Abstract P3-01-15: Significant discordance between clinical and pathological staging in early stage HER2+ and triple negative breast cancers treated with upfront surgery
Authors: Sidda Adarsh , Biglow Layana , Abdallah Mahmoud , Manu Gurusidda , Gress Todd , Tirona Maria 
Published: March 2022

Abstract
Introduction: Treatment of early-stage human epidermal receptor -2 (HER2) positive and triple negative breast cancer (TNBC) remains a challenge as disease recurrences and subsequent morbidity and mortality continues to be high for these tumors. Current guidelines suggest a neoadjuvant approach with chemotherapy alone (in TNBC’s), or in combination with single or dual HER2 directed therapy (in HER2 + tumors), for all ≥cT2 disease. Standard diagnostic modalities have oftentimes failed to confirm the correct size of these aggressive tumors. With recent data showing further survival improvement utilizing regimens for residual disease after neoadjuvant therapy, misrepresentation of the true size of these tumors may lead to patients being treated with upfront surgery and potentially missing the added benefits of residual treatment if they were later found to have ≥T2 disease. We aimed to determine whether there is significant discordance between the clinical and pathological staging of these tumors. Methods: We conducted a retrospective analysis via electronic medical record review of a large institutional database from 2008 to 2020. We reviewed all patients with a diagnosis of early-stage breast cancer (Stage I - III) with triple negative or HER2 positive tumors. Patients who received neoadjuvant chemotherapy were excluded. Data on demographics, comorbidities, receptor status, clinical staging, pathological staging, and mortality were collected. Results: Electronic charts from 448 patients were reviewed. 153 patients had ≤cT1 disease. 33 (21.6%) of the 153 patients were upstaged from cT1 to ≥pT2 tumors. Combined imaging modality with mammogram + ultrasound (US) yielded a statistically significant accuracy in clinical staging compared to US alone (82.6 vs. 44.4%; p=0.02). Comparisons between other imaging methods were not statistically significant (mammogram + US vs. mammogram only, 74.1 vs. 82.6%, p=0.41 and mammogram only vs. US only, 74.1 vs. 44.4%, p= 0.13). Conclusion: Significant discordance (&gt;20%) exists between clinical and pathological staging of T1 TNBC and HER2 positive breast cancers. The possibility that these tumors could indeed be ≥T2 lesions is thus a significant concern. This discordance has considerable therapeutic implications. Landmark studies such as the CREATE-X and KATHERINE trials have provided better survival data with the use of drugs such as capecitabine and trastuzumab emtansine (T-DM1), respectively, in patients with residual disease who have undergone neoadjuvant chemotherapy followed by surgery. Combined imaging with mammography and US may yield the most accurate staging. Based on the data from our retrospective study, a strong consideration may be given to offer neoadjuvant therapy to all clinical T1b and T1c TNBC’s and HER2 positive breast cancers. Meaningful survival analysis was not done due to small sample size. Further studies are needed to validate our findings.
Citation Format: Adarsh Sidda, Layana Biglow, Mahmoud Abdallah, Gurusidda Manu, Todd Gress, Maria Tirona. Significant discordance between clinical and pathological staging in early stage HER2+ and triple negative breast cancers treated with upfront surgery [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-01-15.