It has been well documented that breast cancer is the most common malignancy in adolescent and young adult (AYA) women aged 15 to 39 years, accounting for 30% of cancers among this population.1 In addition, 5.6% of all invasive breast cancers occur in AYA women.1 A presentation by Rebecca H. Johnson, MD, Medical Director of the Adolescent and Young Adult Cancer Center at Mary Bridge Children’s Hospital in Tacoma, Washington, during the 2021 Global Adolescent and Young Adult Conference, revealed more troubling breast cancer trends in AYA women.
According to research by Dr. Johnson and her colleagues, the incidence of invasive breast cancer and all breast cancer in this population has been on the rise since 2004. Most of this change is due to an increase in the prevalence of regional or distant, stage II to IV breast cancer among women between the ages of 25 and 39. As many as 12,000 AYA women have been diagnosed with invasive breast cancer in recent years in the United States.1
“The number of AYA women diagnosed with distant metastatic breast cancer each year has nearly doubled since the 1990s.”— Rebecca H. Johnson, MD
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“The prevalence of breast cancer by stage is quite different between AYA women younger than age 40 and older women,” said Dr. Johnson. “In young AYA women, two-thirds are diagnosed with regional or distant disease, including stage II, III, or IV, whereas in older women, about one-third are diagnosed with stage II, III, or IV disease.”
In addition to advanced disease, young women with breast cancer are more likely to present with unfavorable tumor biology than older women, resulting in poorer survival. Even among patients with early-stage disease, AYAs are 39% more likely to die compared with older women.2
The ASCO Post talked with Dr. Johnson about these survival disparities in young adult women with breast cancer, how young women should be monitored for breast cancer risk, and why the number of late-stage breast cancers is rising faster among AYAs.
Charting Trends in AYA Breast Cancer
Were there specific types of breast cancer that were more common in the younger AYA women?
In teenagers, breast cancer of any type is still very rare. We found that infiltrating ductal carcinoma is the most common type of breast cancer diagnosed in all age groups.
Were you surprised by your findings about breast cancer trends in AYAs?
We had been looking for evidence of this trend for years. In 2013, Dr. Archie Bleyer [Clinical Research Professor, Radiation Medicine at Knight Cancer Institute, Oregon Health & Science University School of Medicine, Portland], Dr. Frank L. Chien [pediatric hematology/oncology fellow at Emory University School of Medicine, Atlanta], and I published a study in JAMA showing that the incidence of distant metastatic disease at diagnosis was increasing exponentially in young women in the United States, but not in older women.3
To date, no other countries have reported an increase in the incidence of advanced breast cancer among AYA women. After publication of our study, we reached out to Canada and other countries to analyze their data on this topic, but many countries do not report breast cancer incidence by age, so it has been difficult to confirm our findings in countries outside of the United States.
As the years have passed, and we have continued to analyze evidence from the U.S. National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database, we found the trend has continued. In fact, as we reported in our most recent study, the number of AYA women diagnosed with distant metastatic breast cancer each year has nearly doubled since the 1990s. This finding translates into a lot of life years lost for these AYA women, because patients with stage IV breast cancer do so poorly. And the incidence of breast cancer with distance metastases at diagnosis is increasing fastest in women between the ages of 25 and 39.
Looking for Clues on the Rise in More Aggressive AYA Breast Cancers
Why do you think the incidence of distant disease in women younger than age 40 is increasing compared with locoregional breast cancer in the same age group?
I don’t have an answer to this question. The main temporal trends in our society that seem to be different in the past 30 years are the higher rates of obesity, sedentary lifestyle, and consumption of processed foods. The use of microplastics in our environment has also increased in recent years. However, there are no data to show definitive cause and effect.
“Young women are more likely than older women to develop biologically aggressive breast tumors, and still, no one knows exactly why.”— Rebecca H. Johnson, MD
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One thing that is clear is the rise of advanced breast cancer in AYA women cannot be related to major genetic changes in the population, since the increases have occurred only within the past 30 years—too fast for a genetic shift. There are not more cases of younger women with BRCA gene mutations, for example.
Did you find any common risk factors in these young women?
We used data from the SEER database for our study, which does not include information about an individual’s lifestyle choices or other factors, such as body mass index. It would be interesting to analyze the rates and subtypes of breast cancer in young adult women in the context of the obesity epidemic that has taken off in the past several decades. Obesity has been shown to be protective against breast cancer in young women, but for older women, obesity is a risk factor for advanced breast cancer and death from the disease.
When we were writing our JAMA paper in 2013, we looked for evidence that exposure to environmental chemicals and consumption of more processed foods—which were less of an issue in the 1970s—might explain the reason for the increase in more aggressive breast cancer in AYAs. However, there were very few studies on the safety of environmental chemicals, such as those in plastic bottles, or the impact of eating more processed foods to draw any conclusions. Alcohol use is a known risk factor for breast cancer in all age groups.
Breast cancer in AYA women is frequently familial, and about half of the women with breast cancer younger than age 30 harbor a germline mutation in BRCA1, BRCA2, or TP53 genes. However, we do not know what risk factors were present in the AYAs in the SEER database, since the database does not track this information.
Understanding Survival Outcome Disparities in Younger and Older Women
What role does age play in the worse survival for young vs older women with metastatic breast cancer?
Younger women with metastatic breast cancer fare better than women older than 50 with metastatic disease. Younger women are generally physically stronger and can tolerate treatment better than older women. Also, young women may be more interested than elderly women to choose clinical trials and aggressive therapy in this setting, which may have an impact on survival.
According to your study, even among patients with early-stage breast cancer, AYA women are 39% more likely to die compared with older women. How can survival outcomes be improved for these younger patients?
Survival outcomes for common AYA cancers such as breast cancer have not improved as much as they have in other age groups. Clinical trials are recommended, particularly for AYA cancers that have inferior survival prospects, to move the needle on survival for this population.
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Brandon Hayes-Lattin, MD, FACP
Even stage I breast cancer may be associated with poor 5-year survival. That statistic has improved somewhat, but not enough. Young women are more likely than older women to develop biologically aggressive breast tumors, and still, no one knows exactly why.
Monitoring for Breast Cancer Risk
Your study results show that just being young is an independent adverse prognostic factor for breast cancer, yet there are no routine screening guidelines for this age group. How should young women be monitored for breast cancer risk?
Screening mammography has its own risks. At the population level, the chances of picking up cancer in AYAs and saving lives are lower than the risks of screening the whole population of young women. Even though breast cancer is the most common cancer among AYA women, the only strategy we currently have is to raise awareness in young women and their physicians that a breast lump could be cancer and should never be ignored.
Investigating the Causes of Advanced Disease
Did race or ethnicity play a role in which women were diagnosed with distant disease?
We did not stratify by race the women in our more recent study. In our 2013 study, we looked at whether race played a role in whether young women presented with advanced disease at diagnosis, but we did not find it made a dramatic impact. Looking at breast cancer of all stages, young Black women diagnosed with breast cancer are more likely to be diagnosed with triple-negative breast cancer and are more likely to die of the disease than White women.
In our recent analysis, we found that the fastest increases in the incidence of AYA breast cancer were in stage II and stage IV disease, and we are not yet sure how to interpret that finding. We looked for evidence of stage shift because that can sometimes be confounding in epidemiology studies, but we did not find any evidence of changes from a lower stage to a higher adjacent stage, for example, from stage III to stage IV.
Stage II and IV are not close to each other, so these findings merit further investigation. It makes me wonder whether different factors could be contributing to the increase in stage II and stage IV disease among young women. AYA women are more likely to be diagnosed with stage II than stage I breast cancer, whereas the reverse is true for older women.
Now, that trend is becoming even more pronounced. More research is urgently needed to find out why the incidence of breast cancer, particularly with regional or distant spread at diagnosis, is increasing in young women.
DISCLOSURE: Dr. Johnson is an occasional consultant for Servier Pharmaceuticals.
REFERENCES
1. Cathcart-Rake EJ, Ruddy KJ, Bleyer A, et al: Breast cancer in adolescent and young adult women under the age of 40 years. JCO Oncol Pract 17:305-313, 2021.
2. Gnerlich JL, Deshpande AD, Jeffe DB, et al: Elevated breast cancer mortality in women younger than age 40 years compared with older women is attributed to poor survival in early-stage disease. J Am Coll Surg 208:341, 2009.
3. Johnson RH, Chien FL, Bleyer A: Incidence of breast cancer with distant involvement among women in the United States, 1976 to 2009. JAMA 309:800-805, 2013.
