Case-Based Review

Genomic Testing in the Management of Early-Stage Breast Cancer

Journal of Clinical Outcomes Management. 2017 May;24(5)

References

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PAM50 has been designed to be carried out in any qualified pathology laboratory. Moreover, the ROR score provides additional prognostic information about risk of late recurrence, which will be discussed in the next section.

70-Gene Breast Cancer Recurrence Assay (MammaPrint)

MammaPrint is a 70-gene assay that was initially developed using an unsupervised, hierarchical clustering algorithm on whole-genome expression arrays with early-stage breast cancer. Among 295 consecutive patients who had MammaPrint testing, those classified with a good-prognosis tumor signature (n = 115) had an excellent 10-year survival rate (94.5%) compared to those with a poor-prognosis signature (54.5%), and the signature remained prognostic upon multivariate analysis [32]. Subsequently, a pooled analysis comparing outcomes by MammaPrint score in patients with node-negative or 1 to 3 node-positive breast cancers treated as per discretion of their medical team with either adjuvant chemotherapy plus endocrine therapy or endocrine therapy alone reported that only those patients with a high-risk score benefited from chemotherapy [33]. Recently, a prospective phase 3 study (MINDACT [Microarray In Node negative Disease may Avoid ChemoTherapy]) evaluating the utility of MammaPrint for adjuvant chemotherapy decision-making reported results [34]. In this study, 6693 women with early-stage breast cancer were assessed by clinical risk and genomic risk using MammaPrint. Those with low clinical and genomic risk did not receive chemotherapy, while those with high clinical and genomic risk all received chemotherapy. The primary goal of the study was to assess whether forgoing chemotherapy would be associated with a low rate of recurrence in those patients with a low-risk prognostic MammaPrint signature but high clinical risk. A total of 1550 patients (23.2%) were in the discordant group, and the majority of these patients had HR-positive disease (98.1%). Without chemotherapy, the rate of survival without distant metastasis at 5 years in this group was 94.7% (95% confidence interval [CI] 92.5% to 96.2%), which met the primary endpoint. Of note, initially, MammaPrint was only available for fresh tissue analysis, but recent advances in RNA processing now allow for this analysis on FFPE tissue [35].

Summary

These genomic and biomarker assays can identify different subsets of HR-positive breast cancers, including those patients who have tumors with an excellent prognosis with endocrine therapies alone. Thus, we now have the tools to help avoid the toxicities of chemotherapy in many women with early-stage breast cancer. A summary of the genomic tests available is shown in Table 1 .

Case Continued

The patient undergoes 21-gene recurrence score testing, which shows a low recurrence score of 10, estimating the 10-year risk of distant recurrence to be approximately 7% with 5 years of tamoxifen. Chemo-therapy is not recommended. The patient completes adjuvant whole breast radiation therapy, and then, based on data supporting AIs over tamoxifen in postmenopausal women, she is started on anastrozole [36]. She initially experiences mild side effects from treatment, including fatigue, arthralgia, and vaginal dryness, but her symptoms are able to be managed. As she approaches 5 years of adjuvant endocrine therapy with anastrozole, she is struggling with rotator cuff injury and is anxious about recurrence, but has no evidence of recurrent cancer. Her bone density scan in the beginning of her fourth year of therapy shows a decrease in bone mineral density, with the lowest T score of –1.5 at the left femoral neck, consistent with osteopenia. She has been treated with calcium and vitamin D supplements.