Invasive breast cancer over four decades reveals persisting poor metastatic outcomes in treatment resistant subgroup – the “ATRESS” phenomenon


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Patriek Jurrius1,Thomas Green1,Hans Garmo1,Matthew Young2,Massimilano Cariati1,Cheryl Gillett1,Anca Mera1,Mark Harries2,Anita Grigoriadis1,Sarah Pinder1,Lars Holmberg1,Arnie Purushotham1
1King's College London,2Guy’s and St Thomas NHS Foundation Trust

Abstract

Background

Since the 1970s, major advances in the diagnosis and treatment of invasive breast cancer have led to a noteworthy reduction in mortality. However, there are still women who are not cured. Therefore, we hypothesised there is a sub-group of treatment-resistant women who succumb to their disease early.

Method

Between January 1st, 1975 and December 31st, 2006 a total of 5,392 women with invasive breast cancer underwent surgery for primary operable breast cancer at Guy’s Hospital, London, United Kingdom. Data on patient demographics, tumour characteristics, treatment regimens, local recurrence, metastasis, and death were prospectively recorded. We considered four time periods (1975-1982, 1983-1990, 1991-1998, 1999-2006). Time to event analysis was performed with Cox proportional hazards model and Kaplan-Meier estimation.

Results

The unadjusted hazard ratio for developing metastasis and overall mortality relative to the 1975-1982 cohort decreased steadily to 0.21 and 0.77, respectively in 1999-2006. However, the metastasis-free interval shortened, with the proportion of women developing metastasis ≤5 years increasing from 73.9% to 83.0%. Furthermore, median survival following the detection of metastasis decreased from 1.49 years in 1975-1982 to 0.94 years in 1999-2006. A filter based on the St. Gallen criteria for high-risk patients and grade 3 tumours identified the presence of approximately 200 patients in each of the time periods who developed metastasis early and died within a much shorter time frame.

Conclusion

Advances in treatment have decreased the risk of metastasis and improved survival in women with invasive breast cancer over the last 40 years. Despite this, a subpopulation with shorter distant disease-free and overall survival who are resistant to available treatment options remains. This subgroup may considerably overlap with women harbouring an underlying genome-based treatment resistance signature.