The risk of developing breast cancer may be increased among some women who undergo menopause prior to age 46, according to a recent study published by Allen-Brady et al in The Journal of Clinical Endocrinology & Metabolism.
Background
Early menopause occurs in women aged 40 to 45 years. Primary ovarian insufficiency—a condition that occurs when the ovaries stop working properly as a result of the early loss of eggs—may cause some women to go through menopause at a relatively young age. The condition is often hereditary, with inherited genetic factors accounting for up to 43% of cases. Previous studies found that some of the genetic mutations that may cause primary ovarian insufficiency were similar to those involved in cancer.
“When women go through primary ovarian insufficiency, they are at risk for a number of diseases like osteoporosis and cardiovascular disease,” explained senior study author Corrine Welt, MD, an endocrinologist and researcher in the Department of Internal Medicine at the University of Utah. “Our results suggest some of these women should be monitored over their lifetimes for cancer risk as well,” she added.
Study Methods and Results
In the recent study, investigators used the Utah Population Database and medical records from the University of Utah Health and Intermountain Healthcare—which serve 85% of the Utah population—to examine whether women with primary ovarian insufficiency had a higher risk of cancer compared with the general population and analyzed the outcomes of women with early menopause.
They identified 613 women who were diagnosed with primary ovarian insufficiency and 165 who were diagnosed with early menopause between 1995 and 2021. These women were cross-referenced with the Utah Cancer Registry to track cancer incidence and mortality in the state. The results on familial cancer risk came from over 26,500 relatives who were represented in the cancer registry and the Utah Population Database.
“[The] Utah Population Database is a multisource data resource with over one billion health-related records, 50 years of cancer data, and at least three generations of family structure for 4.5 million [patients]. It is a perfect platform to ask questions regarding relationships between different diseases with goals of guiding preventive strategies and improving the health of populations,” detailed co–study author Nicola Camp, PhD, Director of the Utah Population Database and a cancer genetic epidemiologist at the Huntsman Cancer Institute at the University of Utah.
The investigators discovered that the women who underwent menopause before the age of 46 were nearly twice as likely to develop breast cancer as women of similar ages in the general population.
Further, the relatives of women with primary ovarian insufficiency were also more likely to develop breast, prostate, or colorectal cancers. Second-degree relatives such as aunts, uncles, grandparents, nieces, and nephews had a 30% higher risk of developing breast cancer and a 50% increased risk of developing colorectal cancer. First-, second-, and third-degree relatives like great-grandparents and first cousins had a 30% to 60% increased risk of prostate cancer.
The investigators noted that including cousins in the findings could have broad health implications. Women with primary ovarian insufficiency and early menopause may benefit from increased cancer screening. Additionally, individuals of reproductive age from families predisposed to these types of cancers may be candidates for infertility testing.
The investigators hypothesized that the connections between early menopause and cancer could lie deep within the cells. To uncover these links, they analyzed the DNA of 6 women and found that each of them had an unusual variation in one of the genes keeping the cells healthy. Defects in these basic processes could compromise the health of the ovaries and increase the likelihood of uncontrolled cell division.
Conclusions
“This work has increased an understanding of the relationship between primary ovarian insufficiency and reproductive cancers, which could guide preventive strategies,” highlighted Dr. Camp. The investigators hope that understanding the root cause of these health conditions could lead to new treatment options in this patient population.
“For women with a [primary ovarian insufficiency’ diagnosis, it’s devastating. Having an explanation helps them find closure,” Dr. Welt concluded.
Disclosure: The research in this study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health/National Cancer Institute, and the Huntsman Cancer Foundation. For full disclosures of the study authors, visit academic.oup.com.
