S. Ong (Singapore, Singapore)

Author Of 1 Presentation

 On-Demand ePoster Display

31P - Association between breast cancer protein truncating variants and febrile neutropenia breast cancer patients treated with taxane or anthracycline chemotherapy in Singapore

Abstract

Background

Febrile neutropenia (FN) incidence across taxane or anthracycline chemotherapy regimens (T/AC) for breast cancer (BC) is high. BC patients (BCp) with FN face higher susceptibility to sepsis and other life-threatening infections, with FN-related mortality rate in BCp at 2-6%. Cancer susceptibility genetic variants can amplify chemotherapy-induced cytotoxicity that result in FN onset. We studied the association between carriership of protein truncating variants (PTV) in 34 BC predisposition genes and FN in T/AC-treated BCp.

Methods

Targeted sequencing (Fludigm Juno 192.48, Illumina Hiseq4000) was performed for 1,596 adult BCp with invasive BC (median age=52 years) treated with adjuvant/neoadjuvant T/AC (2000-2016). Genes known or suspected to predispose BC, including genes on commercial panels for predicting BC risk, were analysed: ABRAXAS1, AKT1, ATM, BABAM2, BARD1, BRCA1, BRCA2, BRIP1, CDHT, CHEK2, EPCAM, FANCC, FANCM, GEN1, MEN1, MLH1, MRE11, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PIK3CA, PMS2, PTEN, RAD50, RAD51C, RAD51D, RECQL, RINT1, STK11, TP53 and XRCC2. 441 BCp who received granulocyte-colony stimulating factor ≤30 days before or during T/AC were excluded. PTVs (frameshift/nonsense mutations or splice sites) were identified and collapsed into a binary variable. Association between PTV carriership (PTVship) and FN was analysed with logistic regression model; single gene PTVship associations were analysed with Fisher’s exact test.

Results

In 1,155 BCp studied, 9% were carriers of at least one PTV. PTVship was found to decrease FN risk (OR=0.27, 95%CI 0.11-0.68, p=0.005, adjusted by site, ethnicity, BMI and first 4 principal components). No single gene was found to be significantly associated with FN.

Conclusions

PTVship appears to be protective against FN. Other FN risk factors need to be considered in future studies.

Legal entity responsible for the study

Agency for Science, Technology and Research (A*STAR).

Funding

National Research Foundation Singapore, National University of Singapore, National University Cancer Institute Singapore (NCIS), Breast Cancer Prevention Programme (BCPP), Asian Breast Cancer Research Fund, and National Medical Research Council (NMRC) Singapore.

Disclosure

S.G.W. Ow: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer. All other authors have declared no conflicts of interest.

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Presenter Of 1 Presentation

 On-Demand ePoster Display

31P - Association between breast cancer protein truncating variants and febrile neutropenia breast cancer patients treated with taxane or anthracycline chemotherapy in Singapore

Abstract

Background

Febrile neutropenia (FN) incidence across taxane or anthracycline chemotherapy regimens (T/AC) for breast cancer (BC) is high. BC patients (BCp) with FN face higher susceptibility to sepsis and other life-threatening infections, with FN-related mortality rate in BCp at 2-6%. Cancer susceptibility genetic variants can amplify chemotherapy-induced cytotoxicity that result in FN onset. We studied the association between carriership of protein truncating variants (PTV) in 34 BC predisposition genes and FN in T/AC-treated BCp.

Methods

Targeted sequencing (Fludigm Juno 192.48, Illumina Hiseq4000) was performed for 1,596 adult BCp with invasive BC (median age=52 years) treated with adjuvant/neoadjuvant T/AC (2000-2016). Genes known or suspected to predispose BC, including genes on commercial panels for predicting BC risk, were analysed: ABRAXAS1, AKT1, ATM, BABAM2, BARD1, BRCA1, BRCA2, BRIP1, CDHT, CHEK2, EPCAM, FANCC, FANCM, GEN1, MEN1, MLH1, MRE11, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PIK3CA, PMS2, PTEN, RAD50, RAD51C, RAD51D, RECQL, RINT1, STK11, TP53 and XRCC2. 441 BCp who received granulocyte-colony stimulating factor ≤30 days before or during T/AC were excluded. PTVs (frameshift/nonsense mutations or splice sites) were identified and collapsed into a binary variable. Association between PTV carriership (PTVship) and FN was analysed with logistic regression model; single gene PTVship associations were analysed with Fisher’s exact test.

Results

In 1,155 BCp studied, 9% were carriers of at least one PTV. PTVship was found to decrease FN risk (OR=0.27, 95%CI 0.11-0.68, p=0.005, adjusted by site, ethnicity, BMI and first 4 principal components). No single gene was found to be significantly associated with FN.

Conclusions

PTVship appears to be protective against FN. Other FN risk factors need to be considered in future studies.

Legal entity responsible for the study

Agency for Science, Technology and Research (A*STAR).

Funding

National Research Foundation Singapore, National University of Singapore, National University Cancer Institute Singapore (NCIS), Breast Cancer Prevention Programme (BCPP), Asian Breast Cancer Research Fund, and National Medical Research Council (NMRC) Singapore.

Disclosure

S.G.W. Ow: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer. All other authors have declared no conflicts of interest.

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