Abstract P6-08-18: Breast cancer in Li-Fraumeni syndrome and risk-reduction mastectomy in <i>TP53</i> p.R337H carriers
Bibliographic record
Abstract
Abstract Li-Fraumeni syndrome (LFS) is a hereditary genetic condition that predisposes to a wide variety of tumors. Early-onset breast cancer is the most prevalent tumor in female carriers, with a 49% risk by age 60. The risk of developing a second primary breast cancer in LFS remains unknown but it is estimated to be 33%. The Toronto protocol was proposed by Villani et al. (2011) and defined effective strategies for cancer screening in carriers. Risk-reduction mastectomy (RRM) may reduce over 90% breast cancer risk. Due to a founder mutation, TP53 p.R337H, LFS has been observed in a higher-than-expected prevalence in Brazil. This mutation occurs in the oligomerization domain and seems to have a milder lifetime penetrance than regular DNA binding domain mutations. Due to its estimated high frequency in the Brazillian population, this is a public health problem and implementation of effective strategies in breast cancer risk-reduction are needed. In this study, we have evaluated risk-reduction mastectomy in women who carried the founder TP53 p.R337H mutation. A total of 106 women from the Brazilian LFS TP53 p.R337H cohort were included in this study. Imaging surveillance was offered and RRM was discussed. All participants received genetic counseling and signed informed consent. The study was approved by the local ethics committee (HSL-02433418.5.0000.5461). A total of 65.1% (69/106) did not develop breast cancer at the time of this study. Among those, four women opted to perform bilateral prophylactic mastectomy (5.8% - 4/69). Overall, 34.9% (37/106) developed breast cancer prior to enrollment and 12 women were lost to follow-up. A total of 25 women opted to continue surveillance. Eleven (44%) opted to undergo RRM and 14 (66%) chose to continue annual breast magnetic resonance imaging (MRI), according to the Toronto protocol. A total of 32% (8/25) had been diagnosed with a second primary breast cancer prior to the study enrollment. The most common breast cancer histopathological subtype was invasive ductal carcinoma, present in 64% (16/25) in our study population. Only one woman was diagnosed with invasive lobular carcinoma (4%). Twelve percent (3/25) were in situ carcinomas. Estrogen and progesterone receptors stained positive in 76% (19/25). HER-2 was negative in 52% (13/25) of all cases. Our findings show that BPM was not a common procedure in carriers (5.8%). Nevertheless, RRM was performed in 44% of all women who have been previously diagnosed with breast cancer. Ductal invasive carcinoma is the most common cancer in TP53 p.R337H women and most of them have hormone receptor status positive. Unlike other previously published studies on LFS breast can cancer, HER-2 gene was non-amplified in most cases (52%). This is the first study to evaluate the frequency of RRM in a cohort of women with breast cancer carrying the same germline pathogenic variant, TP53 p.R337H. Citation Format: Mariana Cartaxo Alves, Renata Lazari Sandoval, Janina Pontes Pisani, Carla Vanessa Quirino, Elizabeth Santana Santos, Maria Isabel Achatz. Breast cancer in Li-Fraumeni syndrome and risk-reduction mastectomy in TP53 p.R337H carriers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-18.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".