TY - JOUR
T1 - TP53-associated early breast cancer
T2 - new observations from a large cohort
AU - Sandoval, Renata L.
AU - Bottosso, Michele
AU - Tianyu, Li
AU - Polidorio, Natalia
AU - Bychkovsky, Brittany L.
AU - Verret, Benjamin
AU - Gennari, Alessandra
AU - Cahill, Sophie
AU - Achatz, Maria Isabel
AU - Caron, Olivier
AU - Imbert-Bouteille, Marion
AU - Noguès, Catherine
AU - Mawell, Kara N.
AU - Fortuno, Cristina
AU - Spurdle, Amanda B.
AU - Tayob, Nabihah
AU - Andre, Fabrice
AU - Garber, Judy E.
N1 - Publisher Copyright:
© The Author(s) 2024. Published by Oxford University Press. All rights reserved.
PY - 2024/8/1
Y1 - 2024/8/1
N2 - Background: A recent large, well-annotated international cohort of patients with Li-Fraumeni syndrome and early-stage breast cancer was examined for shared features. Methods: This multicenter cohort study included women with a germline TP53 pathogenic or likely pathogenic variant and nonmetastatic breast cancer diagnosed between 2002 and 2022. Clinical and genetic data were obtained from institutional registries and clinical charts. Descriptive statistics were used to summarize proportions, and differences were assessed using χ2 or Wilcoxon rank sum tests. Metachronous contralateral breast cancer risk, radiation-induced sarcoma risk, and recurrence-free survival were analyzed using the Kaplan-Meier methodology. Results: Among 227 women who met study criteria, the median age of first breast cancer diagnosis was 37 years (range = 21-71), 11.9% presented with bilateral synchronous breast cancer, and 18.1% had ductal carcinoma in situ only. In total, 166 (73.1%) patients underwent mastectomies, including 67 bilateral mastectomies as first breast cancer surgery. Among those patients with retained breast tissue, the contralateral breast cancer rate was 25.3% at 5 years. Among 186 invasive tumors, 72.1% were stages I to II, 48.9% were node negative, and the most common subtypes were hormone receptor-positive/HER2-negative (40.9%) and hormone receptor positive/HER2 positive (34.4%). At a median follow-up of 69.9 months (interquartile range = 32.6-125.9), invasive hormone receptor–positive/HER2-negative disease had the highest recurrence risk among the subtypes (5-year recurrence-free survival = 61.1%, P = .001). Among those who received radiation therapy (n = 79), the 5-year radiation-induced sarcoma rate was 4.8%. Conclusion: We observed high rates of ductal carcinoma in situ, hormone receptor–positive, and HER2-positive breast cancers, with a worse outcome in the hormone receptor–positive/HER2-negative luminal tumors, despite appropriate treatment. Confirmation of these findings in further studies could have implications for breast cancer care in those with Li-Fraumeni syndrome.
AB - Background: A recent large, well-annotated international cohort of patients with Li-Fraumeni syndrome and early-stage breast cancer was examined for shared features. Methods: This multicenter cohort study included women with a germline TP53 pathogenic or likely pathogenic variant and nonmetastatic breast cancer diagnosed between 2002 and 2022. Clinical and genetic data were obtained from institutional registries and clinical charts. Descriptive statistics were used to summarize proportions, and differences were assessed using χ2 or Wilcoxon rank sum tests. Metachronous contralateral breast cancer risk, radiation-induced sarcoma risk, and recurrence-free survival were analyzed using the Kaplan-Meier methodology. Results: Among 227 women who met study criteria, the median age of first breast cancer diagnosis was 37 years (range = 21-71), 11.9% presented with bilateral synchronous breast cancer, and 18.1% had ductal carcinoma in situ only. In total, 166 (73.1%) patients underwent mastectomies, including 67 bilateral mastectomies as first breast cancer surgery. Among those patients with retained breast tissue, the contralateral breast cancer rate was 25.3% at 5 years. Among 186 invasive tumors, 72.1% were stages I to II, 48.9% were node negative, and the most common subtypes were hormone receptor-positive/HER2-negative (40.9%) and hormone receptor positive/HER2 positive (34.4%). At a median follow-up of 69.9 months (interquartile range = 32.6-125.9), invasive hormone receptor–positive/HER2-negative disease had the highest recurrence risk among the subtypes (5-year recurrence-free survival = 61.1%, P = .001). Among those who received radiation therapy (n = 79), the 5-year radiation-induced sarcoma rate was 4.8%. Conclusion: We observed high rates of ductal carcinoma in situ, hormone receptor–positive, and HER2-positive breast cancers, with a worse outcome in the hormone receptor–positive/HER2-negative luminal tumors, despite appropriate treatment. Confirmation of these findings in further studies could have implications for breast cancer care in those with Li-Fraumeni syndrome.
UR - http://www.scopus.com/inward/record.url?scp=85198355478&partnerID=8YFLogxK
U2 - 10.1093/jnci/djae074
DO - 10.1093/jnci/djae074
M3 - Article
C2 - 38569880
AN - SCOPUS:85198355478
SN - 0027-8874
VL - 116
SP - 1246
EP - 1254
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 8
ER -