Preoperative Systemic Therapy May Improve Survival vs Mastectomy in HER2+ Breast Cancer

Preoperative Systemic Therapy May Improve Survival vs Mastectomy in HER2+ Breast Cancer

Preoperative systemic therapy in patients with HER2-positive breast cancer improved survival after breast-conserving therapy vs mastectomy, particularly if patients obtained a pathological complete response (pCR) in the axillary lymph nodes, according to findings from an observational cohort study published in The Lancet Regional Health.

At a median follow-up of 9.9 years, the overall survival (OS) rate among patients who received breast-conserving therapy (n = 221) was 86.0% (95% CI, 81.3%-90.8%) compared with 79.3% (95% CI, 72.8%-84.5%) for those who underwent mastectomy (n = 221; HR, 1.66; 95% CI, 1.08-2.57; P = .02). Moreover, mastectomy was associated with a worse OS vs breast-conserving therapy in patients who experienced an axillary lymph node pCR both before (HR, 2.17; 95% CI, 1.22-3.86; P < .01) and after (HR, 2.12; 95% CI, 1.15-3.89; P = .02) propensity score matching.

“[Individuals] with HER2-positive breast cancer who have already had preoperative systemic therapy are more likely to survive after breast-conserving therapy, especially if they get a pCR in the axillary lymph nodes,” Aiham Qdaisat, MD, instructor, Department of Emergency Medicine, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, in Houston, Texas, and coauthors wrote. “These findings underscore the necessity for further investigation into how responses to preoperative systemic therapy can inform the choice of surgical intervention and the potential impact on OS. Such insights could lead to the development of innovative tools that support personalized surgical strategies in the management of breast cancer.”

To conduct their study, investigators searched MD Anderson’s electronic medical records and tumor registry system and identified patients with early-stage HER2-positive breast cancer diagnosed between January 1998 and October 2009. To be eligible, patients had to be at least 18 years old, have histologically confirmed primary HER2-positive breast cancer, have known estrogen receptor status, and have received chemotherapy with or without anti-HER2 therapy followed by mastectomy or breast-conserving therapy.

Each patient included in the study only underwent a single surgery following preoperative systemic therapy; those who received breast-conserving therapy also were treated with postoperative moderate-dose radiation to the whole breast. All patients also received standard postoperative adjuvant radiation, trastuzumab (Herceptin), and endocrine therapy as clinically indicated. Patients with high-risk factors who received breast-conserving therapy also received axillary lymph node dissection and postoperative adjuvant radiation to the regional lymph node area.

In terms of outcomes, pCR was defined as the absence of any invasive cancer in the breast and lymph nodes after preoperative systemic therapy, with the exception of residual ductal carcinoma in situ. Patients were followed until June 30, 2018, with the longest follow-up time being 20 years.

After propensity score matching, the baseline characteristics were well balanced between the breast-conserving therapy and the mastectomy cohorts. Most patients in both cohorts experienced a breast complete response following preoperative systemic therapy (50.2% vs 52.9%, respectively), had a lymph node complete response after preoperative systemic therapy (77.4% vs 78.3%), were postmenopausal (54.3% vs 55.7%), had nuclear grade III disease (80.5% vs 75.6%), did not receive adjuvant endocrine therapy (53.8% vs 54.3%), and had stage I or II disease (78.3% vs 78.3%).

Findings from the multivariable analysis demonstrated that breast complete response (HR, 0.48; 95% CI, 0.29-0.81; P < .01), lymph node complete response (HR, 0.49; 95% CI, 0.31-0.78; P < .01), and chemotherapy with trastuzumab (HR, 0.50; 95% CI, 0.30-0.84; P = .01) were associated with improved OS compared with patients who did not experience a breast complete response, a lymph node complete response, and those who received chemotherapy without trastuzumab, respectively. Mastectomy was associated with worse OS compared with breast-conserving therapy (HR, 1.62; 95% CI, 1.05-2.51; P = .03). Age at diagnosis and disease stage did not have a significant association with OS.

“Our finding that breast-conserving therapy patients had better survival outcomes than mastectomy patients is contrary to the traditional consensus that breast-conserving therapy and mastectomy yield similar survival outcomes,” study authors wrote in conclusion. “More research is needed to confirm that making surgical decisions based on radiological responses after preoperative systemic therapy is a good way to predict what will happen in this group of patients and to learn more about the molecular processes that give patients who get a complete lymph node response a better chance of OS.”

Reference

He X, Ji J, Qdaisat A, Esteva FJ, Yeung SCJ. Long-term overall survival of patients who undergo breast-conserving therapy or mastectomy for early operable HER2-positive breast cancer after preoperative systemic therapy: an observational cohort study. Lancet Reg Health Am. 2024;32:100712. doi:10.1016/j.lana.2024.100712