Despite the effectiveness of current antivirals in suppressing viral load in HIV and preventing the development of AIDS, patients are still immunocompromised, which may predispose them to the development of non–AIDS-defining cancers, including breast cancer (BC). Further, as patients with HIV live longer, the odd of developing BC increases, although studies are mixed as to whether the incidence of BC is higher in women with HIV compared with those without HIV.
Hormonal changes induced by HIV and its treatment may impact the development of BC as it tends to present 20 years earlier in HIV-positive women. To complicate the picture even more, younger women on antiretroviral (ART) therapy present a different cancer risk profile than those diagnosed at a more advanced age. When women with HIV present with BC, they also tend be have later stages of the disease and are less often hormone receptor positive/human epidermal growth factor 2 negative (HR+/HER2-), which portends a less favorable outcome.
A recently published critical review takes a detailed look as to what is known about the interplay between HIV and BC. This paper focuses on three areas: immune system impairment, chronic inflammation, and the development of BC. As a result of immune system impairment, patients with HIV have a low CD4 count, reduced immune surveillance to detect and destroy cancer cells, oncogenic virus persistence, immunosenescence, and unchecked cell growth. Chronic inflammation further exacerbates the situation by causing persistent immune activation, microbial translocation, viral replication, and the development of opportunistic infections or coinfections and is associated with aging.
In BC, there is dysregulation of cell cycle proteins; impairment of DNA repair capacity; promotion of cell proliferation; negative factor (Nef) oncogenic effects that result in altered T-cell function, enhanced viral infectivity, and immune evasion of cancer cells; and viral protein R (Vpr)–mediated DNA damage, which induces cell cycle arrest and influences DNA repair and cell proliferation. Immune suppression and chronic inflammation associated with HIV play a critical role in altering gene expression patterns, which may contribute to the development of BC. Some of these harmful effects may be mitigated by readily accessible BC screening and follow up.
Research is also exploring a possible genetic link between HIV and BC as 17 shared genes have been identified as being associated with both conditions. There is 90% homology between BC DNA sequences and the HIV-1 gp41 gene.
ART may also play a role in this HIV-BC interplay. For example, efavirenz binds and activates estrogen receptors in the breast, which has been associated with the development of gynecomastia and could possibly influence BC risk.
Another important consideration is that HIV may negatively affect the response to neoadjuvant chemotherapy (NAC) in BC as lower rates of pathological complete response (pCR) (5% vs. 21%, P = .048) have been observed in HIV+ BC patients, a finding that has been consistent among all BC subgroups. pCR was not related to the use of ART, viral load, or CD4+ count. Two-year overall survival was also markedly reduced in those with stage III BC and HIV (58% vs. 74%) compared with those with BC but no HIV. Reduced chemotherapy dose intensity and discontinuation of NAC is also more common in the HIV+ group.
ART also shares some of the same toxicities (e.g., myelosuppression from zidovudine, peripheral neuropathy from platinum agents, taxanes, vinca alkaloids, and nucleoside reverse transcriptase inhibitors [NRTIs], QTc prolongation from protease inhibitors [PIs] and tyrosine kinase inhibitors) as NAC, further compounding the simultaneous management of both conditions.
ART drug-drug interactions (DDIs) are another major concern. The majority of ART act as inducers or inhibitors in the cytochrome P450 system. The article describes DDIs and/or cross toxicities with the entry, attachment, and capsid inhibitors, integrase inhibitors, non-NRTIs, NRTIs, and PIs.
As the population ages and the medications for HIV maintain their efficacy, more patients with HIV are expected to live longer. With that longevity comes an increased risk of developing BC. This article is a must-read for pharmacists as it can help them navigate the complexity of managing both of these potential life-threatening conditions.
The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.
