Long after childbirth, a persistent risk for metastatic breast cancer

Breast cancers that emerge after a woman gives birth are significantly more likely to spread and become life-threatening. And this elevated risk endures for at least 10 years, a new study has found.

“The window of increased risk extends much longer than anyone knew,” says co-senior author Pepper Schedin, Ph.D., a professor in the Department of Cell, Developmental & Cancer Biology in the OHSU School of Medicine. “This is strong evidence that postpartum breast cancers have a unique biology that is not adequately recognized.”

The new data show that postpartum diagnosis is an independent risk factor for metastatic spreading of breast cancer. Among other implications, doctors may be underestimating the risk when making treatment recommendations for women diagnosed within 10 years of childbirth.

Image: an early 20th century woodcut engraving by Jacques Jeichienus Ottens (public domain/Rijksmuseum)

The researchers published their findings in the journal JAMA Network Open. The co-first authors are Erica Goddard, Ph.D., a postdoctoral researcher at Fred Hutchinson Cancer Research Center who completed her doctoral work in Schedin’s lab at OHSU, and Solange Bassale, M.S., a  biostatistician in the OHSU Knight Cancer Institute. Virginia Borges, M.D., director of the Breast Cancer Research Program and Young Women’s Breast Cancer Translational Program at the University of Colorado Cancer Center, is the co-senior author.

Previous research in Schedin’s lab has helped reveal how changes in the mammary gland after pregnancy create a tumor-promoting environment. At the end of lactation, 80 to 90 percent of milk-secreting cells undergo programmed cell death, in a process called mammary gland involution. The early phase of gland involution resembles an acute inflammatory response that subsides and is followed by an immune response similar to what happens during wound healing.

“Most of the dramatic changes the breast undergoes in pregnancy and lactation have to be reversed with weaning,” Schedin says. “It’s a dramatic tissue loss and remodeling process and that turns out to be tumor promoting.”

Postpartum breast cancer may represent a unique subtype of cancer that requires distinct care.

‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾‾

Earlier studies by these scientists revealed that breast cancers diagnosed within five years of childbirth are about three times more likely to spread and give rise to life-threatening metastatic tumors. But how risks change after five years remained unknown.

In the new study, the research team considered the cases of 701 women 45 years or younger with stage I to III invasive breast cancer diagnosed between January 1, 1981, and December 31, 2014. The women are among those participating in the Colorado Young Women’s Breast Cancer Cohort.

In women with stage I or II breast cancers diagnosed within five years of giving birth, the risk of metastasis was more than triple the risk in those who had not given birth. In those diagnosed five to ten years after giving birth, the risk was five times higher. The increased risk of metastasis remained significant after adjusting for cancer subtype, patient age, and year of diagnosis. (Stage III cancers had a high risk of metastasis regardless of birth status.)

Breast cancer after childbirth also behaved differently than expected based on the presence or absence of estrogen receptors on tumor cells. Estrogen receptor negative status appeared to compound the risk of metastasis in postpartum cases. In women with ER-positive breast cancers diagnosed within 10 years of childbirth, the risk of metastasis was almost identical to women with ER-negative cancers and who had not given birth.

Authors (left to right) Solange Bassale, M.S., Pepper Schedin, Ph.D., Motomi Mori, Ph.D., M.B.A., and Sonali Jindal, M.D.

The researchers calculate that roughly 12,000 women each year in the U.S. have breast cancers that would meet their criteria for postpartum disease that is more likely to metastasize. And there’s reason to expect the incidence of postpartum breast cancer to increase, the researchers say. That’s because more women are opting to delay childbearing, and older age at first birth correlates with increased risk for breast cancer.

Borges said that postpartum breast cancer may represent a unique subtype of cancer that requires distinct care. “All women know when they last gave birth, so this is a readily available, free piece of information that helps us identify young women at highest risk from their breast cancer,” she said in a news release. “If we are aware of the increased risk, we can work towards finding the best means to overcome this risk and treat it appropriately.”

Further reading:

Association Between Postpartum Breast Cancer Diagnosis and Metastasis and the Clinical Features Underlying Risk by Erica T. Goddard, Solange Bassale, Troy Schedin, Sonali Jindal, Jeremy Johnston, Ethan Cabral, Emile Latour, Traci R. Lyons, Motomi Mori, Pepper J. Schedin, and Virginia F. Borges. JAMA Network Open (Jan. 11, 2019)

Pregnancy-associated breast cancer and metastasis, by Pepper Schedin. Nature Reviews Cancer (Apr. 1, 2006)

Leave a Reply