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Absent progesterone receptor expression in the lymph node metastases of ER-positive, HER2-negative breast cancer is associated with relapse on tamoxifen
  1. Cameron E Snell1,2,
  2. Madeline Gough1,2,
  3. Kathryn Middleton3,
  4. Michael Hsieh2,
  5. Lauren Furnas2,
  6. Brenton Seidl3,
  7. Kristen Gibbons4,
  8. Christopher Pyke4,5,
  9. Catherine Shannon3,
  10. Natasha Woodward3,
  11. Jane E Armes2,4
  1. 1Breast Cancer Research Group, Mater Research Institute—The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia
  2. 2The Department of Anatomical Pathology, Mater Pathology, Mater Hospital Brisbane, Mater Health Services, South Brisbane, Queensland, Australia
  3. 3The Department of Medical Oncology, Mater Hospital Brisbane, Mater Health Services, South Brisbane, Queensland, Australia
  4. 4Mater Research Institute—The University of Queensland, South Brisbane, Queensland, Australia
  5. 5The Department of Breast and Endocrine Surgery, Mater Hospital Brisbane, Mater Health Services, South Brisbane, Queensland, Australia
  1. Correspondence to Dr Cameron E Snell, The Department of Anatomical Pathology, Mater Pathology, Mater Hospital Brisbane, Level 3 Duncombe Building, Raymond Terrace, South Brisbane, QLD 4101, Australia; cameron.snell{at}


Aims Progesterone receptor (PR) expression is prognostic in early stage breast cancer. There are several reports of discordant expression between primary tumour and axillary lymph node (ALN) metastasis expression of oestrogen receptor (ER) and PR. We sought to determine whether expression of these biomarkers in the synchronous ALN metastases of ER positive (+), HER2 negative (−) breast cancer could provide more accurate prognostic information.

Methods The retrospective cohort included 229 patients from a single institution with ER+, HER2− breast cancer who had synchronous ALN metastatic disease (2005–2014). PR expression was correlated with relapse-free survival, and subset analysis was performed for patients who received adjuvant tamoxifen or an aromatase inhibitor.

Results One patient had an ER+ primary tumour, which was ER− in the ALN metastasis. 27 (11.3%) were PR− in the primary tumour and 56 (23.6%) in the ALN metastasis. The predominant change was from PR+ in the primary tumour to PR− in the lymph node. Absence of PR expression in the ALN was significantly associated with relapse; however, this was not the case in the primary tumour. In a subset analysis of patients taking adjuvant endocrine therapy, poorer prognosis was limited to those with PR− metastases on tamoxifen (HR=5.203, 95% CI 1.649 to 16.416, p=0.005). No significant prognostic effect of PR− metastases in patients taking aromatase inhibitors was seen (HR=1.519, 95% CI 0.675 to 3.418, p=0.312).

Conclusions Evaluation of PR expression in ALN metastasis may enable prediction of patients who are less likely to benefit from adjuvant tamoxifen. This study should be replicated in other cohorts.


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  • Handling editor Cheok Soon Lee.

  • Contributors CES conceived the study. CES, MG, KM, MH, LF, BS and JEA collected the data. MG constructed tissue microarrays and performed immunohistochemistry. CES, KG, CP, CS, NW and JEA analysed and interpreted the data. All authors were involved in writing and approval of the manuscript.

  • Funding CES is supported by fellowships from the RCPA Foundation (The Royal College of Pathologists of Australasia) and Mater Foundation (Betty McGrath fellowship). The project also has received funding from Mater Foundation. The Translational Research Institute is supported by a grant from the Australian government.

  • Competing interests KM reports receiving travel expenses from Roche. CS reports receiving compensation for being on advisory boards for Roche and AstraZeneca. NW reports receiving honoraria, consulting and travel expenses from Roche; consulting and travel expenses from Novartis and research funding from Medivation.

  • Ethics approval The Mater Health Services Human Research Ethics Committee approved the use of archival tumour blocks and patient information for this study (reference number: HREC/15/MHS/123). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.