Does Adjuvant Therapy Benefit Those with Small HER2-Positive Breast Cancers?

A long-term retrospective study published in Clinical Cancer Research found that adjuvant chemotherapy in combination with trastuzumab yielded better outcomes than chemotherapy alone or no adjuvant therapy among patients with small, node-negative, HER2-positive breast cancer.

Some previous trials have assessed treatments for HER2-positive disease in patients with tumors below 1 cm in size; however, such trials are rare. Because a randomized, controlled trial in the setting of smaller tumors would be difficult, the authors conducted a retrospective review of 587 consecutive patients with pT1N0M0 HER2-positive breast cancer treated between 1998 and 2009.

“Patients with small tumors are expected to benefit less from adjuvant systemic therapy than those with larger tumors or positive lymph nodes,” wrote study authors led by Xuexin He, MD, PhD, of the 2nd Affiliated Hospital of Zhejiang University in Hangzhou, China. “Moreover, the decision to use chemotherapy and trastuzumab is complicated by the potential toxicity of systemic treatment.”

Study researchers compared three groups of patients: those treated with no adjuvant therapy (group A, 249 patients); those treated with adjuvant chemotherapy only (group B, 181 patients); and those treated with adjuvant chemotherapy plus trastuzumab (group C, 157 patients).

The patients were followed for a median of 123.0 months. The 10-year disease-free survival (DFS) rate was 81.0% in group A, 65.4% in group B, and 97.3% in group C (P < 0.001). The trastuzumab group also fared best with regard to distant recurrence-free survival ([DRFS]; P < 0.001), breast cancer-specific survival ([BCCS]; P < 0.001), and overall survival (OS). The 10-year OS rate was 79.0%, 72.8%, and 93.7% in the three groups, respectively (P < 0.001).

 The benefit to trastuzumab remained clear on a multivariate analysis. Compared with group A, patients in group C had a hazard ratio for overall survival of 0.333 (95% CI, 0.182–0.609; P < 0.001). Similar findings were seen with regard to DFS, DRFS, and BCSS.

The researchers found that the optimal tumor cutoff size for predicting survival outcomes was 0.8 cm. After adjustment for other factors, receipt of trastuzumab plus chemotherapy was not associated with better DFS, OS, or DRFS in those patients whose tumors were under 0.8 cm. In those patients with smaller tumors, age of 65 years or older and nuclear grade III disease were risk factors associated with increased all-cause mortality.

“In short, patients treated with both trastuzumab and chemotherapy fared better than those in the other two groups in this cohort,” the authors wrote.

They noted, though, that the percentages of invasive ductal carcinoma and larger tumors were higher in the groups who received chemotherapy only than in those who received no chemotherapy, which could have influenced the results.

“We would suggest chemotherapy combined with trastuzumab for HER2-positive breast cancer ≥8 mm,” they concluded. “Considering the retrospective nature of our study, related meta-analysis may be needed to validate the optimal systemic therapy.”         

In a 2018 review, experts led by Sonia Pernas, MD, PhD, of the Dana-Farber Cancer Institute in Boston, noted that there is likely still benefit to treating many patients with small HER2-positive tumors.

“Retrospective series have demonstrated that even small, lymph node‐negative, HER2‐positive tumors have a significant risk of recurrence that ranges from approximately 10% to 30%,” they wrote.

The APT trial aimed to address this population; it found that adjuvant therapy with paclitaxel and trastuzumab, followed by one year of single-agent trastuzumab, yielded excellent DFS results.

“Another approach to de‐escalating therapy in select patients may be to use less intense chemotherapy regimens with optimized anti‐HER2 therapy or to substitute chemotherapy with effective targeted therapies,” the authors wrote.