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CC BY-NC-ND 4.0 · South Asian J Cancer 2024; 13(02): 090-098
DOI: 10.1055/s-0043-1775807
Original Article
Breast Cancer

Study of Biomarker Discordance between Primary and Recurrent Sites and its Clinical Implications in Metastatic Breast Cancer : A Single Institutional Study from India

S. Shanthala
1   Department of Pathology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
,
Usha Amirtham
1   Department of Pathology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
,
Champaka Gopal
1   Department of Pathology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
,
Suma M. N.
1   Department of Pathology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
,
Linu Jacob
2   Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
,
Govinda Babu
2   Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
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Abstract

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S. Shanthala

Immunophenotypic discordance of receptors between primary and metastatic sites significantly impacts treatment outcomes. Current international guidelines recommend rebiopsy of accessible metastatic lesions to reassess tissue biomarkers. While existing literature on biomarker changes is conflicting and heterogeneous, similar studies on the Indian cohort of breast cancer patients are lacking. In this context, we aimed to evaluate the frequencies of biomarker changes between biopsies from primary and recurrent sites, and their association with various clinicopathological characteristics, including the type of metastasis and treatment in metastatic breast cancer (MBC) patients. This is an ambispective study performed at a single center. Immunohistochemical (IHC) expression of paired primary and recurrence samples of MBC patients was reviewed for the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki-67. Concordance, loss, and gain of receptors were assessed based on the Allred scores for ER, PR, and HER2. Ki-67 was assessed based on a 14% cutoff. Further, receptor changes were studied in relation to age, menopausal status, morphology, grade, stage, metastatic sites, interval between biopsies, and treatment. At progression, biopsies were obtained from 41.18% of locoregional recurrence and 58.82% of metastatic sites. Despite high discordance of 47% for ER and 68.6% for PR, true receptor conversion was observed in 9.8%, 21.56%, and 5.88% for ER, PR, and HER2, respectively. There was a significant correlation between age and ER discordance (p = 0.029). Loss in PR significantly correlated with a gain in Ki-67. Of all the metastatic sites, the lung was significantly associated with PR and Ki-67 concordance (p = 0.008 and p = 0.0425, respectively). Discordance of receptors was neither related to the sites of biopsy (local recurrence or metastatic site) nor to the time interval between biopsies, prior chemotherapy, or hormone therapy. In conclusion, metastatic progression of the disease is accompanied by age-dependent discordance of ER. Unparalleled changes in PR in relation to ER suggest that ER-independent pathways may influence PR expression in MBC. Furthermore, the concurrence of PR loss with Ki-67 gain indicates an aggressive phenotype with disease progression. Hence, follow-up testing of samples for receptor expression is beneficial in determining prognosis and guiding therapeutic decisions.

Keywords

ER - PR - receptor - discordance - metastatic - breast - cancer

Previous Presentation

This study was presented at the 3rd DALOS (Dr. Advani's Legendary Oncology Series) Conference, Mumbai, July 16, 2023.




Publication History

Article published online:
08 December 2023

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  • References

  • 1 Sung H, Ferlay J, Siegel RL. et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71 (03) 209-249
    CrossrefPubMedSearch in Google Scholar
  • 2 Dhillon PK, Mathur P, Nandakumar A. et al; India State-Level Disease Burden Initiative Cancer Collaborators. The burden of cancers and their variations across the states of India: the Global Burden of Disease Study 1990-2016. Lancet Oncol 2018; 19 (10) 1289-1306
    CrossrefPubMedSearch in Google Scholar
  • 3 Mehrotra R, Yadav K. Breast cancer in India: present scenario and the challenges ahead. World J Clin Oncol 2022; 13 (03) 209-218
    CrossrefPubMedSearch in Google Scholar
  • 4 Woo JW, Chung YR, Ahn S. et al. Changes in biomarker status in metastatic breast cancer and their prognostic value. J Breast Cancer 2019; 22 (03) 439-452
    CrossrefPubMedSearch in Google Scholar
  • 5 Brewster AM, Hortobagyi GN, Broglio KR. et al. Residual risk of breast cancer recurrence 5 years after adjuvant therapy. J Natl Cancer Inst 2008; 100 (16) 1179-1183
    CrossrefPubMedSearch in Google Scholar
  • 6 Sun YS, Zhao Z, Yang ZN. et al. Risk factors and preventions of breast cancer. Int J Biol Sci 2017; 13 (11) 1387-1397
    CrossrefPubMedSearch in Google Scholar
  • 7 Wang R, Zhu Y, Liu X, Liao X, He J, Niu L. The clinicopathological features and survival outcomes of patients with different metastatic sites in stage IV breast cancer. BMC Cancer 2019; 19 (01) 1091
    CrossrefPubMedSearch in Google Scholar
  • 8 Dieci MV, Barbieri E, Piacentini F. et al. Discordance in receptor status between primary and recurrent breast cancer has a prognostic impact: a single-institution analysis. Ann Oncol 2013; 24 (01) 101-108
    CrossrefPubMedSearch in Google Scholar
  • 9 Karlsson E, Lindström LS, Wilking U, Skoog L, Johansson U, Bergh J. Discordance in hormone receptor status in breast cancer during tumor progression. J Clin Oncol 2010; 28 (15) 1009-1009
    CrossrefSearch in Google Scholar
  • 10 Yang YF, Liao YY, Yang M, Peng NF, Xie SR, Xie YF. Discordances in ER, PR and HER2 receptors between primary and recurrent/metastatic lesions and their impact on survival in breast cancer patients. Med Oncol 2014; 31 (10) 214
    CrossrefPubMedSearch in Google Scholar
  • 11 Rugo HS, Rumble RB, Macrae E. et al. Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology Guideline. J Clin Oncol 2016; 34 (25) 3069-3103
    CrossrefPubMedSearch in Google Scholar
  • 12 Cardoso F, Senkus E, Costa A. et al. 4th ESO-ESMO International Consensus Guidelines for advanced breast cancer (ABC 4). Ann Oncol 2018; 29 (08) 1634-1657
    CrossrefPubMedSearch in Google Scholar
  • 13 Duffy MJ, Harbeck N, Nap M. et al. Clinical use of biomarkers in breast cancer: updated guidelines from the European Group on Tumor Markers (EGTM). Eur J Cancer 2017; 75: 284-298
    CrossrefPubMedSearch in Google Scholar
  • 14 Shiino S, Ball G, Syed BM. et al. Prognostic significance of receptor expression discordance between primary and recurrent breast cancers: a meta-analysis. Breast Cancer Res Treat 2022; 191 (01) 1-14
    CrossrefPubMedSearch in Google Scholar
  • 15 Schrijver WAME, Suijkerbuijk KPM, van Gils CH, van der Wall E, Moelans CB, van Diest PJ. Receptor conversion in distant breast cancer metastases: a systematic review and meta-analysis. J Natl Cancer Inst 2018; 110 (06) 568-580
    CrossrefPubMedSearch in Google Scholar
  • 16 Yeung C, Hilton J, Clemons M. et al. Estrogen, progesterone, and HER2/neu receptor discordance between primary and metastatic breast tumours-a review. Cancer Metastasis Rev 2016; 35 (03) 427-437
    CrossrefPubMedSearch in Google Scholar
  • 17 Gogia A, Deo SVS, Sharma D. et al. Discordance in biomarker expression in breast cancer after metastasis: single center experience in India. J Glob Oncol 2019; 5: 1-8
    CrossrefPubMedSearch in Google Scholar
  • 18 Lin L, Sirohi D, Coleman JF, Gulbahce HE. 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 (04) 479-485
    CrossrefPubMedSearch in Google Scholar
  • 19 Wolff AC, Hammond MEH, Hicks DG. et al; American Society of Clinical Oncology, College of American Pathologists. 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 (31) 3997-4013
    CrossrefPubMedSearch in Google Scholar
  • 20 Perou CM, Sørlie T, Eisen MB. et al. Molecular portraits of human breast tumours. Nature 2000; 406 (6797) 747-752
    CrossrefPubMedSearch in Google Scholar
  • 21 Brennan MJ, Donegan WL, Appleby DE. The variability of estrogen receptors in metastatic breast cancer. Am J Surg 1979; 137 (02) 260-262
    CrossrefPubMedSearch in Google Scholar
  • 22 Aurilio G, Disalvatore D, Pruneri G. et al. 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 (02) 277-289
    CrossrefPubMedSearch in Google Scholar
  • 23 Kao JY, Tsai JH, Wu TY, Wang CK, Kuo YL. Receptor discordance and phenotype change in metastatic breast cancer. Asian J Surg 2021; 44 (01) 192-198
    CrossrefPubMedSearch in Google Scholar
  • 24 Peng L, Zhang Z, Zhao D, Zhao J, Mao F, Sun Q. Discordance of immunohistochemical markers between primary and recurrent or metastatic breast cancer: a retrospective analysis of 107 cases. Medicine (Baltimore) 2020; 99 (25) e20738
    CrossrefPubMedSearch in Google Scholar
  • 25 Shah SP, Morin RD, Khattra J. et al. Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution. Nature 2009; 461 (7265) 809-813
    CrossrefPubMedSearch in Google Scholar
  • 26 Thompson AM, Jordan LB, Quinlan P. et al; Breast Recurrence in Tissues Study Group. Prospective comparison of switches in biomarker status between primary and recurrent breast cancer: the Breast Recurrence In Tissues Study (BRITS). Breast Cancer Res 2010; 12 (06) R92
    CrossrefPubMedSearch in Google Scholar
  • 27 Amir E, Miller N, Geddie W. et al. Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer. J Clin Oncol 2012; 30 (06) 587-592
    CrossrefPubMedSearch in Google Scholar
  • 28 Nguyen TH, Nguyen VH, Nguyen TL, Qiuyin C, Phung TH. Evaluations of biomarker status changes between primary and recurrent tumor tissue samples in breast cancer patients. BioMed Res Int 2019; 2019: 7391237
    CrossrefPubMedSearch in Google Scholar
  • 29 Amir E, Clemons M, Purdie CA. et al. Tissue confirmation of disease recurrence in breast cancer patients: pooled analysis of multi-centre, multi-disciplinary prospective studies. Cancer Treat Rev 2012; 38 (06) 708-714
    CrossrefPubMedSearch in Google Scholar
  • 30 Cui X, Schiff R, Arpino G, Osborne CK, Lee AV. Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy. J Clin Oncol 2005; 23 (30) 7721-7735
    CrossrefPubMedSearch in Google Scholar
  • 31 Sari E, Guler G, Hayran M, Gullu I, Altundag K, Ozisik Y. Comparative study of the immunohistochemical detection of hormone receptor status and HER-2 expression in primary and paired recurrent/metastatic lesions of patients with breast cancer. Med Oncol 2011; 28 (01) 57-63
    CrossrefPubMedSearch in Google Scholar
  • 32 Lowery AJ, Kell MR, Glynn RW, Kerin MJ, Sweeney KJ. Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype. Breast Cancer Res Treat 2012; 133 (03) 831-841
    CrossrefPubMedSearch in Google Scholar
  • 33 Dowsett M, Nielsen TO, A'Hern R. et al; International Ki-67 in Breast Cancer Working Group. Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer Working Group. J Natl Cancer Inst 2011; 103 (22) 1656-1664
    CrossrefPubMedSearch in Google Scholar
  • 34 Vogel C, Malter W, Morgenstern B. et al. The role of previous therapies and sites of metastasis as influencing factors on discordance of ER, PR and HER2 status between primary and metastasized breast cancer. Anticancer Res 2019; 39 (05) 2647-2659
    CrossrefPubMedSearch in Google Scholar
  • 35 Curtit E, Nerich V, Mansi L. et al. Discordances in estrogen receptor status, progesterone receptor status, and HER2 status between primary breast cancer and metastasis. Oncologist 2013; 18 (06) 667-674
    CrossrefPubMedSearch in Google Scholar
  • 36 Kolberg-Liedtke C, Wuerstlein R, Gluz O. et al. Phenotype discordance between primary tumor and metastasis impacts metastasis site and outcome: results of WSG-DETECT-PriMet. Breast Care (Basel) 2021; 16 (05) 475-483
    CrossrefPubMedSearch in Google Scholar
  • 37 Yang L, Zhong X, Pu T, Qiu Y, Ye F, Bu H. Clinical significance and prognostic value of receptor conversion in hormone receptor positive breast cancers after neoadjuvant chemotherapy. World J Surg Oncol 2018; 16 (01) 51
    CrossrefPubMedSearch in Google Scholar
  • 38 Wang N, Wang B, Wang Y, Hu J. Estrogen receptor positive operable breast cancer: does menopausal status impact on HER2 and progesterone receptor status?. Breast 2011; 20 (06) 519-524
    CrossrefPubMedSearch in Google Scholar
  • 39 Nicolini A, Ferrari P, Duffy MJ. Prognostic and predictive biomarkers in breast cancer: past, present and future. Semin Cancer Biol 2018; 52 (Pt 1): 56-73
    CrossrefPubMedSearch in Google Scholar