Neighborhood and patient characteristics by ADI grouping

A total of 475 patients diagnosed with BC from 2014 and 2018 were initially identified 404 patients met the inclusion criteria and were included in the analysis (CONSORT diagram shown in Fig. 1). Most patients resided in the most disadvantaged areas, with 32.4% in Q5, 27.2% in Q4, and 27.5% in Q3, whereas 11.7% of patients resided in Q2 and only 1.2% of patients in Q1. Figure 2 illustrates the geographic distribution of the ADI across WNY.

Fig. 1

Study design. CONSORT diagram. DCIS ductal carcinoma in situ, ADI area deprivation index, high ADI ≥ 60 most disadvantaged areas, low ADI < 60 less disadvantaged areas

Fig. 2

Adapted from [Ref. 17]

The geographic distribution of the area distribution index (ADI) across WNY

Patients diagnosed with stage I-III BC

The characteristics of stage I-III BC patients by ADI are summarized in Table 1 and Supplementary Table 1. 131 (42%) patients resided in ADI < 60 and 181 (58%) resided in ADI ≥ 60. Most of the patients were females (98%) with a median age of 58 (range 50–67) years. Of these patients, 83% identified as White, 11% Black, 2% Asian, 0.6% Hispanic, and 3% unknown. A total of 81% were diagnosed with hormone receptor positive BC, 12% were diagnosed with HER2+ with or without hormone receptor positive, and only 14.7% TNBC.

Table 1 Demographic and clinical characteristics of stage I-III breast cancer patients according to low (< 60), high (≥ 60) area deprivation index

Notably, patients in the ADI ≥ 60 group were more likely to be Black (15.5% vs. 6.1%, P = 0.04), single (31% vs. 19%, P = 0.001), unemployed (25% vs. 14%, P = 0.02), having governmental type of insurance (46.3% vs. 32.0%, P = 0.01), and higher rates of cardiovascular disease (52% vs. 41%, P = 0.03) compared with the low ADI group. There were no statistically significant differences in age, smoking, alcohol or substance use, obesity, access to contraception, or screening mammograms, diagnosis with a mental health illness at the time of diagnosis, ECOG, or adherence to treatment by ADI group (Supplementary Table 1).

Patients diagnosed with de novo metastatic BC

The characteristics of patients with de novo stage IV BC are summarized in Table 2. A total of 22.8% patients were diagnosed with de novo metastatic BC, 35% (n = 32) of whom resided in the areas with ADI < 60 and 65% (n = 60) in the ADI ≥ 60 areas. The average age was 59 (range 51–68) years. Most of the patients (98%) were females, 83% identified themselves as White, 10% Black, 2% Asian, 3% Hispanic, and 1% an unknown race. Most patients had hormonal receptor positive BC (79%, n = 73), 23% (n = 21) had HER2+ with or without hormone receptor positive BC, and 16% (n = 15) had metastatic TNBC. No significant differences in clinical, pathological, or demographic characteristics were noted between low and high ADI groups (Supplementary Table 2). Supplementary Table 3 presents key characteristics in overall population by ADI.

Table 2 Demographic and clinical characteristics of de novo metastatic breast cancer patients according to low (< 60), high (≥ 60) area deprivation indexAccess to care: time to therapy, rate of germline and somatic mutation testing

There was no statistically significant difference in time to initial therapy by ADI group for patients with either stage I-III or IV disease. Among patients with stage I-III BC, the median time between first diagnosis to therapy was 1.48 months in areas with ADI < 60 compared with 1.51 months among those in areas with ADI ≥ 60 (P = 0.30). For patients with de novo stage IV, the median time from diagnosis to therapy was 1.13 months among those in areas with ADI < 60, and 1.38 months for those in areas with ADI ≥ 60 (P = 0.40).

There was a statistically significant difference in the rate of germline testing by ADI in patients with stage I-III BC, wherein patients residing in areas with ADI ≥ 60 had less germline testing performed compared with those residing in ADI < 60; specifically, only 33.3% patients in the ADI ≥ 60 group had germline testing performed compared with 45.0% in ADI < 60 (P = 0.04) (Table 3). This disparity persisted in multivariate analysis adjusting for age at diagnosis (< 50 vs. ≥ 50 years), TNBC status, self-reported race, marital status, employment status, and type of insurance. Patients in ADI ≥ 60 were significantly less likely to undergo germline testing than those in ADI < 60 (OR 0.52, 95CI% 0.29–0.92, P = 002). Moreover, patients diagnosed at age ≥ 50 were less likely to be tested (OR 0.24, 95%CI 0.12–0.47, P < 0.002). In contrast, patients with TNBC were more likely to undergo germline testing compared to those with non-TNBC stages I-III BC (OR 2.40, 95CI% 1.13–5.13, P = 0.02) (Supplementary Table 4). Notably, no difference in germline testing by ADI was detected in the de novo stage IV BC group (Table 3).

Table 3 Frequency of germline and somatic testing according to cancer stage and area deprivation index

Similarly, there was no difference in the rate of NGS testing by ADI for patients with de novo stage IV BC, where 43.3% patients in the ADI ≥ 60 group had NGS testing performed compared with 41.4% among patients in the ADI < 60 group (P = 1.0) (Table 3). Compared with patients in the ADI < 60 group, those in the ADI ≥ 60 group had higher prevalences of TP53 (23.1% vs. 13.3%, P = 0.7), PIK3CA (19.2% vs. 6.7%, P = 0.4), and ESR1 (26.9% vs. 13.3%, P = 0.4) mutations, although the differences were not statistically significant (Fig. 3).

Fig. 3

Frequency of somatic mutations by ADI. TP53 (13% vs. 23%, P = 0.67), BRCA1 (0% vs. 8%, P = 0.54), BRCA2 (0% vs. 4%, P = 1.00), PIK3CA (7% vs. 19%, P = 0.38), ATM (13% vs. 0%, P = 0.13), ESR1 (13% vs. 27%, P = 0.43), ERBB2 (formerly HER2) (13% vs. 7.7%, P = 0.63), ADI < 60 vs. ADI ≥ 60, respectively. ADI area deprivation index, TP53 tumor protein P53, BRCA1 breast cancer gene 1, BRCA2 breast cancer gene 2, PIK3CA phosphatidylinositol 3-kinase, ATM Ataxia-telangiectasia mutated, ESR1 estrogen receptor 1, ERBB2 Erb-b2 receptor tyrosine kinase 2

Clinical outcomes

As expected, those diagnosed with TNBC had worse OS compared with those with non-TNBC (HR = 4.19, 95% CI: 1.47–11.94, P ≤ 0.001). Being diagnosed at an older age or with a poor PS was associated with worse OS compared with being diagnosed at a younger age or with ECOG PS 0–1 (HR = 1.04, 95% CI: 1.02–1.06, P ≤ 0.001 and HR = 2.46, 95% CI: 1.48–4.08, P ≤ 0.001, respectively). In the overall population, there was a trend towards statistically significant difference in OS between the two groups. Patients residing in areas with an ADI ≥ 60 had a lower 5-year survival rate of 73% compared with 84% for those in areas with an ADI < 60 (95% CI: 67.5–79.7, P = 0.05). Similarly, 3-year and 8-year survival rates were lower in those residing in the ADI ≥ 60 versus < 60 group (82% and 67% vs. 89% and 76% respectively) (Fig. 4). In multivariable analyses adjusting for age, race, ECOG PS, comorbidities, BC subtypes, and stage at diagnosis, a similar trend was observed where those living in areas with an ADI ≥ 60 had worse survival compared with those in areas with an ADI < 60 (HR 1.56, 95% CI: 0.98–2.46, P = 0.058). (Fig. 5).

Fig. 4

Overall survival by ADI. ADI area deprivation index

Fig. 5

Forest plot: multivariable analyses of demographic and clinical characteristics associated with survival in breast cancer patients. ECOG Eastern Cooperative Oncology Group, HR+ hormonal positive (estrogen or progesterone positive), HER2+ human epidermal growth factor receptor 2 positive, TNBC triple-negative breast cancer, late stage stage IV breast cancer, early stage IIII breast cancer, ADI area deprivation index

There was no difference in RFS among patients with stage I-III BC by ADI, such that, for patients in areas with ADI < 60, the median RFS was 112.36 months compared with 175.77 months in areas with an ADI ≥ 60 (P = 0.20). Moreover, there was no difference in TNT among patients with de novo stage IV BC by ADI. The median TNT was 10 months for patients residing in areas with an ADI < 60 (95% CI: 8.00–46.00) compared with 12 months for those residing in areas with an ADI ≥ 60 (95% CI: 6.00–15.00) (P = 0.30).