Abstract 310P
Background
Approximately 20% of patients with early-stage breast cancer (ESBC) have amplification of the HER2 gene and over-expression of the HER2 protein, alterations which are associated with (1) more aggressive behaviour (2) a higher frequency of metastasis (3) a substantial therapeutic benefit from anti HER2 targeted adjuvant and neoadjuvant therapies. We hypothesised that the proportion of all MBC which is HER2+ should have decreased since the introduction of widespread anti HER2 adjuvant treatment for ESBC.
Methods
We conducted a retrospective audit of all patients with a pathological diagnosis of MBC in two time cohorts 2000-2002 (before routine adjuvant HER-2 therapy was introduced) and 2018-2020. HER2+ was defined by FISH amplification and/or 3+ immune-histochemistry.
Results
We identified 231 and 183 patients in the two cohorts 2000-2002 and 2018-2020. The table shows HER2 status. The proportion of all MBC which was HER2+ has reduced from 33.76%-16.69% during that time, a difference which is highly statistically significant (Fischer exact test p<0.0000). The significance remains when adjusting for the HER2 unknowns. Table: 310P
| 2000-2002 (n=231) | 2018-2020 (n=183) | P-value | |
| HER2 negative | 118 (51.08%) | 147 (80.32%) | <0.000 |
| HER2 positive | 78 (33.76%) | 31 (16.69%) | <0.000 |
| Unknown | 35 (15.15%) | 5 (2.59%) | <0.000 |
Conclusions
The proportion of MBC which is HER2+ has decreased substantially since the introduction of anti HER2 therapy for ESBC. These data tend to support the hypothesis that adjuvant anti HER2 therapy of ESBC prevents rather than merely delays MBC. We have previously reported that the percentage of HER2 altered MBC which is diagnosed “de novo” has increased during this time, and that de novo MBC has a better prognosis. Much of the improvement in BC survival may be due to (1) a decreased incidence of HER2+ MBC, (previously the worst prognosis), and (2) a shift within HER2+ MBC to better prognosis de novo disease. Anti HER-2 therapy in ESBC has produced a substantial alteration in the molecular profile and prognosis of metastatic breast cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
St Vincent's University Hospital, Dublin, Ireland.
Funding
Cancer Clinical Research Trust (CCRT) - The Caroline Foundation.
Disclosure
C.M. Quinn, D. Skrobo M. Higgins: Financial Interests, Personal, Invited Speaker, conference attendance support: Roche. G. Gullo: Financial Interests, Personal, Full or part-time Employment, full time employee and shareholder of Regeneron Pharmaceuticals Inc: Regeneron Pharmaceuticals Inc. J.M. Walshe: Financial Interests, Personal, Other, Boards and travel conference attendance: Roche, AstraZeneca, Pfizer. J.P. Crown: Other, Personal, Invited Speaker, conference attendance support: Roche. All other authors have declared no conflicts of interest.