Pregnancy-Associated Breast Cancer May Be Biologically More Aggressive

Tumor-infiltrating lymphocytes (TILs) have significantly higher expression of PD-L1 in pregnancy-associated breast cancer (PABC) compared to nulliparous breast cancer patients, according to a new study; this may help predict response to therapy, among other outcomes. Research is accumulating on PABC, with new data on the immune environment, outcomes, and potential diagnostic delay.

PABC, which is commonly defined as breast cancer diagnosed during pregnancy or within either 1 or 2 years post-partum, accounts for approximately 10% of breast cancer cases among women under the age of 40 in western countries. It is often associated with more aggressive disease and poorer outcomes, though the underlying reasons for this are unclear.

Luis Z. Blanco, Jr, MD, of Northwestern University in Chicago, presented a study on PD-L1 expression in this malignancy during a poster discussion session at the San Antonio Breast Cancer Symposium, held December 6–10. The study included 21 women with PABC (using the 2-year post-partum definition) and 15 age-, stage-, and grade-matched control patients.

Using immunohistochemistry approaches, the study found similar expression of PD-1 between PABC and control patients (P = .28). However, there was a significant difference with regard to PD-L1 expression, with 9 PABC patients having “strong” expression in TILs, compared to none in the control patients (P = .01). “High PD-L1 expression in TILs did not correlate with tumor characteristics,” Blanco said. “There seems to be a very complex interaction between tumor cells and the local immune system,” he added, which may help predict a response to certain therapies.

Jennifer Litton, MD, of MD Anderson Cancer Center in Houston, was the discussant for the session, and agreed that this was “very provocative data suggesting an immune environment influenced by pregnancy.”

In another study presented during the poster discussion session, Katarzyna Jerzak, MD, of Sunnybrook Health Sciences Centre in Toronto, reported on a prospective database study of PABC outcomes. It included 32 PABC patients and 192 non-PABC patients, and used a PABC definition of only 1 year post-partum.

“PABC women are younger, more likely to have locally advanced disease, and less likely to have hormone receptor expression, with a trend toward HER2-positive and higher grade disease,” she said. The 3-year disease-free survival rate was 79% with PABC and 90% with non-PABC, though this did not reach significance (P = 0.22). Overall survival at 3 years was identical, at 97% for both groups.

Jerzak concluded that diagnostic delay in PABC patients could explain the higher rate of locally advanced disease. However, the lower rate of hormone receptor expression suggests that PABC may be biologically more aggressive.

Litton said the existing data on this disease suggests that pregnant patients should receive standard-of-care therapy in the second and third trimesters, and that these women fare just as well as other patients. The primary message, though, is that more research is needed. “These small cohort studies continue to need further collaborative efforts to provide more data,” Litton said.