Delayed initiation of adjuvant chemotherapy linked to poorer outcomes in triple-negative breast cancer

SAN ANTONIO — Longer delays to initiation of adjuvant chemotherapy appeared associated with poorer outcomes among patients with triple-negative breast cancer, according to retrospective study results presented at San Antonio Breast Cancer Symposium.

Patients who started adjuvant chemotherapy more than 30 days after surgery achieved shorter DFS, distant-relapse free survival and OS.

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

Triple-negative breast cancer accounts for 7% to 15% of breast cancer cases worldwide. Outcomes often are poor, with 5-year mortality rates of approximately 30%.

Prior studies suggested delayed initiation of adjuvant chemotherapy for breast was associated with shorter OS and breast cancer-specific survival.

The optimal time to chemotherapy initiation for breast cancer has not been established. Most guidelines recommend starting adjuvant chemotherapy within 4 to 6 weeks after surgery for any subtype, but others recommend starting as early as clinically possible within 31 days of surgery, according to study background.

Morante and colleagues evaluated the influence of time to adjuvant chemotherapy on survival of patients with triple-negative breast cancer diagnosed at their institution between 2000 and 2014.

The analysis included 687 patients (median age, 48; range, 21-89) with stage I (10.5%), stage II (60.1%) or stage III (29.4%) ER-negative, PR-negative and HER2-negative tumors. All patients underwent surgery as first-line treatment and completed adjuvant chemotherapy. Clinical records included complete tumor and treatment information for all patients.

Median follow-up was 101 months, and median time to initiation of adjuvant chemotherapy was 41 days.

Investigators categorized patients into four groups based on time between surgery and first chemotherapy dose: 30 days or less (27.5%), 31 to 60 days (47.9%), 61 to 90 days (16.7%), or 91 days or longer (7.9%).

Results showed a significant association between time to chemotherapy initiation and OS (P = .003).

Longer time to chemotherapy initiation appeared associated with steady declines in 12-month OS (99.5% for 30 days or less; 98.8% for 31 to 60 days; 97.4% for 61 to 90 days; and 94.4% for 91 days or longer) and 120-month OS (82% for 30 days or less; 67.4% for 31 to 60 days; 67.1% for 61 to 90 days; and 65.1% for 91 days or longer).

These differences appeared consistent over three treatment periods evaluated: 2000 to 2004, 2005 to 2009, and 2010 to 2014.

Researchers also assessed the influence of time to chemotherapy initiation on 10-year OS rates by nodal status. The benefit of early initiation persisted for patients with N0 disease (78.8% for 30 days or less vs. 67% for 31 days or more; P = .038) and N1 disease (82.6% for 30 days or less vs. 62.5% for 31 days or more; P = .002). Researchers reported a numerical difference in 10-year OS for those with N2 or N3 disease (87.5% for 30 days or less vs. 68.2% for 31 days or longer), but the difference did not reach statistical significance.

Initiation of chemotherapy within 30 days also appeared associated with significantly improved DFS (P = .005) and distant DFS (P < .001).

The study was limited by its retrospective, single-institution design, Morante said.

However, the findings are convincing, she said.

“Our data show that it must be a priority for patients with triple-negative breast cancer to begin adjuvant chemotherapy within 30 days of completing surgery,” Morante said in a press release. “After this period of time, the benefit of the chemotherapy is significantly diminished.” – by Mark Leiser

Reference:

Morante Z, et al. Abstract GS2-05. Presented at: San Antonio Breast Cancer Symposium; Dec. 4-8, 2018; San Antonio.

Disclosure:

Morante reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.