A recent study suggests that younger breast cancer survivors with a germline pathogenic variant or those with an initial diagnosis of in situ vs invasive primary breast cancer have a significantly higher risk for a second primary breast cancer.
Women diagnosed with breast cancer at 40 or younger are about two to three times more likely to develop second primary breast cancer compared with those who are older when first diagnosed, said the researchers.
However, data are lacking on whether certain factors increase the risk for a second primary breast cancer, reports Medscape.
To classify the risk of developing a second primary breast cancer, the researchers evaluated a main cohort of 685 patients with stages 0-3 breast cancer who were diagnosed at 40 or younger, and had undergone unilateral mastectomy or lumpectomy as primary surgery between August 2006 and June 2015.
The team, led by Kristen Brantley, PhD, from Harvard TH Chan School of Public Health, Boston, and published online in JAMA Oncology, also analysed data on 547 younger women who had a bilateral mastectomy.
Various breast cancer risk factors were assessed, including self-reported ethnicity, race, age, family history of breast or ovarian cancer, germline genetics, tumour stage, grade and receptor status.
The primary outcome was the diagnosis of a second primary breast cancer that occurred at least six months after the initial diagnosis of primary breast cancer.
Among the 685 main study participants, 17 (2.5%) developed a second primary breast cancer (15 contralateral and two ipsilateral) over a median of 4.2 years since their primary diagnosis. The five- and 10-year cumulative incidence of a second primary breast cancer was 1.5% and 2.6%, respectively.
Overall, only 33 women were positive for a germline pathogenic variant, and having a pathogenic variant was associated with a four-fold higher risk for second primary breast cancer compared with non-carriers at five years (5.5% vs 1.3%) and at 10 years (8.9% vs 2.2%). These findings were held in multivariate models.
Patients initially diagnosed with in situ disease had more than a five-fold higher risk for second primary breast cancer compared with those initially diagnosed with invasive disease – 6.2% vs 1.2% at five years and 10.4% vs 2.1% at 10 years (hazard ratio, 5.25; P = .004).
These findings were held in multivariate models (adjusted sub-hazard ratio [sHR], 5.61; 95% CI, 1.52-20.70) and among women without a pathogenic variant (adjusted sHR, 5.67; 95% CI, 1.54-20.90).
The researchers also found a low risk for contralateral breast cancer among women without pathogenic variants, which could inform surgical decision-making.
In practice
Although the number of women positive for a germline pathogenic variant was small (n = 33) and “results should be interpreted cautiously”, the analysis signals “the importance of genetic testing” in younger breast cancer survivors to gauge their risk for a second primary breast cancer, the authors concluded.
They added that their finding of a higher risk of (second primary breast cancer) among those diagnosed with in situ primary (breast cancer) merits further investigation.
Limitations
A small number of second breast cancer events limited the authors’ ability to assess the effects of multiple risk factors together, and data on risk factors might be incomplete.
About 9% of participants completed abbreviated questionnaires that did not include information on body mass index, alcohol, smoking, and family history. Frequencies of pathogenic variants besides BRCA1 and BRCA2 may be underestimated.
Study details
Second primary breast cancer in young breast cancer survivors
Kristen Brantley, Shoshana Rosenberg, Ann Partridge et al.
Published in JAMA Oncology on 11 April 2024
Abstract
Importance
Among women diagnosed with primary breast cancer (BC) at or younger than age 40 years, prior data suggest that their risk of a second primary BC (SPBC) is higher than that of women who are older when they develop a first primary BC.
Objective
To estimate cumulative incidence and characterise risk factors of SPBC among young patients with BC.
Design, Setting, and Participants
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. 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 analysed from January to May 2023.
Main Outcomes and Measures
The 5- and 10- year cumulative incidence of SPBC.
Results
In all, 685 women with stage 0 to III BC (mean [SD] age at primary BC diagnosis, 36 [4] years) who underwent unilateral mastectomy or lumpectomy as the primary surgery for BC were included in the analysis. Over a median (IQR) follow-up of 10.0 (7.4-12.1) years, 17 patients (2.5%) developed an SPBC; 2 of these patients had cancer in the ipsilateral breast after lumpectomy. The median (IQR) time from primary BC 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 (subdistribution hazard ratio [sHR], 5.27; 95% CI, 1.43-19.43) and women with primary in situ BC vs invasive BC (sHR, 5.61; 95% CI, 1.52-20.70).
Conclusions
Findings of this cohort study 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. Findings from germline genetic testing may inform treatment decision-making and follow-up care considerations in this population.
JAMA Oncology article – Second primary breast cancer in young breast cancer survivors (Open access)
Medscape article – Certain Women May Face Higher Risk for Second Breast Cancer (Open access)
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