title: Molecular subtype profiling of invasive breast cancers weakly positive for estrogen receptor.
abstract: The estrogen receptor (ER) is a key predictive biomarker in the treatment of breast cancer. There is uncertainty regarding the use of hormonal therapy in the setting of weakly positive ER by immunohistochemistry (IHC). We report intrinsic subtype classification on a cohort of ER weakly positive early-stage breast cancers. Consecutive cases of breast cancer treated by primary surgical resection were retrospectively identified from 4 centers that engage in routine external proficiency testing for breast biomarkers. ER-negative (Allred 0 and 2) and ER weakly positive (Allred 3-5) cases were included. Gene expression profiling was performed using qRT-PCR. Intrinsic subtype prediction was made based upon the PAM50 gene expression signature. 148 cases were included in the series: 60 cases originally diagnosed as ER weakly positive and 88 ER negative. Of the cases originally assessed as ER weakly positive, only 6 (10 %) were confirmed to be of luminal subtype by gene expression profiling; the remaining 90 % of cases were classified as basal-like or HER2-enriched subtypes. This was not significantly different than the fraction of luminal cases identified in the IHC ER-negative cohort (5 (5 %) luminal, 83(95 %) non-luminal). Recurrence-free, and overall, survival rates were similar in both groups (p = 0.4 and 0.5, respectively) despite adjuvant hormonal therapy prescribed in the majority (59 %) of weakly positive ER cases. Weak ER expression by IHC is a poor correlate of luminal subtype in invasive breast cancer. In the setting of highly sensitive and robust IHC methodology, cutoffs for ER status determination and subsequent systemic therapy should be revisited.
authors: Department of Laboratory Medicine and Pathology, University of British Columbia, 899 W 12th Ave, Vancouver, BC, V5Z 1M9, Canada. brandon.s.sheffield@gmail.com.
authors: Brandon S
authors: BS
authors: Sheffield
authors: Department of Pathology and Laboratory Medicine, University of Ottawa and The Ottawa Hospital, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada.
authors: Zuzana
authors: Z
authors: Kos
authors: Genetic Pathology Evaluation Centre, University of British Columbia, 509-2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
authors: Karama
authors: K
authors: Asleh-Aburaya
authors: Department of Laboratory Medicine and Pathology, University of British Columbia, 899 W 12th Ave, Vancouver, BC, V5Z 1M9, Canada.
authors: Xiu Qing
authors: XQ
authors: Wang
authors: Genetic Pathology Evaluation Centre, University of British Columbia, 509-2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
authors: Samuel
authors: S
authors: Leung
authors: Genetic Pathology Evaluation Centre, University of British Columbia, 509-2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
authors: Dongxia
authors: D
authors: Gao
authors: Genetic Pathology Evaluation Centre, University of British Columbia, 509-2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
authors: Jennifer
authors: J
authors: Won
authors: Genetic Pathology Evaluation Centre, University of British Columbia, 509-2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
authors: Christine
authors: C
authors: Chow
authors: Department of Pathology, University of Utah/Huntsman Cancer Center, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
authors: Rakesh
authors: R
authors: Rachamadugu
authors: Department of Pathology, University of Utah/Huntsman Cancer Center, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
authors: Inge
authors: I
authors: Stijleman
authors: Department of Laboratory Medicine and Pathology, Lions Gate Hospital, 231 East 15 Street, North Vancouver, BC, V7L 4P7, Canada.
authors: Robert
authors: R
authors: Wolber
authors: Department of Laboratory Medicine and Pathology, University of British Columbia, 899 W 12th Ave, Vancouver, BC, V5Z 1M9, Canada.|Genetic Pathology Evaluation Centre, University of British Columbia, 509-2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.|Department of Laboratory Medicine and Pathology, Vancouver General Hospital, 899 West 12th Ave, Vancouver, BC, V5Z 1M9, Canada.
authors: C Blake
authors: CB
authors: Gilks
authors: Department of Laboratory Medicine and Pathology, University of British Columbia, 899 W 12th Ave, Vancouver, BC, V5Z 1M9, Canada.|Department of Laboratory Medicine and Pathology, St. Paul's Hospital, 1082 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.
authors: Nickolas
authors: N
authors: Myles
authors: Department of Laboratory Medicine and Pathology, University of British Columbia, 899 W 12th Ave, Vancouver, BC, V5Z 1M9, Canada.|Department of Laboratory Medicine, British Columbia Cancer Agency, 600 West 10th Ave, Vancouver, BC, V5Z 4E6, Canada.
authors: Tom
authors: T
authors: Thomson
authors: Department of Laboratory Medicine and Pathology, University of British Columbia, 899 W 12th Ave, Vancouver, BC, V5Z 1M9, Canada.|Department of Laboratory Medicine, British Columbia Cancer Agency, 600 West 10th Ave, Vancouver, BC, V5Z 4E6, Canada.
authors: Malcolm M
authors: MM
authors: Hayes
authors: Department of Pathology, University of Utah/Huntsman Cancer Center, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
authors: Philip S
authors: PS
authors: Bernard
authors: Department of Laboratory Medicine and Pathology, University of British Columbia, 899 W 12th Ave, Vancouver, BC, V5Z 1M9, Canada.|Genetic Pathology Evaluation Centre, University of British Columbia, 509-2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.|Department of Laboratory Medicine and Pathology, Vancouver General Hospital, 899 West 12th Ave, Vancouver, BC, V5Z 1M9, Canada.
authors: Torsten O
authors: TO
authors: Nielsen
authors: Department of Laboratory Medicine and Pathology, University of British Columbia, 899 W 12th Ave, Vancouver, BC, V5Z 1M9, Canada. schia@bccancer.bc.ca.|Department of Medical Oncology, British Columbia Cancer Agency, 600 West 10th Ave, Vancouver, BC, V5Z 4E6, Canada. schia@bccancer.bc.ca.
authors: Stephen K L
authors: SK
authors: Chia
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics*; D011980:Receptors, Progesterone / Q000235:genetics; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone
keywords: Breast cancer; Estrogen receptor; Intrinsic subtyping; PAM50; Weakly positive ER