Identifying Biomarkers to Select Patients with Early Breast Cancer Suitable for Extended Adjuvant Endocrine Therapy

Postmenopausal women with early oestrogen receptor-positive breast cancer who have received 5 years of endocrine therapy are at increased risk of developing a recurrence. An important clinical question is how to identify women who are at highest (or lowest) risk of a recurrence. The use of prognostic biomarkers allows individualised breast cancer therapy but correct identification of patients who will benefit most from extended endocrine therapy is essential. Several multigene assays have been developed to determine the likelihood of overall recurrence but so far none exist specifically for the prediction of late recurrence. Recent results from large clinical trials have shown that biomarker assays that include clinical information in their tests might be useful to predict and risk stratify patients for late recurrence. However, further research is needed to specifically offer multigene assays for the identification of late recurrence and thus justify routine use of these tests in the clinical setting.

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Clinical validity of clinical treatment score 5 (CTS5) for estimating risk of late recurrence in unselected, non-trial patients with early oestrogen receptor-positive breast cancer

Breast Cancer Research and Treatment ◽

10.1007/s10549-020-06013-6 ◽

2020 ◽

Author(s):

Juliet Richman ◽

Alistair Ring ◽

Mitch Dowsett ◽

Ivana Sestak

Keyword(s):

Breast Cancer ◽

High Risk ◽

Postmenopausal Women ◽

Endocrine Therapy ◽

Oestrogen Receptor ◽

Premenopausal Women ◽

Clinical Validity ◽

Er Positive ◽

Extended Endocrine Therapy ◽

Positive Breast Cancer

Abstract Purpose Clinical Treatment Score at 5 years (CTS5) is a prognostic tool to estimate distant recurrence (DR) risk after 5 years of endocrine therapy for postmenopausal women with oestrogen receptor-positive (ER-positive) breast cancer. Methods The validity of CTS5 was tested in a retrospective cohort of patients diagnosed with early ER-positive breast cancer. The primary endpoint was DR in years 5–10. The primary analysis cohort consisted of postmenopausal women, with premenopausal women as a secondary analysis cohort. Cox regression models were used to determine the prognostic value of CTS5 and Kaplan–Meier curves were used with associated 10-year DR risks (%). Results 2428 women were included with a median follow-up of 13.4 years. The CTS5 was significantly prognostic in both postmenopausal (N = 1662, HR = 2.18 95% CI (1.78–2.67)) and premenopausal women (N = 766, HR = 1.84 95% CI (1.32–2.56)). The 10-year DR risks were 2.9% (1.9–4.5), 7.2% (5.3–9.9), and 12.9% (10.0–16.7) for low, intermediate and high risk in postmenopausal women and 3.8% (2.2–6.7), 6.9% (4.4–10.8), and 11.1% (7.4–16.5) in premenopausal women, respectively. The number of observed DRs was significantly greater than expected in those predicted to be at high risk by CTS5 but this discordance was lost when those receiving more than 60 months of endocrine therapy were excluded. Conclusions The CTS5 demonstrated clinical validity for predicting late DR within a large cohort of unselected postmenopausal patients but less so in premenopausal patients. Calibration of the CTS5 was good in patients who did not receive extended endocrine therapy. The CTS5 low-risk cohort has risk of DR so low as to not warrant extended endocrine therapy.

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Extended endocrine therapy in early breast cancer: how long and who for?

Future Oncology ◽

10.2217/fon-2019-0254 ◽

2020 ◽

Vol 16 (1) ◽

pp. 4327-4336

Author(s):

John R Benson ◽

Ismail Jatoi

Keyword(s):

Breast Cancer ◽

Endocrine Therapy ◽

Clinical Judgment ◽

Early Stage ◽

Disease Free Survival ◽

Late Recurrence ◽

Disease Recurrence ◽

Estrogen Receptor Positive ◽

Risk Of Disease ◽

Extended Endocrine Therapy

Endocrine therapy for early stage breast cancer is currently in a state of flux with much uncertainty about choice of agents and duration of therapy. The standard treatment span of 5 years usually incorporates an aromatase inhibitor in the majority of postmenopausal patients. Hormonal therapy has a cytostatic action that provides a biological rationale for continuing treatment for more prolonged periods to reduce risk of late recurrence in estrogen receptor-positive disease. Several trials of extended endocrine therapy for periods varying from 7.5 to 10 years have shown mixed results for gains in disease-free survival. The challenge is to assimilate available data and apply clinical judgment to tailor therapies taking account of intrinsic risk of disease recurrence, patient preference, tolerability to date, and co-morbidities.

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