In a National Cancer Database analysis reported in The Lancet Oncology, Crozier et al found that receipt of neoadjuvant or adjuvant chemotherapy was associated with improved overall survival among women aged 70 or older undergoing surgery for stage I to III triple-negative breast cancer.

Study Details

The analysis included data from the National Cancer Database from women aged 70 or older with surgically treated stage I to III invasive triple-negative breast cancer diagnosed between 2004 and 2014. Patients with T1a N0 M0 disease and those with incomplete data on estrogen receptor, progesterone receptor, or HER2 status were excluded from the analysis.

Patients were categorized into three groups: those who received chemotherapy (chemotherapy group), those who were recommended chemotherapy but did not receive it (recommended/not received group), and those for whom chemotherapy was not recommended and not received (not recommended/not received group).

Overall Survival in Total Cohort

A total of 16,602 women were included in the analysis. Of these, 7,485 (46.6%) received chemotherapy; chemotherapy was recommended for but not administered to 2,659 (16.6%); chemotherapy was not recommended for or received by 5,732 (35.7%); and chemotherapy status was not available for 186 (1.2%). Of the patients who received chemotherapy, 5,924 (79.1%) received adjuvant chemotherapy alone; 1,337 (17.9%) received neoadjuvant chemotherapy alone; and 196 (2.6%) received both.

Median follow-up was 38.3 months (interquartile range = 20.7–46.1 months, range = 0–138.0 months).  At data cutoff at the end of January 2016, 3,300 patients (20.5%) had died.

The 5-year overall survival estimate for the entire cohort was 62.3% (95% confidence interval [CI] = 59.7%–64.4%). The 5-year estimates were 68.5% (95% CI = 66.4%–70.6%) in the chemotherapy group, 61.1% (95% CI = 59.0%–63.2%) in the recommended/not received group, and 53.7% (95% CI = 51.8%–55.8%) in the not recommended/not received group (overall P < .0001).

On univariate analysis, hazard ratios were 0.80 (95% CI = 0.73–0.88, P < .0001) for the recommended/not received group and 0.58 (95% CI = 0.54–0.62, P < .0001) for the chemotherapy group vs the not recommended/not received group. There was no apparent correlation of year of diagnosis with overall survival (P = .48).

On multivariate analysis, hazard ratios remained significant at 0.79 (95% CI = 0.71–0.88, P < .0001) and 0.56 (95% CI = 0.51–0.61, P < .0001), respectively. Patients who received radiotherapy (48.7% of entire cohort) also had improved overall survival compared with those who did not receive radiotherapy (50.0% of cohort; HR = 0.62, 95% CI = 0.50–0.79, P < .0001).

Propensity Score–Matching Analysis

A propensity score–matching analysis was performed that included 1,884 patients who received chemotherapy and 1,884 patients in the recommended/not received group, with matching based on age, comorbidity score, tumor grade and size, nodal status, and receipt vs no receipt of radiotherapy.

Estimated 5-year overall survival was 66.8% (95% CI = 65.7%–67.9%) in the chemotherapy group vs 61.8% (95% CI = 60.8%–62.9%) in the recommended/not received group (HR = 0.85, 95% CI = 0.74–0.96, P = .012). The difference remained significant on multivariate analysis (HR = 0.69, 95% CI = 0.60–0.80, P < .0001). There was no clear indication that the benefit of chemotherapy was limited to any age subgroup.

In subset analyses in the propensity-matched cohort, estimated 5-year overall survival among women with node-negative disease (74% vs 66% of cohort, all with tumor size > 5 mm) was 74.4% (95% CI = 72.6%–76.2%) in the chemotherapy group vs 70.7% (95% CI = 68.9%–72.4%) in the recommended/not received group (HR = 0.80, 95% CI = 0.66–0.97, P = .007). Estimated 5-year overall survival among women with node-positive disease was 42.4% (95% CI = 39.9%–44.9%) vs 35.1% (95% CI = 32.6%–37.6%; HR = 0.76, 95% CI = 0.64–0.91, P = .006). Among women with a documented Charlson-Deyo comorbidity score greater than 0 (25% vs 26% of cohort), the hazard ratio was 0.74 (95% CI = 0.59–0.94, P = .013).

On multivariate analysis in the propensity-matched cohort, additional factors significantly associated with overall survival included:

• Age as a continuous variable (HR = 1.03, P = .0010)
• Comorbidity score of 1 (HR = 1.54, P < .001) and 2 (HR =1.38, P = .011) vs 0
• Tumor size > 50 mm vs ≤ 5 mm (HR = 4.38, P = .042)
• pN1, pN2, and pN3 disease (HRs = 1.92, 3.26, and 5.59, all P < .0001) vs pN0 disease
• Receipt vs no receipt of radiotherapy (HR = 0.62, P < .0001).

The investigators concluded: “These data support consideration of chemotherapy in the treatment of women aged 70 years or older with triple-negative breast cancer.”

Christopher M. Pezzi, MD, of the Division of Surgery, Baptist MD Anderson Cancer Center, Jacksonville, is the corresponding author for The Lancet Oncology article.

Disclosure: There was no outside funding for the study. For full disclosures of the study authors, visit thelancet.com.