Small node negative HER2 Positive tumors are defined as T1(<2>node negative). The above cohort is increasing with more awareness and acceptance of mammography screening. This group in itself is a heterogeneous population such as T1a/b versus T1c, Grade I versus II/III and estrogen receptor (ER) positive versus negative tumours. The role of adjuvant therapy for these women is a long-standing dilemma for clinicians due to the lack of prospective randomized trials and a poor representation of this group in pivotal trials. Even guidelines are inconsistent on chemotherapy regimen and the duration of trastuzumab for this subset.

There is increasing evidence from several retrospective studies for an inferior outcome in these patients with recurrence rates as high as 15%-30% ter 5-10 years.[1] In a British Columbia data set [2] of N0 breast cancers, positive HER2 status was an independent predictor of breast cancer death in 10 years in a multivariable model, with odds ratio (OR) of 2.03 (P?= 0.003) and in a European Institute of Oncology [3] population of pT1abN0 breast cancers, it was an independent predictor of 5 years disease-free survival (DFS) with OR of 2.5 (95% confidence interval [CI]: 0.9-6.5; P = 0.09). The available evidence for the efficacy of trastuzumab for these patients has limitations such as subgroup analysis of large randomized trials, retrospective nature, small numbers, few events in trials, and differing end points or durations of follow up. Five large randomized Phase III multicenter studies have shown that the addition of trastuzumab to chemotherapy results in decreased recurrence and better overall survival (OS). The proportion of TIN0 tumors and their survival outcome (subgroup analyses) compared to the overall group is depicted in [Table 1].

|?Figure. 1Proposed schema for adjuvant therapy of Stage 1 HER2+ breast cancer

In summary, both retrospective and meta-analysis data suggest a benefit to trastuzumab treatment in small and/or node-negative HER2+ tumors. The questions of ?how low and how much? and tumor size thresholds remain open to debate. Available data also suggests that, although durations shorter than 1 year are not clearly noninferior to 1 year of adjuvant trastuzumab, the absolute benefits of longer duration are small and may not exist in small, node negative tumors. Thus, durations shorter than 1 year may be appropriate in resource constrained settings. The potential role of novel HER2 directed therapies in this cohort is not clear. Greater integration of translation research and gene signatures may provide further insight for this subset in the future.

Conflict of Interest

There are no conflicts of interest.

References

|?Figure. 1Proposed schema for adjuvant therapy of Stage 1 HER2+ breast cancer

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