Each year, more than a quarter million women die from cancer in the United States alone, according to the Centers for Disease Control and Prevention. Breast and cervical cancer, in particular, are among the most common diseases affecting women across the globe. Silvia Chiara Formenti, Chairman of the Department of Radiation Oncology and the Sandra and Edward Meyer Professor of Cancer Research at Weill Cornell Medicine, has spent much of her professional career studying and developing cancer therapies, with an especial focus treating cancers affecting women.
“As an oncologist I find it necessary to do research, because we continue to lose people to cancer,” says Formenti, who is also radiation oncologist-in-chief at New York-Presbyterian/Weill Cornell Medical Center. “It is our duty to better understand these diseases, and initiate research to make a difference.”
The Outcome of Children Whose Mothers Die of Cancer
While most of Formenti’s research focuses on studying cancer immunology and immunotherapy, she recently took a wide lens to the disease to ask a more global question. After noticing the high incidence—and earlier death—from female cancers in developing countries, she examined how maternal death from breast and cervical cancer affects the outcome of their children.
“We chose breast and cervical cancer because I was interested in the size of the collateral damage of women dying young,” says Formenti. “Another reason is that in both cancers we know how to make a difference. In breast cancer, one can reduce mortality with early detection and appropriate treatment, and cervical can be prevented with vaccination against HPV virus—its main causative agent.”
Formenti worked with one of her former residents, Raymond Mailhot, currently a faculty member at University of Florida, to study child mortality. “There is a robust literature that shows if the mother dies when the children are younger than 10 years old, the children acquire an increased risk of dying that has nothing to do with disease,” says Formenti. “It has to do with losing their moms.”
The questions they sought to answer included these: Can the association between a mother’s death from cancer and her child’s mortality be predicted? How much does maternal mortality from breast and cervical cancer affect child mortality overall in a given country? Thus, how much could child mortality be reduced if maternal death from breast or cervical cancer was prevented?
Global Studies on Mothers’ Deaths from Breast and Cervical Cancer and Child Mortality
Using available large-scale population data from three countries with distinct levels of economic development and medical infrastructure—Bangladesh, Burkina Faso, and Denmark—the researchers looked at incidences of cervical and breast cancer rates in women during their fertile years. They combined this with available data on baseline child mortality, as well as the predicted mortality rates for children who lost their mothers before the age of 10. They then created a simulation model that specifically analyzed the impact of mothers’ deaths from breast and cervical cancer on child mortality in these countries.
The results of the study, which was published in the journal Cancer in 2019, showed that child deaths associated with mothers' deaths from breast and cervical cancer resulted in notable increases in cancer-related mortality—as high as 30 percent in certain African countries. Formenti says that this demonstrates how the burden of cancer affects more than those who have the disease.
“When you look at both incidents of mortality—mother and child—it is clear that in developing countries it's much younger than in richer countries.”
In countries with more resources, however, the increase of child mortality was much smaller, for example, less than one percent in Denmark. “When you look at both incidents of mortality—mother and child—it is clear that in developing countries it's much younger than in richer countries,” says Formenti. “The disease occurs earlier, resources are limited, and women often present with advanced diseases, so they're much more likely to die. The effect is amplified by the collateral death of children.”
Formenti hopes that broad research like this can help shape policy and health changes in the countries most affected.
Combining Radiotherapy and Immunotherapy, a Novel Therapeutic Approach to Cancer
When it comes to working directly with patients with cancer, Formenti has long been interested in how radiotherapy can be combined with immunotherapy to control cancerous tumors. Her earlier work has shown that radiation could modify tumors to make them more recognizable by an individual’s immune system.
Based on these findings, she moved on to studying breast cancer in mouse models. More recently, she and her colleague Sandra Demaria, Professor of Radiation Oncology at Weill Cornell Medicine, performed successful clinical trials using radiotherapy alongside immunotherapy in solid tumors (lung and breast cancer). Building on that evidence, Formenti and Demaria were recently awarded a $5.7 million grant from the Department of Defense to run clinical trials on breast cancer patients.
Led by Formenti, this project consists of a consortium of five groups of investigators—including those at University of Pittsburgh, Cedars-Sinai Medical Center, and the Mount Sinai Hospital—to conduct a novel clinical trial in newly diagnosed breast cancer patients. The research will focus on breast cancers that are hormone receptor-positive (HR+), which make up approximately 75 percent of cases in the United States. Despite therapeutic advances, nearly a third of HR+ breast cancer recurs, and it accounts for the most frequent cause of death from breast cancer. Current available immunotherapy does not have a high success rate with HR+ breast cancer with only a small minority of patients responding to it.
Formenti and the consortium of researchers are addressing this barrier with a multipronged approach. They will perform a randomized trial that tests standard therapy with different immunotherapies targeting specific barriers previously found in mouse models and confirmed in some clinical studies.
“Nobody else has used radiotherapy directed to the tumor with immunotherapy before surgery,” says Formenti. “It’s completely new.” The goal is to demonstrate evidence of a treatment that can convert HR+ breast cancer tumors into an individualized vaccine—essentially immunizing the patient to the tumor. Formenti says that she hopes data from these trials will also spur larger studies and, if confirmed, change the treatment of HR+ breast cancer, potentially reducing tumor recurrence and death.
Weill Cornell Medicine, Ideal for Collaborative Research
As an expert in breast cancer, Formenti has received consultant honoraria and research grants from various commercial entities. Formenti says, “Weill Cornell Medicine is an ideal site to develop forms of interdisciplinary collaboration—not only in the delivery of integrated clinical care, but also for collaborative research.”
Formenti says, “This type of environment is especially conducive to somebody working both as a clinician and a researcher.”