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Breast cancer metastasis risk remains elevated 10 years after childbirth
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Women diagnosed with stage 1 or stage 2 postpartum breast cancer up to 10 years after giving birth may be at increased risk for distant metastasis, according to results of a study published in JAMA Network Open.
The risk for metastasis occurred independently of poor prognostic indicators, including biological subtype, stage, age or year of diagnosis, results showed.
“This is the first study to demonstrate that a postpartum breast cancer diagnosed up to 10 years after last childbirth can independently increase a woman’s risk for developing metastasis to other parts of the body,” Virginia Borges, MD, MMSc, director of the Breast Cancer Research Program and Young Women’s Breast Cancer Translational Program at University of Colorado Cancer Center, said in a press release.
“These findings highlight the need to understand that postpartum breast cancer may represent a unique subtype of cancer that requires distinct care,” Borges added. “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. If we are aware of the increased risk, we can work towards finding the best means to overcome this risk and treat it appropriately.”
Postpartum breast cancer is an unrecognized subset of breast cancer, and few studies have addressed the associated high risk for metastasis, according to the researchers.
Borges and colleagues evaluated data on 701 women aged 45 years or younger (mean age, 37.9 years; standard deviation, 5.1 years) from the Colorado Young Women’s Breast Cancer Cohort who were diagnosed with stage 1 to stage 3 invasive postpartum breast cancer.
Primary exposures included previous childbirth or nulliparity, time from the latest childbirth and breast cancer diagnosis, and time between breast cancer diagnosis and metastasis.
Distant metastasis-free survival served as the study’s primary endpoint.
The researchers found that risk for distant metastasis was more than twice as high for women with postpartum breast cancer less than 5 years after childbirth (HR = 2.13; 95% CI, 1.21-3.74) and 5 to less than 10 years after childbirth (HR = 2.23; 95% CI, 1.26-3.93) compared with nulliparous women.
The elevated risks appeared even more pronounced among women with stage 1 or stage 2 disease, both at less than 5 years of diagnosis (HR = 3.5; 95% CI, 1.56-7.89) and between 5 and 10 years after diagnosis (HR = 5.2; 95% CI, 2.26-11.82), even after adjusting for biologic subtype, age and year of diagnosis.
Women with ER-positive postpartum breast cancer who were diagnosed within 10 years of a completed pregnancy exhibited distant metastasis-free survival comparable to that of nulliparous women with ER-negative cancer (HR = 1.02; 95% CI, 0.49-2.1), with a 40% likelihood of metastasis within 15 years.
Moreover, among women with ER-negative disease, those with postpartum breast cancer diagnosed within 10 years of childbirth had a roughly twofold increased probability of developing metastatic disease compared with nulliparous patients (HR = 2.19; 95% CI, 1.04-4.58).
Further, women with postpartum breast cancer had a greater degree of lymphovascular invasion and lymph node involvement.
“In these cancers, the tumors themselves do not appear different — there’s no difference in the percent that are more aggressive subtypes, such as triple-negative ... no difference in the stage at which they are diagnosed, or other differences in classic measures that you might think would increase the chance of a bad prognosis,” Borges said. “Instead, these data support previous findings from our team’s lab work showing that after childbirth, conditions in surrounding breast tissue may aid the development of metastases. For example, we have shown that the laying down of new lymph channels in breast tissue after childbirth and nursing may allow cancer cells to better travel and seed sites of metastasis; sure enough, the current work finds more women having cancer in their lymph nodes at diagnosis.”
Ki67 analyses identified 129 women with luminal B cancer in the cohort who had a worse prognosis than those with luminal A cancer, independent of parity status. This difference did not reach statistical significance.
“These data provide further evidence that a postpartum breast cancer diagnosis may represent a unique subtype of cancer that requires distinct clinical and translational research initiatives,” the researchers wrote. “These observations should be confirmed in other cohorts of young women with breast cancer for determination of generalizability.” – by Jennifer Byrne
Disclosures: Borges reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Julie R. Palmer, ScD, MPH
Findings from this report suggest that parity status should be included in clinical decision-making algorithms for young women with breast cancer.
Previous research from this group and others has indicated that women diagnosed with breast cancer within 5 years of giving birth have an increased risk for metastasis relative to nulliparous women. However, the previous findings did not influence clinical decision-making recommendations, in part because there was insufficient evidence of the interplay of tumor characteristics with parity status. The new study, which includes a greater number of women followed for a longer period, now provides such data.
The most important findings from the research apply to women who were diagnosed with stage 1 or stage 2 breast cancer when aged younger than 45 years. Among these women, who would generally be expected to have the best prognosis, those who had given birth less than 10 years before breast cancer diagnosis — postpartum breast cancer, or PPBC — were estimated to have 3.5 to 5 times the occurrence of distant metastasis relative to women who were nulliparous, even after controlling for molecular subtype (ER, PR and HER2), age and year of diagnosis.
The higher risk for distant metastasis in women with PPBC was observed for both ER-positive and -negative disease; in fact, women with ER-positive PPBC were estimated to have the same risk for metastasis as nulliparous women with ER-negative disease, with the highest risk in women with ER-negative PPBC. Patients with stage 3 breast cancer exhibited a poor prognosis regardless of parity status.
To date, breast cancer treatment guidelines with regard to chemotherapy are based on stage, tumor characteristics, results from a 21-gene panel, lymph node status and age of the patient. The results of this rigorous study suggest that for young women diagnosed with stage 1 or stage 2 breast cancer, pregnancy history should also be considered as an independent prognostic factor.
In the U.S., women with PPBC comprise approximately 45% of those with early breast cancer, and this proportion may increase as more women delay childbearing. Additional research is needed to determine whether the observed association is consistent across populations. It would also be of interest to include women diagnosed at ages 46 to 50 years, who also may have given birth less than 10 years before diagnosis.
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