Delays in receipt of neoadjuvant chemotherapy compared to upfront surgery in patients with operable breast cancer.
Authors: Wooster Margaux , DeStephano David , Beauchemin Melissa P. , Wang Shikun , Hur Chin , Wright Jason Dennis , Hershman Dawn L. , Accordino Melissa Kate 
Published: September 2024

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Background:
Delays in time from breast cancer (BC) diagnosis to BC treatment initiation (BCTI) including upfront breast surgery (UBS) or neoadjuvant chemotherapy (NACT), can negatively impact BC survival. We evaluated odds of delay in BCTI among patients (pts) who received NACT compared to pts who received UBS.
Methods:
We conducted a retrospective cohort study using the National Cancer Database. Eligibility included age ≥18 years, diagnosis of non-metastatic BC between 1/1/2010 – 12/31/2020, who were treated with NACT followed by surgery or UBS followed by adjuvant chemotherapy (AC). Pts who did not receive NACT or UBS within 180 days of diagnosis were excluded. The cohort was stratified by first BC treatment (NACT or UBS), and time to NACT (TTNACT) or time to surgery (TTS) was recorded for each patient in days. Pts were categorized into sub-cohorts by receptor status and clinical stage: 1) Hormone Receptor positive/HER-2 negative (HR+/HER2-) lymph node (LN)+; 2) HER-2 positive (HER2+) cT2+ or LN+; and 3) triple negative BC (TNBC) cT2+ or LN+. Logistic regression adjusted for demographic, socioeconomic, and tumor characteristics was used to identify delays in BCTI > 60 days. Multiple imputation was used for missing data. Inverse probability treatment weighting (IPTW) was done as a sensitivity analysis.
Results:
We identified 218,049 eligible pts, 75% were White, 18% were Black, and 8.6% were Hispanic. Median age was 53 years (range 18-90). There were 145,697 (67%) pts who received NACT with median TTNACT of 32days (range 0-180), and 9.8% had a delay > 60 days (Table). There were 72,353 (33.0%) pts who received UBS followed by AC, with a median TTS of 33 days (range 0-180), and 13% with a delay > 60 days. In multivariable analysis, pts who received UBS had higher odds of BCTI delays compared to NACT, with OR 1.50 (95%CI 1.42-1.57) [HR+/HER2-], OR 1.49 (95%CI 1.41-1.58) [HER2+], and OR 1.26 (95%CI 1.18-1.34) [TNBC]. Results from IPTW analysis were similar, groups were well balanced, and pts who received UBS had higher odds of BCTI OR 1.50 (95%CI 1.44-1.57) [HR+/HER2-], OR 1.75 (95%CI 1.67-1.83) [HER2+], and OR 1.46 (95%CI 1.38-1.53) [TNBC].
Conclusions:
Among high clinical risk BC patients who received surgery and chemotherapy, those who underwent NACT were less likely to experience delays in BCTI compared to pts who received UBS first. Among eligible pts, use of NACT may reduce delays in BCTI.

Patients who received NACT and UBS and associated delays by sub-cohort (n = 218,050).

Neoadjuvant Chemotherapy
Upfront Surgery

N (%)
Median TTNACT in Days
N (%) Delayed >60 Days
N (%)
Median TTS in Days
N (%) Delayed >60 days

Total Cohort
145,697 (67.0)
32
14,221 (9.8)
72,353 (33.0)
33
9,725 (13)

HR+/HER2
40,345 (27.7)
34
4,773 (11.8)
29, 676 (41.0)
36
4,754 (16.0)

HER+
56,868 (39.0)
32
5,135 (9.0)
21,759 (30.1)
32
2,771 (12.7)

TNBC
48,484 (33.3)
31
4,313 (8.9)
20,917 (28.9)
30
2,200 (10.5)