TNBC subtype and clinical estrogen receptor status of ... · University of Texas San Antonio MD...
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BACKGROUND Triple negative breast cancer (TNBC) is an aggressive histological subtype with few targeted therapies and worse prognosis compared to other BC types. The heterogeneity of TNBC is underpinned by distinct transcriptional profiles including basal-like immunoactive (BLIA), basal- like immunosuppressed (BLIS), luminal androgen receptor (LAR), and mesenchymal (MES) subtypes [1]. These subtypes are associated with differences in survival and may assist in treatment decisions. Studies showed that African American (AA) and Hispanic BC patients have a higher frequency of TNBC tumors and worse survival rates compared to non-Hispanic Caucasian BC patients [2]. Furthermore, previous studies report a significantly higher frequency of BLIS subtype tumors in Hispanic TNBC patients, higher frequency of BLIA and BLIS subtypes in AA TNBC patients, and higher frequency of LAR subtype in Asian American and European American TNBC patients [3-4]. The 80-gene BluePrint assay genomically defines breast tumors as basal, luminal, or HER2-enriched independently of IHC expression. Here, we report the distribution of TNBC subtypes in BluePrint-defined basal tumors from Caucasian American (CA), African American (AA), and Latin American (LA) patients, and the association of estrogen receptor (ER) positivity by immunohistochemistry (IHC). METHODS FLEX Registry: The FLEX Registry (NCT03053193) is an ongoing, prospective study evaluating primary tumors from stage I-III breast cancer patients who receive MammaPrint (MP) risk of recurrence and BluePrint (BP) molecular subtype testing and consent to clinically annotated full transcriptome data collection. Patient Cohort: 143 BP basal-type tumors from patients with self- reported ethnicity (60 CA, 59 AA, and 24 LA) were evaluated. ER status: Tumors were identified as ER+ if 1% or more tumor cells stained positive for estrogen receptor by immunohistochemistry. Subtype Classification: TNBC subtypes BLIA, BLIS, LAR, and MES were derived using an adjusted version of the Burstein centroid signature [1]. Statistical Analysis: Differences in MP index and BP index were assessed by one-way ANOVA. Differences in TNBC subtype and pathological ER expression between ethnicities were assessed by Fisher’s exact test. RESULTS 1. M. Burstein et al., 2015. Clin Cancer Res 2. N. Howlander et al., 2014. J Natl Cancer Inst. 3. Y.C. Ding et al., 2019. Oncotarget 4. R. Lindner et al., 2013. PLoS One 5. F. Groenendijk et al., 2019. npj Breast Cancer. References ASCO 2020 Abstract #556 Contact: [email protected] Caucasian American (n=60) African American (n=59) Latin American (n=24) p-value Age, years 0.02 Median 59 59 49.5 Mean (±SD) 57.1 (±14.1) 56.9 (±13.5) 50.2 (±10.0) Menopausal Status <0.01 Pre or Peri 12 (20%) 10 (21%) 15 (63%) Post 48 (80%) 38 (79%) 9 (37%) Tumor Stage 0.02 cT1 23 (53%) 19 (53%) 3 (17%) cT2 17 (40%) 14 (39%) 12 (66%) cT3 3 (7%) 1 (3%) 3 (17%) cT4 0 2 (5%) 0 Nodal Stage 0.28 N0 32 (76%) 30 (81%) 11 (65%) N1 8 (19%) 5 (14%) 5 (29%) N2 2 (5%) 0 1 (6%) N3 0 2 (5%) 0 Grade 0.35 G1 2 (4%) 2 (4%) 0 G2 8 (15%) 2 (4%) 2 (10%) G3 45 (81%) 49 (92%) 19 (90%) Tumor Type 0.64 IDC 53 (96%) 48 (92%) 21 (91%) Mixed IDC/ILC 0 1 (2%) 0 Other 2 (4%) 3 (6%) 2 (9%) BMI Category 0.02 Normal 11 (19%) 6 (11%) 5 (23%) Overweight 21 (36%) 10 (19%) 10 (45%) Obese 26 (45%) 37 (70%) 7 (32%) ER status CA (n=60) AA (n=58)* LA (n=24) BLIS ER+ 11 (28%) 15 (35%) 4 (27%) ER- 29 (72%) 28 (65%) 11 (73%) BLIA ER+ 7 (50%) 5 (38%) 1 (17%) ER- 7 (50%) 8 (62%) 5 (83%) LAR ER+ 1 (33%) 0 1 (50%) ER- 2 (67%) 1 1 (50%) MES ER+ 1 (33%) 1 0 ER- 2 (67%) 0 1 Figure 1: Distribution of TNBC subtypes across ethnicities. All tumors were classified as MP High Risk and BP basal-type. MP and BP basal indices were not influenced by patient ethnicity (p = 0.207 and p=0.182 respectively; Figure 1A-B). The majority of tumors in all ethnic groups were BLIS subtype, followed by BLIA subtype, with low frequency of LAR and MES subtypes (Figure 1C). The frequency of each subtype did not vary significantly by ethnicity (p = 0.671). Figure 3: ER and PR expression across ethnicity and TNBC subtype. ER expression ranged from 2-90% in CA patients, 1-92% in AA patients, and 5-60% in LA patients. PR expression ranged from 1-30% in CA patients, 1-50% in AA patients, and 1-5% in LA patients. ER and PR expression was not associated with a specific TNBC subtype or ethnicity. 1. University of Texas San Antonio MD Anderson Cancer Center, San Antonio, TX; 2. Emory University School of Medicine, Atlanta, GA; 3. New York Oncology Hematology - Albany, US Oncology, Albany, NY; 4. SUNY Upstate Medical University, Syracuse, NY; 5. Baptist MD Anderson Cancer Center, Jacksonville, FL; 6. Saint Vincent Medical Group, Worchester, MA; 7. Medical Affairs, Agendia Inc., Irvine, CA; 8. FLEX Investigators' Group Virginia G. Kaklamani 1 , Cathy Graham 2 , Karen L. Tedesco 3 , Abirami Sivapiragasam 4 , Jennifer Crozier 5 , Apurva N. Shah 6 , Andrea Menicucci 7 , Shiyu Wang 7 , Michelle L. Bolner 7 , Erin Yoder 7 , William Audeh 7 , FLEX Investigators' Group 8 TNBC subtype and clinical estrogen receptor status of genomically basal breast tumors in Caucasian, African American, and Latin American patients -0.25 -0.50 -0.75 -1.00 CA AA LA MP Index 1.2 0.8 0.4 0.0 CA AA LA BP Basal Index B CONCLUSIONS • This analysis demonstrates that genomically classified basal- type tumors encompass the 4 TNBC subtype categories, a majority of which were BLIS and BLIA subtypes. • In contrast to previous reports, this analysis finds no association between TNBC subtype and patient ethnicity. This difference may be due to intrinsic variations between traditional IHC and genomic methods of identifying TNBC/basal tumors. • Approximately 1/3 of BluePrint basal-type tumors are ER+ by IHC, suggesting that BluePrint identifies a subset of clinically luminal (ER+) tumors as genomically basal-type, independent of ethnicity. Previous studies have shown these cancers to respond to chemotherapy similar to TNBC [5]. • The frequency of IHC ER+ tumors does not vary significantly across TNBC subtypes. • ER and PR expression levels were not associated with ethnicity or TNBC subtype. • These findings confirm the heterogeneous nature of basal breast tumors in CA, AA, and LA patients and highlight the clinical need to delineate basal biology in the ER+ cohort to advance treatment for basal-like tumors. Copies of this poster obtained through Quick Response (QR) Code are for personal use only and may not be reproduced without permission from ASCO® and the author of this poster . * 1 patient with multicentric lesion excluded Table 1. Clinical Characteristics (unknowns excluded) A Figure 2: Frequency of basal-type tumors that are ER+ by IHC. IHC defined ER+ tumors were detected in basal-type tumors of each ethnicity (33% CA, 36% AA, 24% LA). ER status was not significantly associated with a specific TNBC subtype (p = 0.8) or ethnicity (p = 0.76). C % of patients in each group FUTURE DIRECTIONS • The current study was restricted by small sample sizes in non-Caucasian groups, which may have resulted in limited power to assess meaningful differences. Future studies will evaluate the distribution of TNBC subtypes and ER status in a larger dataset. • Future studies will explore the relationship between BluePrint subtypes and TNBC molecular subtypes within IHC defined TNBC tumors. • Future aims will investigate treatment response and prognosis in TNBC subgroups.
Transcript of TNBC subtype and clinical estrogen receptor status of ... · University of Texas San Antonio MD...
B A C K G R O U N DTriple negative breast cancer (TNBC) is an aggressive histological subtypewith few targeted therapies and worse prognosis compared to other BCtypes. The heterogeneity of TNBC is underpinned by distincttranscriptional profiles including basal-like immunoactive (BLIA), basal-like immunosuppressed (BLIS), luminal androgen receptor (LAR), andmesenchymal (MES) subtypes [1]. These subtypes are associated withdifferences in survival and may assist in treatment decisions. Studiesshowed that African American (AA) and Hispanic BC patients have ahigher frequency of TNBC tumors and worse survival rates compared tonon-Hispanic Caucasian BC patients [2]. Furthermore, previous studiesreport a significantly higher frequency of BLIS subtype tumors inHispanic TNBC patients, higher frequency of BLIA and BLIS subtypes inAA TNBC patients, and higher frequency of LAR subtype in AsianAmerican and European American TNBC patients [3-4].The 80-gene BluePrint assay genomically defines breast tumors as basal,luminal, or HER2-enriched independently of IHC expression. Here, wereport the distribution of TNBC subtypes in BluePrint-defined basaltumors from Caucasian American (CA), African American (AA), and LatinAmerican (LA) patients, and the association of estrogen receptor (ER)positivity by immunohistochemistry (IHC).
M E T H O D SFLEX Registry: The FLEX Registry (NCT03053193) is an ongoing,prospective study evaluating primary tumors from stage I-III breastcancer patients who receive MammaPrint (MP) risk of recurrenceand BluePrint (BP) molecular subtype testing and consent to clinicallyannotated full transcriptome data collection.
Patient Cohort: 143 BP basal-type tumors from patients with self-reported ethnicity (60 CA, 59 AA, and 24 LA) were evaluated.
ER status: Tumors were identified as ER+ if 1% or more tumor cellsstained positive for estrogen receptor by immunohistochemistry.
Subtype Classification: TNBC subtypes BLIA, BLIS, LAR, and MES werederived using an adjusted version of the Burstein centroid signature[1].
Statistical Analysis: Differences in MP index and BP index wereassessed by one-way ANOVA. Differences in TNBC subtype andpathological ER expression between ethnicities were assessed byFisher’s exact test.
R E S U LT S
1. M. Burstein et al., 2015. Clin Cancer Res2. N. Howlander et al., 2014. J Natl Cancer Inst.3. Y.C. Ding et al., 2019. Oncotarget4. R. Lindner et al., 2013. PLoS One5. F. Groenendijk et al., 2019. npj Breast Cancer.
References
ASCO 2020 Abstract #556Contact: [email protected]
Caucasian American
(n=60)
African American
(n=59)
Latin American
(n=24)p-value
Age, years 0.02Median 59 59 49.5Mean (±SD) 57.1 (±14.1) 56.9 (±13.5) 50.2 (±10.0)
Menopausal Status <0.01Pre or Peri 12 (20%) 10 (21%) 15 (63%)Post 48 (80%) 38 (79%) 9 (37%)
Tumor Stage 0.02cT1 23 (53%) 19 (53%) 3 (17%)cT2 17 (40%) 14 (39%) 12 (66%)cT3 3 (7%) 1 (3%) 3 (17%)cT4 0 2 (5%) 0
Nodal Stage 0.28N0 32 (76%) 30 (81%) 11 (65%)N1 8 (19%) 5 (14%) 5 (29%)N2 2 (5%) 0 1 (6%)N3 0 2 (5%) 0
Grade 0.35G1 2 (4%) 2 (4%) 0G2 8 (15%) 2 (4%) 2 (10%)G3 45 (81%) 49 (92%) 19 (90%)
Tumor Type 0.64IDC 53 (96%) 48 (92%) 21 (91%)Mixed IDC/ILC 0 1 (2%) 0Other 2 (4%) 3 (6%) 2 (9%)
BMI Category 0.02Normal 11 (19%) 6 (11%) 5 (23%)Overweight 21 (36%) 10 (19%) 10 (45%)Obese 26 (45%) 37 (70%) 7 (32%)
ER status CA(n=60)
AA (n=58)*
LA(n=24)
BLISER+ 11 (28%) 15 (35%) 4 (27%)ER- 29 (72%) 28 (65%) 11 (73%)
BLIAER+ 7 (50%) 5 (38%) 1 (17%)ER- 7 (50%) 8 (62%) 5 (83%)
LARER+ 1 (33%) 0 1 (50%)ER- 2 (67%) 1 1 (50%)
MESER+ 1 (33%) 1 0ER- 2 (67%) 0 1
Figure 1: Distribution of TNBC subtypes across ethnicities. All tumors were classified as MP High Riskand BP basal-type. MP and BP basal indices were not influenced by patient ethnicity (p = 0.207 andp=0.182 respectively; Figure 1A-B). The majority of tumors in all ethnic groups were BLIS subtype,followed by BLIA subtype, with low frequency of LAR and MES subtypes (Figure 1C). The frequency ofeach subtype did not vary significantly by ethnicity (p = 0.671).
Figure 3: ER and PR expression across ethnicity and TNBC subtype. ERexpression ranged from 2-90% in CA patients, 1-92% in AA patients, and 5-60%in LA patients. PR expression ranged from 1-30% in CA patients, 1-50% in AApatients, and 1-5% in LA patients. ER and PR expression was not associatedwith a specific TNBC subtype or ethnicity.
1. University of Texas San Antonio MD Anderson Cancer Center, San Antonio, TX; 2. Emory University School of Medicine, Atlanta, GA; 3. New York Oncology Hematology - Albany, US Oncology, Albany, NY; 4. SUNY Upstate Medical University, Syracuse, NY; 5. Baptist MD Anderson Cancer Center, Jacksonville, FL; 6. Saint Vincent Medical Group, Worchester, MA; 7. Medical Affairs, Agendia Inc., Irvine, CA; 8. FLEX Investigators' Group
Virginia G. Kaklamani1, Cathy Graham2, Karen L. Tedesco3, Abirami Sivapiragasam4, Jennifer Crozier5, Apurva N. Shah6, Andrea Menicucci7, Shiyu Wang7, Michelle L. Bolner7, Erin Yoder7, William Audeh7, FLEX Investigators' Group8
TNBC subtype and clinical estrogen receptor status of genomically basal breast tumors in Caucasian, African American, and Latin American patients
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C O N C L U S I O N S• This analysis demonstrates that genomically classified basal-
type tumors encompass the 4 TNBC subtype categories, amajority of which were BLIS and BLIA subtypes.
• In contrast to previous reports, this analysis finds noassociation between TNBC subtype and patient ethnicity. Thisdifference may be due to intrinsic variations betweentraditional IHC and genomic methods of identifying TNBC/basaltumors.
• Approximately 1/3 of BluePrint basal-type tumors are ER+ byIHC, suggesting that BluePrint identifies a subset of clinicallyluminal (ER+) tumors as genomically basal-type, independentof ethnicity. Previous studies have shown these cancers torespond to chemotherapy similar to TNBC [5].
• The frequency of IHC ER+ tumors does not vary significantlyacross TNBC subtypes.
• ER and PR expression levels were not associated with ethnicityor TNBC subtype.
• These findings confirm the heterogeneous nature of basalbreast tumors in CA, AA, and LA patients and highlight theclinical need to delineate basal biology in the ER+ cohort toadvance treatment for basal-like tumors.
Copies of this poster obtained through Quick Response (QR)Code are for personal use only and may not be reproducedwithout permission from ASCO® and the author of this poster .
* 1 patient with multicentric lesion excluded
Table 1. Clinical Characteristics (unknowns excluded) A
Figure 2: Frequency of basal-type tumors that are ER+ by IHC. IHC definedER+ tumors were detected in basal-type tumors of each ethnicity (33% CA,36% AA, 24% LA). ER status was not significantly associated with a specificTNBC subtype (p = 0.8) or ethnicity (p = 0.76).
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f pat
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each
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F U T U R E D I R E C T I O N S• The current study was restricted by small sample sizes in
non-Caucasian groups, which may have resulted in limitedpower to assess meaningful differences. Future studies willevaluate the distribution of TNBC subtypes and ER status in alarger dataset.
• Future studies will explore the relationship betweenBluePrint subtypes and TNBC molecular subtypes within IHCdefined TNBC tumors.
• Future aims will investigate treatment response andprognosis in TNBC subgroups.
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