Neoadjuvant and Adjuvant Therapy Elicit Similar Efficacy in Early-Stage HER2+ Breast Cancer

Neoadjuvant therapy generated similar benefits to adjuvant therapy in patients with early-stage, HER2-positive breast cancer treated in China, suggesting that neoadjuvant therapy should be used in this patient population, according to data from a real-world retrospective study published in The Breast.¹

At a median follow-up of 54.1 months (interquartile range, 40.8-68.9), all patients treated with neoadjuvant therapy (n = 538) had a 5-year overall survival (OS) rate of 86.5% compared with 95.6% for patients treated with adjuvant therapy (n = 2684; P < .0001). Additionally, the overall 5-year disease-free survival (DFS) rate for patients treated with neoadjuvant therapy was 80.7% vs 91.4% for patients treated with adjuvant therapy (P < .0001).

However, when patients were stratified using the propensity score matching (PSM) method, patients with a clinical tumor size of no more than 5 cm saw no significant difference in OS (HR, 0.70; 95% CI, 0.43-1.13; P = .11) or DFS (HR, 1.37, 95% CI, 0.96-1.95; P = .08) when treated with neoadjuvant therapy (n = 346) vs adjuvant therapy (n = 952). Similarly, rates of OS (HR, 1.76; 95% CI, 0.76-4.09; P = .25) and DFS (HR, 1.22; 95% CI, 0.63-2.34; P = .57) were comparable for neoadjuvant therapy (n = 145) and adjuvant therapy (n = 62) in patients with a clinical tumor size of greater than 5 cm. Notably, the 5-year OS rates were 83.2% and 91.2% in patients with a clinical tumor size of greater than 5 cm who received neoadjuvant and adjuvant therapy, respectively.

“Due to the limitations of retrospective studies, the types of chemotherapy administered to patients who received neoadjuvant therapy and those who received adjuvant therapy are different. However, under actual conditions, the chemotherapy regimens selected for these patients were determined by multidisciplinary experts and complied with international department standards,” lead study author Shuyue Zheng, MD, of the Department of Breast Surgery at Fudan University Shanghai Cancer Center in Shanghai, China, and colleagues, wrote.

A prior meta-analysis of individual patient data from relevant randomized trials demonstrated that long-term outcomes of patients with early-stage breast cancer who were treated with neoadjuvant chemotherapy vs adjuvant chemotherapy achieved similar distant recurrence rates and OS.² However, this study did not account for HER2 positivity, and this real-world study aimed to address this specific patient population.

The retrospective study analyzed outcomes of patients with primary invasive HER2-positive breast cancer who were treated with neoadjuvant or adjuvant therapy at Fudan University Shanghai Cancer Center between 2012 and 2016.

Patients were between the ages of 18 and 85 years and had HER2-positive breast cancer diagnosed by core-needle aspiration. Patients with a HER2 expression score of 3+ by immunohistochemical staining were considered positive, and patients with a HER2 expression score of 2+ required verification by fluorescence in situ hybridization (FISH). FISH positivity indicated HER2 amplification.

Exclusion criteria included the presence of other cancers or recurrent breast cancer. Male patients or patients who had metastatic disease before surgery were excluded.

The primary objective of the retrospective study was to compare OS and DFS for patients with HER2-positive breast cancer who received neoadjuvant or adjuvant therapy. Additionally, the study aimed to identify which patients with HER2-positive breast cancer would most likely benefit from neoadjuvant therapy and to evaluate the current regimens for the treatment of patients with HER2-positive breast cancer with neoadjuvant therapy or adjuvant therapy.

Most patients analyzed were between the ages of 36 and 64 years (85.5% and 85.1% in the neoadjuvant and adjuvant groups, respectively). Patients had tumor stages of T1 (7.8% and 53.4%), T2 (57.2% and 44.1%), or T3/4 (34.9% and 2.5%). Nodal statuses included N0 (26.2% and 57.2%), N+ (73.8% and 42.8%), estrogen receptor positive (42% and 51.8%), progesterone receptor­ positive (32.7% and 38.8%), less than 20% Ki-67 (8.9% and 8%), at least 20% Ki-67 (91.1% and 91.3%), and unknown (0% and 0.7%).

Chemotherapy regimens included a taxane (75.7% and 23.8% in the neoadjuvant and adjuvant groups, respectively), an anthracycline (3% and 11.9%), a taxane plus an anthracycline (21.4% and 59.9%), or other (0% and 4.4%). Radiotherapy was administered to 70.4% and 37.3% of patients in the neoadjuvant and adjuvant groups, respectively. Additionally, trastuzumab (Herceptin) was given to 78.8% and 69.7% of patients in the neoadjuvant and adjuvant groups, respectively. Endocrine therapy was received by 35% and 45.2% of patients in the neoadjuvant and adjuvant groups, respectively.

Additional data showed that among all patients, patients treated with a neoadjuvant taxane without anthracycline had a higher OS rate (HR, 0.23; 95% CI, 0.14-0.40; P < .0001) and DFS rate (HR, 0.14; 95% CI, 0.09-0.22; P < .0001) compared with those who received adjuvant treatment. Additionally, those who received neoadjuvant taxane with anthracycline had a higher OS rate (HR, 0.28; 95% CI, 0.12-0.64; P < .0001) and DFS rate (HR, 0.36; 95% CI, 0.19-0.68; P < .0001) vs patients who received adjuvant therapy.

In all patients, achieving a pathological complete response (pCR) after neoadjuvant therapy was associated with a significantly improved 5-year OS rate of 98.5% compared with 78.6% in patients who did not achieve a pCR (P < .0001).

In the 346 patients with a clinical tumor size of no more than 5 cm who received neoadjuvant therapy, pCR data were available for 135 patients, and 39% achieved a pCR. A pCR was significantly related to improved OS (HR, 0.13; 95% CI, 0.02-0.92; P = .04) and DFS (HR, 0.37; 95% CI, 0.16-0.85; P = .02).

After PMS for patients with a clinical tumor size of greater than 5 cm, patients who did not achieve a pCR had a worse prognosis, with a 5-year OS rate of 73.8%. Additionally, patients who achieved pCR during neoadjuvant therapy had better DFS than patients treated with adjuvant therapy (HR, 0.29; 95% CI, 0.09-0.92; P = 0.04).

The study found that neoadjuvant therapy was primarily used in patients with higher clinical stages of disease, and the study authors noted that it should be utilized across all patients with HER2-positive breast cancer.

“For patients treated with neoadjuvant therapy, cytotoxic and targeted drugs are usually administered at the same time at the beginning of treatment to achieve a better tumor-killing effect,” the study authors wrote. “For patients treated with adjuvant therapy, considering the substantial cardiac side effects of combination therapy, targeted therapy is often used after anthracycline therapy. This may be one of the possible factors that contributes to the better prognosis of patients who receive neoadjuvant therapy than patients who receive adjuvant therapy. To further confirm these results, multicenter prospective studies are needed.”

References

1. Zheng S, Li L, Chen M, et al. Benefits of neoadjuvant therapy compared with adjuvant chemotherapy for the survival of patients with HER2-positive breast cancer: a retrospective cohort study at FUSCC. Breast. 2022;63:177-186. doi:10.1016/j.breast.2022.03.015
2. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol. 2018;19(1):27-39. doi:10.1016/S1470-2045(17)30777-5