Is breast-conserving therapy in the genetically predisposed breast cancer patient a reasonable and appropriate option?

We will begin by answering the question posed in the title of this commentary regarding the appropriateness of breast-conserving therapy in a genetically predisposed patient with a definitive ‘yes’. We continue to offer breastconserving therapy to genetically predisposed breast cancer patients and will present in this commentary the rationale for this position based on the available data. The issue of breast-conserving therapy in women diagnosed with breast cancer who have a genetic predisposition to the disease is a complicated issue. Even prior to a diagnosis of breast cancer, the genetically predisposed patient may often be considering prophylactic mastectomy and/or prophylactic oophorectomy as risk-reducing strategies [1–3]. Although the impact of these prophylactic measures on survival remains debatable, it is clear that prophylactic bilateral mastectomy substantially reduces the risk of subsequent breast cancers. It would therefore appear that when a patient with a genetic predisposition is faced with a new diagnosis of breast cancer, ipsilateral therapeutic mastectomy as well as contralateral prophylactic mastectomy would be strongly considered. In addition, BRCA1 and BRCA2 are known to be involved in DNA repair. Hypothetically the administration of radiation, with its known damaging effects on DNA, may be associated with adverse normal tissue reactions, and increased rates of radiation-induced second malignancies [4–10]. Based on these considerations the issue of breast-conserving therapy followed by radiation therapy in the genetically predisposed patient is obviously approached with some trepidation. In this issue of the European Journal of Cancer, Seynaeve and colleagues report on a series of conservatively managed breast cancer patients with a genetic predisposition [11]. In this series they observed a higher rate of ipsilateral breast tumour relapse (30% at 10 years) in the genetically predisposed cohort compared to a rate of 16% at 10 years in an age-matched ‘sporadic’ control group. As expected, contralateral events were also more frequent in the genetic cohort. On the surface these rates of relapse are high, and one might assume from these data that breast-conserving therapy should be avoided in the genetically predisposed patient. First, a few caveats regarding the Seynaeve study should be highlighted. As they acknowledge, not all patients in their series underwent full genetic testing. A majority of the hereditary group was ‘unspecified hereditary breast cancer’, based on very strong family histories. Similarly, the sporadic controls were presumed to be negative for a genetic predisposition based on family history. The lack of specific sequencing data on all patients weakens the impact of the findings. Another limitation of their study is the relatively short, 6-year median follow up. Despite these limitations, their ipsilateral and contralateral event rates were remarkably similar to those in a recently published study from our institution, where both the sporadic and genetic groups underwent complete sequencing of both BRCA1 and BRCA2 genes, and follow up exceeded 12 years [12]. The 12-year rates of ipsilateral and contralateral events in our genetic cohort with knownmutations in BRCA1 or BRCA2 were 49% and 42%, respectively, compared to an ipsilateral relapse rate of 21% and contralateral relapse rate of 9% in sporadic patients (who were sequenced and tested negative for BRCA1 and BRCA2). Selection criteria for our study were conservatively managed patients who were less than 42 years of age at diagnosis. The observations of a higher rate of late local relapse are also consistent with the recent series by Robson, who reported a 10-year local relapse rate of 22% in hereditary patients compared to 6.9% in sporadic controls [13]. Although the difference in local control