Risk of ipsilateral breast tumor recurrence and contralateral breast cancer in patients with and without TP53 variant in a large series of breast cancer patients.

Background: The association between breast cancer patients with a TP53 pathogenic variant and risk of local recurrence and contralateral breast cancer remains largely unknown.

Methods: The study population of 11093 patients was derived from two cohorts at the Breast Center of Peking University Cancer Hospital in China from November 2003, to March 2018. TP53 germline variants were determined for all patients.

Results: In the study, forty-one (0.37%) carried a TP53 germline pathogenic variant, and 11052 were non-carriers (99.63%). Nineteen TP53 carriers (46.3%) and 4173 non-carriers (37.8%) were treated with breast-conserving therapy (BCT), while the remaining were treated with mastectomy. After a median follow-up of 6.7 years, the rate of ipsilateral breast tumor recurrence (IBTR) in TP53 carriers was significantly higher than that in non-carriers when treated with BCT (21.1% vs 3.8%, P = 0.006). No difference in the rate of IBTR was found between TP53 carriers and non-carriers when treated with mastectomy (0.0% vs 2.6%, P = 1.0). Furthermore, the rate of IBTR in TP53 carriers treated with BCT was significantly higher than that in those treated with mastectomy (21.1% vs 0.0%, P = 0.038). The 10-year cumulative risk of contralateral breast cancer in TP53 carriers was significantly higher than that in non-carriers (17.9% vs 3.6%, hazard ratio (HR) = 7.0, 95% CI: 3.3-14.9, P < 0.001).

Conclusions: Patients with TP53 variants have a high risk of IBTR when treated with BCT, and exhibit a very high risk of contralateral breast cancer. TP53 carriers may not be suitable for BCT and prophylactic contralateral mastectomy might be considered.