Breast cancer study

Researcher focuses her inquiry on postpartum tumors

By now, the figures are all too familiar: One out of every eight American women will develop breast cancer in her lifetime, and some 40,000 U.S. women die of the disease each year. Charlotte Kuperwasser is working to lower those numbers.

Charlotte Kuperwasser © Mark Morelli

An assistant professor of anatomy at the School of Medicine, Kuperwasser is investigating the role that pregnancy—especially in older women—plays in promoting breast cancer. Her work is funded by a $117,000 grant from the U.S. Department of Defense Breast Cancer Research Program and a new three-year, $150,000 grant awarded in March by the Raymond and Beverly Sackler Foundation.

Researchers have known since the 1970s that pregnancy cuts a woman’s risk of developing breast cancer over her lifetime in half. However, women who have their first child after age 30 are actually at an increased risk for developing the disease within five years of childbirth.

The hormone question
Conventional wisdom held that the hormone surges and growth factors associated with pregnancy triggered these postpartum tumors. But that explanation never sat well with Kuperwasser, who has been studying breast cancer since she was an undergraduate at the University of Massachusetts, because these postpartum tumors are quite different from the breast cancers common in older women.

For one thing, postpartum tumors are more aggressive. But more importantly, the cells in these tumors don’t have the hormone receptors found in the majority of breast cancers.

“So it didn’t make sense to me,” Kuperwasser says, “that hormones could be the driving force behind these tumors.”

Reconsidering what goes on in a mother’s body not just during pregnancy but also after, Kuperwasser realized that the body’s process of reverting to a pre-pregnancy state after childbirth and lactation might be the more critical period. “It’s a time where you get a lot of cell death and a lot of remodeling and reorganization of the tissue,” she says. “And those changes on a molecular level resemble some of the things that happen in cancer.”

Disease of the system
The process by which a mother’s breast tissues revert to a pre-pregnancy, non-lactating state is called involution. Working with mouse models, Kuperwasser has found that estrogen produced during involution seems to stimulate blood vessel growth all over the body. Moreover, this growth, called angiogenesis, is mediated by cells produced in the bone marrow.

“That’s kind of exciting,” Kuperwasser says, “because it launches it into looking at cancer not only as a disease of the cell…but also as a disease of the whole system.”

These findings could translate into better prevention of these aggressive postpartum breast cancers, Kuperwasser says. Doctors could one day identify their high-risk patients and give them a course of anti-angiogenesis or anti-estrogen therapy during that one- to five-year window after childbirth. Angiogenesis inhibitors would prevent the growth of blood vessels that ultimately feed a malignant tumor. Because Kuperwasser has demonstrated that estrogen itself can trigger the angiogenesis, the benefits of an estrogen blocker are twofold: Such a therapy could stop the growth of certain types of tumors as well as the blood vessels supporting them.

Kuperwasser is poised to enter the next phase of her work. “I’m very excited to take what we’ve learned from this project and see if it applies to other phenomena in cancer progression,” she says. “Could something similar be happening with the switch from pre-menopausal to post-menopausal [stages of life]?”

The Department of Defense established the Breast Cancer Research Program (BCRP) in 1992, when Congress allocated $25 million for research on breast cancer screening and diagnosis for women in the military. Since then, the BCRP has awarded $1.66 billion to more than 3,670 research projects.

Kuperwasser came to Tufts last year after working as a postdoctoral researcher at the Whitehead Institute in Cambridge. She is also one of 24 nominees for the defense department’s Era of Hope Scholar Awards, which awards grants worth $2.5 million each to promising young scientists who “challenge current dogma and demonstrate an ability to look beyond tradition and convention.” The recipients will be announced later this spring.

Jacqueline Mitchell is a senior health sciences writer in Tufts’ Office of Publications. She can be reached at