Breast cancer risk according to molecular subtype among people living with HIV in the United States

Background: Breast cancer (BC) is the most common non-AIDS-defined cancer (NADCs) among women living with HIV (WLWH), yet incidence rates are lower than expected compared to the general population. This analysis investigates subtype-specific trends of breast cancer in WLWH. Methods: We analyzed linked data from SEER and NPCR cancer registries and HIV surveillance systems from 12 states, Washington, D.C., and Puerto Rico (2010-2019). We identified in situ and invasive BC cases classified by estrogen receptor (ER) and HER2 status, size, and grade. We estimated incidence rates standardized to the 2010 age distribution of WLWH, average annual percentage changes (AAPCs) in rates using Poisson regression and standardized incidence ratios (SIR) as observed number of cases divided by expected based on incidence in the general population, accounting for age, race/ethnicity, year, and registry. Tumor sizes were categorized as small (<2 cm), medium (2-4.9 cm), and large (>5 cm). Results: Among BC cases with HIV, there were 286 in situ and 1120 invasive BC cases of which 676 were ER+ and 379 were ER-. Of the ER- cases, about 68.9% (261 cases) were triple-negative and 20.1% (76 cases) were HER2-enriched. AAPCs showed no changes in incidence rates of BC for WLWH across all subtypes. Compared to the general population, WLWH demonstrated a 33% (SIR= 0.67, 95% CI 0.63-0.71) lower risk of invasive BC overall, including a 43% (SIR= 0.57, 95% CI 0.53-0.61) reduction in ER+ BC incidence and statistically non-significant 7% (SIR= 0.93, 95% CI 0.84-1.03) (SIR ER+ vs. SIR ER- p heterogeneity >0.001) reduction in ER- BC incidence. HER2-enriched and triple-negative tumors had similar reductions in risk, 15% (SIR= 0.85, 95% CI 0.67-1.06) and 4% (SIR= 0.96, 95% CI 0.84-1.08) respectively. WLWH in situ BC rates had a 38% (SIR= 0.62, 95% CI 0.55-0.69) lower risk compared to the general population. Overall, SIRs were consistent throughout the 2010-2019 period. Across tumor size and grade, WLWH have reduced incidence compared to the general population. Reductions were most pronounced for small (SIR= 0.66, 95% 0.59-0.73) and medium-sized tumors (SIR= 0.65, 95% 0.57-0.73) while large tumors had 20% (SIR= 0.80, 95% 0.66-0.98) decreased incidence. Low- and intermediate-grade tumors (Grade 1 and 2) showed 46% (SIR= 0.54, 95% CI 0.45-0.65) and 45% (SIR= 0.55, 95% CI 0.49-0.61) reductions in risk while Grade 3 tumors showed a smaller, but still significant reduction in risk (SIR=0.70, 95% CI 0.67-0.80). Conclusion: While relative risk for BC overall is lower for WLWH compared to the general population, the reduction in risk is significantly greater for ER+ tumors than ER- tumors. The lower risk in smaller and in situ tumors may also demonstrate less screening participation among WLWH. Clarifying factors underlying reduced BC risk in immunocompromised populations, including WLWH, may inform prevention and treatment strategies for WLWH and the general population.