DTCs in marrow herald worse outcomes for early breast cancer

SAN ANTONIO – When disseminated tumor cells – even a single cell – are detected in the bone marrow of patients with early breast cancer, it’s not a good sign, according to results of pooled international analysis.

The presence of disseminated tumor cells (DTCs) in marrow at the time of primary diagnosis was an independent prognostic factor for overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS), reported Andreas Daniel Hartkopf, MD, MSc, of the University of Tübingen, Germany, on behalf of colleagues in the PADDY study.

“The DTC detection was associated with higher local tumor burden and more aggressive biological subtype,” he said at the San Antonio Breast Cancer Symposium.

The PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) study is an international cooperative effort designed to evaluate the association between DTC detection in patients with early breast cancer and clinical outcomes.

The investigators collected individual data sets including information on bone marrow samples from 10,307 patients treated at 11 centers in the United States and Europe.

The patients had early invasive breast cancer (T1-4, NO-3, M0) and for inclusion in the study had to have had bone marrow aspiration performed at the time of diagnosis or during primary surgery, with no prior systemic therapy. DTCs were detected by cytokeratin staining.

Patients were defined as being DTC positive if one or more DTCs were detected.

A total of 2,814 of the 10,307 patients (27.3%) were DTC positive. DTC status was not significantly associated with menopausal status or tumor histology (invasive ductal, invasive lobular, or other), but was positively associated with tumor grade, with 21.1% of patients with grade 1 tumors being DTC positive, compared with 27.2% with grade 2 tumors, and 29.9% with grade 3 tumors (P less than .001).

At a median follow-up of 7.6 years from bone marrow sampling DTC positivity was significantly associated with, in addition to higher tumor grade, higher T stage, nodal positivity, estrogen and progesterone receptor negativity, and HER2 positivity (P less than .001 for all).

Univariate analysis showed that DTC-positive patients had significantly shorter OS, breast cancer–specific survival, and DDFS compared with DTC negative patients (P less than .001 for all).

In a multivariate model stratified by center and controlling for age, menopausal status, histology, tumor size, nodal status, and biological subtype, DTC was an independent prognostic marker for OS (hazard ratio 1.23, P = .006), DFS (HR 1.30, P less than .001) and DDFS (HR 1.30, P = .006), but not for locoregional relapse-free survival.

“These results confirm that DTC detection is an independent risk factor for metastatic relapse and poor overall survival in early breast cancer,” Dr. Hartkopf said.

There was a statistically significant interaction between DTCs and subtypes with regard to DDFS, with a HR of 2.34 for patients with luminal B disease (P = .014).

“Future trials must evaluate the predictive value of DTC detection and/or their characterization on adjuvant therapy efficacy,” Dr. Hartkopf concluded.

Dr. Hartkopf did not disclose a study funding source or potential conflicts of interest.

SOURCE: Hartkopf AD et al. SABCS 2018. Abstract GS5-07.

SAN ANTONIO – When disseminated tumor cells – even a single cell – are detected in the bone marrow of patients with early breast cancer, it’s not a good sign, according to results of pooled international analysis.

The presence of disseminated tumor cells (DTCs) in marrow at the time of primary diagnosis was an independent prognostic factor for overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS), reported Andreas Daniel Hartkopf, MD, MSc, of the University of Tübingen, Germany, on behalf of colleagues in the PADDY study.

“The DTC detection was associated with higher local tumor burden and more aggressive biological subtype,” he said at the San Antonio Breast Cancer Symposium.

The PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) study is an international cooperative effort designed to evaluate the association between DTC detection in patients with early breast cancer and clinical outcomes.

The investigators collected individual data sets including information on bone marrow samples from 10,307 patients treated at 11 centers in the United States and Europe.

The patients had early invasive breast cancer (T1-4, NO-3, M0) and for inclusion in the study had to have had bone marrow aspiration performed at the time of diagnosis or during primary surgery, with no prior systemic therapy. DTCs were detected by cytokeratin staining.

Patients were defined as being DTC positive if one or more DTCs were detected.

A total of 2,814 of the 10,307 patients (27.3%) were DTC positive. DTC status was not significantly associated with menopausal status or tumor histology (invasive ductal, invasive lobular, or other), but was positively associated with tumor grade, with 21.1% of patients with grade 1 tumors being DTC positive, compared with 27.2% with grade 2 tumors, and 29.9% with grade 3 tumors (P less than .001).

At a median follow-up of 7.6 years from bone marrow sampling DTC positivity was significantly associated with, in addition to higher tumor grade, higher T stage, nodal positivity, estrogen and progesterone receptor negativity, and HER2 positivity (P less than .001 for all).

Univariate analysis showed that DTC-positive patients had significantly shorter OS, breast cancer–specific survival, and DDFS compared with DTC negative patients (P less than .001 for all).

In a multivariate model stratified by center and controlling for age, menopausal status, histology, tumor size, nodal status, and biological subtype, DTC was an independent prognostic marker for OS (hazard ratio 1.23, P = .006), DFS (HR 1.30, P less than .001) and DDFS (HR 1.30, P = .006), but not for locoregional relapse-free survival.

“These results confirm that DTC detection is an independent risk factor for metastatic relapse and poor overall survival in early breast cancer,” Dr. Hartkopf said.

There was a statistically significant interaction between DTCs and subtypes with regard to DDFS, with a HR of 2.34 for patients with luminal B disease (P = .014).

“Future trials must evaluate the predictive value of DTC detection and/or their characterization on adjuvant therapy efficacy,” Dr. Hartkopf concluded.

Dr. Hartkopf did not disclose a study funding source or potential conflicts of interest.

SOURCE: Hartkopf AD et al. SABCS 2018. Abstract GS5-07.

SAN ANTONIO – When disseminated tumor cells – even a single cell – are detected in the bone marrow of patients with early breast cancer, it’s not a good sign, according to results of pooled international analysis.

The presence of disseminated tumor cells (DTCs) in marrow at the time of primary diagnosis was an independent prognostic factor for overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS), reported Andreas Daniel Hartkopf, MD, MSc, of the University of Tübingen, Germany, on behalf of colleagues in the PADDY study.

“The DTC detection was associated with higher local tumor burden and more aggressive biological subtype,” he said at the San Antonio Breast Cancer Symposium.

The PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) study is an international cooperative effort designed to evaluate the association between DTC detection in patients with early breast cancer and clinical outcomes.

The investigators collected individual data sets including information on bone marrow samples from 10,307 patients treated at 11 centers in the United States and Europe.

The patients had early invasive breast cancer (T1-4, NO-3, M0) and for inclusion in the study had to have had bone marrow aspiration performed at the time of diagnosis or during primary surgery, with no prior systemic therapy. DTCs were detected by cytokeratin staining.

Patients were defined as being DTC positive if one or more DTCs were detected.

A total of 2,814 of the 10,307 patients (27.3%) were DTC positive. DTC status was not significantly associated with menopausal status or tumor histology (invasive ductal, invasive lobular, or other), but was positively associated with tumor grade, with 21.1% of patients with grade 1 tumors being DTC positive, compared with 27.2% with grade 2 tumors, and 29.9% with grade 3 tumors (P less than .001).

At a median follow-up of 7.6 years from bone marrow sampling DTC positivity was significantly associated with, in addition to higher tumor grade, higher T stage, nodal positivity, estrogen and progesterone receptor negativity, and HER2 positivity (P less than .001 for all).

Univariate analysis showed that DTC-positive patients had significantly shorter OS, breast cancer–specific survival, and DDFS compared with DTC negative patients (P less than .001 for all).

In a multivariate model stratified by center and controlling for age, menopausal status, histology, tumor size, nodal status, and biological subtype, DTC was an independent prognostic marker for OS (hazard ratio 1.23, P = .006), DFS (HR 1.30, P less than .001) and DDFS (HR 1.30, P = .006), but not for locoregional relapse-free survival.

“These results confirm that DTC detection is an independent risk factor for metastatic relapse and poor overall survival in early breast cancer,” Dr. Hartkopf said.

There was a statistically significant interaction between DTCs and subtypes with regard to DDFS, with a HR of 2.34 for patients with luminal B disease (P = .014).

“Future trials must evaluate the predictive value of DTC detection and/or their characterization on adjuvant therapy efficacy,” Dr. Hartkopf concluded.

Dr. Hartkopf did not disclose a study funding source or potential conflicts of interest.

SOURCE: Hartkopf AD et al. SABCS 2018. Abstract GS5-07.