Summary
Clinical observations about lack of survival benefit after extensive axillary surgery and biological discordance between primary breast tumors and axillary lymph nodes raise the question of the actual metastatic potential of axillary nodal disease. The exploration of intratumoral heterogeneity and detection of genomic differences between the primary and lymph nodes indicate some similarity between the number of mutations in synchronous axillary node metastases and those in the primary lesion, suggesting a favorable prognosis. The hematogenous route of metastasis needs to be considered in findings of different subclones between nodal and distant metastases. Modern tools such as whole-genome sequencing applied in multiple tumor areas may guide more precisely the extent of axillary surgery.
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References
1.
Saez RA, McGuire WL, Clark GM: Prognostic factors in breast cancer. Semin Surg Oncol 1989;5:102-110.
[PubMed]
2.
Bromham N, Schmidt-Hansen M, Astin M, Hasler E, Reed MW: Axillary treatment for operable primary breast cancer. Cochrane Database Syst Rev 2017;1: CD004561.
[PubMed]
3.
Zavagno G, De Salvo GL, Scalco G, Bozza F, Barutta L, Del Bianco P, Renier M, Racano C, Carraro P, Nitti D; GIVOM Trialists: A randomized clinical trial on sentinel lymph node biopsy versus axillary lymph node dissection in breast cancer: results of the Sentinella/GIVOM trial. Ann Surg 2008;247:207-213.
[PubMed]
4.
Veronesi U, Viale G, Paganelli G, Zurrida S, Luini A, Galimberti V, Veronesi P, Intra M, Maisonneuve P, Zucca F, Gatti G, Mazzarol G, De Cicco C, Vezzoli D: Sentinel lymph node biopsy in breast cancer: ten-year results of a randomized controlled study. Ann Surg 2010;251:595-600.
[PubMed]
5.
Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Costantino JP, Ashikaga T, Weaver DL, Mamounas EP, Jalovec LM, Frazier TG, Noyes RD, Robidoux A, Scarth HM, Wolmark N: Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomized phase 3 trial. Lancet Oncol 2010;11:927-933.
[PubMed]
6.
Mansel RE, Fallowfield L, Kissin M, Goyal A, Newcombe RG, Dixon JM, Yiangou C, Horgan K, Bundred N, Monypenny I, England D, Sibbering M, Abdullah TI, Barr L, Chetty U, Sinnett DH, Fleissig A, Clarke D, Ell PJ: Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. J Natl Cancer Inst 2006;98:599-609.
[PubMed]
7.
Giuliano AE, Ballman KV, McCall L, Beitsch PD, Brennan MB, Kelemen PR, Ollila DW, Hansen NM, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, Hunt KK, Morrow M: Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA 2017;318:918-926.
[PubMed]
8.
Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, Jeong JH, Wolmark N: Twenty-five-year follow- up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med 2002;347:567-575.
[PubMed]
9.
Harris LN, Ismaila N, McShane LM, Andre F, Collyar DE, Gonzalez-Angulo AM, Hammond EH, Kuderer NM, Liu MC, Mennel RG, Van Poznak C, Bast RC, Hayes DF; American Society of Clinical Oncology: Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2016;34:1134-1150.
[PubMed]
10.
Hoadley KA, Siegel MB, Kanchi KL, Miller CA, Ding L, Zhao W, He X, Parker JS, Wendl MC, Fulton RS, Demeter RT, Wilson RK, Carey LA, Perou CM, Mardis ER: Tumor evolution in two patients with basal-like breast cancer: a retrospective genomics study of multiple metastases. PLoS Med 2016;13:e1002174.
[PubMed]
11.
Savas P, Teo ZL, Lefevre C, Flensburg C, Caramia F, Alsop K, Mansour M, Francis PA, Thorne HA, Silva MJ, Kanu N, Dietzen M, Rowan A, Kschischo M, Fox S, Bowtell DD, Dawson SJ, Speed TP, Swanton C, Loi S: Correction: the subclonal architecture of metastatic breast cancer: results from a prospective community-based rapid autopsy program ‘CASCADE'. PLoS Med 2017;14:e1002302.
[PubMed]
12.
Yates LR, Knappskog S, Wedge D, et al: Genomic evolution of breast cancer metastasis and relapse. Cancer Cell 2017;32:169-184.
[PubMed]
13.
Turajlic S, Swanton C: Metastasis as an evolutionary process. Science 2016;8;352:169-175.
[PubMed]
14.
Norton L, Massagué J: Is cancer a disease of self-seeding? Nat Med 2006;2:875-878.
[PubMed]
15.
Hong MK, Macintyre G, Wedge DC, et al: Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer. Nat Commun 2015;6:6605.
[PubMed]
16.
Lindström LS, Karlsson E, Wilking UM, Johansson U, Hartman J, Lidbrink EK, Hatschek T, Skoog L, Bergh J: Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and HER2 are unstable throughout tumor progression. J Clin Oncol 2012;30:2601-2608.
[PubMed]
17.
Sun Y, Liu X, Cui S, Li L, Tian P, Liu S, Li Y, Yin M, Zhang C, Mao Q, Wang J: The inconsistency of molecular subtypes between primary foci and metastatic axillary lymph nodes in luminal A breast cancer patients among Chinese women, an indication for chemotherapy? Tumour Biol 2016;37:9555-9563.
[PubMed]
18.
Bao L, Qian Z, Lyng MB, Wang L, Yu Y, Wang T, Zhang X, Yang H, Brünner N, Wang J, Ditzel HJ: Coexisting genomic aberrations associated with lymph node metastasis in breast cancer. J Clin Invest 2018;128:2310-2324.
[PubMed]
19.
Blighe K, Kenny L, Patel N, Guttery DS, Page K, Gronau JH, Golshani C, Stebbing J, Coombes RC, Shaw JA: Whole genome sequence analysis suggests intratumoral heterogeneity in dissemination of breast cancer to lymph nodes. PLoS One 2014;9:e115346.
[PubMed]
20.
Ullah I, Karthik GM, Alkodsi A, Kjällquist U, Stålhammar G, Lövrot J, Martinez NF, Lagergren J, Hautaniemi S, Hartman J, Bergh J: Evolutionary history of metastatic breast cancer reveals minimal seeding from axillary lymph nodes. J Clin Invest 2018;128:1355-1370.
[PubMed]
21.
Liang F, Qu H, Lin Q, Yang Y, Ruan X, Zhang B, Liu Y, Yu C, Zhang H, Fang X, Hao X: Molecular biomarkers screened by next-generation RNA sequencing for non-sentinel lymph node status prediction in breast cancer patients with metastatic sentinel lymph nodes. World J Surg Oncol 2015;13:258.
[PubMed]
22.
Valente AL, Kane JL, Ellsworth DL, Shriver CD, Ellsworth RE: Molecular response of the axillary lymph node microenvironment to metastatic colonization. Clin Exp Metastasis 2014;31:565-572.
[PubMed]
23.
Park K, Lee JH, Han HH, Mun SG, Kang S, Cha YJ, Koo JS, Kim MJ, Lee HS, Moon J, Cho NH: Nodal metastasis signatures in breast cancer. Pathol Res Pract 2017;213:680-687.
[PubMed]
24.
Miller CA, Gindin Y, Lu C, Griffith OL, Griffith M, Shen D, Hoog J, Li T, Larson DE, Watson M, Davies SR, Hunt K, Suman VJ, Snider J, Walsh T, Colditz GA, DeSchryver K, Wilson RK, Mardis ER, Ellis MJ: Aromatase inhibition remodels the clonal architecture of estrogen-receptor-positive breast cancers. Nat Commun 2016;7:12498.
[PubMed]
25.
Gellert P, Segal CV, Gao Q, et al.; POETIC Trial Management Group and Trialists: Impact of mutational profiles on response of primary oestrogen receptor-positive breast cancers to oestrogen deprivation. Nat Commun 2016;7:13294.
[PubMed]
26.
Tan S-H, Sapari NS, Miao H, Hartman M, Loh M, Chng WJ, Iau P, Buhari SA, Soong R, Lee SC: High-throughput mutation profiling changes before and 3 weeks after chemotherapy in newly diagnosed breast cancer patients. PLoS One 2015;10:e0142466.
[PubMed]
27.
Jiang YZ, Yu KD, Bao J, Peng WT, Shao ZM: Favorable prognostic impact in loss of TP53 and PIK3CA mutations after neoadjuvant chemotherapy in breast cancer. Cancer Res 2014;74;3399-3407.
[PubMed]
28.
Peintinger F, Kühn T, Schermann C, Regitnig P, Moinfar F, Sauseng S, Symmans W: AGO Austria-35: Prospektive Validierung der genomischen Signaturen zur Erfassung der Chemosensitivität der axillären Lymphknoten nach neoadjuvanter Chemotherapie beim HER2 negativem Mammakarzinom. Senologie 2015;12:A113.
29.
Nanda M, Peintinger F, Sieghartsleitner E, Klaasen F, Reitsamer R, Kolberg HC, Schmatloch S, Kühn T; Arbeitsgemeinschaft Gynäkologische Onkologie Österreich: Accuracy of surgical opinion case report forms to predict type of axillary surgery after neoadjuvant chemotherapy in the AGO-35 trial. Senologie 2018;15:e34-e35.
30.
Coutant C, Olivier C, Lambaudie E, Fondrinier E, Marchal F, Guillemin F, Seince N, Thomas V, Levêque J, Barranger E, Darai E, Uzan S, Houvenaeghel G, Rouzier R: Comparison of models to predict nonsentinel lymph node status in breast cancer patients with metastatic sentinel lymph nodes: a prospective multicenter study. J Clin Oncol 2009;27:2800-2808.
[PubMed]
31.
Liedtke C, Görlich D, Bauerfeind I, Fehm T, Fleige B, Helms G, Lebeau A, Stäbler A, Ataseven B, Denkert C, Gerber B, Heil J, Krug D, Kümmel S, Schwentner L, von Minckwitz, Loibl S, Untch M, Kühn T: Validation of a nomogram predicting non-sentinel lymph node (SLN) metastases among patients with breast cancer after primary systemic therapy (PST) - a transSENTINA substudy. Breast Care 2018;DOI: 10.1159/000489565.
32.
Liedtke C, Kolberg HC, Kerschke L, Görlich D, Bauerfeind I, Fehm T, Fleige B, Hausschild M, Helms G, Lebeau A, Schmatloch S, Schrenk P, Schwentner L, Staebler A, von Minckwitz G, Loibl S, Untch M, Kuehn T: Systematic analysis of parameters predicting pathological axillary status (ypN0 vs. ypN+) among patients converting from cN+ to ycN0 through primary systemic therapy (PST) - a transSENTINA substudy. J Clin Oncol 2017;35(suppl):abstr 560.
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