BCRF investigators are advancing our understanding of — and improving treatment for — breast cancer in women under 50
Quick fact: While rare, breast cancer can develop in women under 40 — often linked to genetic mutations or other risk factors BCRF-funded scientists are studying.
Anyone who has breast tissue can develop breast cancer, but age—along with being a woman—is one of the main risk factors. Most breast cancers occur in women aged 50 or older, with rates of new diagnosis peaking between the ages of 64 and 74. But now, doctors are seeing more and more younger women get breast cancer, for reasons that remain unclear.
Although breast cancer in younger women is still uncommon, experts are alarmed by the uptick in cases. While breast cancer deaths in women have decreased by 58 percent in the last 40 years, women under 40 at diagnosis are nearly 40 percent more likely to die from breast cancer than women over 40. Breast cancer is also the leading cause of cancer death in women aged 20 to 49 in the United States. And a recent report from the American Cancer Society found that cancer incidence rates in women under 50 are now 82 percent higher than those in men under 50—a trend that’s been driven by increases in breast cancer.
Read on to learn how BCRF is investing in research to stop this troubling trend.
Understanding the rise of breast cancer in younger women
Scientists can’t say for certain why breast cancer incidence is on the rise among younger women, but studies by BCRF researchers and others have identified several factors that contribute to the trend:
- Tumor biology: Breast cancers with aggressive biological features that contribute to poorer prognoses and outcomes are more common in women under 40. Examples include larger tumor size, advanced tumor stage, negative hormone receptor status, and an overexpression of the HER2 protein (HER2-positive breast cancer). Younger women are also more likely to be diagnosed with triple-negative breast cancer (TNBC), a particularly aggressive subtype with few targeted therapies.
- Racial and ethnic disparities: Black women aged 20 to 39 are more likely to develop breast cancer compared to younger women of other racial and ethnic groups. They’re also nearly twice as likely to be diagnosed with TNBC compared to white women aged 20 to 44.
- Genetics: About 6 percent of all women with breast cancer carry BRCA gene mutations, but in breast cancer patients under 45 the number is closer to 12 percent. Women of Ashkenazi Jewish descent are at a higher risk because of an increased incidence of BRCA mutations in this population. A younger woman’s breast cancer risk is also higher if one or more family members were diagnosed with: breast cancer under age 50; cancer in both breasts; male breast cancer; ovarian, pancreatic, or metastatic prostate cancer; or TNBC.
- Reproductive risk factors: The risk of premenopausal breast cancer is higher if a woman had her first menstrual period before age 12, is older than 30 at her first pregnancy, or has not had children.
These are key research areas for BCRF-funded investigators who, over the organization’s more than 30-year history, have made major contributions to our knowledge about breast cancer in younger women. BCRF researchers are also conducting vital work to address the unique issues younger patients face, including fertility preservation, access to appropriate screening, early temporary or permanent menopause, and the risk of long-term heart health complications from certain breast cancer treatments.
Emerging insights on breast cancer, pregnancy, and fertility
Research has also uncovered new insights about breast cancer, pregnancy, and fertility. While pregnancy at a younger age can protect against breast cancer, women who are diagnosed while pregnant or in the postpartum period are at risk of serious disease. Pregnancy-associated breast cancer (PABC) occurs during pregnancy, one year postpartum, or during lactation. About 10 percent of women with breast cancer under 40 are diagnosed with PABC. Recent studies suggest PABC is more likely to have an aggressive tumor profile compared to breast cancer in nonpregnant younger women.
Postpartum breast cancer (PPBC) is diagnosed within five to 10 years of childbirth. Studies have shown that it is associated with an increased risk of metastasis and death compared to breast cancers in younger women before or during pregnancy. This is especially concerning given that more women are postponing childbearing. Experts have found that PPBC exhibits unique molecular profiles that warrant further investigation to identify targeted therapies.
Breast cancer in younger women strikes at a time when many women are planning future pregnancies, filling an otherwise hopeful time with anxiety and uncertainty. Breast cancer treatments can impact conception, and chemotherapy can have a toxic effect on the ovaries. Researchers are investigating strategies to safeguard patients’ fertility.
Breast cancer treatments may also include estrogen-blocking hormone therapies for up to 10 years after diagnosis to prevent recurrence. BCRF investigator Dr. Ann Partridge leads the POSITIVE trial, which is investigating if a temporary pause in this treatment to attempt pregnancy impacts breast cancer recurrence in patients with hormone-receptor positive breast cancer. Follow-up is ongoing to confirm long-term safety of pausing therapy, but promising initial results indicate that the interruption does not cause greater short-term risk of breast cancer, giving hope to many younger patients.
BCRF’s research focuses on breast cancer in younger women
BCRF investigators continue to focus on understanding breast cancer risk factors and developing new treatments, interventions, and preventative measures that will benefit younger women and reverse this alarming trend.
“We’ve seen the rising incidence of cancer in younger women for years now,” BCRF Chief Scientific Officer Dr. Dorraya El-Ashry said. “Breast cancer specifically has been the largest driver in women under 50. We must get to the root of the problem by identifying those at high risk so they benefit from screening—and even potentially intercepting the disease before it becomes invasive—and improving screening technology so that younger women, who are especially likely to have dense breasts, can benefit from early detection. Awareness of this trend is critical because we must change our perception of cancer so that younger women who present concerns at the doctor’s office are taken seriously.”
Below is a selection of BCRF-supported studies that are currently underway.
Genetic testing and hereditary risk
- To better predict whether a woman is at a high risk of breast cancer, Dr. Fergus Couch is identifying gene mutations beyond the well-known BRCA1 and BRCA2 mutations that increase breast cancer risk. His Cancer Risk Estimates Related to Susceptibility (CARRIERS) study examines inherited DNA from nearly 65,000 women to ascertain how often mutations occur in genes and if they provide an accurate estimate of breast cancer risk. Read about the 2021 findings here.
- Dr. Gad Rennert is working to advance our understanding of the origins of breast cancer by investigating the genetics of more than 30,000 people. He is currently studying women who developed cancer under age 45 to add to his comprehensive dataset on genetic mutations and biological drivers that may increase risk.
Triple-negative breast cancer
- Dr. Jenny Chang and her team developed and are now testing new TNBC treatments they developed in clinical trials to move them closer to FDA approval—thereby expanding the arsenal of tools to treat this aggressive form of the disease.
- Dr. Ian Krop and his colleagues are testing a newer antibody drug conjugate, datopotamab deruxtecan, to treat patients with TNBC who are not candidates for immunotherapy.
Treatment and prevention in pre-menopausal women
- Through the the Young Women’s Breast Cancer Study (YWS) and the Young, Empowered and Strong (YES) study, Dr. Partridge is focused on developing and testing interventions to improve care, outcomes, and our understanding of the biology of breast cancer in younger women.
- Dr. Sherene Loi is analyzing tumor samples in premenopausal women with breast cancer from the Suppression of Ovarian Function Trial (SOFT), which has shown that adding ovarian function suppression to chemotherapy and endocrine therapy after surgery was beneficial in women under 40.
Screening and risk assessment
- Dr. Constance Lehman has leveraged artificial intelligence tools to develop methods to improve breast cancer screening and identify women at high risk. This AI tool, Clairity Breast, has recently received de novo FDA approval as the first of its kind to be cleared for risk assessment.
- Drs. Regina Barzilay and Adam Yala developed a novel targeted screening strategy to improve breast cancer risk prediction models with a mammography-based deep learning model called MIRAI. They are testing its efficacy compared to MRI.
- Dr. Wendie Berg is improving the precision of breast cancer detection in women with higher-than-average risk. She is assessing alternative methods of screening, such as contrast-enhanced mammography, that could provide more precise results for women with recurrent breast cancer or dense breasts, the latter of which is more common in younger women.
- Dr. Christopher Comstock is evaluating the use of contrast-enhanced spectral mammography as a breast cancer screening option for women with dense breasts. He is leading the Contrast-Enhanced Mammography Imaging Screening Trial (CMIST) to improve early detection while reducing false positives in women with dense breasts.
- Dr. James Ford is improving breast cancer genetic risk assessment and screening by identifying genetic alterations associated with breast cancer that could be used to refine lifetime risk. He is also developing new early detection blood-based tools to detect cancer earlier in high-risk individuals.
Special projects and clinical trials
- The Women Informed to Screen Depending on Measures of Risk Study (WISDOM), led by Dr. Laura Esserman, is recruiting 100,000 diverse women between the ages of 30 and 74 to find the safest and most effective way to detect breast cancer. The study compares two screening approaches: annual mammograms for all women starting at age 40 or a personalized approach based on a woman’s individual risk factors, including breast density, genes, and family health history.
- Dr. Meredith Regan is assessing long-term effects and survival benefits of anti-estrogen therapies in premenopausal women. She and her colleagues at the International Breast Cancer Study Group are extending follow up of women participating in the SOFT and Triptorelin with either Exemestane or Tamoxifen (TEXT) trials, which is critical to ensure that ovarian suppression is effective at reducing late recurrence and to identify of any long-term side effects.
BCRF’s Precision Prevention Initiative
- Dr. Darren Mays is creating a counter-marketing intervention to reduce alcohol use and prevent breast cancer in younger women. Intervention content will be used in a randomized clinical trial to test if it is effective at changing young women’s beliefs about alcohol-related breast cancer risk and their alcohol use behavior.
- Dr. Seema Khan is testing personalized dosing of tamoxifen to prevent breast cancer in high-risk premenopausal women. Previous studies have shown that low-dose tamoxifen is also effective for cancer prevention and that it reduces a woman’s breast density, thereby increasing its risk reduction benefit in women who have dense breasts.
- Dr. Mark Robson is working to understand how genes influence breast cancer risk to guide personalized screening and risk reduction strategies. He is using genomic markers to define a risk modifying panel, known as polygenic risk score (PRS), to help women gain a better understanding of their breast cancer risk and lead to more informed decisions about preventative and screening care.
