By Lynda Williams, medwireNews Reporter
medwireNews: Survivors of early invasive breast cancer have a slightly higher risk of developing a second primary breast cancer and other malignancies than women without a history of the disease, demonstrates research published in The BMJ.
While describing the absolute excess risk among survivors versus women without a history of invasive breast cancer as “small”, David Dodwell (University of Oxford, UK) and co-authors believe that “[t]he risks in this study can inform patients with breast cancer and the clinicians who treat and support them.”
The analysis included all 476,373 women aged 20–75 years who were diagnosed with breast cancer as their first invasive malignancy in England between 1993 and 2016 and underwent breast conserving surgery or mastectomy as their primary treatment for local or axillary node disease.
All participants were followed up for at least 3 months; the majority (86%) were followed up for at least 5 years, 54% for at least 10 years, and 11% for 20 years or longer, during which time 64,747 of the women developed a second primary tumour.
Specifically, 13.6% were diagnosed with a non-breast cancer and 5.6% were diagnosed with contralateral breast cancer, with excess risks of 2.1% and 3.1% versus the general population, respectively.
Of note, the 20-year absolute excess risk of contralateral breast cancer was higher among younger than older women, with rates compared with the general population of 6.9% versus 1.3% among those aged 20–39 years, falling to 5.0% versus 2.7% among women aged 60–69 years.
By contrast, the 20-year absolute excess risk of non-breast cancer did not differ by age at index diagnosis, with risks for women with and without an index breast cancer diagnosis at age 20–39 years of 4.6% and 2.8%, respectively, and comparable risks between the two groups for those aged 60–69 years of 18.3% and 16.1%.
Among second non-breast tumours, the highest absolute excess diagnoses were non-cervix uterine cancer (0.74%) and lung cancer (0.41%), “which together accounted for more than 50% of the total 20 year excess”, Dodwell et al observe.
There were also higher risks of acute leukaemia and cancers in soft tissues, joints, bones and salivary glands in patients with a history of invasive breast cancer versus the general population but the 20-year absolute excess risk of each of these was 0.2% or less, they note.
Further analysis indicated that women who received radiotherapy were significantly more likely to develop contralateral breast cancer in the first 9 years after their initial diagnosis than those who did not, and then significantly more likely to develop lung cancer after 10 years of follow-up.
In addition, patients given chemotherapy had an increased risk of developing cancer of the ovary, fallopian tubes or stomach, as well as leukaemia in the first 9 years of follow-up compared with those who did not receive chemotherapy, and an increased risk of malignancies affecting the uterus (non-cervix), head and neck (not salivary gland) and pancreas thereafter.
Receipt of endocrine therapy was associated with a greater risk of uterine cancer (non-cervix) and a reduced risk of contralateral breast cancer, both of which occurred throughout follow-up.
Dodwell et al estimate that 2% of the second primary cancers diagnosed and 7% of the 15,813 excess second cancers recorded in the study may be attributable to adjuvant therapies for invasive breast cancer. Nevertheless, they emphasize that “trial data show that their benefits outweigh this risk in almost all circumstances.”
Discussing the findings in an accompanying editorial, Maria-José Sánchez and Dafina Petrova, both from Escuela Andaluza de Salud Pública in Grenada, Spain, write that “the findings from this and other recent studies support a clinical shift towards risk based, personalised follow-up strategies, accounting for both tumour biology and age and time dependent risks, complemented by broader population level prevention efforts.”
They point out that the study is limited by the lack of information on family history and genetic markers, such as pathogenic BRCA1 or BRCA2 mutations that confer an increased risk of second primary tumours.
“Stratifying risk by genetic susceptibility could improve risk estimation and may further reduce the estimated excess risk among women without such inherited factors”, they suggest.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2025 Springer Healthcare Ltd, part of Springer Nature
BMJ 2025; 390: e083975
https://pubmed.ncbi.nlm.nih.gov/40865997/
BMJ 2025; 390: r1798
https://pubmed.ncbi.nlm.nih.gov/40876899/
Keywords: breast cancer, secondary primary breast cancer, early invasive breast cancer