- •We report the change of the hormone receptors (HRs) and HER2 in lobular breast cancer.
- •We describe the discordance in HR and HER2 between primary cancer and metastasis.
- •The majority of discordances regarded a reduced expression or loss of HR.
- •We observed a shift from luminal-like to triple-negative and to HER2-low cancers.
- •HR but not HER2-low changes have prognostic implications.
Invasive lobular carcinoma (ILC) has unique clinical-biological features. Phenotypical differences between primary tumours (PTs) and metastases (M) have been described for invasive ductal carcinoma, but data on ILC are limited.
We retrospectively analysed patients with recurrent ILC from our institution from 2013 to 2020. We evaluated the discordance of the oestrogen receptor (ER), progesterone receptor (PgR) and HER2 between PT and M, to understand prognostic and therapeutic implications.
Thirteen percent (n = 91) of all patients had ILC. We observed 15%, 44% and 5% of ER, PgR and HER2 status discordance between PT and M. ER/PgR discordance was related to receptor loss and HER2 mainly due to gain. PT presented a luminal-like phenotype (93%); 6% and 1% were triple-negative (TNBC) and HER2-positive. In M, there was an increase in TNBC (16%) and HER2-positive (5%). Metastasis-free survival and overall survival (OS) were different according to clinical phenotype, with poorer prognosis for HER2+ and TNBC (p < 0.001); OS after metastatic progression did not differ across phenotypes (p = 0.079). In luminal-like ILC (n = 85) at diagnosis, we found that OS after relapse was poorer in patients experiencing a phenotype switch to TNBC but improved in patients with HER2 gain (p = 0.0028). Poorer survival was reported in patients with a PgR and/or ER expression loss of ≥25%. There was HER2-low enrichment in M1 (from 37% to 58%): this change was not associated with OS (p > 0.05).
Our results suggest that phenotype switch after metastatic progression may be associated with patients’ outcomes. Tumour biopsy in recurrent ILC could drive treatment decision-making, with prognostic implications.
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- WHO classification of tumours of the breast. 5th ed. International Agency for Research on Cancer, Lyon2019
- Collective wisdom: lobular carcinoma of the breast.Am Soc Clin Oncol Educ Book Am Soc Clin Oncol Annu Meet. 2016; 35: 18-21https://doi.org/10.1200/EDBK_100002
- Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome.Breast Cancer Res. 2004; 6: R149-R156https://doi.org/10.1186/bcr767
- Frequency, clinicopathologic characteristics, and follow-up of HER2-positive nonpleomorphic invasive lobular carcinoma of the breast.Am J Clin Pathol. 2020; 153: 583-592https://doi.org/10.1093/ajcp/aqz194
- Human epidermal growth factor receptor 2 positive rates in invasive lobular breast carcinoma: the Singapore experience.World J Clin Oncol. 2020; 11: 283-293https://doi.org/10.5306/wjco.v11.i5.283
- Biological and clinical features of triple negative invasive lobular carcinomas of the breast. Clinical outcome and actionable molecular alterations.Breast. 2021; 59: 94-101https://doi.org/10.1016/j.breast.2021.06.011
- Triple-negative breast lobular carcinoma: a luminal androgen receptor carcinoma with specific ESRRA mutations.Mod Pathol. 2021; 34: 1282-1296https://doi.org/10.1038/s41379-021-00742-9
- Distinct clinical and prognostic features of infiltrating lobular carcinoma of the breast: combined results of 15 International Breast Cancer Study Group clinical trials.J Clin Oncol. 2008; 26: 3006-3014https://doi.org/10.1200/JCO.2007.14.9336
- Invasive lobular carcinoma classic type: response to primary chemotherapy and survival outcomes.J Clin Oncol. 2005; 23: 41-48https://doi.org/10.1200/JCO.2005.03.111
- Risk of contralateral breast cancer. Associations with histologic, clinical, and therapeutic factors.Cancer. 1988; 62: 412-424https://doi.org/10.1002/1097-0142(19880715)62:2<412::aid-cncr2820620228>3.0.co;2-3
- Mammographic and ultrasound features of invasive lobular carcinoma of the breast.J Med Imaging Radiat Oncol. 2014; 58: 1-10https://doi.org/10.1111/1754-9485.12080
- The effectiveness of MR imaging in the assessment of invasive lobular carcinoma of the breast.Magn Reson Imaging Clin N Am. 2010; 18 (ix): 259-276https://doi.org/10.1016/j.mric.2010.02.005
- E-Cadherin as a diagnostic biomarker in breast cancer.N Am J Med Sci. 2011; 3: 227-233https://doi.org/10.4297/najms.2011.3227
- Epigenetic and genetic alterations of APC and CDH1 genes in lobular breast cancer: relationships with abnormal E-cadherin and catenin expression and microsatellite instability.Int J Cancer. 2003; 106: 208-215https://doi.org/10.1002/ijc.11197
- Invasive pleomorphic lobular carcinoma of the breast: clinicopathologic characteristics and prognosis compared with invasive ductal carcinoma.J Breast Cancer. 2012; 15: 313-319https://doi.org/10.4048/jbc.2012.15.3.313
- Signet-ring cell variant of invasive lobular carcinoma of the breast. A clinicopathologic study of 11 cases.Arch Pathol Lab Med. 1994; 118 ([Online]. Available from:): 245-248
- Benefit of adjuvant chemotherapy in patients with lobular breast cancer: a systematic review of the literature and metanalysis.Cancer Treat Rev. 2021; 97: 102205https://doi.org/10.1016/j.ctrv.2021.102205
- How to treat lobular cancer in the adjuvant setting?.Curr Opin Oncol. 2020; 32: 561-567https://doi.org/10.1097/CCO.0000000000000674
- Breast cancer metastasis to gynaecological organs: a clinico-pathological and molecular profiling study.J Pathol Clin Res. 2019; 5: 25-39https://doi.org/10.1002/cjp2.118
- Specific sites of metastases in invasive lobular carcinoma: a retrospective cohort study of metastatic breast cancer.Breast Cancer. 2017; 24: 667-672https://doi.org/10.1007/s12282-017-0753-4
- Patient treatment and outcome after breast cancer orbital and periorbital metastases: a comprehensive case series including analysis of lobular versus ductal tumor histology.Breast Cancer Res. 2020; 22: 70https://doi.org/10.1186/s13058-020-01309-3
- Estrogen, progesterone, and HER2/neu receptor discordance between primary and metastatic breast tumours – a review.Cancer Metastasis Rev. 2016; 35: 427-437https://doi.org/10.1007/s10555-016-9631-3
- Profile and outcome of receptor conversion in breast cancer metastases: a nation-wide multicenter epidemiological study.Int J Cancer. 2021; 148: 692-701https://doi.org/10.1002/ijc.33227
- Discordance in biomarker expression in breast cancer after metastasis: single center experience in India.J Glob Oncol. 2019; 5: 1-8https://doi.org/10.1200/JGO.18.00184
- A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases.Eur J Cancer. 2014; 50: 277-289https://doi.org/10.1016/j.ejca.2013.10.004
- Receptor conversion in distant breast cancer metastases.Breast Cancer Res. 2010; 12: R75https://doi.org/10.1186/bcr2645
- Should liver metastases of breast cancer be biopsied to improve treatment choice.Ann Oncol Off J Eur Soc Med Oncol. 2011; 22: 2227-2233https://doi.org/10.1093/annonc/mdq751
- Discordance in receptor status between primary and recurrent breast cancer has a prognostic impact: a single-institution analysis.Ann Oncol Off J Eur Soc Med Oncol. 2013; 24: 101-108https://doi.org/10.1093/annonc/mds248
- Biomarker discordance between primary breast cancer and bone or bone marrow metastases.Jpn J Clin Oncol. 2019; 49: 426-430https://doi.org/10.1093/jjco/hyz018
- Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update.J Clin Oncol. 2020; 38: 1346-1366https://doi.org/10.1200/JCO.19.02309
- 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: 2105-2122https://doi.org/10.1200/JCO.2018.77.8738
- “HER2-low breast cancer: pathological and clinical landscape.J Clin Oncol. 2020; 38: 1951-1962https://doi.org/10.1200/JCO.19.02488
- Distinct mechanisms of resistance to fulvestrant treatment dictate level of ER independence and selective response to CDK inhibitors in metastatic breast cancer.Breast Cancer Res. 2021; 23: 26https://doi.org/10.1186/s13058-021-01402-1
- LBA3 – Atezolizumab with carboplatin as immune induction in metastatic lobular breast cancer: first results of the GELATO-trial.Ann Oncol. 2021; 32: S58-S59https://doi.org/10.1016/annonc/annonc507
- Characterisation of stromal tumor-infiltrating lymphocytes and genomic alterations in metastatic lobular breast cancer.Clin Cancer Res. 2020; 26: 6254-6265https://doi.org/10.1158/1078-0432.CCR-20-2268
- Entinostat for the treatment of breast cancer.Expert Opin Investig Drugs. 2017; 26: 965-971https://doi.org/10.1080/13543784.2017.1353077
- Elevated levels of epidermal growth factor receptor/c-erbB2 heterodimers mediate an autocrine growth regulatory pathway in tamoxifen-resistant MCF-7 cells.Endocrinology. 2003; 144: 1032-1044https://doi.org/10.1210/en.2002-220620
- Evolution of low HER2 expression between early and advanced-stage breast cancer.Eur J Cancer. 2022; 163: 35-43https://doi.org/10.1016/j.ejca.2021.12.022
- The prognostic relevance of HER2-positivity gain in metastatic breast cancer in the ChangeHER trial.Sci Rep. 2021; 11: 13770https://doi.org/10.1038/s41598-021-92774-z
- Receptor conversion in distant breast cancer metastases: a systematic review and meta-analysis.J Natl Cancer Inst. 2018; 110: 568-580https://doi.org/10.1093/jnci/djx273
- Influence of decalcification procedures on immunohistochemistry and molecular pathology in breast cancer.Mod Pathol. 2016; 29: 1460-1470https://doi.org/10.1038/modpathol.2016.116
- Tumor heterogeneity in breast cancer.Front Med. 2017; 4: 227https://doi.org/10.3389/fmed.2017.00227
- Intratumor genetic heterogeneity of breast carcinomas as determined by fine needle aspiration and TaqMan low density array.Cell Oncol. 2007; 29: 361-372https://doi.org/10.1155/2007/860194
- Tumoral heterogeneity of breast cancer.Ann Biol Clin (Paris). 2016; 74: 653-660https://doi.org/10.1684/abc.2016.1192
- Breast cancer intra-tumor heterogeneity.Breast Cancer Res. 2014; 16: 210https://doi.org/10.1186/bcr3658
- Clonal evolution in breast cancer revealed by single nucleus genome sequencing.Nature. 2014; 512: 155-160https://doi.org/10.1038/nature13600
- Tumor heterogeneity: causes and consequences.Biochim Biophys Acta. 2010; 1805: 105-117https://doi.org/10.1016/j.bbcan.2009.11.002
- Genomic and transcriptomic analyses of breast cancer primaries and matched metastases in AURORA, the Breast International Group (BIG) molecular screening initiative.Cancer Discov. 2021; 11: 2796-2811https://doi.org/10.1158/2159-8290.CD-20-1647
- ESR1 mutations in metastatic lobular breast cancer patients.NPJ Breast Cancer. 2019; 5: 9https://doi.org/10.1038/s41523-019-0104-z
- Immunohistochemical analysis of estrogen receptor in breast cancer with ESR1 mutations detected by hybrid capture-based next-generation sequencing.Mod Pathol. 2019; 32: 81-87https://doi.org/10.1038/s41379-018-0116-5
- Characterisation of estrogen receptor-low-positive breast cancer.Breast Cancer Res Treat. 2021; 188: 225-235https://doi.org/10.1007/s10549-021-06148-0
- Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer.J Clin Oncol. 2012; 30: 587-592https://doi.org/10.1200/JCO.2010.33.5232
Published online: March 07, 2023
Accepted: February 27, 2023
Received in revised form: February 24, 2023
Received: January 10, 2023
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