In the Journals

Residual cancer burden predicts long-term breast cancer survival

A residual cancer burden index provided long-term prognostic data for patients with breast cancer after receiving neoadjuvant chemotherapy alone or with HER-2 targeted treatment regardless of breast cancer subtype, according to results of a pathologic review.

Residual cancer burden (RCB) is one of two main measures of residual disease in pathologic resection specimen, along with American Joint Commission on Cancer yp-stage. RCB uses pathologic sampling and reporting that also are necessary to determine presence and yp-stage of residual disease after neoadjuvant treatment.

“Hence, it provides a standardized operating procedure for the prospective evaluation of postneoadjuvant specimens, requiring only standard pathology materials, minimal time from the pathologist, and no additional cost,” W. Fraser Symmans, MB, ChB, professor of pathology and director of research operations at The University of Texas MD Anderson Cancer Center, and colleagues wrote.

Researchers evaluated three cohorts of patients with breast cancer treated with paclitaxel followed by fluorouracil, doxorubicin and cyclophosphamide — T/FAC-1 (n = 219), the original development cohort for RCB; T/FAC-2 (n = 262), the validation cohort for RCB; and T/FAC-3 (n = 342), the independent validation cohort for RCB. The analysis also included an original RCB validation cohort of patients treated with fluorouracil, doxorubicin and cyclophosphamide (FAC, n = 132) and a fifth cohort of patients with HER-2–positive cancer who received neoadjuvant trastuzumab (Herceptin, Genentech) with sequential paclitaxel, fluorouracil, doxorubicin and cyclophosphamide (H+T/FEC, n = 203).

Patients were divided into phenotypic subsets based on hormone receptor and HER-2 status at diagnosis: hormone receptor–positive/HER-2–negative, HER-2–positive or triple receptor–negative.

Researchers calculated the continuous RCB index, in which pathologic complete response (pCR) has an RCB of 0 and residual disease is categorized into three predefined classes of RCB index — RCB-I, RCB-II and RCB-III — and yp-stage of residual disease. Researchers monitored each patient prospectively for survival.

The median event-free follow-up was 13.5 years for T/FAC-1, 9.1 years for T/FAC-2, 6.8 years for T/FAC-3, 16.4 years for FAC and 7.1 years for the H+T/FEC cohorts.

Thirty-five percent of patients had a pCR, 25% were in the RCB-1 class, 33% in the RCB-II class and 17% in the RCB-III class.

Among patients who were triple receptor negative, rates of 10-year RFS were higher among those who achieved pCR (86%) or RCB-I (81%) compared with patients in the RCB-II (55%) and RCB-III classes (23%).

Among HR–positive/HER-2–negative patients, rates of 10-year RFS were 83% in those who achieve pCR, 97% in RCB-I, 74% in RCB-II and 52% in RCB-III.

In the H+T/FEC cohort, rates of 10-year RFS were 95% with pCR, 77% with RCB-I, 47% with RCB-II and 21% with RCB-III.

The continuous RCB index was associated with risk for relapse or mortality, and after adjustment of age at diagnosis, c-stage and tumor grade, all HRs per unit of RCB index were significant, the researchers wrote.

These data confirm a prognostic value of RCB; however, the question remains whether an assessment of the exact prognosis by RCB is required in all patients after treatment with neoadjuvant chemotherapy, Sibylle Loibl, MD, PhD, and Carsten Denkert, MD, from the German Breast Group in Germany, wrote in a related editorial.

“The granularity of the prognostic information needed after neoadjuvant chemotherapy clearly depends on the clinical consequences,” they wrote. “Today, the impact that such information has on future clinical management might be limited,” adding that it may change if new postneoadjuvant treatment strategies become available. – by Melinda Stevens

Disclosures: Symmans reports stock or other ownership in ISIS Pharmaceuticals and Nuvera Biosciences; honoraria from Affymetrix, Australasian Society for Breast Disease and Celgene; consultant/advisory roles with Genentech; patent co-inventor status on a patent co-owned by Texas MD Anderson and Nuvera Biosciences; and travel, accommodations and expenses from AbbVie. Please see the full study for all other researchers’ relevant financial disclosures. Loibl and Denkert report no relevant financial disclosures.

A residual cancer burden index provided long-term prognostic data for patients with breast cancer after receiving neoadjuvant chemotherapy alone or with HER-2 targeted treatment regardless of breast cancer subtype, according to results of a pathologic review.

Residual cancer burden (RCB) is one of two main measures of residual disease in pathologic resection specimen, along with American Joint Commission on Cancer yp-stage. RCB uses pathologic sampling and reporting that also are necessary to determine presence and yp-stage of residual disease after neoadjuvant treatment.

“Hence, it provides a standardized operating procedure for the prospective evaluation of postneoadjuvant specimens, requiring only standard pathology materials, minimal time from the pathologist, and no additional cost,” W. Fraser Symmans, MB, ChB, professor of pathology and director of research operations at The University of Texas MD Anderson Cancer Center, and colleagues wrote.

Researchers evaluated three cohorts of patients with breast cancer treated with paclitaxel followed by fluorouracil, doxorubicin and cyclophosphamide — T/FAC-1 (n = 219), the original development cohort for RCB; T/FAC-2 (n = 262), the validation cohort for RCB; and T/FAC-3 (n = 342), the independent validation cohort for RCB. The analysis also included an original RCB validation cohort of patients treated with fluorouracil, doxorubicin and cyclophosphamide (FAC, n = 132) and a fifth cohort of patients with HER-2–positive cancer who received neoadjuvant trastuzumab (Herceptin, Genentech) with sequential paclitaxel, fluorouracil, doxorubicin and cyclophosphamide (H+T/FEC, n = 203).

Patients were divided into phenotypic subsets based on hormone receptor and HER-2 status at diagnosis: hormone receptor–positive/HER-2–negative, HER-2–positive or triple receptor–negative.

Researchers calculated the continuous RCB index, in which pathologic complete response (pCR) has an RCB of 0 and residual disease is categorized into three predefined classes of RCB index — RCB-I, RCB-II and RCB-III — and yp-stage of residual disease. Researchers monitored each patient prospectively for survival.

The median event-free follow-up was 13.5 years for T/FAC-1, 9.1 years for T/FAC-2, 6.8 years for T/FAC-3, 16.4 years for FAC and 7.1 years for the H+T/FEC cohorts.

Thirty-five percent of patients had a pCR, 25% were in the RCB-1 class, 33% in the RCB-II class and 17% in the RCB-III class.

Among patients who were triple receptor negative, rates of 10-year RFS were higher among those who achieved pCR (86%) or RCB-I (81%) compared with patients in the RCB-II (55%) and RCB-III classes (23%).

Among HR–positive/HER-2–negative patients, rates of 10-year RFS were 83% in those who achieve pCR, 97% in RCB-I, 74% in RCB-II and 52% in RCB-III.

In the H+T/FEC cohort, rates of 10-year RFS were 95% with pCR, 77% with RCB-I, 47% with RCB-II and 21% with RCB-III.

The continuous RCB index was associated with risk for relapse or mortality, and after adjustment of age at diagnosis, c-stage and tumor grade, all HRs per unit of RCB index were significant, the researchers wrote.

These data confirm a prognostic value of RCB; however, the question remains whether an assessment of the exact prognosis by RCB is required in all patients after treatment with neoadjuvant chemotherapy, Sibylle Loibl, MD, PhD, and Carsten Denkert, MD, from the German Breast Group in Germany, wrote in a related editorial.

“The granularity of the prognostic information needed after neoadjuvant chemotherapy clearly depends on the clinical consequences,” they wrote. “Today, the impact that such information has on future clinical management might be limited,” adding that it may change if new postneoadjuvant treatment strategies become available. – by Melinda Stevens

Disclosures: Symmans reports stock or other ownership in ISIS Pharmaceuticals and Nuvera Biosciences; honoraria from Affymetrix, Australasian Society for Breast Disease and Celgene; consultant/advisory roles with Genentech; patent co-inventor status on a patent co-owned by Texas MD Anderson and Nuvera Biosciences; and travel, accommodations and expenses from AbbVie. Please see the full study for all other researchers’ relevant financial disclosures. Loibl and Denkert report no relevant financial disclosures.