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Treatment Delays & Worse Outcomes for Triple-Negative Breast Cancer

Bennett, Christina, MS

doi: 10.1097/01.COT.0000553544.99499.81
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SAN ANTONIO—Triple-negative breast cancer (TNBC) patients who initiated adjuvant chemotherapy within the first 30 days after surgery had improved survival and lower risk of disease recurrence compared with those who did not, according to a retrospective, single-center study presented at the 2018 San Antonio Breast Cancer Symposium (Abstract GS2-05). The findings suggest TNBC patients should start adjuvant chemotherapy as soon as possible after surgery.

“These results represent a feasible opportunity for improving the outcomes of triple-negative breast cancer,” said study presenter Zaida Morante, MD, a medical oncologist at Instituto Nacional de Enfermedades Neoplásicas in Lima, Peru. “We encourage researchers from around the world to replicate our study to confirm our results.”

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Research Details

To conduct the study, investigators retrospectively reviewed the medical records of TNBC patients who received adjuvant chemotherapy between 2000 and 2014 at Instituto Nacional de Enfermedades Neoplásicas. Eligible patients had stage I, II, or III disease, underwent surgery upfront, and completed adjuvant chemotherapy. Patients who received neoadjuvant chemotherapy were excluded.

Patients were stratified into four groups on the basis of time to chemotherapy (TTC) interval: 30 days or less, 31-60 days, 61-90 days, or 91 or more days. TTC was defined as the number of days between surgery and the first dose of chemotherapy. Overall survival (OS), disease-free survival (DFS), and distant recurrence-free survival (DRFS) were assessed.

A total of 687 patients were eligible for analysis. Patients had a mean age at diagnosis of 48 years, most had stage II (60.1%) or III (29.45%) disease, and most underwent mastectomy (62.9%). More than half (54.6%) received an anthracycline plus a taxane-based regimen, and 41.5 percent received an anthracycline-containing regimen. On the basis of TTC interval, 27.5 percent of patients initiated adjuvant chemotherapy within 30 days, 47.9 percent between 31 and 60 days, 16.7 percent between 61 and 90 days, and 7.9 percent at 91 days or later. The median TTC was 41 days, and median follow-up was 101 months.

The 10-year OS rate was 82 percent for patients who initiated adjuvant chemotherapy within the first 30 days and 67 percent for those who initiated it between 31 and 60 days. The trend was similar for the other two groups, with an OS rate of 67.1 percent for patients who initiated adjuvant chemotherapy between 61 and 90 days and 65.1 percent for patients who initiated adjuvant chemotherapy 91 days or later.

The 10-year DFS rate was 81.4 percent for patients who initiated adjuvant chemotherapy within 30 days compared with 68.6 percent for those who initiated it between 31 and 60 days. The trend was similar for the other two groups, with a DFS rate of 70.8 percent for patients who initiated adjuvant chemotherapy between 61 and 90 days and 68.1 percent for patients who initiated adjuvant chemotherapy 91 days or later.

The 10-year DRFS rate was 80.2 percent for patients who initiated adjuvant chemotherapy within 30 days compared with 64.9 percent for those who initiated it between 31 and 60 days. The DRFS rate was 67.5 percent for patients who initiated adjuvant chemotherapy between 61 and 90 days and 58.6 percent for patients who initiated adjuvant chemotherapy 91 days or later.

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Commentary

“In triple-negative breast cancer patients, our results show that the greater the delay in the initiation of adjuvant chemotherapy, the worse the outcomes,” said Morante. “Delay in initiation of adjuvant chemotherapy over 30 days is associated with decreased DFS, DRFS, and OS rates.”

Although the study shows that TNBC patients who begin adjuvant chemotherapy within the first 30 days after surgery have the best outcomes, that time frame may not translate to a new standard practice, as the typical time frame to initiate adjuvant chemotherapy in this patient population in the U.S. is 4-6 weeks after surgery to allow the patient sufficient time to recover.

Charles Shapiro, MD, FASCO, Director of Translational Breast Cancer Research at the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, shared with Oncology Times one major limitation to keep in mind when interpreting the findings. “We don't know what caused the [adjuvant chemotherapy] delays. For example, postoperative complications such as poor wound healing could be associated with worse outcomes.

“However, this finding has been observed in prior publications in the triple-negative subset, so it is prudent to start adjuvant chemotherapy as soon as possible after breast surgery.”

Large population-based studies have shown that a delay in the initiation of adjuvant chemotherapy can hinder survival benefit, particularly for patients with TNBC. Specifically, Gagliato and colleagues showed that the initiation of adjuvant chemotherapy at 61 days or later after surgery was associated with worse survival outcomes for breast cancer patients (J Clin Oncol 2014;32(8):735-744).

In addition, Chavez-MacGregor and colleagues reported that breast cancer patients who started adjuvant chemotherapy at 91 days or later after surgery had worse OS and breast cancer-specific survival than those who started adjuvant therapy within the first 31 days of surgery. A subgroup analysis further revealed that TNBC patients treated 91 or more days after surgery had worse OS (HR=1.53; 95% CI, 1.17-2.00) and breast cancer-specific survival (HR=1.53; 95% CI, 1.17-2.07) than those who began treatment within 31 days of surgery (JAMA Oncol 2016;2(3):322-329).

A systematic review and meta-analysis, which included nearly 80,000 patients from 12 reports, compared less than 30 days versus greater than 30 days and likewise demonstrated inferior OS for TNBC patients who initiated treatment after 30 days, but not for other subtypes, explained study discussant Joseph Sparano, MD, an oncologist at Montefiore Medical Center (Oncotarget 2018;9(2):2739-2751).

“A deficiency of these other analyses was there was no adjustment for comorbidities or type of surgery or other covariates that could impact prognosis,” Sparano noted.

Morante and colleagues conducted a multivariate analysis, which included surgery type among other variables, and showed that TTC was an independent prognostic variable for survival. “The conclusions and implications here are that the findings are consistent with the meta-analysis, but strengthened by the adjustment for covariates,” he concluded.

Christina Bennett is a contributing writer.

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
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