woman lymph armpit examination. Node-Positive Breast Cancer
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Genetic testing could determine which young breast cancer survivors are at highest risk of a second primary breast cancer (SPBC) and thus help others avoid unnecessary treatment, according to a new study. Their findings suggests young breast cancer survivors without a germline pathogenic variant have a low risk of developing a SPBC in the first 10 years after diagnosis.

This is an especially important finding, as the rate of breast cancer in young women has been steadily increasing.

The research about the risk of SPBC’s appears today in JAMA Oncology. The lead author is Kristen D. Brantley, PhD, of Harvard’s T. H. Chan School of Public Health.

The authors note that prior research suggests the risk that SPBC may be two to three times higher among women who are younger than 40 years old at the time of primary BC diagnosis compared with women diagnosed later in life. As a result, some young BC patients choose unilateral or bilateral mastectomies.

But, Brantley and her colleagues point out, all young women may not be at a heightened risk of SPBC and germline genetic testing offers one means of determining who is. Note: The authors define SPBC as a new breast cancer, distinct from the original, arising in either the ipsilateral or contralateral breast. In their analysis they only counted contralateral breast cancers, and two women with ipsilateral SPBC were treated as having local recurrences.

Breast cancer diagnoses have increased steadily in women under age 50 over the past two decades, with steeper increases in more recent years, according to a recent Washington University School of Medicine study. In analysis on data from 217,000 U.S. women diagnosed with any type of breast cancer from 2000 through 2019 they found that in 2000, the incidence of breast cancer among women ages 20 to 49 was about 64 cases per 100,000 people. By 2019 the rate had reached 74 cases per 100,000.

In this study of recurrence participants were enrolled in the Young Women’s Breast Cancer Study, a prospective study of 1297 women aged 40 years or younger who were diagnosed with stage 0 to III BC from August 2006 to June 2015. Demographic, genetic testing, treatment, and outcome data were collected by patient surveys and medical record review. The team evaluated demographic factors, primary tumor characteristics, treatments, and germline genetics with risk of SPBC.

A time-to-event analysis was used to account for competing risks when determining cumulative incidence of SPBC, and Fine-Gray subdistribution hazard models were used to evaluate associations between clinical factors and SPBC risk. Data were analyzed from January to May 2023. 

The five- and ten-year cumulative incidence of SPBC. In all, 685 women with stage 0 to 3 breast cancer at primary breast cancer diagnosis, 36 who underwent unilateral mastectomy or lumpectomy as the primary surgery for breast cancer were included in the analysis. Over a median follow-up of 10.0 years, 17 patients (2.5%) developed an SPBC; 2 of these patients had cancer in the ipsilateral breast after lumpectomy. 

The median time from primary breast cancer diagnosis to SPBC was 4.2 (3.3-5.6) years. Among 577 women who underwent genetic testing, the 10-year risk of SPBC was 2.2% for women who did not carry a pathogenic variant (12 of 544) and 8.9% for carriers of a pathogenic variant (3 of 33). In multivariate analyses, the risk of SPBC was higher among PV carriers vs noncarriers.

These findings, the authors say, suggest that young BC survivors without a germline pathogenic variant have a low risk of developing a SPBC in the first 10 years after diagnosis. Germline genetic testing may inform treatment decision-making and follow-up care considerations in this population. 

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