One in 18 patients with breast cancer is under 40 years old. These young women are relatively often diagnosed with triple-negative breast cancer, which is known as a particularly aggressive variety. To prevent metastases, nearly all patients with triple-negative breast cancer are treated with chemotherapy (before or after their surgery and/or radiotherapy), even if the lymph nodes in their armpits are clean.
But there are many side effects associated with chemotherapy, and it can negatively affect fertility and health later in life. There is even a 1% chance that chemotherapy treatment proves fatal for the patient. This is why our current motto is: “less when possible, more where necessary.”
Physician-scientist Vincent de Jong: “The side effects of chemotherapy are especially unfortunate for younger patients, who still have long lives ahead of them. You really want to reserve chemotherapy for when it is absolutely essential. But how can you tell whether it’s required for a particular patient?”
To be able to predict whether chemotherapy can be left out of the treatment plan because the risk of metastases is very small, gene expression tests were developed for other types of breast cancer - MammaPrint or Oncotype DX. These tests don’t work on triple-negative breast cancer, however.
Thankfully, the immune system turns out to be on our side against triple-negative breast cancer. De Jong: “We had already noticed that the presence of tumor-infiltrating lymphocytes (TIL) often predicted a positive outcome. Those immune cells fight off intruders. Our question was: can you use the presence of these immune cells near the tumor as a reliable test to predict whether a young woman with triple negative breast cancer has a favorable prognosis, so you can safely leave chemotherapy out of their treatment plan?”
In order to find an answer to this question, the researchers consulted the archives. They analyzed the tissue and the disease progression of all patients under 40 years old who had been diagnosed with triple negative breast cancer in the Netherlands between 1989 and 2000, and whose lymph nodes had been clean. In the 90s, women with breast cancer and clean lymph nodes did not receive chemotherapy, which is different from the current situation. This allowed the investigators to find out more about the risk of metastases without chemotherapy treatment.
The results: women with a high percentage of TIL (75% or higher) around their tumors had a favorable prognosis: their risk of metastases or death after 15 years without chemotherapy was approximately 2%. This had been the case for one in five women in the study.
“This means that there are no additional benefits to chemotherapy treatment,” research leader Sabine Linn explains. “Because chemotherapy can halve the risk of metastases, this treatment would reduce the risk faced by this group to 1%. But chemotherapy by itself is not without risks either – its potentially fatal immediate and long-term side effects also add up to a 1% risk of death.”
The guidelines will not be adjusted immediately, Vincent de Jong knows. “But we are making a case for a clinical trial involving this category of women to confirm that chemotherapy can be avoided safely.”
“Unfortunately, we did also encounter a group of women who did not do well without chemotherapy,” he immediately adds. “This concerns women whose TIL percentage was below 30%. But do keep in mind that these women did not receive chemotherapy in the 90s because their lymph nodes had been clean. They do now, so we cannot adequately compare their prognoses to patients who are diagnosed today.”