Can prior radiation cause breast cancer?

Dr Mia Hugo answers this complex question; ultimately there is a minute chance, however, it’s far-outweighed by the risk of the cancer you are currently facing.

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Radiation (RT), as with all the other cancer treatment modalities, carries some risk of adverse effects, including rare secondary cancers, but the effectiveness of radiation in controlling the current cancer makes it an invaluable tool in the fight against cancer.

Looking at the research

We owe a great deal of our knowledge of radiation-related cancer to the epidemiological studies of the Japanese atomic bomb survivors. The Life Span Study of Japanese atomic bomb survivors, including 70 165 women from Hiroshima and Nagasaki, provides detailed risk estimates on radiation-associated breast cancer risk; with an overall rate of female breast cancer of 7.59 per 10 000 person-years^.9 They found that the younger the patient was at exposure to atomic bomb radiation (especially younger than 10 years old), the higher the excess relative risk (ERR) for breast cancer (or other cancers) later in life^.1

In therapeutic radiation, age also has an impact on risk, with women younger than 20 years at higher risk of therapeutic radiation-associated breast cancer than those exposed at older ages.¹

Childhood cancer survivors provide useful data on therapeutic radiation-associated breast cancer, in particular female Hodgkin lymphoma (HL) patients who received high-dose radiotherapy to the chest. Some reports on childhood HL survivors showed high risks of breast cancer later in life among patients diagnosed before age 15.¹

Secondary malignancies

The early detection of breast cancer through mammographic screening, and improvements in breast cancer treatment, including therapeutic RT, have increased the number of breast cancer survivors who are potentially cured of their disease and live long enough to develop late effects of treatment, which may include secondary malignancies, such as therapy-related contralateral breast cancer (CBC) and breast sarcomas. CBC is a tumour in the opposite breast.

There is some data that suggests that there is a slight excess risk of CBC after breast or chest wall RT compared with non-irradiated patients.² Data suggests that the risk may be higher with younger age at treatment.² In the WECARE study, they found that women <40 years of age who received >1.0 Gy of absorbed dose to the specific quadrant of the CBC had a 2.5-fold greater risk for CBC than unexposed women. No excess risk was observed in women >40 years of age.³

Similarly, another study found that fewer than 3% of all second breast cancers in this study could be attributed to previous radiation treatment; the risk, however, increased among women who underwent irradiation at a relatively young age (less than 45 years). Radiation exposure after the age of 45 entails little, if any, risk of radiation-induced breast cancer.⁴

One study showed that CBC was higher for women who had received orthovoltage radiotherapy (an older technology), which increases the amount of scattered radiation to surrounding tissues. The absolute radiation-induced risk of CBC in the non-orthovoltage RT trials was reported to be 1% (1 out of a hundred patients).⁵

BRCA1/BRCA 2

For patients with known BRCA1/BRCA2 mutations, the risk of breast cancer after radiation is unclear. A nested case-control study didn’t find an increase in CBC in carriers irradiated for breast cancer, irrespective of age.² Several cell-based studies of BRCA1 and BRCA2 mutation carriers failed to show increased radio-sensitivity.¹ Whole breast hypofractionated radiotherapy is a shorter course of treatment given usually over three weeks and it’s non-inferior in comparison to the conventional five weeks with respect to ipsilateral (same side) breast tumour control. There is no evidence that modest hypofractionation, such as used in these trials, impact either late cardiac toxicity or the risk of secondary malignancy.⁵

RT-associated sarcoma

The incidence of an RT-associated sarcoma has been estimated to be well under 1% in exposed adult populations, ranging from 0,05-0,4% (5 in 10 000 to 4 in 1000 patients).⁶ Although, women who undergo RT for breast cancer have an increased risk of in-field sarcomas that persist for 20 to 30 years or longer; the absolute magnitude of the risk appears to be small.

Nevertheless, women who have inherited mutations in the ataxia-telangiectasia mutated (ATM) gene, which are associated with an increased risk of radiation-associated sarcoma, may choose to avoid breast-conserving therapy, opting instead for mastectomy.⁷

In the future, we may be able to fine-tune the risk of CBC or breast sarcoma. Very early data indicate that diagnostic or therapeutic chest radiation may predispose patients with decreased stromal PTEN expression to secondary breast cancer, and that prophylactic EGFR inhibition may reduce this risk^.8

What do I tell my patients when they ask?

When asked about the risks and benefits of radiation, I explain that the risk for a secondary radiation-induced cancer is real but very small and is far-outweighed by the risk of the cancer they are dealing with today.

MEET THE EXPERT – Dr Mia Hugo

Dr Mia Hugo works in private practice as a radiation oncologist. She participates in weekly multi-disciplinary oncology team meetings for breast, urology, gastrointestinal/gynaecological, and head and neck cancers. She provides radiation to patients at Wits Donald Gordon, Netcare Milpark, Pinehaven and Olivedale Hospitals, as well as at Busamed and 200 Rivonia Medical Centre.

References

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Stovall M, Smith SA, Langholz BM, Boice JD Jr, Shore RE, Andersson M, Buchholz TA, Capanu M, Bernstein L, Lynch CF, Malone KE, Anton-Culver H, Haile RW, Rosenstein BS, Reiner AS, Thomas DC, Bernstein JL (2008) Women’s Environmental, Cancer, and Radiation Epidemiology Study Collaborative Group . Int J Radiat Oncol Biol Phys. 2008;72(4):1021. Epub 2008 Jun 14.
Boice JD Jr, Harvey EB, Blettner M, Stovall M, Flannery JT (1992) Cancer in the contralateral breast after radiotherapy for breast cancer. N Engl J Med. 1992;326(12):781.
Hooning MJ, Aleman BM, Hauptmann M, Baaijens MH, Klijn JG, Noyon R, Stovall M, van Leeuwen FE (2008) Roles of radiotherapy and chemotherapy in the development of contralateral breast cancer. J Clin Oncol. 2008;26(34):5561.
Brownlee Z, Garg R, Listo M, Zavitsanos P, Wazer DE, Huber KE. (2018) Late complications of radiation therapy for breast cancer: evolution in techniques and risk over time. Gland Surg. 2018 Aug;7(4):371-378. doi: 10.21037/gs.2018.01.05. PMID: 30175054; PMCID: PMC6107587. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107587/
Robert Maki, Alberto S Pappo, Raphael E Pollock, Elizabeth H Baldini, Melinda Yushak (2023) Radiation induced sarcomas. UpToDate. Literature review current through: Jul 2023. This topic last updated: Jun 01, 2023. https://www.uptodate.com/contents/radiation-associated-sarcomas?search=radiation%20induced%20cancer%20in%20breast%20cancer&source=search_result&selectedTitle=19~150&usage_type=default&display_rank=19
Rashmi Chugh, Michael S Sabel, Mary Feng, Robert Maki,Daniel F Hayes, Anees B Chagpar, Elizabeth H Baldini, Sonali Shah (2021) Breast sarcoma. UpToDate. Literature review current through: Jul 2023. This topic last updated: Oct 20, 2021. https://www.uptodate.com/contents/breast-sarcoma-epidemiology-risk-factors-clinical-presentation-diagnosis-and-staging?sectionName=Radiation%20exposure%20in%20breast%20cancer%20survivors&search=radiation%20induced%20cancer%20in%20breast%20cancer&topicRef=14261&anchor=H9239667&source=see_link#H9239667
Sizemore, G.M., Balakrishnan, S., Thies, K.A. et al. (2018) Stromal PTEN determines mammary epithelial response to radiotherapy. Nat Commun 9, 2783 (2018). https://doi.org/10.1038/s41467-018-05266-6
Alina V. Brenner, Dale L. Preston, Ritsu Sakata, Hiromi Sugiyama, Amy Berrington de Gonzalez, Benjamin French, Mai Utada, Elizabeth K. Cahoon, Atsuko Sadakane, Kotaro Ozasa, Eric J. Grant, Kiyohiko Mabuchi “Incidence of Breast Cancer in the Life Span Study of Atomic Bomb Survivors: 1958–2009,” Radiation Research, 190(4), 433-444, (25 July 2018)