There are some markers to predict early recurrence in less than 5 years. But certain subtypes of breast cancer (ER+, luminal) has been shown to undergo relapse in 10-20 years. I was wondering whether there is any marker to predict late recurrence.
Unfortunately, good prognostic markers associated with very late breast cancer relapse are missing. However, some histotypes (e.g. lobular carcinoma) are associated with late relapse and unusual metastatic sites (e.g. GI tract, meninges). I have seen metastatic lobular cancer 26 years after the surgery (subcutaneous metastasis).
Hello
i agree with Semir Vranic , and you can see this artical , i hope help you
Good Luck
The PAM50 risk-of-recurrence score appears to be a promising tool:
Clin Cancer Res. 2014 Mar 1;20(5):1298-305. doi: 10.1158/1078-0432.CCR-13-1845. Epub 2014 Feb 11.
The PAM50 risk-of-recurrence score predicts risk for late distant recurrence after endocrine therapy in postmenopausal women with endocrine-responsive early breast cancer.
Filipits M1, Nielsen TO, Rudas M, Greil R, Stöger H, Jakesz R, Bago-Horvath Z, Dietze O, Regitnig P, Gruber-Rossipal C, Müller-Holzner E, Singer CF, Mlineritsch B, Dubsky P, Bauernhofer T, Hubalek M, Knauer M, Trapl H, Fesl C, Schaper C, Ferree S, Liu S, Cowens JW, Gnant M; Austrian Breast and Colorectal Cancer Study Group.
Author information
Abstract
PURPOSE:
To assess the prognostic value of the PAM50 risk-of-recurrence (ROR) score on late distant recurrence (beyond 5 years after diagnosis and treatment) in a large cohort of postmenopausal, endocrine-responsive breast cancer patients.
EXPERIMENTAL DESIGN:
The PAM50 assay was performed on formalin-fixed paraffin-embedded whole-tumor sections of patients who had been enrolled in the Austrian Breast and Colorectal Cancer Study Group Trial 8 (ABCSG-8). RNA expression levels of the PAM50 genes were determined centrally using the nCounter Dx Analysis System. Late distant recurrence-free survival (DRFS) was analyzed using Cox models adjusted for clinical and pathologic parameters.
RESULTS:
PAM50 analysis was successfully performed in 1,246 ABCSG-8 patients. PAM50 ROR score and ROR-based risk groups provided significant additional prognostic information with respect to late DRFS compared with a combined score of clinical factors alone (ROR score: ΔLRχ(2) 15.32, P < 0.001; ROR-based risk groups: ΔLRχ(2) 14.83, P < 0.001). Between years 5 and 15, we observed an absolute risk of distant recurrence of 2.4% in the low ROR-based risk group, as compared with 17.5% in the high ROR-based risk group. The DRFS differences according to the PAM50 ROR score were observed for both node-positive and node-negative disease.
CONCLUSION:
PAM50 ROR score and ROR-based risk groups can differentiate patients with breast cancer with respect to their risk for late distant recurrence beyond what can be achieved with established clinicopathologic risk factors.
©2014 AACR
Certainly, OncotypeDX has been used as another tool for prediction; its use is however limited for several reasons including the disease itself (early stage, ER+, pNo disease) and price. OncotypeDx is mainly used in US, much less in Europe.
Thank you Semir. All of these tools deal with many genes and cost effective as you mentioned. Actually I was thinking whether we can reduce number of genes to 1 or 3. May be long way to go.
The clinicopathological parameters, specifically nodal status and tumor size, are well-established predictors for late recurrence in postmenopausal women with HR-positive breast cancer. However, it has become evident that molecular signatures improve the prediction of late relapse and can identify women who are at sufficiently low risk, even with node-positive disease, who do not warrant extended endocrine therapy.
I think Dr Semir give good conclusions for this question. In addition to reference added by Dr Saleh.
A number of gene signatures including PAM50 Risk of Recurrence (ROR) score, EndoPredict and Breast Cancer Index (BCI) have been reported to predict late recurrence.
Zhang Y, Schnabel CA, Schroeder BE, Jerevall PL, Jankowitz RC, Fornander T, Stål O, Brufsky AM, Sgroi D, Erlander MG. Breast cancer index identifies early-stage estrogen receptor-positive breast cancer patients at risk for early- and late-distant recurrence. Clin Cancer Res 2013;19:4196-205.
Sestak I, Cuzick J, Dowsett M, Lopez-Knowles E, Filipits M, Dubsky P, Cowens JW, Ferree S, Schaper C, Fesl C, Gnant M. Prediction of Late Distant Recurrence After 5 Years of Endocrine Treatment: A Combined Analysis of Patients From the Austrian Breast and Colorectal Cancer Study Group 8 and Arimidex, Tamoxifen Alone or in Combination Randomized Trials Using the PAM50 Risk of Recurrence Score 2014;
Dubsky P, Brase JC, Jakesz R, Rudas M, Singer CF, Greil R, Dietze O, Luisser I, Klug E, Sedivy R, Bachner M, Mayr D, Schmidt M, Gehrmann MC, Petry C, Weber KE, Fisch K, Kronenwett R, Gnant M, Filipits M; Austrian Breast and Colorectal Cancer Study Group (ABCSG). The EndoPredict score provides prognostic information on late distant metastases in ER+/HER2- breast cancer patients. Br J Cancer 2013;109(12):2959-64.
Sgroi DC, Carney E, Zarrella E, Steffel L, Binns SN, Finkelstein DM, Szymonifka J, Bhan AK, Shepherd LE, Zhang Y, Schnabel CA, Erlander MG, Ingle JN, Porter P, Muss HB, Pritchard KI, Tu D, Rimm DL, Goss PE. Prediction of late disease recurrence and extended adjuvant letrozole benefit by the HOXB13/IL17BR biomarker. J Natl Cancer Inst 2013;105:1036-42.
The breast cancer index (BCI) has been validated in two prospective retrospective randomized controlled trials (Simon-Hayes level 1 evidence) to predict late recurrence (years 5-10) in ER+, early stage breast cancers and has the added benefit of providing individualized predictive information on whether a patient is likely to benefit from extended endocrine therapy (more than 5 years of tamoxifen or the addition of AI therapy; validated in the landmark MA.17 cohort).
The key to concluding whether a biomarker is valid for late prognosis is ensuring that the survival curves continue to separate at increasing rates in the years of interest (5-10). If the lines separate from years 0-5, but then maintain identical slopes in years 5-10, then the bookmaker does not provide late prognosis. Said another way, the 0-10 year prognostic ability is driven by the 0-5 year signal. This is why subset analyses are critical!