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Irish Journal of Medical Science (1971 -)

27-09-2024 | Breast Cancer | Review Article

Risk of locoregional recurrence after breast cancer surgery by molecular subtype—a systematic review and network meta-analysis

Authors: Lily Nolan, Matthew G. Davey, Gavin G. Calpin, Éanna J. Ryan, Michael R. Boland

Published in: Irish Journal of Medical Science (1971 -)

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Abstract

Background

The prevention of locoregional recurrence (LRR) is crucial in breast cancer, as it translates directly into reduced breast cancer–related death. Breast cancer is subclassified into distinct intrinsic biological subtypes with varying clinical outcomes.

Aims

To perform a systematic review and network meta-analysis (NMA) to determine the rate of LRR by breast cancer molecular subtype.

Methods

A NMA was performed as per PRISMA-NMA guidelines. Molecular subtypes were classified by St Gallen expert consensus statement (2013). Analysis was performed using R and Shiny.

Results

Five studies were included including 6731 patients whose molecular subtypes were available. Overall, 47.3% (3182/6731) were Luminal A (LABC: estrogen receptor (ER) + /human epidermal growth factor receptor-2 (HER2) − /progesterone receptor (PR) + or Ki-67 < 20%), 25.5% (1719/6731) were Luminal B (LBBC: ER + /HER2 − /PR − or Ki-67 ≥ 20%), 11.2% (753/6731) were Luminal B-HER2 + (LBBC-HER2: ER + /HER2 +), 6.9% (466/6731) were HER2 + (HER2 ER − /HER2 +), and finally 9.1% (611/6731) were triple-negative breast cancer (TNBC: ER − /HER2 −). The median follow-up was 74.0 months and the overall LRR rate was 4.0% (271/6731). The LRR was 1.7% for LABC (55/3182), 5.1% for LBBC (88/1719), 6.0% for LBBC-HER2 (45/753), 6.0% for HER2 (28/466), and 7.9% for TNBC (48/611). At NMA, patients with TNBC (odds ratio (OR) 3.73, 95% confidence interval (CI) 1.80–7.74), HER2 (OR 3.24, 95% CI 1.50–6.99), LBBC-HER2 (OR 2.38, 95% CI 1.09–5.20), and LBBC (OR 2.20, 95% CI 1.07–4.50) were significantly more likely to develop LRR compared to LABC.

Conclusion

TNBC and HER2 subtypes are associated with the highest risk of LRR. Multidisciplinary team discussions should consider these findings to optimize locoregional control following breast cancer surgery.
Appendix
Available only for authorised users
Literature
1.
Sung H, Ferlay J, Siegel RL et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 71(3):209–49
2.
McVeigh TP, Boland MR, Lowery AJ (2017) The impact of the biomolecular era on breast cancer surgery. Surgeon 15(3):169–181PubMedCrossRef
3.
Perou CM, Sørlie T, Eisen MB and others (2000) Molecular portraits of human breast tumours. Nature 406(6797):747–752PubMedCrossRef
4.
Kneubil MC, Brollo J, Botteri E and others (2013) Breast cancer subtype approximations and loco-regional recurrence after immediate breast reconstruction. Eur J Surg Oncol 39(3):260–265PubMedCrossRef
5.
Sørlie T, Perou CM, Tibshirani R and others (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci 98(19):10869–10874PubMedPubMedCentralCrossRef
6.
Rakha EA, Green AR (2017) Molecular classification of breast cancer: what the pathologist needs to know. Pathology 49(2):111–119PubMedCrossRef
7.
Parker JS, Mullins M, Cheang MC and others (2009) Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 27(8):1160–1167PubMedPubMedCentralCrossRef
8.
Goldhirsch A, Wood WC, Coates AS, (2011) 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. 22(8):1736–47
9.
Goldhirsch A, Winer EP, Coates AS and others (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(9):2206–2223PubMedPubMedCentralCrossRef
10.
Vuong D, Simpson PT, Green B and others (2014) Molecular classification of breast cancer. Virchows Arch 465(1):1–14PubMedCrossRef
11.
Meyers MO, Klauber-Demore N, Ollila DW and others (2011) Impact of breast cancer molecular subtypes on locoregional recurrence in patients treated with neoadjuvant chemotherapy for locally advanced breast cancer. Ann Surg Oncol 18(10):2851–2857PubMedCrossRef
12.
Wu X, Baig A, Kasymjanova G et al (2016) Pattern of local recurrence and distant metastasis in breast cancer by molecular subtype. Cureus. 8(12).
13.
Park HS, Kim S, Kim K and others (2012) Pattern of distant recurrence according to the molecular subtypes in Korean women with breast cancer. World journal of surgical oncology 10:1–7CrossRef
14.
Jwa E, Shin KH, Kim JY and others (2016) Locoregional recurrence by tumor biology in breast cancer patients after preoperative chemotherapy and breast conservation treatment. Cancer Res Treat 48(4):1363–1372PubMedPubMedCentralCrossRef
15.
Truong PT, Sadek BT, Lesperance MF and others (2014) Is biological subtype prognostic of locoregional recurrence risk in women with pT1-2N0 breast cancer treated with mastectomy? Int J Radiat Oncol Biol Phys 88(1):57–64PubMedCrossRef
16.
Darby S, McGale P, Correa C and others (2011) 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 378(9804):1707–1716CrossRef
17.
Ebctcg, McGale P, Taylor C, Correa C et al (2014) Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 383(9935):2127–35
18.
Christiansen P, Al-Suliman N, Bjerre K, Møller S (2008) Recurrence pattern and prognosis in low-risk breast cancer patients - data from the DBCG 89-A programme. Acta Oncol 47(4):691–703PubMedCrossRef
19.
Belkacemi Y, Hanna NE, Besnard C et al (2018) Local and regional breast cancer recurrences: salvage therapy options in the New Era of molecular subtypes. Frontiers in Oncology. 8(APR)
20.
Haffty BG, Fischer D, Beinfield M, McKhann C (1991) Prognosis following local recurrence in the conservatively treated breast cancer patient. Int J Radiat Oncol Biol Phys 21(2):293–298PubMedCrossRef
21.
Giuliano AE, McCall L, Beitsch P et al (2010) Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg. 252(3):426–32; discussion 32–3
22.
Clarke M, Collins R, Darby S and others (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):2087–2106PubMedCrossRef
23.
Lowery AJ, Kell MR, Glynn RW and others (2012) Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype. Breast Cancer Res Treat 133(3):831–841PubMedCrossRef
24.
Lowery AJ, Kell MR, Glynn RW et al (2011) Locoregional recurrence after breast cancer surgery: a meta-analysis by molecular subtype. J Clinic Oncol. 29(15).
25.
McGuire A, Lowery AJ, Kell MR and others (2017) Locoregional recurrence following breast cancer surgery in the Trastuzumab era: a systematic review by subtype. Ann Surg Oncol 24(11):3124–3132PubMedCrossRef
26.
Wolff AC, Hammond MEH, Hicks DG and others (2014) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med 138(2):241–256PubMedCrossRef
27.
Arteaga CL, Sliwkowski MX, Osborne CK and others (2012) Treatment of HER2-positive breast cancer: current status and future perspectives. Nat Rev Clin Oncol 9(1):16–32CrossRef
28.
Slamon DJ, Clark GM, Wong SG and others (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785):177–182PubMedCrossRef
29.
PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Annals of Internal Medicine. 2018;169(7):467–73
30.
Allison KH, Hammond MEH, Dowsett M and others (2020) Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update. J Clin Oncol 38(12):1346–1366PubMedCrossRef
31.
Cheang MC, Chia SK, Voduc D and others (2009) Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 101(10):736–750PubMedPubMedCentralCrossRef
32.
Fodor A, Brombin C, Mangili P and others (2021) Impact of molecular subtype on 1325 early-stage breast cancer patients homogeneously treated with hypofractionated radiotherapy without boost: should the indications for radiotherapy be more personalized? Breast 55:45–54PubMedCrossRef
33.
Armstrong EC (1999) The well-built clinical question: the key to finding the best evidence efficiently. WMJ 98(2):25–28PubMed
34.
35.
Owen RK, Bradbury N, Xin Y and others (2019) MetaInsight: an interactive web-based tool for analyzing, interrogating, and visualizing network meta-analyses using R-shiny and netmeta. Res Synth Methods 10(4):569–581PubMedPubMedCentralCrossRef
36.
Wells GA, Shea B, O’Connell D et al The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Oxford; 2000.
37.
Arvold ND, Taghian AG, Niemierko A and others (2011) Age, breast cancer subtype approximation, and local recurrence after breast-conserving therapy. J Clin Oncol 29(29):3885–3891PubMedPubMedCentralCrossRef
38.
Park S, Koo JS, Kim MS and others (2012) Characteristics and outcomes according to molecular subtypes of breast cancer as classified by a panel of four biomarkers using immunohistochemistry. The Breast 21(1):50–57PubMedCrossRef
39.
Desmedt C, Haibe-Kains B, Wirapati P and others (2008) Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin Cancer Res 14(16):5158–5165PubMedCrossRef
40.
Howlader N, Cronin KA, Kurian AW, Andridge R (2018) Differences in breast cancer survival by molecular subtypes in the United States. Cancer Epidemiol Biomark Prev 27(6):619–626CrossRef
41.
Hennigs A, Riedel F, Gondos A and others (2016) Prognosis of breast cancer molecular subtypes in routine clinical care: a large prospective cohort study. BMC Cancer 16(1):734PubMedPubMedCentralCrossRef
42.
Prat A, Pineda E, Adamo B and others (2015) Clinical implications of the intrinsic molecular subtypes of breast cancer. The Breast 24:S26–S35PubMedCrossRef
43.
Bauer KR, Brown M, Cress RD and others (2007) Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype. Cancer 109(9):1721–1728PubMedCrossRef
44.
Sørlie T, Tibshirani R, Parker J and others (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci 100(14):8418–8423PubMedPubMedCentralCrossRef
45.
McGuire A, Lowery A, Kell M and others (2016) Locoregional recurrence following breast cancer surgery in the trastuzumab era: a systematic review by subtype. Eur J Surg Oncol 42(5):S9CrossRef
46.
Yin W, Jiang Y, Shen Z et al (2011) Trastuzumab in the adjuvant treatment of HER2-positive early breast cancer patients: a meta-analysis of published randomized controlled trials. PLoS ONE 6(6):e21030PubMedPubMedCentralCrossRef
47.
Cao L, Cai G, Xu F and others (2016) Trastuzumab improves locoregional control in HER2-positive breast cancer patients following adjuvant radiotherapy. Medicine (Baltimore) 95(32):e4230PubMedCrossRef
48.
Piccart-Gebhart MJ, Procter M, Leyland-Jones B and others (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353(16):1659–1672PubMedCrossRef
49.
Swisher SK, Vila J, Tucker SL and others (2016) Locoregional control according to breast cancer subtype and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast-conserving therapy. Ann Surg Oncol 23(3):749–756PubMedCrossRef
50.
Martin M, Holmes FA, Ejlertsen B and others (2017) Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 18(12):1688–1700PubMedCrossRef
51.
Perez EA, Romond EH, Suman VJ and others (2011) Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol. 29(25):3366–73PubMedPubMedCentralCrossRef
52.
Davey MG, Cleere EF, O’Donnell JP and others (2022) Value of the 21-gene expression assay in predicting locoregional recurrence rates in estrogen receptor-positive breast cancer: a systematic review and network meta-analysis. Breast Cancer Res Treat 193(3):535–544PubMedPubMedCentralCrossRef
Metadata
Title
Risk of locoregional recurrence after breast cancer surgery by molecular subtype—a systematic review and network meta-analysis
Authors
Lily Nolan
Matthew G. Davey
Gavin G. Calpin
Éanna J. Ryan
Michael R. Boland
Publication date
27-09-2024
Publisher
Springer International Publishing
Published in
Irish Journal of Medical Science (1971 -)
Print ISSN: 0021-1265
Electronic ISSN: 1863-4362
DOI
https://doi.org/10.1007/s11845-024-03809-z

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