When it comes to a woman’s risk for a breast cancer recurrence, hormone status appears to matter.

New research shows that patients with ER-negative disease have a higher risk of a second breast cancer within a 5-year window post-diagnosis compared with patients with ER-positive disease.

“Our findings suggest that primary breast cancer ER status could be used to identify women at highest risk of second breast cancer events during the early posttreatment period and should be a consideration for guidelines and decision making regarding surveillance imaging regimens for breast cancer survivors,” the study authors, led by Kathryn P. Lowry, MD, of Fred Hutchinson Cancer Center in Seattle, Washington, concluded.

The study was published online in Cancer earlier this month.

Breast cancer survivors are at risk for a second breast cancer, making ongoing surveillance essential. Surveillance could be informed by better understanding an individual’s recurrence risk, but whether differences exist for women with ER‐positive vs ER‐negative cancers remains unclear.

Lowry and colleagues analyzed women diagnosed with stage I-III breast cancer between 2000 and 2017, drawing from six Breast Cancer Surveillance Consortium registries. The team collected information on patients’ ER status as well as second breast cancer events detectable by surveillance imaging. Second breast cancer rates were assessed 1-5 years and 6-10 years after diagnosis. The final study cohort included 23,139 women with ER-positive disease and 4605 with ER-negative disease.

The researchers found that, at the 5-year mark, the cumulative breast cancer incidence was 7.1% for ER‐negative disease and 3.6% for ER‐positive disease. At the 10-year mark, the cumulative breast cancer incidence was still higher for women with ER-negative disease — 11.8% vs 7.5% among those with ER-positive disease. 

Patients with ER-negative disease also had higher rates of second breast cancers within the first 5 years of follow-ups — 16.0 per 1000 person‐years vs 7.8 per 1000 person‐years for those with ER‐positive breast cancer — though after 5 years, the rates by ER-status were similar among the two groups (12.1 per 1000 vs 9.3 per 1000 person‐years, respectively).

Overall, the findings indicate that the “ER status of the primary invasive cancer was an important prognostic factor for both the magnitude and the timing of second breast cancer events,” the authors concluded.

The team noted several limitations to their study, including that information on the presence of pathogenic variants, such as BRCA1 and BRCA2, were not available. Given that these variants tend to be more common among women with ER‐negative breast cancers, this could represent a confounder.

Marisa C. Weiss, MD, chief medical officer and founder of Breastcancer.org who was not involved in the research, highlighted two important details to keep in mind.

“We do know that triple negative breast cancers are associated with a higher risk of having an inherited genetic abnormality like BRCA1, which predicts a higher risk of second malignancies,” said Weiss, a breast oncologist at Lankenau Medical Center in Wynnewood, Pennsylvania. “Also, it should be noted that patients with HR-positive breast cancer have a higher incidence of local recurrence spread out over 10-plus years.”

What might these results mean for practice and following patients over the long term? 

According to the researchers, “[f]urther study is needed to evaluate whether women with ER‐negative primary cancers may potentially benefit from more intensive surveillance in the early postdiagnosis period.”

Weiss noted as well that “each person’s situation is unique,” and it is “very important to develop a customized survivorship care plan with close surveillance,” which includes genetic testing.

Lowry reported grants from the American Cancer Society and personal fees from the Radiological Society of North America outside the submitted work. Several coauthors also reported disclosures. Weiss reported no relevant financial relationships.

Cancer. Published online February 15, 2023. Abstract.

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