Who Is at Risk for Triple-Negative Breast Cancer?

While triple-negative breast cancer is rare and only accounts for about 10 to 15 percent of all breast cancers according to the American Cancer Society, it has fewer treatment options than other breast cancers and grows and spreads more rapidly than most other breast cancer types.

This type of cancer lacks certain hormone receptors that contribute to cancer growth. These receptors attach the cell to certain substances in the blood, like hormones. Both healthy breast cells and breast cancer cells need estrogen and progesterone to grow and have receptors that attach to those hormones specifically.

But sometimes, a breast cancer cell does not have receptors for estrogen, progesterone, or human epidermal growth factor 2 (HER2). These cells are called triple negative. Without these receptors, oncologists can only treat triple-negative breast cancer by removing tumors surgically and prescribing chemotherapy and radiation to kill any remaining cells.

Those at High Risk

People with a family history of breast cancer are always at a higher risk of getting cancer. Family members with genetic changes (called mutations) that cause breast cancer pass it on to future generations. Some people with a family history of cancer inherit a mutation in the BRCA genes.

BRCA1 and BRCA2 genes help regulate how breast, ovarian, and other cells grow and divide. Cancer is when these cells grow too rapidly or in an uncontrolled way, so these genes are essential in helping to fight off the disease.

However, according to the Centers for Disease Control and Prevention (CDC), roughly 1 in every 500 women in the United States has a mutation in one of her BRCA genes. And about half of the women with a BRCA gene mutation will get breast cancer by the time they turn 70.

People with a mutation in their BRCA1 gene are at risk of developing triple-negative breast cancer, specifically, per the American Cancer Society. And people of Ashkenazi Jewish heritage are at a higher risk of inheriting BRCA gene mutations that can cause breast cancers, such as triple-negative breast cancer, according to the CDC.

Black women are also at risk of developing triple-negative breast cancer. Recent research published in Breast Cancer Research in June 2022 that analyzed data from over 3,300 people with breast cancer found that women with triple-negative were twice as likely to be Black. And according to the American Cancer Society’s 2021 Cancer Statistics, Black women are 40 percent more likely to die from breast cancer than white women.

The reasons are not entirely well understood by researchers yet. But Rita Nanda, MD, associate professor of medicine and director of the breast oncology program at the University of Chicago, who was not involved with either study, suspects genetic or socioeconomic factors may contribute.

“I also think some of [the disparity] is driven by the fact that Black women generally develop breast cancer at a younger age,” Dr. Nanda says “And we know that younger women are more likely to have triple-negative breast cancer than hormone-positive breast cancer.”

To her point, that Breast Cancer Research study, as well as a study published in Cancer in October 2020, found that women diagnosed with triple-negative breast cancer were, on average, around three years younger than those diagnosed with other types. The Cancer study also found that women under 40 had the highest odds of a triple-negative breast cancer diagnosis.

Newer Treatments Are Helping to Improve Outcomes

“For most patients with triple-negative breast cancer, the standard of care is chemotherapy or immunotherapy prior to surgery,” says Nanda. Undergoing chemo or immunotherapy before surgery is called neoadjuvant therapy.

“However, it depends on the size of the tumor and whether the cancer has spread to the lymph nodes or not,” she notes. For triple-negative breast cancer tumors over 2 centimeters or that have spread to the lymph nodes, Nanda says neoadjuvant therapy is standard practice.

According to Nanda, oncology teams have historically used neoadjuvant therapy to shrink tumors before operating to preserve breast tissue or to make more accurate prognoses. “But now, the approach changes what we do after surgery in a way that improves outcomes,” she says.

“For patients who have a complete response to neoadjuvant therapy, meaning no cancer left in the breast or the lymph nodes, we continue immunotherapy or give radiation as needed.” But for those who have residual cancer in either their breast tissue or lymph nodes after neoadjuvant therapy, it's recommended they receive additional chemotherapy after surgery, according to the American Cancer Society.

“There are many ongoing trials analyzing newer therapies that might further improve outcomes for women at higher risk for recurrence,” says Nanda. One such study that Nanda is working on is the GLORIA trial, a phase 3, randomized, open-label study analyzing the efficacy of a new immunotherapy option on patients with high risk, early stage triple-negative breast cancer that is slated to wrap up by 2027. The novel immunotherapy in the GLORIA trial, which takes the form of a vaccine, targets lipids on the cancer cell membrane that, when unchecked, helps cancer cells multiply.

According to Nanda, preliminary data from the GLORIA trial and other trials suggest that incorporating additional chemotherapies and immunotherapies developed in recent years into the mix of options for treating triple-negative breast cancer is improving long-term outcomes and helping more women. Regarding treatments on the horizon, she says drugs called antibody-drug conjugates (ADCs) “are showing a lot of promise.”

Antibody-drug conjugates target and bind to the receptors triple-negative breast cancer cells do have, delivering chemotherapy to each cell directly. Nanda calls this treatment targeted chemotherapy. “These more targeted chemotherapy approaches are still chemotherapy. They still have chemotherapy side effects,” she says. “They are targeted to a particular protein, so they can be more effective than traditional chemotherapy, which isn’t targeted.”

A review published in 2020 in Therapeutic Advances in Medical Oncology notes that, although antibody-drug conjugates are gaining traction as a reliable cancer therapy, each drug’s success in treating advance triple-negative breast cancer in the clinic heavily depends on how that drug is engineered, and whether the oncologist matches the right drug to the right patient.

Still, Nanda thinks that while the last decade of cancer treatment advances have focused on developing immunotherapies for various tumor types, the next decade will be focused on developing antibody-drug conjugates to treat different cancers, including triple-negative breast cancer.

Efforts to better tailor treatment to each patient is also helping improve outcomes, she adds. These advances also impact patients’ side effects and quality of life during and after treatment.

“We've certainly made great strides in the last few years,” Nanda says. “And there are a lot of really exciting times ahead for us.”