Breast cancer phenotype in women with TP53 germ-line mutations: An LFS consortium effort.

Masciari, Serena; Dillon, Drupadi; Dick, Michelle; Robson, M. E.; Weitzel, Jeffrey N.; Ford, Jane B.; Balmaña, J.; Gruber, S. B.; Euhus, David M.; Garber, J. E.

doi:10.1200/jco.2011.29.15_suppl.1519

Cited by 3 publications

(2 citation statements)

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“…Recent reports have identified an increased frequency of HER2 positive breast cancer in women with LFS [18, 20, 26]. Among young women with breast cancer, HER2 positive tumors comprise 20–25% of tumors, but in series of breast cancers in women with germline TP53 mutations, approximately 63–83% of tumors are HER2 positive by clinical determinations [19, 20, 26]. Therefore, we investigated the frequency of germline TP53 mutations among women aged 50 years or below at diagnosis of HER2 positive breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of germline TP53 mutations in HER2+ breast cancer patients

Rath

Masciari

Gelman

et al. 2013

Breast Cancer Res Treat

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Background Breast cancer is the most frequent tumor in Li-Fraumeni syndrome (LFS), a rare inherited cancer syndrome associated with germline mutations in the TP53 gene. Recent data show that breast cancer in germline TP53 mutation carriers is commonly HER2-positive (63–83%). We assessed the prevalence of germline TP53 mutations in a cohort of women with HER2+ breast cancer diagnosed age ≤ 50 years. Material & Methods We identified blood specimens from 213 women with primary invasive HER2+ breast cancer age ≤ 50 years from a single center. EGAN sequencing and MLPA techniques were used to screen for germline TP53 mutations. Results Among 213 women with HER2+ breast cancer age ≤ 50 years, 3 (ages at diagnosis 23, 32, 44 years) were found to carry a TP53 mutation (1.4%, 95%CI 0.3%–4.1%). ER/PR status was not uniform. Two TP53-carriers met Chompret criteria for LFS; none met classic LFS criteria. Conclusion Although two-thirds of breast cancers in women with TP53 mutations are HER2+, we observed a low prevalence of germline TP53 mutations among unselected young women with HER2+ breast cancer. Given the potential clinical impact, consideration of germline TP53 testing should be given to young women with HER2+ breast cancer, especially if family cancer history is notable.

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Section: Introductionmentioning

confidence: 99%

Prevalence of germline TP53 mutations in HER2+ breast cancer patients

Rath

Masciari

Gelman

et al. 2013

Breast Cancer Res Treat

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“…19 Research now indicates that most breast cancer in patients with LFS exhibits a "triple-positive" phenotype (ER+/PR+/HER2+). [20][21][22] Although family history alone may not be enough to detect all patients with LFS, a thorough family history, attention to tumor histology, and a high level of clinical suspicion may allow physicians to identify and optimize therapy for their LFS patients and minimize the potential late effects associated with this syndrome.…”

Section: Discussionmentioning

confidence: 99%

Chest Wall Leiomyosarcoma After Breast-Conservative Therapy for Early-Stage Breast Cancer in a Young Woman With Li-Fraumeni Syndrome

Henry¹,

Villalobos²,

Million³

et al. 2012

J Natl Compr Canc Netw

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Li-Fraumeni syndrome (LFS) is one of the most penetrant forms of familial cancer susceptibility syndromes, characterized by early age at tumor onset and a wide spectrum of malignant tumors. Identifying LFS in patients with cancer is clinically imperative because they have an increased sensitivity to ionizing radiation and are more likely to develop radiation-induced secondary malignancies. This case report describes a young woman whose initial presentation of LFS was early-onset breast cancer and whose treatment of this primary malignancy with breast conservation likely resulted in a secondary malignancy arising in her radiation field. As seen in this case, most breast cancers in patients with LFS exhibit a triple-positive phenotype (estrogen receptor-positive/progesterone receptor-positive/HER2-positive). Although this patient met classic LFS criteria based on age and personal and family history of cancer, the NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian Cancer endorse genetic screening for TP53 mutations in a subset of patients with early-onset breast cancer, even in the absence of a suggestive family history, because of the potential for de novo TP53 mutations.

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Breast cancer phenotype in women with TP53 germline mutations: a Li-Fraumeni syndrome consortium effort

Masciari

Dillon

Rath

et al. 2012

Breast Cancer Res Treat

157

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Background Breast cancer is the most common tumor in women with Li Fraumeni Syndrome (LFS), an inherited cancer syndrome associated with germline mutations in the TP53 tumor suppressor gene. Their lifetime breast cancer risk is 49% by age 60. Breast cancers in TP53 carriers have recently been reported to more often be hormone receptor and HER-2 positive by immunohistochemistry and FISH in small series. We seek to expand this small literature with this report of a histopathologic analysis of breast cancers from women with documented LFS. Methods Unstained slides and paraffin-embedded tumor blocks from breast cancers from 39 germline TP53 mutations carriers were assembled from investigators in the LFS consortium. Central histology review was performed on 93% of the specimens by a single breast pathologist from a major university hospital. Histology, grade and hormone receptor status was assessed by immunohistochemistry; HER-2 status was defined by immunohistochemistry and/or FISH. Results The 43 tumors from 39 women comprise 32 invasive ductal carcinomas and 11 ductal carcinomas in situ (DCIS). No other histologies were observed. The median age at diagnosis was 32 years (range 22–46). Of the invasive cancers, 84% were positive for ER and/or PR; 81% were high grade. Sixty three percent of invasive and 73% of in situ carcinomas were positive for Her2/neu (IHC 3+ or FISH amplified). Of the invasive tumors, 53% were positive for both ER, and HER2+; other ER/PR/HER2 combinations were observed. The DCIS were positive for ER and HER2 in 27% of the cases. Conclusions This report of the phenotype of breast cancers from women with Li Fraumeni syndrome nearly doubles the literature on this topic. Most DCIS and invasive ductal carcinomas in Li Fraumeni syndrome are hormone receptor positive and/or HER-2 positive. These findings suggest that modern treatments may improve outcomes for women with LFS-associated breast cancer.

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Breast cancer phenotype in women with TP53 germ-line mutations: An LFS consortium effort.

Cited by 3 publications

References 0 publications

Prevalence of germline TP53 mutations in HER2+ breast cancer patients

Prevalence of germline TP53 mutations in HER2+ breast cancer patients

Chest Wall Leiomyosarcoma After Breast-Conservative Therapy for Early-Stage Breast Cancer in a Young Woman With Li-Fraumeni Syndrome

Breast cancer phenotype in women with TP53 germline mutations: a Li-Fraumeni syndrome consortium effort

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