Identifying Occult Maternal Malignancies From 1.93 Million Pregnant Women Undergoing Noninvasive Prenatal Screening Tests

Ji, Xing; Li, Jia; Huang, Yonghua; Sung, Pi-Lin; Yuan, Yuying; Liu, Qiang; Chen, Yan; Ju, Jia; Zhou, Yafeng; Huang, Shu-Jia; Chen, Fang; Han, Yuan; Wen, Yiping; Fan, Cheng; Zhao, Qiang; Wu, Hao; Sui-hua, Feng; Liu, Weiqiang; Li, Zhihua; Chen, Jingsi; Chen, Min; Yao, Hong; Zeng, Li; Ma, Tao; Fan, Shushu; Zhang, Jinman; Yuen, Ka Yiu; Cheng, So Hin; Chik, Irene Wing Shan; Liu, Nien-Tzu; Zhu, Jianyu; Lin, Siyuan; Cao, Jérémy Do; Tong, Steven Y. C.; Shan, Zhiyuan; Li, Wenyan; Hekmat, Mohammad Reza; Garshasbi, Masoud; Suela, Javier; Torres, Yaima de los Angeles Hidalgo; Cigudosa, Juan C.; Ruiz, F. J. Pérez; Rodríguez, Laura; García, Mónica; Bernik, Janez; Traven, Eva; Reš, Uršula; Tul, Nataša; Tseng, Ching-Fong; Zhao, Depeng; Sun, Luming; Pan, Qiong; Shen, Li; Dai, Mengyao; Wang, Yuying; Wang, Jian; Yang, Huanming; Yin, Yongqiang; Duan, Tao; Zhu, Baosheng; Choolani, Mahesh; Jin, Xin; Chen, Yingwei; Mao, Mao

doi:10.1097/01.ogx.0000657372.14204.f0

Cited by 10 publications

(22 citation statements)

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“…Interestingly, in retro-and prospective studies on the detection of occult malignancies in asymptomatic pregnant women following routine NIPT, about 14% of identified cancers were breast cancers (own analysis of data reported in (7,(9)(10)(11)25,26)). However, according to data from our International Network on Cancer in Pregnancy, breast cancer is the most frequently encountered cancer type in pregnancy, accounting for 39% of registered cases (13).…”

Section: Discussionmentioning

confidence: 99%

“…Together, these points underscore the need for appropriate tests for timely cancer detection. Lately, a growing number of papers have reported on the incidental finding of an occult maternal malignancy upon routine non-invasive prenatal testing (NIPT) (7)(8)(9)(10)(11). In these cases, NIPT, originally designed to screen placenta-derived cell-free DNA (cfDNA) in the bloodstream of pregnant women for the presence of fetal aneuploidies, also detected the presence of cancer-specific copy number alterations (CNAs) in tumor-derived circulating DNA (ctDNA).…”

Section: Introductionmentioning

confidence: 99%

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Breast Cancer Detection and Treatment Monitoring Using a Noninvasive Prenatal Testing Platform: Utility in Pregnant and Nonpregnant Populations

et al. 2020

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Background Numerous publications have reported the incidental detection of occult malignancies upon routine noninvasive prenatal testing (NIPT). However, these studies were not designed to evaluate the NIPT performance for cancer detection. Methods We investigated the sensitivity of a genome-wide NIPT pipeline, called GIPSeq, for detecting cancer-specific copy number alterations (CNAs) in plasma tumor DNA (ctDNA) of patients with breast cancer. To assess whether a pregnancy itself, with fetal cell-free DNA (cfDNA) in the maternal circulation, might influence the detection of ctDNA, results were compared in pregnant (n = 25) and nonpregnant (n = 25) cancer patients. Furthermore, the ability of GIPSeq to monitor treatment response was assessed. Results Overall GIPSeq sensitivity for detecting cancer-specific CNAs in plasma cfDNA was 26%. Fifteen percent of detected cases were asymptomatic at the time of blood sampling. GIPSeq sensitivity mainly depended on the tumor stage. Also, triple negative breast cancers (TNBC) were more frequently identified compared to hormone-positive or HER2-enriched tumors. This might be due to the presence of high-level gains and losses of cfDNA or high ctDNA loads in plasma of TNBC. Although higher GIPSeq sensitivity was noted in pregnant (36%) than in nonpregnant women (16%), the limited sample size prohibits a definite conclusion. Finally, GIPSeq profiling of cfDNA during therapy allowed monitoring of early treatment response. Conclusions The results underscore the potential of NIPT-based tests, analyzing CNAs in plasma cfDNA in a genome-wide and unbiased fashion for breast cancer detection, cancer subtyping and treatment monitoring in a pregnant and nonpregnant target population.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Breast Cancer Detection and Treatment Monitoring Using a Noninvasive Prenatal Testing Platform: Utility in Pregnant and Nonpregnant Populations

et al. 2020

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“…Since the introduction of NIPT in prenatal diagnostics, incidental findings of an occult maternal malignancy following a “false‐positive” NIPT test have been reported repeatedly. Common cancer types encountered in pregnancy (such as breast cancer, lymphoma, and leukemia) and also other cancers (like ovarian cancer, multiple myeloma, digestive cancers, malignant melanoma, or sarcomas) and benign tumors (uterine leiomyomas) have been accidentally identified upon aberrant NIPT testing (previous work and unpublished results). From these cases, it is now appreciated that the presence of tumor‐derived cfDNA can skew the NIPT profile and confound its interpretation.…”

Section: Risk Of False Positive and False Negative Nipt Scores For Chmentioning

confidence: 96%

Pregnant women with confirmed neoplasms should not have noninvasive prenatal testing

et al. 2019

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What's already known about this topic? Incidental diagnoses of an occult maternal malignancy have been reported upon aberrant routine noninvasive prenatal testing (NIPT).The presence of tumor‐derived cell‐free DNA in the maternal circulation can skew the NIPT profile. What does this study add? Pregnant women with a confirmed neoplastic disease should not have NIPT testing for fetal aneuploidy screening since NIPT results cannot accurately be applied to assess the fetal chromosomal constitution in this condition.

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“…In a 2015 study of 3757 pregnant patients with abnormal cfDNA findings, there were 10 cases of maternal malignancy, 7 of which were positive for more than 1 aneuploidy 31 . Another study of 639 pregnant patients with multiple chromosomal aneuploidies on initial cfDNA identified 41 cases of maternal cancer, with a PPV of 7.6% 32 . Multiple cancer types were noted, the most common being breast, liver, and lymphoma.…”

Section: Rare Autosomal Trisomiesmentioning

confidence: 99%

Diagnostic testing after positive results on cell free DNA screening: CVS or Amnio?

Mardy

Norton

2021

Prenatal Diagnosis

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Objective The positive predictive values of cell free DNA (cfDNA) and rates of confined placental mosaicism (CPM), imprinting and other factors vary by chromosome. Methods We sought to review the literature for each of these features for each chromosome and provide recommendations on chorionic villus sampling (CVS) versus amniocentesis after an abnormal cfDNA result. Results For chromosomes with high rates of CPM (trisomy 13, monosomy X and rare autosomal trisomies [RATs]), an amniocentesis should be considered if the first trimester ultrasound is normal. For monosomy X on cfDNA with an unaffected fetus, maternal karyotyping should be considered after normal fetal diagnostic testing. In cfDNA cases with a trisomy involving a chromosome with imprinted genes (6, 7, 11, 14, 15 and 20), CVS should be considered, followed by amniocentesis if abnormal. If the fetus is unaffected, methylation studies should be considered given the risk of uniparental disomy. A third trimester growth ultrasound should be considered for patients with a positive cfDNA screen for a RAT and an unaffected fetus, especially in the case of trisomy 16. For patients with multiple aneuploidy results on cfDNA, a work‐up for maternal malignancy should be considered. Conclusions Clinicians should consider rates of CPM, imprinting, ultrasound findings and maternal factors when considering whether to recommend amniocentesis or CVS after an abnormal cfDNA result.

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Identifying Occult Maternal Malignancies From 1.93 Million Pregnant Women Undergoing Noninvasive Prenatal Screening Tests

Cited by 10 publications

References 0 publications

Breast Cancer Detection and Treatment Monitoring Using a Noninvasive Prenatal Testing Platform: Utility in Pregnant and Nonpregnant Populations

Breast Cancer Detection and Treatment Monitoring Using a Noninvasive Prenatal Testing Platform: Utility in Pregnant and Nonpregnant Populations

Pregnant women with confirmed neoplasms should not have noninvasive prenatal testing

Diagnostic testing after positive results on cell free DNA screening: CVS or Amnio?

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