Systemic treatment and radiotherapy, breast cancer subtypes, and survival after long-term clinical follow-up

Background: It remains unclear whether breast cancer subtypes are associated with clinical outcome in patients without any treatment including systemic and radiation therapy as an independent entity. Understanding the survival profiles among subtypes by treatment status could impact optimal selection of treatments. Methods: Patients were diagnosed with invasive breast cancer from the community hospitals across four geographical regions of the United States. Expression of hormone receptor (HR) and HER2 in tumor specimens from 1169 patients was centrally determined by immunohistochemistry and fluorescence in situ; breast cancer was classified into HR⁺/HER2⁻, HR⁺/HER2⁺, triple-negative, and HER2⁺ subtypes. Overall survival (OS) at a median follow-up of about 15 years among subtypes in untreated patients and those with systemic treatments and radiotherapy was analyzed by Kaplan–Meier method and multivariable analysis adjusting for age, tumor size and grade, number of positive nodes, stage and breast cancer subtypes. Results: Without treatment, breast cancer subtypes were not associated with OS (P = 0.983) and remained insignificant for prognosis by multivariable analysis after adjusting for confounders. This contrasted with a significant survival difference across the subtypes in patients with conventional therapies (P < 0.0001). Compared with HR⁺/HER2⁻ subtype, triple-negative subtype (HR 1.5, 95% CI 1.11–2.04; P = 0.009) and HER2⁺ subtype (HR 2.18, 95% CI 1.48–3.28; P = 0.0001) were significantly associated with worse survival by multivariable analyses. Conclusion: Breast cancer subtypes are not associated with survival in untreated patient population and, in contrast, significantly associated with prognosis in patients with conventional therapy. The data provide evidence of treatment-associated differential outcomes among breast cancer subtypes.