Association of circulating tumor cell status with benefit of radiotherapy and survival in early-stage breast cancer

Chelain R. Goodman*, Brandon Luke L. Seagle, Thomas W.P. Friedl, Brigitte Rack, Krisztian Lato, Visnja Fink, Massimo Cristofanilli, Eric Donald Donnelly, Wolfgang Janni, Shohreh Shahabi, Jonathan B Strauss

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

IMPORTANCE Circulating tumor cells (CTCs) represent the liquid component of solid tumors and are a surrogate marker for residual cancer burden. Although CTC status is prognostic of recurrence and death in breast cancer, its role in guiding clinical management remains unknown. OBJECTIVE To determine whether CTC status is predictive of radiotherapeutic benefit in early-stage breast cancer. DESIGN, SETTING, AND PARTICIPANTS The cohort studies in the present analysis included patients with stages pT1 to pT2 and pN0 to pN1 breast cancer and known CTC status from the National Cancer Database (NCDB) and the multicenter phase 3 SUCCESS clinical trial. Multivariable parametric accelerated failure time models were used to evaluate the association of CTC status and radiotherapy (RT) with survival outcomes. Data were collected from January 1, 2004, through December 31, 2014, from the NCDB cohort. The SUCCESS trial collected data from September 1, 2005, through September 30, 2013. The analyses were completed from November 1, 2016, through December 17, 2017. EXPOSURE Adjuvant RT. MAIN OUTCOMES AND MEASURES Overall survival (OS), local recurrence-free survival (LRFS), and disease-free survival (DFS). RESULTS A total of 1697 patients from the NCDB (16 men [0.9%] and 1681 women [99.1%]; median age, 63 years; interquartile range, 53-71 years) and 1516 patients from the SUCCESS clinical trial (median age, 52 years; interquartile range, 45-60 years) were identified. Circulating tumor cells were detected in 399 patients (23.5%) in the NCDB cohort and 294 (19.4%) in the SUCCESS cohort. The association of RT with survival was dependent on CTC status within the NCDB cohort (4-year OS, 94.9% for CTC-positive RT vs 88.0% for CTC-positive non-RT vs 93.9% for CTC-negative RT vs 93.4% for CTC-negative non-RT groups; P < .001) and 5-year DFS within the SUCCESS cohort (88.0% for CTC-positive RT vs 75.2% for CTC-positive non-RT vs 92.3% for CTC-negative RT vs 88.3% for CTC-negative non-RT; P = .04). In the NCDB cohort, RT was associated with longer OS in patients with CTCs (time ratio [TR], 2.04; 95% CI, 1.55-2.67; P < .001), but not in patients without CTCs (TR, 0.80; 95% CI, 0.52-1.25; P = .33). In the SUCCESS cohort, CTC-positive patients treated with RT exhibited longer LRFS (TR, 2.73; 95% CI, 1.62-4.80; P < .001), DFS (TR, 3.03; 95% CI, 2.22-4.13; P < .001), and OS (TR, 1.83; 95% CI, 1.23-2.72; P = .003). Among patients from both cohorts who underwent breast-conserving surgery, RT was associated with longer OS in patients with CTCs (TR, 4.37; 95% CI, 2.71-7.05; P < .001) but not in patients without CTCs (TR, 0.87; 95% CI, 0.47-1.62; P = .77). Radiotherapy was not associated with OS after mastectomy in CTC-positive or CTC-negative patients. CONCLUSIONS AND RELEVANCE Treatment with RT was associated with longer LRFS, DFS, and OS in patients with early-stage breast cancer and detectable CTCs. These results are hypothesis generating; a prospective trial evaluating CTC-based management for RT after breast-conserving surgery in women with early-stage breast cancer is warranted.

Original languageEnglish (US)
Article numbere180163
JournalJAMA Oncology
Volume4
Issue number8
DOIs
StatePublished - Aug 1 2018

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Circulating Neoplastic Cells
Radiotherapy
Breast Neoplasms
Survival
Databases
Disease-Free Survival
Neoplasms
Recurrence
Segmental Mastectomy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Goodman, Chelain R. ; Seagle, Brandon Luke L. ; Friedl, Thomas W.P. ; Rack, Brigitte ; Lato, Krisztian ; Fink, Visnja ; Cristofanilli, Massimo ; Donnelly, Eric Donald ; Janni, Wolfgang ; Shahabi, Shohreh ; Strauss, Jonathan B. / Association of circulating tumor cell status with benefit of radiotherapy and survival in early-stage breast cancer. In: JAMA Oncology. 2018 ; Vol. 4, No. 8.
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title = "Association of circulating tumor cell status with benefit of radiotherapy and survival in early-stage breast cancer",
abstract = "IMPORTANCE Circulating tumor cells (CTCs) represent the liquid component of solid tumors and are a surrogate marker for residual cancer burden. Although CTC status is prognostic of recurrence and death in breast cancer, its role in guiding clinical management remains unknown. OBJECTIVE To determine whether CTC status is predictive of radiotherapeutic benefit in early-stage breast cancer. DESIGN, SETTING, AND PARTICIPANTS The cohort studies in the present analysis included patients with stages pT1 to pT2 and pN0 to pN1 breast cancer and known CTC status from the National Cancer Database (NCDB) and the multicenter phase 3 SUCCESS clinical trial. Multivariable parametric accelerated failure time models were used to evaluate the association of CTC status and radiotherapy (RT) with survival outcomes. Data were collected from January 1, 2004, through December 31, 2014, from the NCDB cohort. The SUCCESS trial collected data from September 1, 2005, through September 30, 2013. The analyses were completed from November 1, 2016, through December 17, 2017. EXPOSURE Adjuvant RT. MAIN OUTCOMES AND MEASURES Overall survival (OS), local recurrence-free survival (LRFS), and disease-free survival (DFS). RESULTS A total of 1697 patients from the NCDB (16 men [0.9{\%}] and 1681 women [99.1{\%}]; median age, 63 years; interquartile range, 53-71 years) and 1516 patients from the SUCCESS clinical trial (median age, 52 years; interquartile range, 45-60 years) were identified. Circulating tumor cells were detected in 399 patients (23.5{\%}) in the NCDB cohort and 294 (19.4{\%}) in the SUCCESS cohort. The association of RT with survival was dependent on CTC status within the NCDB cohort (4-year OS, 94.9{\%} for CTC-positive RT vs 88.0{\%} for CTC-positive non-RT vs 93.9{\%} for CTC-negative RT vs 93.4{\%} for CTC-negative non-RT groups; P < .001) and 5-year DFS within the SUCCESS cohort (88.0{\%} for CTC-positive RT vs 75.2{\%} for CTC-positive non-RT vs 92.3{\%} for CTC-negative RT vs 88.3{\%} for CTC-negative non-RT; P = .04). In the NCDB cohort, RT was associated with longer OS in patients with CTCs (time ratio [TR], 2.04; 95{\%} CI, 1.55-2.67; P < .001), but not in patients without CTCs (TR, 0.80; 95{\%} CI, 0.52-1.25; P = .33). In the SUCCESS cohort, CTC-positive patients treated with RT exhibited longer LRFS (TR, 2.73; 95{\%} CI, 1.62-4.80; P < .001), DFS (TR, 3.03; 95{\%} CI, 2.22-4.13; P < .001), and OS (TR, 1.83; 95{\%} CI, 1.23-2.72; P = .003). Among patients from both cohorts who underwent breast-conserving surgery, RT was associated with longer OS in patients with CTCs (TR, 4.37; 95{\%} CI, 2.71-7.05; P < .001) but not in patients without CTCs (TR, 0.87; 95{\%} CI, 0.47-1.62; P = .77). Radiotherapy was not associated with OS after mastectomy in CTC-positive or CTC-negative patients. CONCLUSIONS AND RELEVANCE Treatment with RT was associated with longer LRFS, DFS, and OS in patients with early-stage breast cancer and detectable CTCs. These results are hypothesis generating; a prospective trial evaluating CTC-based management for RT after breast-conserving surgery in women with early-stage breast cancer is warranted.",
author = "Goodman, {Chelain R.} and Seagle, {Brandon Luke L.} and Friedl, {Thomas W.P.} and Brigitte Rack and Krisztian Lato and Visnja Fink and Massimo Cristofanilli and Donnelly, {Eric Donald} and Wolfgang Janni and Shohreh Shahabi and Strauss, {Jonathan B}",
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Association of circulating tumor cell status with benefit of radiotherapy and survival in early-stage breast cancer. / Goodman, Chelain R.; Seagle, Brandon Luke L.; Friedl, Thomas W.P.; Rack, Brigitte; Lato, Krisztian; Fink, Visnja; Cristofanilli, Massimo; Donnelly, Eric Donald; Janni, Wolfgang; Shahabi, Shohreh; Strauss, Jonathan B.

In: JAMA Oncology, Vol. 4, No. 8, e180163, 01.08.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association of circulating tumor cell status with benefit of radiotherapy and survival in early-stage breast cancer

AU - Goodman, Chelain R.

AU - Seagle, Brandon Luke L.

AU - Friedl, Thomas W.P.

AU - Rack, Brigitte

AU - Lato, Krisztian

AU - Fink, Visnja

AU - Cristofanilli, Massimo

AU - Donnelly, Eric Donald

AU - Janni, Wolfgang

AU - Shahabi, Shohreh

AU - Strauss, Jonathan B

PY - 2018/8/1

Y1 - 2018/8/1

N2 - IMPORTANCE Circulating tumor cells (CTCs) represent the liquid component of solid tumors and are a surrogate marker for residual cancer burden. Although CTC status is prognostic of recurrence and death in breast cancer, its role in guiding clinical management remains unknown. OBJECTIVE To determine whether CTC status is predictive of radiotherapeutic benefit in early-stage breast cancer. DESIGN, SETTING, AND PARTICIPANTS The cohort studies in the present analysis included patients with stages pT1 to pT2 and pN0 to pN1 breast cancer and known CTC status from the National Cancer Database (NCDB) and the multicenter phase 3 SUCCESS clinical trial. Multivariable parametric accelerated failure time models were used to evaluate the association of CTC status and radiotherapy (RT) with survival outcomes. Data were collected from January 1, 2004, through December 31, 2014, from the NCDB cohort. The SUCCESS trial collected data from September 1, 2005, through September 30, 2013. The analyses were completed from November 1, 2016, through December 17, 2017. EXPOSURE Adjuvant RT. MAIN OUTCOMES AND MEASURES Overall survival (OS), local recurrence-free survival (LRFS), and disease-free survival (DFS). RESULTS A total of 1697 patients from the NCDB (16 men [0.9%] and 1681 women [99.1%]; median age, 63 years; interquartile range, 53-71 years) and 1516 patients from the SUCCESS clinical trial (median age, 52 years; interquartile range, 45-60 years) were identified. Circulating tumor cells were detected in 399 patients (23.5%) in the NCDB cohort and 294 (19.4%) in the SUCCESS cohort. The association of RT with survival was dependent on CTC status within the NCDB cohort (4-year OS, 94.9% for CTC-positive RT vs 88.0% for CTC-positive non-RT vs 93.9% for CTC-negative RT vs 93.4% for CTC-negative non-RT groups; P < .001) and 5-year DFS within the SUCCESS cohort (88.0% for CTC-positive RT vs 75.2% for CTC-positive non-RT vs 92.3% for CTC-negative RT vs 88.3% for CTC-negative non-RT; P = .04). In the NCDB cohort, RT was associated with longer OS in patients with CTCs (time ratio [TR], 2.04; 95% CI, 1.55-2.67; P < .001), but not in patients without CTCs (TR, 0.80; 95% CI, 0.52-1.25; P = .33). In the SUCCESS cohort, CTC-positive patients treated with RT exhibited longer LRFS (TR, 2.73; 95% CI, 1.62-4.80; P < .001), DFS (TR, 3.03; 95% CI, 2.22-4.13; P < .001), and OS (TR, 1.83; 95% CI, 1.23-2.72; P = .003). Among patients from both cohorts who underwent breast-conserving surgery, RT was associated with longer OS in patients with CTCs (TR, 4.37; 95% CI, 2.71-7.05; P < .001) but not in patients without CTCs (TR, 0.87; 95% CI, 0.47-1.62; P = .77). Radiotherapy was not associated with OS after mastectomy in CTC-positive or CTC-negative patients. CONCLUSIONS AND RELEVANCE Treatment with RT was associated with longer LRFS, DFS, and OS in patients with early-stage breast cancer and detectable CTCs. These results are hypothesis generating; a prospective trial evaluating CTC-based management for RT after breast-conserving surgery in women with early-stage breast cancer is warranted.

AB - IMPORTANCE Circulating tumor cells (CTCs) represent the liquid component of solid tumors and are a surrogate marker for residual cancer burden. Although CTC status is prognostic of recurrence and death in breast cancer, its role in guiding clinical management remains unknown. OBJECTIVE To determine whether CTC status is predictive of radiotherapeutic benefit in early-stage breast cancer. DESIGN, SETTING, AND PARTICIPANTS The cohort studies in the present analysis included patients with stages pT1 to pT2 and pN0 to pN1 breast cancer and known CTC status from the National Cancer Database (NCDB) and the multicenter phase 3 SUCCESS clinical trial. Multivariable parametric accelerated failure time models were used to evaluate the association of CTC status and radiotherapy (RT) with survival outcomes. Data were collected from January 1, 2004, through December 31, 2014, from the NCDB cohort. The SUCCESS trial collected data from September 1, 2005, through September 30, 2013. The analyses were completed from November 1, 2016, through December 17, 2017. EXPOSURE Adjuvant RT. MAIN OUTCOMES AND MEASURES Overall survival (OS), local recurrence-free survival (LRFS), and disease-free survival (DFS). RESULTS A total of 1697 patients from the NCDB (16 men [0.9%] and 1681 women [99.1%]; median age, 63 years; interquartile range, 53-71 years) and 1516 patients from the SUCCESS clinical trial (median age, 52 years; interquartile range, 45-60 years) were identified. Circulating tumor cells were detected in 399 patients (23.5%) in the NCDB cohort and 294 (19.4%) in the SUCCESS cohort. The association of RT with survival was dependent on CTC status within the NCDB cohort (4-year OS, 94.9% for CTC-positive RT vs 88.0% for CTC-positive non-RT vs 93.9% for CTC-negative RT vs 93.4% for CTC-negative non-RT groups; P < .001) and 5-year DFS within the SUCCESS cohort (88.0% for CTC-positive RT vs 75.2% for CTC-positive non-RT vs 92.3% for CTC-negative RT vs 88.3% for CTC-negative non-RT; P = .04). In the NCDB cohort, RT was associated with longer OS in patients with CTCs (time ratio [TR], 2.04; 95% CI, 1.55-2.67; P < .001), but not in patients without CTCs (TR, 0.80; 95% CI, 0.52-1.25; P = .33). In the SUCCESS cohort, CTC-positive patients treated with RT exhibited longer LRFS (TR, 2.73; 95% CI, 1.62-4.80; P < .001), DFS (TR, 3.03; 95% CI, 2.22-4.13; P < .001), and OS (TR, 1.83; 95% CI, 1.23-2.72; P = .003). Among patients from both cohorts who underwent breast-conserving surgery, RT was associated with longer OS in patients with CTCs (TR, 4.37; 95% CI, 2.71-7.05; P < .001) but not in patients without CTCs (TR, 0.87; 95% CI, 0.47-1.62; P = .77). Radiotherapy was not associated with OS after mastectomy in CTC-positive or CTC-negative patients. CONCLUSIONS AND RELEVANCE Treatment with RT was associated with longer LRFS, DFS, and OS in patients with early-stage breast cancer and detectable CTCs. These results are hypothesis generating; a prospective trial evaluating CTC-based management for RT after breast-conserving surgery in women with early-stage breast cancer is warranted.

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