Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK)
BMJ 2012; 345 doi: https://doi.org/10.1136/bmj.e5660 (Published 06 September 2012) Cite this as: BMJ 2012;345:e5660
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Radiation from mammography increases the risk of breast cancer in susceptible women.1 However, screening has been mostly carried out in the 50 to 69 age groups who are most likely to be taking HRT and who have also had most increases in breast cancer. Please see the England and Wales breast cancer incidence graphs from 1962 to 1999 attached below.
It is important to recognise that increases and reductions in hormone use can either increase or reduce breast cancer registrations and mortality. The carcinogenic effect of progestogens has been underestimated for decades. The combined effects of progestogen use from an early age, plus repeated exposure to radiation from mammography, is even harder to clarify. Reductions in mortality are claimed.2,3
Dr Ann Johnson is concerned that carcinoma in situ is often discovered by screening can lead to overdiagnosis and overtreatment. Carcinoma-in-situ is not usually life threatening in contrast to most malignant tumours which can grow rapidly.4 Dr Johnson thinks that screening has raised the standards of diagnosis and management, but, by removing more slowly growing tumours, it has become harder to elucidate the significance of changes in survival rates.
Also some simple breast tumours regress as soon as hormone use is stopped in my experience. One of the simplest ways to reduce excessive use of screening radiation and increases in breast cancer mortality is to avoid the use of hormones, especially progestogens.5
1 Pijpe A, Andrieu N, Easton D et al. Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK). BMJ2012;345:e5660
2 Hawkes N. Lives saved by breast screening outnumber cases of overdiagnosis, review says :BMJ2012;345:e6155
3 Euroscreen Working Group. Summary of the evidence of breast cancer screening outcomes in Europe and first estimate of the benefit and harm balance sheet. J Med Screening 2012;19:suppl 1.
4 Johnson A. ‘Overdiagnosis’ and mortality in breast cancer screening. JR Soc Med 2012:105:317-319
5. Grant ECG. Reductions in hormone use and breast cancer mortality. BMJ;2011: 7 September Rapid Reposnse to Autier P, Boniol M, Gavin A, Vatten L.J. Breast cancer mortality in neighbouring European countries with different levels of screening but similar access to treatment: trend analysis of WHO mortality database. BMJ2011;343:d4411
Competing interests: No competing interests
This is interesting research. When I was in my late 30's I miscarried and a week or two later I had a baseline mammogram which appeared to be normal. A few months later a thickening appeared in one breast and shortly after that I was diagnosed with breast cancer. At the time I wondered if having the mammogram so close to the miscariage, while my hormones were still adjusting, could have triggered the cancer. Now in my late 50's I recently learned that I carry the brca2 gene.....so I once again wonder if there could have been a connection.
Competing interests: No competing interests
Exposure to diagnostic radiation has been cited as one of the predisposing factors to breast cancer. Age at the time of exposure has been shown to influence the differential development of breast cancer with children and adolescents having a higher chance (Neighmond, 2012). Radiography uses rays (radioactive) that have harmful impact on organs, tissues and cells. X-ray radiography, fluoroscopy and mammography may have negative effects in various ways. Firstly, they may cause mutation of cells leading to alteration of even the genes. Secondly, radiation has carcinogenic properties. This means that cancer cells may develop following exposure to radiation (Neighmond, 2012). The age at which radiation is administered may influence development of breast cancer; with children and adolescents having a higher risk than older women (>30 years). Individuals with BRCA1/2 have increased sensitivity and therefore stand a higher risk as mentioned in this study.
In this study the Authors explore our current understanding behind radiation exposure and risk of breast cancer. In my opinion, the results boost the existing evidence.
It should however be highlighted the limitations of the study: recall bias, as acknowledged by the Authors. It is also not clear from the report how the rate of non participation can affect the result with an intention to treat analysis. I agree with the Authors that the large sample is an important strength of the study.
Reference:
1.Neighmond, P. (2012). X-Ray Tests May Heighten Cancer Risk In Susceptible Women. Retrieved on September 8 2012 from: http://www.npr.org/blogs/health/2012/09/06/160708989/x-ray-tests-may-hei...
Competing interests: No competing interests
Re: Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK)
Dear Editor
The study by Pijpe and colleagues describes a markedly increased risk of breast cancer in BRCA1/2 carriers less than 30 years of age, which is directly attributable to exposure to diagnostic radiation such as screening mammography. The authors concluded that MRI may be a safer screening alternative for these women. However, little is known about whether mammogram detects cancers that are missed by MRI in young women. Therefore, in order to further examine the conclusion put forth by this study, we sought to determine the likelihood of breast cancer seen only on mammogram but not on breast MRI in young women.
In order to answer this question we conducted a study of young women at our institution. We evaluated all women age 35 or younger at time of breast cancer diagnosis treated at UNC between 2001 and 2011. Women were retrospectively selected from a prospective, IRB approved, single institution database. Of the 229 women initially screened, 42 had undergone pre-therapy MRI and mammogram and were included in the analysis.
Forty two women were included in our study group. The average age at diagnosis was 31 years (range 26-35). The median T stage was T2 (range T1-T3). The median stage was IIA (range I-IIIC). All 42 women underwent both diagnostic MRI and mammogram prior to initiation of any surgical or medical therapy. In our study 7 women (18%) who underwent BRCA analysis detected positive for BRCA mutation. Four patients were BRCA1 positive, and 3 patients were BRCA 2 positive. All 42 women had positive tumor identification by MRI (100%) and 38 had positive identification by mammogram (90%). There were no tumors that were seen on mammogram but not on MRI
In our retrospective analysis we demonstrate that no patients under age 35 had tumors that were only seen on mammogram but not on MRI. Our study is limited in its retrospective nature. Additionally, the women in our study underwent breast MRI as a diagnostic tool, rather than a screening tool. However, our initial evaluation of 42 patients suggests that MRI only (without mammogram) could potentially be used as a screening tool in order to reduce radiation exposure for young women who are subject to frequent lifetime screening. This suggests that MRI only (without mammogram) could be used as a screening tool in order to reduce radiation exposure for young women with BRCA1/2 mutations who are subject to frequent lifetime screening which supports the conclusion of the authors study.
Raeshell S. Sweeting, MD
Nancy Klauber-DeMore, MD, FACS
Professor of Surgery
References:
(1) Pijpe, A et al. Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK). BMJ. 2012 Sep 6; 345
(2) Berrington de Gonzalez, A et al. Estimated risk of radiation-induced breast cancer from mammographic screening for young BRCA mutation carriers. J Natl Cancer Inst. 2009 Feb 4; 101(3):205-9.
(3) Peters, NH et al. Preoperative MRI and surgical management in patients with nonpalpable breast cancer: the MONET - randomised controlled trial. Eur J of Cancer. 2011 Apr;47(6):879-86
Competing interests: No competing interests