Abstract
Tamoxifen is known to reduce the risk of breast cancer in women at high risk and also reduces mammographic breast density (MD) in a preventive setting. We investigated the efficacy of MD reduction (MDR) for predicting recurrence in estrogen receptor (ER)-positive patients in an adjuvant setting. A total of 1,066 ER-positive breast cancer patients who were enrolled in this study underwent curative surgery and received adjuvant tamoxifen for at least 2 years at our institution between January 2003 and December 2008. Using a computerized system, a single radiologist reviewed all mammograms and classified MD patterns on the basis of the Breast Imaging Reporting and Data System. MDR was assessed using the baseline mammogram taken before surgery (preMD) and the follow-up mammogram taken after the start of adjuvant tamoxifen (postMD). MDR positivity was defined as downgrading of the postMD grade, with the preMD grade as a reference. Patients were divided into 2 groups, MDR-positive and MDR-negative, for statistical analysis. Patients who showed MDR after an average of 19 months of adjuvant tamoxifen treatment had a 65 % lower risk of recurrence than patients who did not show MDR. Furthermore, significant risk reduction according to MDR had a predictive power for any type of recurrence pattern including loco-regional recurrence (87 % reduction) and systemic recurrence (52 % reduction) in ER-positive breast cancer patients, especially in women ≤50 years. In our study, only 4 patients (0.4 %) showed contralateral breast recurrence during the mean 61-month follow-up period and none of them experienced MDR. In conclusion, MDR during adjuvant tamoxifen therapy was independently associated with a lower risk of systemic and loco-regional recurrence in ER-positive breast cancer patients, especially in young women. For patients who do not experience MDR after approximately 1.5 years of tamoxifen therapy, more caution should be taken and other treatment strategies are warranted.
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References
Jensen EV, Jordan VC (2003) The estrogen receptor: a model for molecular medicine. Clin Cancer Res 9(6):1980–1989
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365(9472):1687–1717. doi:10.1016/S0140-6736(05)66544-0
Prowell TM, Blackford AL, Byrne C, Khouri NF, Dowsett M, Folkerd E, Tarpinian KS, Powers PP, Wright LA, Donehower MG, Jeter SC, Armstrong DK, Emens LA, Fetting JH, Wolff AC, Garrett-Mayer E, Skaar TC, Davidson NE, Stearns V et al (2011) Changes in breast density and circulating estrogens in postmenopausal women receiving adjuvant anastrozole. Cancer Prev Res (Phila) 4(12):1993–2001. doi:10.1158/1940-6207.capr-11-0154
Johns PC, Yaffe MJ (1987) X-ray characterisation of normal and neoplastic breast tissues. Phys Med Biol 32(6):675–695
Boyd NF, Martin LJ, Yaffe MJ, Minkin S (2006) Mammographic density: a hormonally responsive risk factor for breast cancer. J Br Menopause Soc 12(4):186–193. doi:10.1258/136218006779160436
Boyd NF, Guo H, Martin LJ, Sun L, Stone J, Fishell E, Jong RA, Hislop G, Chiarelli A, Minkin S, Yaffe MJ (2007) Mammographic density and the risk and detection of breast cancer. New Engl J Med 356(3):227–236. doi:10.1056/NEJMoa062790
Ursin G, Ma H, Wu AH, Bernstein L, Salane M, Parisky YR, Astrahan M, Siozon CC, Pike MC (2003) Mammographic density and breast cancer in three ethnic groups. Cancer Epidemiol Biomarkers Prev 12(4):332–338
Nagata C, Matsubara T, Fujita H, Nagao Y, Shibuya C, Kashiki Y, Shimizu H (2005) Mammographic density and the risk of breast cancer in Japanese women. Br J Cancer 92(12):2102–2106. doi:10.1038/sj.bjc.6602643
Cuzick J, Warwick J, Pinney E, Duffy SW, Cawthorn S, Howell A, Forbes JF, Warren RM (2011) Tamoxifen-induced reduction in mammographic density and breast cancer risk reduction: a nested case–control study. J Natl Cancer Inst 103(9):744–752. doi:10.1093/jnci/djr079
Kim J, Han W, Moon HG, Ahn SK, Shin HC, You JM, Han SW, Im SA, Kim TY, Koo HR, Chang JM, Cho N, Moon WK, Noh DY (2012) Breast density change as a predictive surrogate for response to adjuvant endocrine therapy in hormone receptor positive breast cancer. Breast Cancer Res 14(4):R102. doi:10.1186/bcr3221
Bartlett JM, Bloom KJ, Piper T, Lawton TJ, van de Velde CJ, Ross DT, Ring BZ, Seitz RS, Beck RA, Hasenburg A, Kieback D, Putter H, Markopoulos C, Dirix L, Seynaeve C, Rea D (2012) Mammostrat as an immunohistochemical multigene assay for prediction of early relapse risk in the tamoxifen versus exemestane adjuvant multicenter trial pathology study. J Clin Oncol. doi:10.1200/jco.2012.42.8896
Musgrove EA, Sutherland RL (2009) Biological determinants of endocrine resistance in breast cancer. Nat Rev Cancer 9(9):631–643. doi:10.1038/nrc2713
Vachon CM, Brandt KR, Ghosh K, Scott CG, Maloney SD, Carston MJ, Pankratz VS, Sellers TA (2007) Mammographic breast density as a general marker of breast cancer risk. Cancer Epidemiol Biomarkers Prev 16(1):43–49. doi:10.1158/1055-9965.epi-06-0738
Jeon JH, Kang JH, Kim Y, Lee HY, Choi KS, Jun JK, Oh DK, Lee CY, Ko K, Park EC (2011) Reproductive and hormonal factors associated with fatty or dense breast patterns among Korean women. Cancer Res Treat 43(1):42–48. doi:10.4143/crt.2011.43.1.42
Verheus M, Maskarinec G, Erber E, Steude JS, Killeen J, Hernandez BY, Cline JM (2009) Mammographic density and epithelial histopathologic markers. BMC Cancer 9:182. doi:10.1186/1471-2407-9-182
Ghosh K, Brandt KR, Reynolds C, Scott CG, Pankratz VS, Riehle DL, Lingle WL, Odogwu T, Radisky DC, Visscher DW, Ingle JN, Hartmann LC, Vachon CM (2012) Tissue composition of mammographically dense and non-dense breast tissue. Breast Cancer Res Treat 131(1):267–275. doi:10.1007/s10549-011-1727-4
Bines J, Oleske DM, Cobleigh MA (1996) Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol 14(5):1718–1729
Fornier MN, Modi S, Panageas KS, Norton L, Hudis C (2005) Incidence of chemotherapy-induced, long-term amenorrhea in patients with breast carcinoma age 40 years and younger after adjuvant anthracycline and taxane. Cancer 104(8):1575–1579. doi:10.1002/cncr.21385
Boyd NF, Martin LJ, Bronskill M, Yaffe MJ, Duric N, Minkin S (2010) Breast tissue composition and susceptibility to breast cancer. J Natl Cancer Inst 102(16):1224–1237. doi:10.1093/jnci/djq239
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This work was supported by grant from the National Cancer Center Korea (1211200-1).
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Kyoung Lan Ko and In Suk Shin contributed equally to this paper.
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Ko, K.L., Shin, I.S., You, J.Y. et al. Adjuvant tamoxifen-induced mammographic breast density reduction as a predictor for recurrence in estrogen receptor-positive premenopausal breast cancer patients. Breast Cancer Res Treat 142, 559–567 (2013). https://doi.org/10.1007/s10549-013-2726-4
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DOI: https://doi.org/10.1007/s10549-013-2726-4