Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
World Journal of Surgical Oncology
Published in: World Journal of Surgical Oncology 1/2014

Open Access 01-12-2014 | Research

The efficacy of molecular subtyping in predicting postoperative recurrence in breast-conserving therapy: a 15-study meta-analysis

Authors: Jing Chen, Peng Jiang, Han-jin Wang, Jia-yi Zhang, Yang Xu, Mu-hong Guo, Bin Zhang, Chong-yin Tang, Hong-yong Cao, Shui Wang

Published in: World Journal of Surgical Oncology | Issue 1/2014

Login to get access

Abstract

Background

Recent research displays that breast cancer (BC) is a heterogeneous disease and distinct molecular subtypes yield different prognostic outcomes.

Methods

We conducted a meta-analysis to clarify the role of molecular subtypes in recurrence risk after breast-conserving therapy (BCT). Eligible studies of single- (ER, PR, Her-2, and p53) and triple-molecular (Luminal A, Luminal B, Her-2, triple-negative) subtypes were identified through multiple search strategies. Pooled hazard ratios with 95% confidence intervals were calculated to assess this research topic.

Results

Fifteen studies involving 21,645 participants were included in the meta-analysis. Her-2 positive patients had a significantly higher recurrence risk in both overall merge (HR = 1.97, 95% CI: 1.41-2.75) and subtotal merge of local recurrence (LR) (HR = 1.93, 95% CI: 1.34-2.78). Significantly higher risk of recurrence was also observed in p53 positive patients by overall merge (HR = 1.78, 95% CI: 1.49 -2.12) and subtotal merge of LR (HR = 1.73, 95% CI: 1.44-2.07). When setting Luminal A as a baseline, Luminal B, Her-2, and triple-negative all showed significantly increased risk for both LR and distant recurrence (DR). Comparing triple-negative and non-triple-negative subtypes showed the biggest risk for overall recurrence (HR = 3.19, 95% CI: 1.91-5.31) and LR (HR = 3.31, 95% CI: 1.69-6.45).

Conclusions

Our meta-analysis showed significant differences in recurrence risk among various molecular subtypes after BCT. Although Her-2 and p53 positive subtypes can be considered independent prognostic biomarkers for indicating high LR risk, triple-molecular biomarkers showed higher clinical value. Triple-negative subtype showed the highest recurrence risk among all subtypes, and adjuvant chemotherapy should be considered for it.
Appendix
Available only for authorised users
Literature
1.
Bartelink H, Horiot JC, Poortmans PM, Struikmans H, Van den Bogaert W, Fourquet A, Jager JJ, Hoogenraad WJ, Oei SB, Wárlám-Rodenhuis CC, Pierart M, Collette L: Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial. J Clin Oncol. 2007, 25: 3259-3265.CrossRefPubMed
2.
Clark RM, Whelan T, Levine M, Roberts R, Willan A, McCulloch P, Lipa M, Wilkinson RH, Mahoney LJ: Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: an update. J Natl Cancer Inst. 1996, 88: 1659-1664.CrossRefPubMed
3.
Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, Jeong JH, Wolmark N: Twenty-year follow-up of randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002, 347: 1233-1241.CrossRefPubMed
4.
Freedman GM, Anderson PR, Hanlon AL, Eisenberg DF, Nicolaou N: Pattern of local recurrence after conservative surgery and whole-breast irradiation. Int J Radiat Oncol Biol Phys. 2005, 61: 1328-1336.CrossRefPubMed
5.
Anderson SJ, Wapnir I, Dignam JJ, Fisher B, Mamounas EP, Jeong JH, Geyer CE, Wickerham DL, Costantino JP, Wolmark N: Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in patients treated by breast-conserving therapy in five National Surgical Adjuvant Breast and Bowel Project protocols of node-negative breast cancer. J Clin Oncol. 2009, 27: 2466-2473.PubMedCentralCrossRefPubMed
6.
Veronesi U, Marubini E, Del Vecchio M, Manzari A, Andreola S, Greco M, Luini A, Merson M, Saccozzi R, Rilke F: Local recurrences and distant metastases after conservative breast cancer treatments: partly independent events. J Natl Cancer Inst. 1995, 87: 19-27.CrossRefPubMed
7.
Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, Aguilar M, Marubini E: Twenty year follow-up of a randomized study comparing breastconserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002, 347: 1227-1232.CrossRefPubMed
8.
Jacobson JA, Danforth DN, Cowan KH, d’Angelo T, Steinberg SM, Pierce L, Lippman ME, Lichter AS, Glatstein E, Okunieff P: Ten-year results of a comparison of conservation with mastectomy in the treatment of stage I and II breast cancer. N Engl J Med. 1995, 332: 907-911.CrossRefPubMed
9.
Blichert-Toft M, Rose C, Andersen JA, Overgaard M, Axelsson CK, Andersen KW, Mouridsen HT: Danish randomized trial comparing breast conservation therapy with mastectomy: Six years of life-table analysis—Danish Breast Cancer Cooperative Group. J Natl Cancer Inst Monogr. 1992, 11: 19-25.PubMed
10.
van Dongen JA, Voogd AC, Fentiman IS, Legrand C, Sylvester RJ, Tong D, van der Schueren E, Helle PA, van Zijl K, Bartelink H: Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial. J Natl Cancer Inst. 2000, 92 (14): 1143-1150.CrossRefPubMed
11.
Fisher B, Bryant J, Dignam JJ, Wickerham DL, Mamounas EP, Fisher ER, Margolese RG, Nesbitt L, Paik S, Pisansky TM, Wolmark N: Tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less. J Clin Oncol. 2002, 20: 4141-4149.CrossRefPubMed
12.
Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D: Molecular portraits of human breast tumours. Nature. 2000, 406: 747-752.CrossRefPubMed
13.
Konecny GE: Impact of molecular breast cancer portraits on new treatment strategies for gynecologic malignancies. Curr Opin Obstet Gynecol. 2013, 25 (1): 38-39.CrossRefPubMed
14.
Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lønning PE, Børresen-Dale AL: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001, 98: 10869-10874.PubMedCentralCrossRefPubMed
15.
Oh DS, Troester MA, Usary J, Hu Z, He X, Fan C, Wu J, Carey LA, Perou CM: Estrogenregulated genes predict survival in hormone receptorpositive breast cancers. J Clin Oncol. 2006, 24: 1656-1664.CrossRefPubMed
16.
Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, Hess KR, Stec J, Ayers M, Wagner P, Morandi P, Fan C, Rabiul I, Ross JS, Hortobagyi GN, Pusztai L: Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005, 11: 5678-5685.CrossRefPubMed
17.
Nguyen PL, Taghian AG, Katz MS, Niemierko A, Abi Raad RF, Boon WL, Bellon JR, Wong JS, Smith BL, Harris JR: 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. 2008, 26: 2373-2378.CrossRefPubMed
18.
Albert JM, Gonzalez-Angulo AM, Guray M, Sahin A, Strom EA, Tereffe W, Woodward WA, Tucker SL, Hunt KK, Hortobagyi GN, Buchholz TA: Estrogen/progesterone receptor negativity and HER2 positivity predict locoregional recurrence in patients with T1a, bN0 breast cancer. Int J Radiat Oncol Biol Phys. 2010, 77: 1296-1302.CrossRefPubMed
19.
Voduc KD, Cheang MCU, Tyldesley S, Gelmon K, Nielsen TO, Kennecke H: Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol. 2010, 28: 1684-1691.CrossRefPubMed
20.
Tang P, Skinner KA, Hicks DG: Molecular classification of breast carcinomas by immunohistochemical analysis: Are we ready?. Diagn Mol Pathol. 2009, 18: 125-132.CrossRefPubMed
21.
Tamaki K, Ishida T, Miyashita M, Amari M, Mori N, Ohuchi N, Tamaki N, Sasano H: Multidetector row helical computed tomography for invasive ductal carcinoma of the breast: correlation between radiological findings and the corresponding biological characteristics of patients. Cancer Sci. 2012, 103: 67-72.CrossRefPubMed
22.
Tamaki K, Sasano H, Ishida T, Miyashita M, Takeda M, Amari M, Tamaki N, Ohuchi N: The comparison of core needle biopsy (CNB) and surgical specimens for accurate preoperative evaluation of ER, PgR and HER2 status of breast cancer patients. Cancer Sci. 2010, 101: 2074-2079.CrossRefPubMed
23.
Tamaki K, Ishida T, Miyashita M, Amari M, Ohuchi N, Tamaki N, Sasano H: Correlation between mammographic findings and corresponding histopathology: potential predictors for biological characteristics of breast diseases. Cancer Sci. 2011, 102: 2179-2185.CrossRefPubMed
24.
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB: Meta-analysis of observational studies in epidemiology: aproposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000, 283: 2008-2012.CrossRefPubMed
25.
Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR: Practical methods for incorporating summary time-to-event data into metaanalysis. Trials. 2007, 8: 16-PubMedCentralCrossRefPubMed
26.
Parmar MK, Torri V, Stewart L: Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998, 17: 2815-2834.CrossRefPubMed
27.
Williamson PR, Smith CT, Hutton JL, Marson AG: Aggregate data meta-analysis with time-to-event outcomes. Stat Med. 2002, 21: 3337-3351.CrossRefPubMed
28.
29.
30.
Hattangadi-Gluth JA, Wo JY, Nguyen PL, Abi Raad RF, Sreedhara M, Niemierko A, Freer PE, Georgian-Smith D, Bellon JR, Wong JS, Smith BL, Harris JR, Taghian AG: Basal subtype of invasive breast cancer is associated with a higher risk of true recurrence after conventionalbreast-conserving therapy. Int J Radiat Oncol Biol Phys. 2012, 82: 1185-1191.CrossRefPubMed
31.
Zauls AJ, Watkins JM, Wahlquist AE, Brackett NC, Aguero EG, Baker MK, Jenrette JM, Garrett-Mayer E, Harper JL: Outcomes in women treated with MammoSite brachytherapy or whole breast irradiation stratified by ASTRO Accelerated Partial Breast Irradiation Consensus Statement Groups. Int J Radiat Oncol Biol Phys. 2012, 82: 21-29.CrossRefPubMed
32.
Han K, Nofech-Mozes S, Narod S, Hanna W, Vesprini D, Saskin R, Taylor C, Kong I, Paszat L, Rakovitch E: Expression of HER2neu in ductal carcinoma in situ is associated with local recurrence. Clin Oncol (R Coll Radiol). 2012, 24: 183-189.CrossRef
33.
Millar EK, Graham PH, McNeil CM, Browne L, O’Toole SA, Boulghourjian A, Kearsley JH, Papadatos G, Delaney G, Fox C, Nasser E, Capp A, Sutherland RL: Prediction of outcome of early ER+ breast cancer is improved using a biomarker panel, which includes Ki-67 and p53. Breast Cancer Res Treat. 2012, 134: 683-692.CrossRef
34.
Moran MS, Yang Q, Goyal S, Harris L, Chung G, Haffty BG: Evaluation of vascular endothelial growth factor as a prognostic marker for local relapse in early-stage breastcancer patients treated with breast-conserving therapy. Int J Radiat Oncol Biol Phys. 2011, 81: 1236-1243.CrossRefPubMed
35.
Wong FY, Chin FK, Lee KA, Soong YL, Chua ET: Hormone receptors and HER-2 status as surrogates for breast cancer molecular subtypes prognosticate for disease control in node negative Asian patients treated with breast conservation therapy. Ann Acad Med Singapore. 2011, 40: 90-96.PubMed
36.
Kim HJ, Han W, Yi OV, Shin HC, Ahn SK, Koh BS, Moon HG, You JH, Son BH, Ahn SH, Noh DY: Young age is associated with ipsilateral breast tumor recurrence after breast conserving surgery and radiation therapy in patients with HER2-positive/ER-negative subtype. Breast Cancer Res Treat. 2011, 130: 499-505.CrossRefPubMed
37.
Bantema-Joppe EJ, van der Laan HP, de Bock GH, Wijsman R, Dolsma WV, Busz DM, Langendijk JA, Maduro JH: Three-dimensional conformal hypofractionated simultaneous integrated boost in breast conserving therapy: results on local control and survival. Radiother Oncol. 2011, 100: 215-220.CrossRefPubMed
38.
Arvold ND, Taghian AG, Niemierko A, Abi Raad RF, Sreedhara M, Nguyen PL, Bellon JR, Wong JS, Smith BL, Harris JR: Age, breast cancer subtype approximation, and local recurrence after breast-conserving therapy. J Clin Oncol. 2011, 29: 3885-3891.PubMedCentralCrossRefPubMed
39.
Truong PT, Jones SO, Kader HA, Wai ES, Speers CH, Alexander AS, Olivotto IA: Patients with t1 to t2 breast cancer with one to three positive nodes have higher local and regional recurrence risks compared with node-negative patients after breast-conserving surgery and whole-breast radiotherapy. Int J Radiat Oncol Biol Phys. 2009, 73: 357-364.CrossRefPubMed
40.
Nofech-Mozes S, Spayne J, Rakovitch E, Kahn HJ, Seth A, Pignol JP, Lickley L, Paszat L, Hanna W: Biological markers predictive of invasive recurrence in DCIS. Clin Med Oncol. 2008, 2: 7-18.PubMedCentralPubMed
41.
de Roos MA, van der Vegt B, Peterse JL, Patriarca C, de Vries J, de Bock GH, Wesseling J: The expression pattern of MUC1 (EMA) is related to tumour characteristics and clinical outcome in ‘pure’ ductal carcinoma in situ of the breast. Histopathology. 2007, 51: 227-238.CrossRefPubMed
42.
Yau TK, Soong IS, Chan K, Chan M, Cheung P, Lau HW, Chang AT, Lee AW: Clinical outcome of breast conservation therapy for breast cancer in Hong Kong: prognostic impact of ipsilateral breast tumor recurrence and 2005 St. Gallen risk categories. Int J Radiat Oncol Biol Phys. 2007, 68: 667-672.CrossRefPubMed
43.
Smith BD, Gross CP, Smith GL, Galusha DH, Bekelman JE, Haffty BG: Effectiveness of radiation therapy for older women with early breast cancer. J Natl Cancer Inst. 2006, 98: 681-690.CrossRefPubMed
44.
Silvestrini R, Veneroni S, Benini E, Daidone MG, Luisi A, Leutner M, Maucione A, Kenda R, Zucali R, Veronesi U: Expression of p53, glutathione S-transferase-pi, and Bcl-2 proteins and benefit from adjuvant radiotherapy inbreast cancer. J Natl Cancer Inst. 1997, 89: 639-645.CrossRefPubMed
45.
Brenton JD, Carey LA, Ahmed AA, Caldas C: Molecular classification and molecular forecasting of breast cancer: ready for clinical application?. J Clin Oncol. 2005, 23: 7350-7360.CrossRefPubMed
46.
Althuis MD, Dozier JM, Anderson WF, Devesa SS, Brinton LA: Global trends in breast cancer incidence and mortality 1973-1997. Int J Epidemiol. 2005, 34: 405-412.CrossRefPubMed
47.
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010, 127: 2893-2917.CrossRefPubMed
48.
Hou N, Huo D: A trend analysis of breast cancer incidence rates in the United States from 2000 to 2009 shows a recent increase. Breast Cancer Res Treat. 2013, 138: 633-641.CrossRefPubMed
49.
No authors listed: Advanced breast cancers increasing in young women. BMJ. 2013, 346: f1234-CrossRef
50.
Forrest AP, Stewart HJ, Everington D, Prescott RJ, McArdle CS, Harnett AN, Smith DC, George WD: Randomised controlled trial of conservation therapy for breast cancer: 6-years analysis of the Scottish trial. Lancet. 1996, 348: 708-713.CrossRefPubMed
51.
Liljegren G, Holmberg L, Bergh J, Lindgren A, Tabár L, Nordgren H, Adami HO: 10-year results after sector resection with or without postoperative radiotherapy for stage I breast cancer: A randomized trial. J Clin Oncol. 1999, 17: 2326-2333.PubMed
52.
White J: Do we need to irradiate all small invasive breast cancers and DCIS?. Am Soc Clin Oncol Educ Book. 2013, 2013: 40-44.CrossRef
53.
Wo JY, Taghian AG, Nguyen PL, Raad RA, Sreedhara M, Bellon JR, Wong JS, Gadd MA, Smith BL, Harris JR: The association between biological subtype and isolated regional nodal failure after breast-conserving therapy. Int J Radiat Oncol Biol Phys. 2010, 77: 188-196.CrossRefPubMed
54.
Thompson AM, Lane DP: p53 transcriptional pathways in breast cancer: the good, the bad and the complex. J Pathol. 2010, 220: 401-403.PubMed
55.
Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ, Panel members: Strategies for subtypes–dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011, 22: 1736-1747.PubMedCentralCrossRefPubMed
56.
Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V: Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007, 109: 1721-1728.CrossRefPubMed
57.
Andreu FJ: Histologic diagnosis in young women with breast cancer. Breast Cancer Res Treat. 2010, 123: 15-18.CrossRefPubMed
Metadata
Title
The efficacy of molecular subtyping in predicting postoperative recurrence in breast-conserving therapy: a 15-study meta-analysis
Authors
Jing Chen
Peng Jiang
Han-jin Wang
Jia-yi Zhang
Yang Xu
Mu-hong Guo
Bin Zhang
Chong-yin Tang
Hong-yong Cao
Shui Wang
Publication date
01-12-2014
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2014
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/1477-7819-12-212

Other articles of this Issue 1/2014

World Journal of Surgical Oncology 1/2014 Go to the issue

Correspondence

Enucleation of giant esophageal schwannoma of the upper thoracic esophagus: reports of two cases

Research

Inferior oncological prognosis of surgery without oral chemotherapy for stage III colon cancer in clinical settings

Research

Can surgical management of bone metastases improve quality of life among women with gynecologic cancer?

Research

Combined ultrasonic aspiration and saline-linked radiofrequency precoagulation: a step toward bloodless liver resection without the need of liver inflow occlusion: analysis of 313 consecutive patients

Research

Role of laparoscopy in patients with peritoneal metastases considered for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC)

Case report

Leptomeningeal metastases from a primary central nervous system melanoma: a case report and literature review