ASO Author Reflections: The Changing Role of Gene Expression Profiling in ER+/HER2- Breast Cancer.

Past

International guidelines increasingly question the benefit of adjuvant chemotherapy in selections of estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer patients.1 At the same time, and in the same selection of patients, gene expression profiles (GEPs), such as the 70-gene signature (70-GS), are used as a means to better guide chemotherapy decisions. Previous studies demonstrated that use of the 70-GS was associated with a significant reduction in chemotherapy administration in patients with ER+/HER2− disease of low or intermediate malignancy grade without overt lymph node metastasis (≤ Nmi).2 In the present study, we assessed recent trends in the administration of adjuvant chemotherapy in patients eligible for GEPs and evaluated the role of the 70-GS on chemotherapy administration in lymph node-negative (N0) and lymph node-positive (N+) breast cancer patients.

Present

At a nationwide level, the overall administration of adjuvant chemotherapy in patients eligible for GEP use decreased from 49 to 23%, while 70-GS use increased from 24 to 51%.4 The decline in chemotherapy administration occurred without a change in national breast cancer guidelines,3 but coincided with recent international guideline recommendations.1 In contrast to previous studies,2 the observed decline in chemotherapy use between 2013 and 2016 occurred in N0 patients irrespective of 70-GS use, and mainly in N0 patients in whom the 70-GS was not used. In contrast, in N+ patients, use of the 70-GS was strongly associated with a decreased likelihood of receiving chemotherapy throughout the study period.4 In the present study, the effect of age on the decision to administer adjuvant chemotherapy was remarkable. In patients < 50 years of age and 50–59 years of age, the 70-GS was strongly associated with a decreased probability of receiving chemotherapy, whereas in older patients (60–69 years), a reversed association was observed.4

Future

The present study reflects a growing restraint of clinicians to administer chemotherapy in selections of ER+/HER2 patients. In clinical low-risk (N0) patients, this leads to less patients receiving chemotherapy irrespective of 70-GS deployment. This is in line with the results of the recently published MINDACT trial, showing no additional value of the 70-GS in clinical low-risk patients.5 Efforts should be made to better delineate the category of ER+/HER2− patients who are to be considered as clinical ‘low risk’ patients and who will not be candidates for chemotherapy use or 70-GS deployment. On the other hand, in categories of patients who are still considered as ‘clinical high risk’, e.g. younger women and node-positive patients, 70-GS use has an important impact in terms of a 70-GS use-associated decrease in the proportion of patients treated with adjuvant chemotherapy. In these latter patient categories, gene expression profiling should be more strongly advocated in order to avoid overtreatment. Long-term follow-up of ongoing trials into gene expression profiling will be crucial to corroborate this de-escalating approach.