A Multiparametric Serum Marker Panel as a Complementary Test to Mammography for the Diagnosis of Node-Negative Early-Stage Breast Cancer and DCIS in Young Women

Lacombe, Jérôme; Mangé, Alain; Bougnoux, Anne-Claire; Prassas, Ioannis; Solassol, Jérôme

doi:10.1158/1055-9965.epi-14-0267

Cited by 21 publications

(20 citation statements)

References 61 publications

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“…Recently, a multi-parametric serum marker panel was reported to distinguish breast cancer from healthy control groups. However, the auto-antibodies of this panel, including PAK2, as an individual marker, displayed relative weak discriminatory performance [44]. In our study, almost all tumor cells had some level of PAK2 staining in the majority of tested specimens.…”

Section: Discussioncontrasting

confidence: 62%

IGF1R signaling drives antiestrogen resistance through PAK2/PIX activation in luminal breast cancer

Zhang

Wester

et al. 2018

Oncogene

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Antiestrogen resistance in estrogen receptor positive (ER) breast cancer is associated with increased expression and activity of insulin-like growth factor 1 receptor (IGF1R). Here, a kinome siRNA screen has identified 10 regulators of IGF1R-mediated antiestrogen with clinical significance. These include the tamoxifen resistance suppressors BMPR1B, CDK10, CDK5, EIF2AK1, and MAP2K5, and the tamoxifen resistance inducers CHEK1, PAK2, RPS6KC1, TTK, and TXK. The p21-activated kinase 2, PAK2, is the strongest resistance inducer. Silencing of the tamoxifen resistance inducing genes, particularly PAK2, attenuates IGF1R-mediated resistance to tamoxifen and fulvestrant. High expression of PAK2 in ER metastatic breast cancer patients is correlated with unfavorable outcome after first-line tamoxifen monotherapy. Phospho-proteomics has defined PAK2 and the PAK-interacting exchange factors PIXα/β as downstream targets of IGF1R signaling, which are independent from PI3K/ATK and MAPK/ERK pathways. PAK2 and PIXα/β modulate IGF1R signaling-driven cell scattering. Targeting PIXα/β entirely mimics the effect of PAK2 silencing on antiestrogen re-sensitization. These data indicate PAK2/PIX as an effector pathway in IGF1R-mediated antiestrogen resistance.

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Section: Discussioncontrasting

confidence: 62%

IGF1R signaling drives antiestrogen resistance through PAK2/PIX activation in luminal breast cancer

Zhang

Wester

et al. 2018

Oncogene

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“…Pontin was also identified in screens of biomarker/autoantigen panels for ductal carcinoma in situ (DCIS) as well as node negative early stage breast cancers (Table 1 ) (Lacombe et al, 2013 , 2014 ). This could prove to be important for early diagnosis of DCIS and could be a complement to mammography.…”

Section: Roles Of Pontin/reptin In Cancermentioning

confidence: 99%

The Role of Pontin and Reptin in Cellular Physiology and Cancer Etiology

Mao

Houry

2017

Front. Mol. Biosci.

103

101

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Pontin (RUVBL1, TIP49, TIP49a, Rvb1) and Reptin (RUVBL2, TIP48, TIP49b, Rvb2) are highly conserved ATPases of the AAA+ (ATPases Associated with various cellular Activities) superfamily and are involved in various cellular processes that are important for oncogenesis. First identified as being upregulated in hepatocellular carcinoma and colorectal cancer, their overexpression has since been shown in multiple cancer types such as breast, lung, gastric, esophageal, pancreatic, kidney, bladder as well as lymphatic, and leukemic cancers. However, their exact functions are still quite unknown as they interact with many molecular complexes with vastly different downstream effectors. Within the nucleus, Pontin and Reptin participate in the TIP60 and INO80 complexes important for chromatin remodeling. Although not transcription factors themselves, Pontin and Reptin modulate the transcriptional activities of bona fide proto-oncogenes such as MYC and β-catenin. They associate with proteins involved in DNA damage repair such as PIKK complexes as well as with the core complex of Fanconi anemia pathway. They have also been shown to be important for cell cycle progression, being involved in assembly of telomerase, mitotic spindle, RNA polymerase II, and snoRNPs. When the two ATPases localize to the cytoplasm, they were reported to promote cancer cell invasion and metastasis. Due to their various roles in carcinogenesis, it is not surprising that Pontin and Reptin are proving to be important biomarkers for diagnosis and prognosis of various cancers. They are also current targets for the development of new therapeutic anticancer drugs.

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“…The incidence of breast cancer varies markedly across the world; indeed, data from Northern countries that have a high technical plateau and cancer registries are challenging to compare with those of Southern countries typically do not (8,9). Continuous and comprehensive recording of all cancer cases (cancer registry) is a guarantee of the quality of the data, and allows estimation of the incidence as well as the various epidemiological parameters (3)(4)(5)(6)(7)(8)(9). In France, the national incidence for cancer is estimated using data from the French network of cancer registries (FRANCIM) (10).…”

Section: Discussionmentioning

confidence: 99%

“…Hereditary forms of breast cancer are rare and affect <10% of young female patients with the disease, with only three contributing genes currently recognized: BRCA 1 and BRCA 2, for which mutations have frequently been identified in young female patients with breast cancer (4 be performed as a first-line diagnosis test. The breast tissue of young females is dense, with a satisfactory echogenicity allowing the effective exploration of the mass lesions (6). This can limit the use of mammography in the detection of breast lesions; however, complementary mammography may be used, particularly when screening non-mass lesions.…”

Section: Introductionmentioning

confidence: 99%

“…This can limit the use of mammography in the detection of breast lesions; however, complementary mammography may be used, particularly when screening non-mass lesions. These two medical imaging techniques make it possible to characterize the lesions found, and to identify any signs of malignancy or benignity (6,7). In Africa in general, and in Togo in particular, data regarding patients with cancer are scarce due to the unavailability of effective collection and collation tools, including a national cancer registry (8).…”

Section: Introductionmentioning

confidence: 99%

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Breast cancer cases of female patients under 35ï¿½years of age in Togo: A series of 158ï¿½cases

et al. 2017

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Abstract. Breast cancer in young female patients represents a public health problem in developing countries. The objectives of the study were to study the epidemiological and histological characteristics of breast cancer in female patients under 35 years of age. This was a retrospective analytical study of a series of 158 cases of breast cancer in female patients under 35 years of age, conducted at the University Teaching Hospital of Lomé between 2000 and 2015. A total of 158 cases were collected, representing 36.2% (436) of all breast cancer cases. The average age of the patients was 30.9 years (range, 16-35 years). A family history of breast cancer at the 1st or 2nd degree was identified in 13.9% of cases. Genetic mutation studies were carried out for 7 patients, 5 of which revealed mutations (4 BRCA1 and 1 BRCA2). According to the locus, the cancer was located preferentially in the left breast in 88 cases (55.7%). Malignant mammary lesions were epithelial tumors (n=144 cases, 91.1%), infiltrating (n=125 cases, 79.1%) and non-infiltrating (n=19 cases, 12.0%). The other histological groups consisted of 8 cases of sarcomas (5 cases of angiosarcoma, 2 cases of fibrosarcoma and 1 case of Kaposi's sarcoma), 5 cases of lymphomas and one case of melanoma. Not otherwise specified infiltrating ductal carcinomas were SBR II and III in 43.2 and 35.2% of cases, respectively. The tumors classified as T4 were the most frequent (30.4%). Regarding the lymph node status, lymph node metastasis was noted in 22.8% of cases. Studies of hormone receptors were carried out in 23 patients and were positive for 11 patients: Estrogen receptor (ER)+plus progesterone receptor (PR)+(7 patients), ER+PR-(4 patients). Of the aforementioned 8 cases of sarcoma, 5 were angiosarcoma. The lymphomas were predominantly Burkitt's type for 4 cases. Mammary ultrasonography was performed in 45.6% of the patients and 54.4% underwent the combined ultrasonography and mammography. Ultrasound identified one or more sign of malignancy in 67 patients (42.4%), and combined ultrasonography and mammography classified 51.9% of lesions in BIRADS 4 and 5. The incidence of breast cancer in young Togolese patients is high. It is a disease distinguished by a delay in diagnosis, which contributes to the high number of cases that initially diagnosed at an advanced stage, particularly the high histo-prognosis grades of infiltrating ductal carcinoma. These results indicate a genetic origin; therefore, a thorough investigation into genetic mutations should be carried. In addition, further collaborative studies are required to verify these results.

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A Multiparametric Serum Marker Panel as a Complementary Test to Mammography for the Diagnosis of Node-Negative Early-Stage Breast Cancer and DCIS in Young Women

Cited by 21 publications

References 61 publications

IGF1R signaling drives antiestrogen resistance through PAK2/PIX activation in luminal breast cancer

IGF1R signaling drives antiestrogen resistance through PAK2/PIX activation in luminal breast cancer

The Role of Pontin and Reptin in Cellular Physiology and Cancer Etiology

Breast cancer cases of female patients under 35ï¿½years of age in Togo: A series of 158ï¿½cases

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