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Abstract
Studies have shown that delayed initiation of surgery and adjuvant chemotherapy is associated with lower rates of breast cancer survival. However, it remains unclear whether delayed initiation of adjuvant hormone therapy (AHT) is associated with survival. To assess the association of time to adjuvant hormone therapy (TTH) with breast cancer survival and evaluate the factors associated with AHT. This cohort study examined data from the National Cancer Database from 2004 through 2014 to assess the association of TTH (stratified as ≤150 and >150 days) with cancer survival. All patients included were diagnosed with stage I to stage III hormone receptor-positive, human epidermal growth factor receptor-2 (ERBB2; formerly HER2)-negative invasive breast cancer and underwent AHT without chemotherapy. Data were analyzed from April 2019 to May 2020. AHT was administered at different time points following surgical procedures for breast cancer treatment. An inverse probability of treatment weighting (IPTW) model was constructed to evaluate overall survival by adjusting for treatment facility, patient demographics, tumor characteristics, and treatment; multivariable logistic regression was conducted to assess factors associated with delayed treatment. A total of 144 103 patients (median [IQR] follow-up, 36.6 months [25.5-49.2 months]; mean [SD] age, 63.7 [11.6] years) were identified, which included 142 916 (99.2%) women, 11 574 (8.0%) Black patients, and 126 013 (87.4%) White patients. Of these, 134 873 patients (93.6%) had a TTH of 150 days or less and 9230 patients (6.4%) had a TTH longer than 150 days. The IPTW-based Cox model demonstrated that patients with delayed AHT (ie, a TTH past 150 days) were associated with decreased survival (hazard ratio [HR], 1.31; 95% CI, 1.26-1.35; P < .001) compared with those receiving the timely treatment (TTH ≤150 days). Several sensitivity analyses (including IPTW with stabilized weight [HR, 1.31; 95% CI, 1.19-1.45; P < .001], propensity score matching [HR, 1.41; 1.13-1.76; P = .002], and propensity score regression adjustment [HR, 1.29; 95% CI, 1.16-1.43; P < .001]) and exploratory subgroup analyses yielded similar trends. Factors associated with delayed AHT included Black racial identity (OR, 1.66; 95% CI, 1.55-1.77), nonprivate insurance (eg, no insurance: OR, 1.46; 95% CI, 1.26-1.70), living in large metropolitan or metropolitan areas (reference vs urban, less urban, or rural: OR, 0.82; 95% CI, 0.76-0.87), treatment in a community hospital (reference vs academic or research: OR, 0.91; 95% CI, 0.84-0.98), Charlson-Deyo Comorbidity Index score 2 or higher (OR, 1.17; 95% CI, 1.04-1.32), poor grade differentiation (OR, 1.42; 95% CI, 1.32-1.53), II and III pathological stage (stage III: OR, 3.13; 95% CI, 2.76-3.54), estrogen receptor-positive (ER+)/progesterone receptor-negative (PR-) or ER-/PR+ (OR, 1.22; 95% CI, 1.13-1.31), receiving breast conservation surgery (reference vs mastectomy: OR, 0.87; 95% CI, 0.79-0.94), and radiotherapy (reference vs no radiotherapy: OR, 0.56; 95% CI, 0.52-0.61). The delay of the initiation of AHT past 150 days was associated with diminished survival in hormone receptor-positive, ERBB2-negative patients with breast cancer who did not receive chemotherapy. Efforts should be made to address factors associated with delayed treatment to improve survival.
Highlights
Hormone receptor (HR)–positive breast cancer is the most common subtype of breast cancer, accounting for about two-thirds of all breast malignant neoplasms.[1,2] Among patients with hazard ratios (HRs)-positive early breast cancer, hormone therapy is considered an integral treatment that reduces recurrence and mortality.[3]
The inverse probability of treatment weighting (IPTW)-based Cox model demonstrated that patients with delayed adjuvant hormone therapy (AHT) were associated with decreased survival compared with those receiving the timely treatment (TTH Յ150 days)
Several sensitivity analyses and exploratory subgroup analyses yielded similar trends
Summary
Hormone receptor (HR)–positive breast cancer is the most common subtype of breast cancer, accounting for about two-thirds of all breast malignant neoplasms.[1,2] Among patients with HR-positive early breast cancer, hormone therapy is considered an integral treatment that reduces recurrence and mortality.[3]. AHT for HR-positive early breast cancer has become a consensus treatment, the specific timing of initiating treatment remains unknown. Studies have revealed that delays in the initiation of surgical procedures or postoperative chemotherapy were associated with diminished survival.[10,11,12,13] Recently, concerns have emerged whether delayed AHT has a similar correlation with survival. Preclinical experiments have reported that hormone therapy might affect cell cycle kinetics, inhibit tumor cell proliferation, and prevent the accelerated growth of micrometastases after primary tumor removal.[14,15,16] A 2020 study[17] found that patients with HR-positive breast cancer without chemotherapy experienced worse survival when initiating AHT after more than 180 days. Given that relevant studies are limited, the timing of initiation of AHT and whether delays in AHT lead to a poor prognosis need to be further explored
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