The efficacy of neoadjuvant chemotherapy (NAC), as measured by the pathological complete response (pCR), varies between molecular subtypes in breast cancer (BC). Oestrogen receptor (ER)-positive, human epidermal growth factor 2 receptor (HER2)-negative patients tend to have lower pCR rates. The transcription of the progesterone receptor (PR) is dependent on the ER therefore PR negativity may suggest an erroneous oestrogen signalling pathway rendering resistance to endocrine therapy. PR- tumours tend to be more aggressive but more chemosensitive. This study aimed to determine if PR status, no longer routinely tested in ER+ BC in the UK, can identify which ER+/HER2- patients will achieve pCR. This would enable more appropriate selection of patients for NAC.
Patients undergoing NAC at the Royal Victoria Infirmary, Newcastle, between 2013 and 2021 were identified and their clinicopathological features were collated in a retrospective dataset. PR status was ascertained with standard immunohistochemistry. The PR score was correlated with the pCR rate. Overall survival (OS) and disease-free survival (DFS) were calculated against pCR.
244 patients were included in the analysis (78 triple-negative BC (TNBC); 25 ER+/HER2-; 141 HER2+). In the ER+/HER2- group, PR- patients achieved higher rates of pCR compared to PR+ patients (31% and 9%; χ2; p=0.327). The pCR rate in the ER+/HER2-/PR- group was not statistically different to that of TNBC (31% and 29%; Fisher’s exact test; p=1.000). In the ER+/HER2+ group, PR- patients achieved higher rates of pCR than PR+ patients (23% and 4%; χ2; p=0.090). The breast pCR rate in the ER+/HER2+ group was statistically different (52% and 24%; χ2; p = 0.015) when comparing PR- and PR+ patients. Oncological outcomes of patients that achieved pCR were significantly improved (DFS p = 0.005; OS p = 0.032).
PR- patients achieved higher rates of pCR in both ER+/HER2- and ER+/HER2+ subtypes. ER+/HER2-/PR- tumours may behave more like TNBCs than hormone-positive BCs and require more aggressive chemotherapeutic strategies. PR status has value in determining which ER+ patients might benefit from NAC with improved oncological outcomes.
Newcastle University.
Roche.
H.J. Cain: Financial Interests, Personal, Advisory Board, Honorarium for speaking, research grant, support with travel: Roche Medical; Financial Interests, Personal, Invited Speaker, Ad board, research grant: Exact Health; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker, Ad board: Baxter; Financial Interests, Personal, Advisory Board, Honorarium for speaking: Lilly, Merck&Co (MSD), AstraZeneca; Financial Interests, Personal, Advisory Board: Veracyte. All other authors have declared no conflicts of interest.