A postpartum diagnosis increases risk for and determines an altered profile of metastasis in young women's breast cancer

Abstract

A diagnosis of breast cancer in a woman in the early years after a childbirth has been shown to increase risk for metastasis and death, however, limited data exists on how many years postpartum does this risk prevail, what known clinically prognostic factors are associated with this risk, and what are the pattern of metastasis in these women. This study was conducted to determine how many years after the most recent childbirth that a postpartum breast cancer diagnosis is associated with the increased development of distant metastatic disease. Also, to evaluate known clinical prognostic factors, including tumor proliferation status on influencing the increased risk for metastasis for postpartum breast cancer. This cohort study enrolled 802 cases as a sub study of the larger Colorado Young Women’s Breast Cancer Cohort (>9000 cases), with cases collected from 1991-2014. This is a multicenter study involving a tertiary care, academic hospital-based breast center and its regional affiliate. Included subjects are women diagnosed with stage I-III invasive breast cancer age 45 and under for whom parity data on timing of last childbirth was available, had undergone treatment with curative intent, and had known metastatic disease specific data. The studies primary objective is metastasis-free survival, based on first clinical documentation of metastasis by radiologic or physical exam findings, or date of pathologic confirmation. The primary exposure was prior childbirth or no prior childbirth and the time between the most recent childbirth and diagnosis of breast cancer. The results demonstrate that a diagnosis of breast cancer up to ten years postpartum increases the risk for metastasis. This increased risk is most associated with stage I/II diagnosis and is present in both ER+ and ER- cases. ER+ cases show a prolonged timeline of risk up to 15 years post diagnosis, highlighting an under-recognized risk for young mothers with luminal cancer. Postpartum breast cancer is also associated with an increase in lymph node involvement and lymphovascular invasion, which aligns with the known mechanism of increased lymphangiogenesis in preclinical models. Lastly, increased liver metastasis occurs in postpartum breast cancer at time of first metastasis in comparison to nulliparous controls, highlighting the increased risk for mortality from a postpartum diagnosis.