journal of the National Cancer Institute, no. 41, pp. 162–177, 2010.
[8]
S. Emdin, B. Granstrand, A. Ringberg et al., “SweDCIS: radiotherapy after sector resection for ductal carcinoma in situ of the breast. Results of a randomised trial in a population offered mammography screening,” Acta Oncologica, vol. 45, no. 5, pp. 536–543, 2006.
[9]
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.
[10]
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.
[11]
L. A. Lee, M. J. Silverstein, C. T. Chung et al., “Breast cancer-specific mortality after invasive local recurrence in patients with ductal carcinoma-in-situ of the breast,” American Journal of Surgery, vol. 192, no. 4, pp. 416–419, 2006.
[12]
M. Donker, S. Litière, G. Werutsky, et al., “Breast-conserving treatment with or without radiotherapy in ductal carcinoma in situ: 15-year recurrence rates and outcome after a recurrence, from the EORTC, 10853 randomized phase III trial,” Journal of Clinical Oncology, 2013.
[13]
A. Ringberg, H. Nordgren, S. Thorstensson et al., “Histopathological risk factors for ipsilateral breast events after breast conserving treatment for ductal carcinoma in situ of the breast—results from the Swedish randomised trial,” European Journal of Cancer, vol. 43, no. 2, pp. 291–298, 2007.
[14]
G. F. Schwartz, L. J. Solin, I. A. Olivotto, V. L. Ernster, and P. I. Pressman, “Consensus conference on the treatment of in situ ductal carcinoma of the breast, April 22–25, 1999,” Cancer, vol. 88, no. 4, pp. 946–954, 2000.
[15]
L. J. Solin, R. Gray, F. L. Baehner, et al., “A multigene expression assay to predict local recurrence risk for ductal carcinoma in situ,” Journal of the National Cancer Institute, vol. 105, no. 10, pp. 701–710, 2013.
[16]
D. B. Cornfield, J. P. Palazzo, G. F. Schwartz et al., “The prognostic significance of multiple morphologic features and biologic markers in ductal carcinoma in situ of the breast: a study of a large cohort of patients treated with surgery alone,” Cancer, vol. 100, no. 11, pp. 2317–2327, 2004.
[17]
K. Kerlikowske, A. M. Molinaro, M. L. Gauthier et al., “Biomarker expression and risk of subsequent tumors after initial ductal carcinoma in situ diagnosis,” Journal of the National Cancer Institute, vol. 102, no. 9, pp. 627–637, 2010.
[18]
E. Provenzano, J. L. Hopper, G. G. Giles, G. Marr, D. J. Venter, and J. E. Armes, “Biological markers that predict clinical recurrence in ductal carcinoma in situ of the breast,” European Journal of Cancer, vol. 39, no. 5, pp. 622–630, 2003.
[19]
A. Ringberg, L. Anagnostaki, H. Anderson, I. Idvall, and M. Fern？, “Cell biological factors in ductal carcinoma in situ (DCIS) of the breast-relationship to ipsilateral local recurrence and histopathological characteristics,” European Journal of Cancer, vol. 37, no. 12, pp. 1514–1522, 2001.
[20]
K. Jirstr？m, A. Ringberg, M. Fern？, L. Anagnostaki, and G. Landberg, “Tissue microarray analyses of G1/S-regulatory proteins in ductal carcinoma in situ of the breast indicate that low cyclin D1 is associated with local recurrence,” British Journal of Cancer, vol. 89, no. 10, pp. 1920–1926, 2003.
[21]
F. W？rnberg, R.-M. Amini, M. Goldman, and K. Jirstr？m, “Quality aspects of the tissue microarray technique in a population-based cohort with ductal carcinoma in situ of the breast,” Histopathology, vol. 53, no. 6, pp. 642–649, 2008.
[22]
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.
[23]
R. Diallo-Danebrock, E. Ting, O. Gluz et al., “Protein expression profiling in high-risk breast cancer patients treated with high-dose or conventional dose-dense chemotherapy,” Clinical Cancer Research, vol. 13, no. 2, pp. 488–497, 2007.
[24]
C. U. Ihemelandu, L. D. Leffall Jr., R. L. Dewitty et al., “Molecular breast cancer subtypes in premenopausal African-American women, tumor biologic factors and clinical outcome,” Annals of Surgical Oncology, vol. 14, no. 10, pp. 2994–3003, 2007.
[25]
M. Jumppanen, S. Gruvberger-Saal, P. Kauraniemi et al., “Basal-like phenotype is not associated with patient survival in estrogen-receptor-negative breast cancers,” Breast Cancer Research, vol. 9, no. 1, article R16, 2007.
[26]
C. A. Livasy, G. Karaca, R. Nanda et al., “Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma,” Modern Pathology, vol. 19, no. 2, pp. 264–271, 2006.
[27]
E. K. A. Millar, P. H. Graham, C. M. McNeil et al., “Prediction of outcome of early ER breast cancer is improved using a biomarker panel, which includes Ki-67 and p53,” British Journal of Cancer, vol. 105, no. 2, pp. 272–280, 2011.
[28]
L. M. McShane, D. G. Altman, W. Sauerbrei, S. E. Taube, M. Gion, and G. M. Clark, “REporting recommendations for tumor MARKer prognostic studies (REMARK),” Breast Cancer Research and Treatment, vol. 100, no. 2, pp. 229–235, 2006.
[29]
M. J. Silverstein, K. A. Skinner, and T. J. Lomis, “Predicting axillary nodal positivity in 2282 patients with breast carcinoma,” World Journal of Surgery, vol. 25, no. 6, pp. 767–772, 2001.
[30]
E. Rakovitch, S. Nofech-Mozes, W. Hanna et al., “HER2/neu and Ki-67 expression predict non-invasive recurrence following breast-conserving therapy for ductal carcinoma in situ,” British Journal of Cancer, vol. 106, no. 6, pp. 1160–1165, 2012.
[31]
E. K. Latta, S. Tjan, R. K. Parkes, and F. P. O'Malley, “The role of HER2/neu overexpression/amplification in the progression of ductal carcinoma in situ to invasive carcinoma of the breast,” Modern Pathology, vol. 15, no. 12, pp. 1318–1325, 2002.
[32]
T. Perin, V. Canzonieri, S. Massarut et al., “Immunohistochemical evaluation of multiple biological markers in ductal carcinoma in situ of the breast,” European Journal of Cancer A, vol. 32, no. 7, pp. 1148–1155, 1996.
[33]
A. W. Burgess, “EGFR family: structure physiology signalling and therapeutic target,” Growth Factors, vol. 26, no. 5, pp. 263–274, 2008.
[34]
G. Viale, N. Rotmensz, P. Maisonneuve et al., “Invasive ductal carcinoma of the breast with the “triple- negative” phenotype: prognostic implications of EGFR immunoreactivity,” Breast Cancer Research and Treatment, vol. 116, no. 2, pp. 317–328, 2009.
[35]
H. Nogi, T. Kobayashi, M. Suzuki et al., “EGFR as paradoxical predictor of chemosensitivity and outcome among triple-negative breast cancer,” Oncology Reports, vol. 21, no. 2, pp. 413–417, 2009.
[36]
W. Hwangbo, J. H. Lee, S. Ahn, et al., “EGFR gene amplification and protein expression in invasive ductal carcinoma of the breast,” The Korean Journal of Pathology, vol. 47, no. 2, pp. 107–115, 2013.
[37]
W. Zhou, K. Jirstr？m, C. Johansson et al., “Long-term survival of women with basal-like ductal carcinoma in situ of the breast: a population-based cohort study,” BMC Cancer, vol. 10, article 653, 2010.
