Abstract PS04-06: Breast cancer recurrence among women with pre-diagnostic major depression and co-existing substance abuse disorder: A retrospective study in the United States Veterans Health Administration Cohort
Authors: Aboumrad Maya , Visvanathan Kala 
Published: May 2024

Abstract
Background:
Our prior study observed a 34% higher risk of breast cancer (BC) recurrence among women with major depressive disorder (MDD) at the time of their BC diagnosis compared to women without MDD after adjusting for sociodemographic, clinical, and prognostic factors. Given the high prevalence of substance abuse disorders among individuals with MDD and the positive association between alcohol use and mortality among BC survivors, we were interested to examine whether the risk of BC recurrence was compounded for women with both conditions.
Objective:
To investigate whether pre-diagnostic substance abuse disorders modify the association between MDD and BC recurrence.
Methods:
We established a retrospective cohort of women (age ≥ 18 years) with incident, early-stage BC diagnosed from 2010 through 2019 using the VHA’s electronic medical record database. A two-year window was used to identify women with MDD and co-existing substance abuse disorders prior to their BC diagnosis. We examined potential interactions between MDD and alcohol abuse and MDD and other substance abuse using multivariable proportional hazards regression, accounting for competing risk of death. Our outcome of interest was BC recurrence. The reference group for all analyses was women with BC alone. The models were adjusted for patient characteristics including age, race, ethnicity, marital status, rurality of primary residence, priority group rating (proxy for socioeconomic status), any homelessness or economic problems, comorbidity burden, body mass index, smoking status, receipt of a screening mammography, year of BC diagnosis, cancer stage, cancer subtype, and cancer treatment. Subgroup analyses were conducted by cancer subtype.
Results:
Our cohort comprised 6,045 women with BC, of whom 1,754 (29%) had a pre-diagnostic MDD diagnosis and 1,509 (25%) had a substance abuse disorder. Among women with MDD, 386 (22%) abused alcohol and 336 (19%) abused other substances. The median length of follow-up from BC diagnosis was 4.5 years (IQR=4.8 years). The average age at BC diagnosis was 57 years (SD=11 years) overall, 56 years (SD=10 years) among women with MDD, and 57 years (SD=9 years) among women with substance abuse disorders. On multivariable analysis, MDD (HR=1.33; 95% CI: 1.14, 1.53), alcohol abuse disorder (HR=1.37; 95% CI: 1.12, 1.68), and other substance abuse disorders (HR=1.33; 95% CI: 1.13, 1.56) were independent risk factors for BC recurrence. Further, there was a statistically significant interaction between pre-diagnostic MDD and alcohol abuse disorder (p-interaction=0.003). Women with BC who had both pre-diagnostic MDD and alcohol abuse disorder were at a 65% (HR=1.65; 95% CI: 1.29, 2.11) higher risk of BC recurrence compared to women with BC alone. A statistically significant interaction was also observed between pre-diagnostic MDD and other substance abuse disorders (p-interaction &lt; 0.001). Women with BC who had both pre-diagnostic MDD and other substance abuse disorders were at a 90% (HR=1.90; 95% CI: 1.50, 2.42) higher risk of BC recurrence compared to women with BC alone. In subgroup analyses, the interaction between MDD and alcohol abuse disorders (p-interaction=0.001) and MDD and other substance abuse disorders (p-interaction &lt; 0.001) was limited to women with estrogen receptor positive cancer but not estrogen receptor negative cancer.
Conclusion:
Women with incident BC who have prior diagnoses of both MDD and substance abuse disorder are at higher risk of recurrence than women with either exposure independently. Further research is needed to examine the etiology of our findings and to evaluate whether this newly defined risk group would benefit from closer monitoring and more tailored treatment options.
Citation Format: Maya Aboumrad, Kala Visvanathan. Breast cancer recurrence among women with pre-diagnostic major depression and co-existing substance abuse disorder: A retrospective study in the United States Veterans Health Administration Cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS04-06.