Risk of locoregional recurrence by receptor status in breast cancer patients receiving modern systemic therapy and post-mastectomy radiation
- 516 Downloads
We assessed differences in locoregional outcome based on receptor status combinations in a cohort of stage II–III breast cancer patients treated with modern trimodality therapy. Medical records of 582 consecutively treated patients receiving post-mastectomy radiation (PMRT) between 1/1999 and 12/2009 were reviewed. Rate of local regional recurrence (LRR) was estimated by the method of cumulative incidence allowing for competing risks. The effect of prognostic factors was examined by Gray’s test and by Fine and Gray’s modeling approach. Median follow-up was 44.7 months. Five-year progression-free survival (PFS) was 73.9% and overall survival (OS) was 84%. The cumulative 5-year incidence of LRR as first site of failure was 6.2% (95% CI 4.2–8.7). Five-year cumulative incidence of LRR was 8.6 versus 4.4% for estrogen receptor (ER) negative versus ER positive (P = 0.017), 8.5 versus 3.4% for progesterone receptor (PR) negative versus PR positive (P = 0.011), and 1.7 versus 7.5% for HER2 positive (86% received trastuzamab) versus HER2 negative (P = 0.032). Five-year cumulative incidence of LRR was 11.8% for the triple negative subtype and 3.9% for other receptor combinations (P < 0.001). Among patients whose disease is ER positive, 5-year LRR rate was 7.8 versus 3.4% for PR negative versus PR positive (P = 0.130). The prognostic value of the triple negative and HER2 negative subtypes was maintained on multivariate analysis. In the era of HER-2 targeted therapy, tumors that are HER-2 over expressing and are treated with trastuzumab have a very low rate of LRR. ER negative, PR negative, and triple negative status are associated with increased risk of LRR.
KeywordsEstrogen Receptor Trastuzumab Progesterone Receptor Progesterone Receptor Status Triple Negative Tumor
The authors would like to acknowledge the contribution of Vijayalakshmi Gunaseelan, database manager, for her work in the development of the database used for this work.
Conflict of interest
The authors have no disclaimer or disclosures.
- 1.Woodward WA, Truong PT, Yu TK, Tereffe W, Oh J, Perkins G, Strom E, Meric-Bernstam F, Gonzalez-Angulo AM, Speers C et al (2010) Among women who experience a recurrence after postmastectomy radiation therapy irradiation is not associated with more aggressive local recurrence or reduced survival. Breast Cancer Res Treat 123(2):597–605PubMedCrossRefGoogle Scholar
- 2.Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, Kjaer M, Gadeberg CC, Mouridsen HT, Jensen MB et al (1997) Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med 337(14):949–955PubMedCrossRefGoogle Scholar
- 3.Overgaard M, Jensen MB, Overgaard J, Hansen PS, Rose C, Andersson M, Kamby C, Kjaer M, Gadeberg CC, Rasmussen BB et al (1999) Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet 353(9165):1641–1648PubMedCrossRefGoogle Scholar
- 4.Ragaz J, Olivotto IA, Spinelli JJ, Phillips N, Jackson SM, Wilson KS, Knowling MA, Coppin CM, Weir L, Gelmon K et al (2005) Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst 97(2):116–126PubMedCrossRefGoogle Scholar
- 5.Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans E, Godwin J, Gray R, Hicks C, James S et al (2005) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366(9503):2087–2106PubMedGoogle Scholar
- 8.Hurley J, Doliny P, Reis I, Silva O, Gomez-Fernandez C, Velez P, Pauletti G, Powell JE, Pegram MD, Slamon DJ (2006) Docetaxel, cisplatin, and trastuzumab as primary systemic therapy for human epidermal growth factor receptor 2-positive locally advanced breast cancer. J Clin Oncol 24(12):1831–1838PubMedCrossRefGoogle Scholar
- 10.The R Development Core Team. R: a language and environment for statistical computing. R Foundation for Statistical Computing. Version 2.8.0 (2008-10-20), ISBN 3-900051-07-0. http://cran.r-project.org/doc/manuals/refman.pdf
- 15.Nguyen PL, Taghian AG, Katz MS, Niemierko A, Abi Raad RF, Boon WL, Bellon JR, Wong JS, Smith BL, Harris JR (2008) Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol 26(14):2373–2378PubMedCrossRefGoogle Scholar
- 16.Millar EK, Graham PH, O’Toole SA, McNeil CM, Browne L, Morey AL, Eggleton S, Beretov J, Theocharous C, Capp A (2009) Prediction of local recurrence, distant metastases, and death after breast-conserving therapy in early-stage invasive breast cancer using a five-biomarker panel. J Clin Oncol 27(28):4701–4708PubMedCrossRefGoogle Scholar
- 18.Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, Goldhirsch A, Untch M, Mariani G, Baselga J et al (2007) 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 369(9555):29–36PubMedCrossRefGoogle Scholar
- 19.Chumsri S, Jeter S, Jacobs LK, Nassar H, Armstrong DK, Emens LA, Fetting JH, Lange JR, Riley C, Tsangaris TN et al (2010) Pathologic complete response to preoperative sequential doxorubicin/cyclophosphamide and single-agent taxane with or without trastuzumab in stage II/III HER2-positive breast cancer. Clin Breast Cancer 10(1):40–45PubMedCrossRefGoogle Scholar
- 20.Peintinger F, Buzdar AU, Kuerer HM, Mejia JA, Hatzis C, Gonzalez-Angulo AM, Pusztai L, Esteva FJ, Dawood SS, Green MC et al (2008) Hormone receptor status and pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab. Ann Oncol 19(12):2020–2025PubMedCrossRefGoogle Scholar
- 21.Kyndi M, Overgaard M, Nielsen HM, Sorensen FB, Knudsen H, Overgaard J (2009) High local recurrence risk is not associated with large survival reduction after postmastectomy radiotherapy in high-risk breast cancer: a subgroup analysis of DBCG 82 b&c. Radiother Oncol 90(1):74–79PubMedCrossRefGoogle Scholar