HIV-positive women with breast cancer appear to have
decreased survival compared with HIV-negative women, according to a cohort
study from Botswana presented yesterday at the Conference on Retroviruses and
Opportunistic Infections (CROI 2019) in Seattle.
Having HIV was associated with a nearly twofold
reduction in survival, and this finding held for women on antiretroviral
therapy (ART) with suppressed virus and higher CD4 T cell counts, reported Dr Katrin Sadigh of Brigham and Women’s Hospital in Boston.
As people with HIV live longer thanks to effective antiretroviral
treatment, AIDS-related mortality has declined dramatically while
non-communicable diseases such as cancer and cardiovascular disease account for
a growing proportion of deaths. Breast cancer is the leading cause of
cancer-related death for women with HIV who have access to effective ART, as it is also for HIV-negative women.
Sadigh's team performed
a prospective analysis to evaluate the impact of HIV on overall survival of
women with breast cancer in a resource-constrained setting. While prior
research in the US and Africa has found that women with HIV do not have higher
breast cancer incidence, or likelihood of developing cancer, some studies with
a small number of HIV-positive participants suggested that survival may be
reduced.
The current analysis drew
from the Thabatse Cancer Cohort, which enrolled nearly 4000 people with cancer
at four major oncology centres in Botswana. Participants are evaluated at study
entry and followed for five years. Causes of death are obtained from providers,
family members and death certificates.
The breast cancer cohort
included 510 women who sought cancer care at public or private facilities
between October 2010 and September 2018. Of these, 151 were HIV positive and
327 were HIV negative.
The HIV-positive group
was younger on average than the HIV-negative women (media 47 vs 56 years,
respectively). In both groups, about 5% were diagnosed with stage I early
breast cancer, about 25% with stage II, about 40% with stage III and about 15%
with stage IV or metastatic cancer. Both groups also had similar proportions of
women with oestrogen receptor-positive tumours (about 35%) and triple-negative
breast cancer that doesn't respond to commonly used medications (about 15%);
however, more than 40% were not tested for this.
Both HIV and cancer care
are provided for free by the government in Botswana, Dr Sadigh said. Before
2016, people with HIV started ART when their CD4 count fell below 350 cells/mm3,
but thereafter everyone was treated regardless of CD4 count. Most women (85%)
were taking ART at the time of cancer diagnosis, three-quarters had done so for
at least two years and 70% had HIV viral load below 1000 copies/ml. The most common
regimens were zidovudine/lamivudine/efavirenz and
tenofovir DF/emtricitabine/efavirenz, at just over 30% each.
Breast cancer treatment in
Botswana typically involves surgery followed by preventive (adjuvant)
chemotherapy for early-stage cancer, or pre-surgery (neoadjuvant) chemotherapy
followed by surgery or radiation therapy for those with more advanced disease.
Both tamoxifen, a type of hormone therapy for oestrogen receptor-positive
breast cancer, and trastuzumab (Herceptin),
a targeted therapy for HER2-positive tumours, are generally available,
according to Dr Sadigh.
Types of treatment did
not differ significantly by HIV status, with about 70% of women undergoing
mastectomy, about 10% having lumpectomies, about 60% receiving some type of
chemotherapy and just under half receiving radiation therapy. Most received
multi-modality treatment.
During the course of the
study, 70 HIV-positive women (46%) and 101 HIV-negative women (31%) died. In
both groups, cancer was by far the most frequent cause of death, accounting for
around 90% of cases; around 3% of deaths were attributed to adverse effects of
treatment. None of the women with HIV died of directly AIDS-related causes. In
a multivariate analysis controlling for other factors, HIV-positive women had
an 82% reduction in survival compared with HIV-negative women.
Having HIV was
associated with higher mortality in most subgroups. There was little difference
among women with stage IV cancer, who had a high death rate regardless of HIV
status. HIV appeared to have a greater effect on mortality in women with early-stage
breast cancer, hormone receptor-negative tumours and – unexpectedly – higher CD4
counts (above 350 cells/mm3), a finding Dr Sadigh was unable to explain.
"HIV infection was
associated with nearly two-fold reduction in breast cancer survival despite
good access to ART," the researchers concluded. "Differences
in cancer stage, cancer subtype or access to cancer treatment does not explain
the disparity."
Dr Sadigh emphasised
that survival was poor for both HIV-positive and HIV-negative women in this
study, and better strategies are needed to speed up diagnosis and improve care.