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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2017

01-06-2017 | Epidemiology

Failure patterns according to molecular subtype in patients with invasive breast cancer following postoperative adjuvant radiotherapy: long-term outcomes in contemporary clinical practice

Authors: Yu Jin Lim, Sea-Won Lee, Noorie Choi, Jeanny Kwon, Keun-Yong Eom, Eunyoung Kang, Eun-Kyu Kim, Sung-Won Kim, Jee Hyun Kim, Yu Jung Kim, Se Hyun Kim, So Yeon Park, Jae-Sung Kim, In Ah Kim

Published in: Breast Cancer Research and Treatment | Issue 3/2017

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Abstract

Purpose

Although gene expression profiling provides critical information, knowledge remains limited regarding the differential effects of molecular subtype on clinical course. This study evaluated the impact of molecular status on long-term patterns of failure in patients with non-metastatic breast cancer.

Methods

We analyzed data from 1181 individuals with invasive breast cancer undergoing surgery plus PORT from 2003 to 2011. Molecular subtypes were defined as luminal A (LA), luminal B (LB)-HER2(−), LB-HER2(+), HER2, and triple-negative (TN) based on the 2013 St. Gallen Consensus criteria. Competing risks analysis and baseline hazard rate function plots were used to explore subtype-specific recurrence patterns.

Results

The 10-year overall survival rates of LA, LB-HER2(−), LB-HER2(+), HER2, and TN groups were 96, 93, 94, 84, and 85%, respectively (P < 0.001). Distant metastatic events differed significantly according to molecular subtype (P < 0.001). In competing risks regression analysis, initial development of distant metastasis was the highest with TN tumors, followed by HER2, LB-HER2(−), and LB-HER2(+) subtypes (P = 0.005). Regarding preferential sites of distant metastasis, the risk of initial brain metastasis was significantly higher with HER2 tumors, followed by TN tumors (P = 0.001). A low-level but sustained metastatic risk increment was observed in luminal tumors, whereas TN and HER2 subtypes showed a short-term risk surge within 5 years.

Conclusion

From the significant impact of molecular profile on distant metastasis, subtype-specific individualization of systemic treatment and close surveillance are suggested. The preferential and long-term risk of brain metastasis in the HER2 subtype underlines the importance of alternative anti-HER2 therapies.
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Literature
1.
Weigelt B, Baehner FL, Reis-Filho JS (2010) The contribution of gene expression profiling to breast cancer classification, prognostication and prediction: a retrospective of the last decade. J Pathol 220:263–280CrossRefPubMed
2.
van de Vijver MJ, He YD, van’t Veer LJ et al (2002) A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347:1999–2009CrossRefPubMed
3.
Sotiriou C, Neo SY, McShane LM et al (2003) Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci USA 100:10393–10398CrossRefPubMedPubMedCentral
4.
Goldhirsch A, Winer EP, Coates AS et al (2013) Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 24:2206–2223CrossRefPubMedPubMedCentral
5.
6.
7.
8.
9.
Ross JS, Slodkowska EA, Symmans WF et al (2009) The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist 14:320–368CrossRefPubMed
10.
Sorlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98:10869–10874CrossRefPubMedPubMedCentral
11.
12.
13.
Scrucca L, Santucci A, Aversa F (2007) Competing risk analysis using R: an easy guide for clinicians. Bone Marrow Transplant 40:381–387CrossRefPubMed
14.
Scrucca L, Santucci A, Aversa F (2010) Regression modeling of competing risk using R: an in depth guide for clinicians. Bone Marrow Transplant 45:1388–1395CrossRefPubMed
15.
Voduc KD, Cheang MC, Tyldesley S et al (2010) Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol 28:1684–1691CrossRefPubMed
16.
Lee Y, Kang E, Lee AS et al (2015) Outcomes and recurrence patterns according to breast cancer subtypes in Korean women. Breast Cancer Res Treat 151:183–190CrossRefPubMed
17.
Hennigs A, Riedel F, Gondos A et al (2016) Prognosis of breast cancer molecular subtypes in routine clinical care: a large prospective cohort study. BMC Cancer 16:734CrossRefPubMedPubMedCentral
18.
Shim HJ, Kim SH, Kang BJ et al (2014) Breast cancer recurrence according to molecular subtype. Asian Pac J Cancer Prev 15:5539–5544CrossRefPubMed
19.
Haffty BG, Yang Q, Reiss M et al (2006) Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol 24:5652–5657CrossRefPubMed
20.
Millar EK, Graham PH, O’Toole SA et al (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 27:4701–4708CrossRefPubMed
21.
Sihto H, Lundin J, Lundin M et al (2011) Breast cancer biological subtypes and protein expression predict for the preferential distant metastasis sites: a nationwide cohort study. Breast Cancer Res 13:R87CrossRefPubMedPubMedCentral
22.
Soni A, Ren Z, Hameed O et al (2015) Breast cancer subtypes predispose the site of distant metastases. Am J Clin Pathol 143:471–478CrossRefPubMed
23.
Alqaisi A, Chen L, Romond E et al (2014) Impact of estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER2) co-expression on breast cancer disease characteristics: implications for tumor biology and research. Breast Cancer Res Treat 148:437–444CrossRefPubMed
24.
Kaplan MA, Arslan UY, Isikdogan A et al (2016) Biological subtypes and distant relapse pattern in breast cancer patients after curative surgery (Study of anatolian society of medical oncology). Breast Care 11:248–252CrossRefPubMed
25.
Park HS, Kim S, Kim K et al (2012) Pattern of distant recurrence according to the molecular subtypes in Korean women with breast cancer. World J Surg Oncol 10:4CrossRefPubMedPubMedCentral
26.
Wu SG, Sun JY, Yang LC et al (2016) Patterns of distant metastasis in Chinese women according to breast cancer subtypes. Oncotarget 7:47975–47984PubMedPubMedCentral
27.
Smid M, Wang Y, Zhang Y et al (2008) Subtypes of breast cancer show preferential site of relapse. Cancer Res 68:3108–3114CrossRefPubMed
28.
Kimbung S, Loman N, Hedenfalk I (2015) Clinical and molecular complexity of breast cancer metastases. Semin Cancer Biol 35:85–95CrossRefPubMed
29.
Musolino A, Ciccolallo L, Panebianco M et al (2011) Multifactorial central nervous system recurrence susceptibility in patients with HER2-positive breast cancer: epidemiological and clinical data from a population-based cancer registry study. Cancer 117:1837–1846CrossRefPubMed
30.
Kennecke H, Yerushalmi R, Woods R et al (2010) Metastatic behavior of breast cancer subtypes. J Clin Oncol 28:3271–3277CrossRefPubMed
31.
Gaedcke J, Traub F, Milde S et al (2007) Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer. Mod Pathol 20:864–870CrossRefPubMed
32.
Gabos Z, Sinha R, Hanson J et al (2006) Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer. J Clin Oncol 24:5658–5663CrossRefPubMed
33.
Palmieri D, Bronder JL, Herring JM et al (2007) Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain. Cancer Res 67:4190–4198CrossRefPubMed
34.
Yonemori K, Tsuta K, Ono M et al (2010) Disruption of the blood brain barrier by brain metastases of triple-negative and basal-type breast cancer but not HER2/neu-positive breast cancer. Cancer 116:302–308CrossRefPubMed
35.
Romond EH, Perez EA, Bryant J et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:1673–1684CrossRefPubMed
36.
Koo T, Kim IA (2016) Brain metastasis in human epidermal growth factor receptor 2-positive breast cancer: from biology to treatment. Radiat Oncol J 34:1–9CrossRefPubMedPubMedCentral
37.
38.
Ribelles N, Perez-Villa L, Jerez JM et al (2013) Pattern of recurrence of early breast cancer is different according to intrinsic subtype and proliferation index. Breast Cancer Res 15:R98CrossRefPubMedPubMedCentral
Metadata
Title
Failure patterns according to molecular subtype in patients with invasive breast cancer following postoperative adjuvant radiotherapy: long-term outcomes in contemporary clinical practice
Authors
Yu Jin Lim
Sea-Won Lee
Noorie Choi
Jeanny Kwon
Keun-Yong Eom
Eunyoung Kang
Eun-Kyu Kim
Sung-Won Kim
Jee Hyun Kim
Yu Jung Kim
Se Hyun Kim
So Yeon Park
Jae-Sung Kim
In Ah Kim
Publication date
01-06-2017
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2017
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-017-4206-8

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