In their previous research, Virginia F. Borges, MD, MMSc, and colleagues identified an increased risk of metastasis for women diagnosed with breast cancer within five years after giving birth. However, in their latest study, Dr. Borges and her fellow researchers from the University of Colorado Cancer Center and Oregon Health & Science University found that the increased risk of metastasis actually lasts for 10 years after the most recent childbirth. In this interview with i3 Health, Dr. Borges shares insights regarding her research and its implications for women with postpartum breast cancer.
What prompted you to investigate the increased risk for metastasis with postpartum breast cancer more than five years after childbirth?
Virginia F. Borges, MD, MMSc: I have been focused on young women's breast cancer since 2004. It has been known for a long time that younger women fare more poorly with breast cancer than older women. That interested me and led me to start the Young Women's Breast Cancer Translational Research Program. We have a specialized clinic, and my collaborator, Pepper Schedin, and I have been doing research on the negative impact of a prior pregnancy on breast cancer outcomes for many years. In 2013, we published a smaller data set that showed that the risk for developing metastasis was higher in postpartum women up to five years after their last childbirth, with a clear signal that the effect could last longer. Therefore, we expanded our data set and looked again to show that indeed, even up to 10 years after the birth of her last child, a mother diagnosed with breast cancer has a higher risk for metastatic spread of her cancer than a young woman with a nearly identical cancer who has not had a child or had her child more than 10 years prior to diagnosis.
How does giving birth increase the risk for metastasis?
Dr. Borges: We do not yet know all the reasons why a prior completed childbirth can result in a higher risk for metastatic spread. My collaborators, Pepper Schedin and Traci Lyons, and I have researched the reasons extensively in the lab. In research models of breast cancer, our team was the first to show that the normal involution or weaning of the breast after lactation stops—or after pregnancy if a woman does not nurse—can increase the ability of breast cancer to invade and metastasize.
The lab models show that there is an increased presence of immune cells that can promote the tumor to behave aggressively; there is a background of inflammation and desmoplasia [the growth of fibrous or connective tissue surrounding a tumor] in the involuting breast as well. There is also an increase in new lymphatic channels that get laid down, providing more escape routes for cancer cells. We've been able to show that these mechanisms that are present in lab models are also mirrored in the breast tissue from women with breast cancer, so it suggests that the same mechanisms may be what are occurring in our postpartum women.
When we look at our postpartum women who have the highest risk for recurrence, we see a couple of striking patterns. First, early stage diagnosis in these women still carries a high risk, which means that we could be underestimating risk assessments for our patients when discussing treatment recommendations if their birth history and time since last childbirth are not considered. Also, we saw that the increased risk for postpartum women held true whether the cancer was estrogen receptor (ER) positive, ER negative, or triple negative. The risk is not just in the breast cancer subtypes that are classically thought of as being the most aggressive.
Could you comment on your findings regarding the interaction between ER-negative disease and metastasis in postpartum breast cancer?
Dr. Borges: Surprisingly, our young women who had not yet had a child at the time of their diagnosis had very good prognoses; even with ER-negative cancer, their prognoses were almost as good as women with ER-positive breast cancers. It was our young mothers with ER-negative or triple-negative breast cancer (TNBC) who had the much higher risk for recurrence. However, if a woman with an ER-negative cancer was out past five years in her breast cancer survivorship and a recurrence had not occurred, the data looks like it is then very unlikely that a later recurrence will happen.
Conversely, our young postpartum women with ER-positive breast cancer continue to develop metastatic recurrences up to 15 years after diagnosis. Their ultimate risk for recurrence is similar to a young postpartum woman with ER-negative cancer or TNBC and is higher than many current methods of assessing prognosis would predict.
How should oncologists apply the results of your study to their practice? What changes do you hope that this research will bring to the field?
Dr. Borges: My team's hope is that doctors will start asking women when their most recent pregnancy occurred and take their reproductive history into a different level of consideration.
Are any further investigations needed in relation to this topic?
Dr. Borges: There is a lot more work to do to refine how we can best treat young postpartum women to overcome this increased risk. We and our collaborators have a number of ongoing projects to do so.
About Dr. Borges
Virginia F. Borges, MD, MMSc, is the Deputy Division Head of Medical Oncology at the University of Colorado School of Medicine, as well as the Robert F. & Patricia Young Connor Endowed Chair in Young Women's Breast Cancer Research. She is also Director of the Breast Cancer Research Program and Director of the Young Women's Breast Cancer Translational Program at the University of Colorado Cancer Center.
For More Information
Goddard ET, Bassale S, Schedin T, et al (2019). Association between postpartum breast cancer diagnosis and metastasis and the clinical features underlying risk. JAMA Netw Open, 2(1):e186997. DOI:10.1001/jamanetworkopen.2018.6997
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily represent the views of i3 Health.
Image credit: University of Colorado Cancer Center