Yoanna Pumpalova, MD
People infected with human immunodeficiency virus (HIV) have a substantially higher risk of certain types of cancer -Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer - compared to uninfected people. HIV infection weakens the immune system and reduces the body's ability to fight viral infections that cause these cancers.
More recent research has investigated how HIV impacts cancers that are not linked to infections, including common cancers like breast cancer, prostate cancer, and colorectal cancer. In November, a study by researchers at the Herbert Irving Comprehensive Cancer Center (HICCC) found that HIV-positive patients with breast cancer were 40% more likely to have triple-negative breast cancer - the most aggressive subtype - than those without HIV.
The work included 3,883 women with breast cancer living in South Africa, which has the largest population of people with HIV in the world. Below, Yoanna Pumpalova, MD, assistant professor of medicine and a medical oncologist at Columbia University Irving Medical Center, discusses the link between HIV and triple-negative breast cancer, the implications of the results, and her future work on this topic.
First, how did this study come about? What drove your interest in HIV and cancer?
This project is an idea that I had during my fellowship in medical oncology working with Alfred Neugut, MD, a senior epidemiologist and practicing medical oncologist here at Columbia. His research focuses on cancer outcomes in low- and middle-income countries. When I became his mentee, he had been working on a study to understand the impact of HIV on breast cancer in South Africa.
South Africa has one of the highest prevalences of HIV infection, especially in young Black women. I had a specific interest in understanding whether breast cancer subtypes were different in women with HIV.
Why would women with HIV be more likely to have triple-negative breast cancer?
The immune system of women with HIV is very different. Their immune system's ability to perform immune surveillance and potentially prevent the development and progression of cancer is much lower. We also have learned that triple-negative breast cancer is very responsive to immunotherapy - meaning that once the immune system is able to recognize triple-negative breast cancer, it is quite effective at killing it.
It served as a clue that the immune system may play a prominent role in how triple-negative breast cancer develops, and for that reason, women with HIV might develop triple negative breast cancers at a higher rate versus the more common hormone positive breast cancers.
What is the link between infections, in general, and cancer?
Traditionally we think about HIV-related cancers or AIDS-defining cancers as being driven by infections. These are cancers that are directly caused by a viral infection and that occur at a higher frequency in people with HIV because of their inability to clear viral infections. For example, human papillomavirus (HPV) can cause anal cancer and cervical cancer. We know that even people with well-controlled HIV have a harder time clearing HPV, so they're more likely to develop those cancers.
What is much less understood, but very interesting and relevant today, is cancers that are not driven by infection and are more common as people age, such as breast cancer, colorectal cancer, or prostate cancer. As more people with HIV have access to antiretroviral therapy, their lifespan is longer, and they're developing age-related cancers.
What is the interaction between their abnormal immune system and the development of these kinds of cancers?
Our study is just one little part of the puzzle that lends more credibility to the idea that the immune system is involved in the pathogenesis of these non-virally mediated cancers. There's much more work that needs to be done at the intersection between oncology and immunology to understand how people with abnormal immune systems develop cancer.
What follow-up studies are you doing on the topic of HIV and cancer?
Our collaborators in Johannesburg are working with basic scientists in Germany to look at the actual tumor tissue in women with and without HIV. They are finding differences in the immune cells that are infiltrating the breast cancers of women with and without HIV. It doesn't directly explain the difference in triple-negative versus non-triple negative breast cancer, but it does lend credibility to this idea that the immune system may be responsible for a distinct cancer tumorigenesis in women with HIV, compared to those without HIV.
Another follow-up study that we are considering is using that same cohort to look at breast cancers that develop in the five years after a woman has given birth. We want to investigate whether women with HIV are more or less likely to develop postpartum breast cancer as a question that could be related to the triple-negative finding, because postpartum breast cancers tend to be hormone-positive.
References
About this Study
"The association of HIV status with triple-negative breast cancer in patients with breast cancer in South Africa: a cross-sectional analysis of case-only data from a prospective cohort study"
