Highlights
- •HER2 FISH group 2 comprises 0.6% of breast cancer in our study.
- •Repeat testing on FISH group 2 tumors may change the initial results.
- •pCR is seen with anti-HER2 therapy when repeat testing converts to HER2 positive.
- •All three cases with pCR are ER ≤ 10% and Ki67 ≥40%.
- •Repeat HER2 testing in selected group 2 cases may impact therapeutic decision.
Abstract
Background
Breast cancer with fluorescence in situ hybridization (FISH) group 2 pattern (HER2 <4 and HER2/CEP17 ratio ≥2, a subset of monosomy CEP17) was historically considered HER2-positive,
but mostly HER2-negative according to updated 2018 American Society of Clinical Oncology
(ASCO)/College of American Pathologists (CAP) guidelines unless 3+ by immunohistochemistry
(IHC). Therapeutic relevance of this group remained elusive, therefore we assessed
if repeat IHC and FISH can assist final HER2 classification.
Patient and Methods
We retrospectively reviewed HER2 FISH performed at our institution from 2014 to 2018 and identified 23 of 3554 (0.6%)
breast cancer cases with at least one-time measurement of HER2 FISH categorized as group 2. Repeat HER2 tests were performed for cases with available alternative tumor samples and compared
with initial testing following 2018 ASCO/CAP guidelines.
Results
Only 1 of 23 group 2 cases was HER2-positive, 0/18 in primary and 1/5 in metastatic/recurrent
tumors. Of 13 primary tumors with repeat HER2 results; 10 (77%) remained HER2-negative;
3 (23%) changed from HER2-negative (group 2 and IHC 2+) to HER2-positive (group 1
and IHC 2+). Among 8 of these 13 patients receiving neoadjuvant systemic therapy containing
anti-HER2 agent, 3 (38%) achieved pathologic complete response (pCR). Two of 3 pCR
cases were HER2-positive converters on repeat testing. Three pCR cases were ER-negative
or -low positive and Ki67 ≥40%, while 5 partial responders were ER-positive and Ki67
<40% (P < .05).
Conclusion
Breast cancer with HER2 FISH group 2 result may represent heterogeneous populations
of tumor cells being originated de novo or preferentially selected secondary to therapy.
Repeat HER2 tests on alternative samples may be considered to guide anti-HER2 therapy.
Keywords
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References
- HER2 expression status in diverse cancers: review of results from 37,992 patients.Cancer Metastasis Rev. 2015; 34: 157-164
- Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.Science. 1987; 235: 177-182
- HER2 in breast cancer: a review and update.Adv Anat Pathol. 2014; 21: 100-107
- American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer.J Clin Oncol. 2007; 25: 118-145
- Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update.J Clin Oncol. 2013; 31: 3997-4013
- HER2 gene amplification testing by fluorescent in situ hybridization (FISH): comparison of the ASCO-College of American Pathologists Guidelines with FISH scores used for enrollment in Breast Cancer International Research Group clinical trials.J Clin Oncol. 2016; 34: 3518-3528
- Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline focused update.J Clin Oncol. 2018; 36: 2105-2122
- Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update.J Clin Oncol. 2020; 38: 1346-1366
- Which threshold for ER positivity? a retrospective study based on 9639 patients.Ann Oncol. 2014; 25: 1004-1011
- Intratumoral heterogeneity of HER2 gene amplification in breast cancer: its clinicopathological significance.Mod Pathol. 2012; 25: 938-948
- Genetic heterogeneity in HER2 testing in breast cancer: panel summary and guidelines.Arch Pathol Lab Med. 2009; 133: 611-612
- Genetic heterogeneity of HER2 in breast cancer: impact on HER2 testing and its clinicopathologic significance.Breast Cancer Res Treat. 2012; 134: 1095-1102
- Monosomy of chromosome 17 in breast cancer during interpretation of HER2 gene amplification.Am J Cancer Res. 2015; 5: 2212-2221
- Breast cancers with a HER2/CEP17 ratio of 2.0 or greater and an average HER2 copy number of less than 4.0 per cell: frequency, immunohistochemical correlation, and clinicopathological features.Hum Pathol. 2019; 83: 7-13
- American Society of Clinical Oncology/College of American Pathologists 2018 focused update of breast cancer HER2 FISH Testing guidelines results from a National Reference Laboratory.Am J Clin Pathol. 2019; 152: 479-485
- Impact of the 2018 ASCO/CAP HER2 guideline focused update.Am J Clin Pathol. 2019; 152: 17-26
- The differences of clinicopathologic characteristics among subgroups of reclassified HER2 fluorescence in situ hybridization (FISH) according to the ASCO/CAP 2018 breast cancer HER2 testing guidelines.J Clin Pathol. 2020; 73: 283-290
- Implementation of the 2018 American Society of Clinical Oncology/College of American Pathologists Guidelines on HER2/neu assessment by FISH in breast cancers: predicted impact in a single institutional cohort.Mod Pathol. 2019; 32: 1566-1573
- Non-classical' HER2 FISH results in breast cancer: a multi-institutional study.Mod Pathol. 2017; 30: 227-235
- Integrated analysis of HER2 copy number by cytogenomic microarray in breast cancers with nonclassical in situ hybridization results.Am J Clin Pathol. 2018; 149: 135-147
- A clinicopathological study of 30 breast cancer cases with a HER2/CEP17 ratio of >/=2.0 but an average HER2 copy number of <4.0 signals per cell.Mod Pathol. 2020; 33: 1557-1562
- Monosomy 17 in potentially curable HER2-amplified breast cancer: prognostic and predictive impact.Breast Cancer Res Treat. 2018; 167: 547-554
- Neoadjuvant treatment of breast cancer.Ann Oncol. 2012; 23: x231-x236
- Standardizing of pathology in patients receiving neoadjuvant chemotherapy.Ann Surg Oncol. 2016; 23: 3153-3161
- Reproducibility of residual cancer burden for prognostic assessment of breast cancer after neoadjuvant chemotherapy.Mod Pathol. 2015; 28: 913-920
- Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration.Ann Oncol. 2015; 26: 1280-1291
- Pathologic and molecular responses to neoadjuvant trastuzumab and/or lapatinib from a phase II randomized trial in HER2-positive breast cancer (TRIO-US B07).Nat Commun. 2020; 11: 5824
- Neoadjuvant trastuzumab emtansine and pertuzumab in human epidermal growth factor receptor 2-positive breast cancer: three-year outcomes from the phase III KRISTINE study.J Clin Oncol. 2019; 37: 2206-2216
- Hormone receptor status and pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab.Ann Oncol. 2008; 19: 2020-2025
- Retrospective observational study of HER2 immunohistochemistry in borderline breast cancer patients undergoing neoadjuvant therapy, with an emphasis on Group 2 (HER2/CEP17 ratio >/=2.0, HER2 copy number <4.0 signals/cell) cases.Br J Cancer. 2021; 124: 1836-1842
Article info
Publication history
Published online: February 12, 2023
Accepted:
February 9,
2023
Received in revised form:
February 8,
2023
Received:
December 21,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
The first four authors, M. W., Q. D., J. G., and S. M. S. contributed equally to this work and share co-first authorship.
Identification
Copyright
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