phenotype and prognosis of patients with breast cancer and pathogenic variants of tp53

Conditions: Breast Cancer; TP53 R337H; Li-Fraumeni Syndrome; Prognosis Breast Cancer

Summary: a prospective and retrospective cohort study of patients with a documented pathogenic or likely pathogenic variants of tp53 were identified using blood dna colection and breast cancer diagnosis by histological confirmation, between 1999 and 2022. all patients were followed by the hereditary group of a single cancer center (instituto do cancer do estado de sao paulo). patients were included if they had a histopathological diagnosis of localized invasive carcinoma or in situ carcinoma of the breast and with localized disease. patients met revised chompret criteria, li fraumeni like syndrome,family member of carrier tp53 or hereditary breast and ovarian syndrome for germline test.

the primary outcome was progression free survival from specific breast cancer from patients with bc and tp53 mutation versus bc and no pathogenic variants documented in genetic test. we proposed 45 cases tp53 pathogenic carriers and localized breast cancer diagnosed for each case included we will be selected 2 controls resulting in 90 control patients, for control with no documented pathogenic variants in genetic test. with a sample of 135 patients with distribution 2:1, considering a two-tailed alpha of 5%, the study will have 80% power to identify a hazard hatio of 0.62 in the comparison of progression-free survival between the groups. descriptive statistics will be used to summarize clinical characteristics and treatments performed. continuous variables may be compared between groups using t student test or mann-whitney test, in the case of normal and non-normal data distribution, respectively. categorical variables may be compared between groups using the fisher exact test. progression-free survival will be estimated from the date of breast cancer diagnosis until the date of progression or date of recurrence (in cases of localized disease treated) of breast cancer. death will not be considered as an event for progression-free survival, since patients with pv tp53 may have an increased risk of deaths from other neoplasms. the breast cancer specific survival will be estimated from the date of diagnosis of breast cancer until the date of death from the breast cancer. patients without the specific events will be censored on the date of last follow-up. the kaplan-meyer method will be used for survival estimates, comparing survival curves with log-rank testing. the cox regression model will be used for hazard-ratio calculation and 95% confidence-interval. p value less than 0.05 will be considered statistically significant. statistical analyses will be performed through stata program, version 15.1 (statacorp, texas, usa).

Eligibility criteria:
inclusion criteria: * breast cancer (histopathological diagnosis of localized invasive carcinoma or in situ carcinoma of the breast) and documented germline pathogenic variants of tp53. exclusion criteria: * patients with only other types of breast cancer such as sarcoma and phyllodes tumor were excluded from the analysis. * metastatic breast cancer at diagnosis ("denovo")

Keywords: breast cancer tp53