In a National Cancer Database analysis reported in The Lancet Oncology, Jennifer A. Crozier, MD, of the Division of Cancer Medicine, Baptist MD Anderson Cancer Center, Jacksonville, and colleagues found that receipt of neoadjuvant or adjuvant chemotherapy was associated with improved overall survival among women aged 70 and older undergoing surgery for stage I to III triple-negative breast cancer.¹

Jennifer A. Crozier, MD

As stated by the investigators: “There is a scarcity of data exploring the benefits of adjuvant or neoadjuvant chemotherapy in the treatment of breast cancer in older women. We aimed to explore the effect of adding chemotherapy to local therapy on overall survival in older women with triple-negative breast cancer.”

Study Details

The analysis included data from the National Cancer Database from women aged 70 and older with surgically treated stage I to III invasive triple-negative breast cancer diagnosed between 2004 and 2014. Patients with T1aN0M0 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 women, 7,485 (46.6%) received chemotherapy, chemotherapy was recommended for but not administered to 2,659 (16.6%), chemotherapy was not recommended for nor 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 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 the 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; hazard ratio [HR] = 0.62, 95% CI = 0.50–0.79, P < .0001).

Propensity Score–Matched Analysis

A propensity score–matched analysis was performed and 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, tumor size, nodal status, and receipt vs no receipt of radiotherapy.

The 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 score–matched cohort, the 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). The 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 score–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; and receipt vs no receipt of radiotherapy (HR = 0.62, P < .0001).

The investigators concluded: “The findings of this study suggest a significant overall survival benefit of systemic chemotherapy in older women with triple-negative breast cancer. The benefit was seen in both lymph node-negative patients (with tumours > 5 mm in size) and lymph node-positive patients. The survival benefit of chemotherapy persisted in a subgroup analysis in women with comorbid conditions.

“[T]hese data support a continued consideration of chemotherapy in the treatment of women aged 70 years and older with triple-negative breast cancer. These results can further inform the complex discussion about the benefits, to be weighed against the potential toxicities, associated with the administration of chemotherapy in older women with triple-negative breast cancer.” 

DISCLOSURE: Dr. Crozier has served as a consultant or advisor to Novartis and Puma Biotechnology, has participated in a speakers bureau for Agendia, and has received institutional research funding from Agendia and Seattle Genetics.

REFERENCE

1. Crozier JA, Pezzi TA, Hodge C, et al: Addition of chemotherapy to local therapy in women aged 70 years or older with triple-negative breast cancer: A propensity-matched analysis. Lancet Oncol 21:1611-1619, 2020.