Untangling the mystery of rising breast cancer rates

After invasive breast cancer rates declined sharply in the early 2000s, clinicians cheered what seemed to be a major trend. The drop paralleled a big decline in the use of hormone replacement therapy among postmenopausal women after an influential study—the Women’s Health Initiative—found an association between estrogen–progesterone therapy and an increased risk of breast cancer and heart disease.¹

The overall incidence, however, soon leveled off and then began to rise again, with troubling increases over the decade ending in 2021, especially among women younger than 50 years and those of Asian American/Pacific Islander (AAPI) or Hispanic heritage. The highest relative increase, in fact, has occurred among women in their 20s and 30s. Researchers have launched investigations into a complex stew of mitigating and contributing factors—from increases in obesity and alcohol consumption to shifting reproductive patterns and earlier ages at first menstruation—but have yet to determine which are playing the biggest roles.

Although overall mortality rates continue to fall, they remain elevated for Native American and Alaska Native women in particular and for Black women. Changing that dynamic may require not only untangling the complex mix of molecular and environmental risk factors but also improving mammography methods and expanding access to medical care for underserved populations.

One of the biggest challenges has been understanding which factors are influencing breast cancer rates across the board and which are associated with particular risk groups. According to a 2024 report led by researchers at the American Cancer Society (ACS), the upswing in estrogen or progesterone receptor–positive (hormone receptor–positive) malignancies accounted for most of the recent increase in breast cancer incidence (the ACS publishes Cancer Cytopathology).²

The first author, Angela N. Giaquinto, MSPH, an associate scientist II in the ACS Surveillance Research Program, says that changing reproductive patterns have likely contributed to that upturn. “Having fewer children and/or having children later in life increases breast cancer risk by increasing lifetime exposure to estrogen, which is the driver for most breast cancers,” she explains. “However, pregnancy has a dual effect on breast cancer risk; risk is increased during pregnancy and in the first 5 years following childbirth and is only reduced after about 2 decades compared to those who have not given birth.”

That seemingly contradictory risk pattern may be mediated by changing hormone levels during and after pregnancy. Although the hormone levels likely play a role in the increased postpartum risk, Giaquinto says, “the biological mechanism is not fully understood.”

Adetunji T. Toriola, MD, PhD, MPH, a professor of surgery and a breast cancer researcher in the Division of Public Health Sciences at Washington University in St. Louis, notes that every birth reduces the risk of breast cancer by roughly 10%. The biggest protective effect, in fact, has been observed in women with more than five children.

Given that larger families are increasingly uncommon, Dr Toriola says that the phenomenon raises an intriguing question: “How can women still benefit from this risk reduction linked to reproductive experience, and can we apply that to mitigating risk, especially in younger women?” Dr Toriola adds that the recent trend toward a younger average age at first menstrual period (menarche) may be contributing to rising breast cancer rates as well, though for reasons that are not yet understood.

Early-onset breast cancers, technically defined as cancers diagnosed in adults younger than 45 years, often evade initial detection because they are unexpected. In 2024, the growing danger spurred the US Preventive Services Task Force to change its recommended starting age for routine mammography screening from 50 to 40 years.

The relative abundance of cancer types also can change with age. Whereas slower growing estrogen receptor–positive or progesterone receptor–positive breast tumors are more common among older women, aggressive HER2-linked and hormone receptor–negative/HER2-negative (triple-negative) breast cancers are more common among younger women. Mutations in the well-known BRCA gene, meanwhile, only account for approximately 1 in 5 early-onset cases.

Overall, breast cancer is still far more common in older women, but younger women are starting to close the gap. The 2024 ACS report showed that women younger than 50 years had a 2-fold higher increase in breast cancer incidence over the past decade than older women did (1.4% per year vs. 0.7% per year).²

A separate study by Dr Toriola and his colleagues likewise found that breast cancer is increasing markedly in younger women. “What’s most notable is that this increase is in all racial and ethnic groups,” he says. Over the past 20 years, he and his colleagues found that incidence rates for estrogen receptor–positive, stage I, and stage IV tumors all increased among women aged 20–49 years, whereas the rates decreased for estrogen receptor–negative, stage II, and stage III tumors in that same age group.³

The overall decrease in estrogen receptor–negative tumors has likewise been hard to explain, although the divergence has suggested another enticing question to Dr Toriola: “Can we learn from the reduction of estrogen-negative tumors to mitigate the increase in estrogen-positive tumors?”

Initial research by Dr Toriola’s group has documented a recent improvement in breast cancer mortality rates among women between the ages of 20 and 39 years, although they remain higher than those for women between the ages of 40 and 49 years—a difference seen across all racial and ethnic groups.⁴ Dr Toriola agrees that a higher likelihood of developing a more aggressive type of cancer and delays in diagnosis due to a relative lack of screening have probably combined to elevate the mortality rate in this group of women.

Other distinct patterns have emerged. Although body weight has been increasing across all ages, “excess body weight only increases breast cancer risk in postmenopausal women, so it is not contributing to increasing incidence rates in younger women,” Giaquinto says. “While the relationship between excess body weight and breast cancer is not fully understood, adipose tissue produces estrogen that in turn increases risk along with increased inflammation.” Asian women have the lowest prevalence of obesity, whereas Black women have the highest.

Studies have found a different pattern for alcohol-related risk. Giaquinto notes that alcohol consumption accounts for roughly 16% of breast cancers and that heavy drinking has risen in women in their 30s and 40s. A higher percentage of White and American Indian or Alaska Native adults consume alcohol heavily (8%) than Black (4%), Hispanic (4%), or Asian adults (2%).⁵ “There has also been more evidence that use of chemical hair relaxers or permanent hair dye is also associated with increased risk, especially among Black women who are more likely to use these products,” Giaquinto says. Dr Toriola calls hair products an “emerging risk factor” and agrees that the danger has been borne out by data, at least so far.

Other risk factors remain poorly or only partially understood. As another example, Giaquinto cites recent research reporting that newly immigrated Asian and Pacific Islander women have a higher breast cancer incidence than their US-born AAPI counterparts. “While the exact cause of this increased risk is unknown, these immigration patterns also likely contribute to the steep increase in young AAPI women.”

Clarifying the factors that can raise or lower breast cancer risk could open the door to more outreach efforts aimed at changing modifiable risk factors and heightening surveillance. Dr Toriola agrees that targeted screening could be beneficial for younger women with a family history or known risk factors. However, many patients with cancer have no apparent risk factors, meaning that the field still has much to learn about how to address the growing danger.