The Potential Use of Tumour-Based Prognostic and Predictive Tools in Older Women with Primary Breast Cancer: A Narrative Review

Abstract

A move is under way towards personalised cancer treatment, where tumour biology of an individual patient is examined to give unique predictive and prognostic information. This is extremely important in the setting of older women, who have treatment-specific goals which may differ from their younger counterparts, and may include conservation of quality of life rather than curative intent of treatment. One method employed to assist with this is the use of tumour-based prognostic and predictive tools. This article explores six of the most common tumour-based tools currently available on the market: MammaPrint, Oncotype DX, Mammostrat, Prosigna, EndoPredict, IHC4. The article discusses the creation and validation of these tools, their use and validation in older women, and future directions in the field. With the exception of Oncotype Dx, which has also been licensed for prediction of response from adjuvant chemotherapy, these tools have been licensed for use as prognostic tools only, mainly in the setting of adjuvant therapy following surgery. The evidence base for use in older women is strongest for Mammostrat and PAM50, although overall the evidence is much weaker than that in younger women. Where older women have been included in validation studies, this is often in small numbers, or the exact proportion of older women is unknown. In practice, all six of the tools are recommended to be utilised on surgical excision specimens, as well as in core needle biopsy (CNB) specimens in all of the tools except Mammostrat. This is extremely important in the setting of older women, of whom a large proportion do not undergo surgery. The suggested nature of the sample is formalin-fixed paraffin-embedded in all the tools except MammaPrint, which can also be performed on fresh-frozen samples. Future development of prognostic tools in older women with breast cancer should focus on treatment dilemmas specific to this population. This includes the decision of primary treatment between surgery or endocrine therapy and decisions regarding adjuvant therapy, in particular, chemotherapy.

Validation of the 70-gene signature test (MammaPrint) to identify patients with breast cancer aged ≥ 70 years with ultralow risk of distant recurrence: A population-based cohort study

“…The use of other genetic profiling tools, such as the Breast Cancer Index, PAM50, Prosigna and Endopredict as prognostic or predictive tools in the older patient population has not been validated as of yet, either [18]. The prognostic ability of the Oncotype Dx has been validated in older patients with HR+ breast cancer [19].…”

Biology of primary breast cancer in older women beyond routine biomarkers

“…Current predictive and prognostic tools available on the market for example Oncotype DX [ 11 ], a genomic test and Adjuvant! Online [ 12 ], which uses standard clinico-pathological features, are focussed towards adjuvant rather than primary treatment and recruitment of older women in their conception is lacking [ 13 ]. These existing tools were developed from patients undergoing primary surgery following which they were used to determine prognosis and as such, potential benefit from adjuvant therapies.…”