Relative Dose Intensity and Pathologic Response Rates in Patients With Breast Cancer and With and Without HIV Who Received Neoadjuvant Chemotherapy

Abstract

PURPOSE Patients who are HIV-positive and have breast cancer have worse overall survival (OS) compared with patients who are HIV-negative. Pathologic complete response (pCR) and relative dose intensity (RDI) of chemotherapy are associated with survival. We assessed whether pCR and RDI rates were lower for patients who are HIV-positive and received neoadjuvant chemotherapy (NACT). METHODS This was a prospective cohort analysis of patients initiating NACT in Botswana (February 2017 to September 2019). Primary outcomes were pCR and RDI; secondary outcomes were OS and toxicity. HIV status and zidovudine (ZDV) treatment were stratification factors. Multivariable analysis was used to control for confounding. RESULTS In total, 26 of 110 enrolled individuals were HIV-positive. In univariable analysis, HIV-positive (odds ratio [OR] = 0.2; P = .048) and RDI < 0.85 (OR = 0.30; P = .025) were associated with pCR. In multivariable analysis, the magnitude of association decreased for HIV-positive (OR = 0.28; P = .11), but RDI < 0.85 remained independently associated with pCR (OR = 0.32; P = .035). Patients who are HIV-positive had significantly lower mean RDI, and those on ZDV had significantly lower RDI. Ninety-one (83%) were stage III with 2-year OS significantly worse for patients who are HIV-positive (58% v 74%). Hazard ratio for all-cause mortality was 2.68 (95% CI, 1.17 to 6.13; P = .028) in patients who are HIV-positive compared with patients who are HIV-negative. Toxicity rates were similar despite patients who are HIV-positive receiving significantly lower dose intensity chemotherapy. CONCLUSION Patients who are HIV-positive and have breast cancer in Botswana have lower pCR rates and also receive lower dose intensity therapy, which may contribute to worse OS. Patients who are HIV-positive on ZDV-containing regimens received even lower dose intensity of NACT. Administering optimal dose intensity in patients who are HIV-positive remains a challenge, and targeted interventions that address modifiable risk factors are needed to improve therapy delivery and outcomes.

Time to Cancer Treatment and Chemotherapy Relative Dose Intensity for Patients With Breast Cancer Living With HIV

“…Existing literature on chemotherapy dose intensity in patients with breast cancer living with HIV comes from sub-Saharan Africa. Botswanan patients with breast cancer did demonstrate a reduction in chemotherapy RDI associated with comorbid HIV infection, but the mean RDI for all patients was just 0.78 . Conflicting results come from South Africa, where a large cohort study of breast cancer showed parity in RDI by HIV status and a median of 0.88 for all women .…”

“…Botswanan patients with breast cancer did demonstrate a reduction in chemotherapy RDI associated with comorbid HIV infection, but the mean RDI for all patients was just 0.78. 20 Conflicting results come from South Africa, where a large cohort study of breast cancer showed parity in RDI by HIV status and a median of 0.88 for all women. 21 In the US academic setting, we found patients with breast cancer living with HIV reaching a median RDI comparable to South African WLHIV.…”

“…19 Conflicting reports from Botswana and South Africa suggest that WLHIV may or may not be less tolerant of chemotherapies used for breast cancer, but even patients without HIV in those studies received a lower chemotherapy dose intensity than is typically given in the US. 20,21 We aimed to overcome these challenges to studying the associations between comorbid HIV and breast cancer care by pooling retrospective data from 3 large, urban cancer centers. Specifically, we assessed associations between HIV infection and 2 care quality indicators: time to treatment initiation after cancer diagnosis and neoadjuvant and adjuvant chemotherapy relative dose intensity (RDI).…”

“…Analysis from the SEER-Medicare registry shows that patients with cancer living with HIV experienced a longer delay between cancer diagnosis and first treatment (42.5 vs 36 days) but that analysis included only women aged 65 years or older and just 12 patients with breast cancer living with HIV . Conflicting reports from Botswana and South Africa suggest that WLHIV may or may not be less tolerant of chemotherapies used for breast cancer, but even patients without HIV in those studies received a lower chemotherapy dose intensity than is typically given in the US …”

Development, acceptability and usability of culturally appropriate survivor narrative videos for breast cancer treatment in Botswana: a pilot study

“…Reasons for the observed breast cancer survival disparities in SSA are likely multifactorial and have been attributed to health system factors (eg, health system and diagnostic delays, drug stock-outs),9 10 patient factors (eg, delays that lead to advanced stage at presentation, limited breast cancer and treatment knowledge, and breast cancer stigma),11–13 and other social determinants of health (eg, financial toxicity and food insecurity),14 as well as biology (eg, more aggressive molecular subtypes such as ‘triple negative’ breast cancer) 15. Some of these factors ultimately lead to breast cancer care that deviates from guideline-concordant therapy 16–19…”