The Risk Of A Second Primary Breast Cancer Related To Estrogen Receptor Status

After a woman has developed an initial primary breast cancer, the risk of a second breast cancer takes on greater importance as it relates to surveillance and having the potential to impact the initial primary surgical approach. Multiple studies have been published that suggest the risk of a second cancer is between 0.2% per year and 0.6% per year. However, the risk can vary greatly depending on factors such as breast density, family history, and genetic testing. This large multi-institutional study is based on six Breast Cancer Surveillance Consortium Registries from 2000 to 2017 (Cancer 2023, February 15, Published Online before Print).

The study cohort included women aged 18 and older with unilateral stage I-III, who had imaging performed within the Breast Cancer Surveillance Consortium. The authors identified 36,165 women diagnosed with unilateral breast cancer but after applying appropriate exclusions the final study population was 27,744

Throughout the period of follow-up women with estrogen receptor-negative (ER-negative) primary breast cancers at a higher incidence of second breast cancers compared to women with ER-positive breast cancers. These differences were less pronounced in women presenting with more advanced-stage primary breast cancers. For women with advanced primary breast cancer followed over a 10-year period the risk of death was the most common outcome (16.2% for women with ER-negative cancers and 13.9% for women with ER-positive cancers). This exceeded the risk of the second primary cancer which was 10.4% for women with ER-negative cancers and 7.5% for those with E-positive cancers.

Women with ER-negative cancers had a higher risk of second cancers compared with those women with ER-positive cancers across all treatment groups. This included women who underwent breast-conserving surgery with and without radiation as well as mastectomy. In a majority of women who developed second cancers, ER status tended to be concordant with that of the primary cancer. Of those women developing second cancer in which ER status was available, 82% of ER-positive primary breast cancers and 53% of ER-negative primary breast cancers had the same ER status and supple subsequent cancers. Most importantly, the 10-year cumulative incidence of a second breast cancer was 8.0% in ER-positive women, 7.9% in ER-positive/HER-2 negative,10.5% in ER-negative/HER-2 positive women, and 12.4% in ER-negative/HER-2 negative women.

Summary: In this study of second breast cancer risk among women with a history of breast cancer, the authors found 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 treatments. This was particularly true for the higher risk seen in ER-negative patients within the first five years after diagnosis. However, the risk of second breast cancer after five years was similar for ER-negative and ER-positive primary cancers. The authors point out that this is a similar pattern observed in the risk of regional and distant recurrences which tend to occur early in women with a history of ER-negative cancers compared to ER-positive cancers. A simple look at the graph included here would suggest that the yearly risk in the first 10 years after diagnosis of initial breast cancer is approximately 0.8% per year for women with ER-positive cancers and 1.1 to 1.2% per year for those with ER-negative cancers.

Dr. Alan Stolier, MD, FACS, clinical breast oncologist, shares his expert medical perspective with a series of educational and scientific articles.