Clinicopathological Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer and Its Relationship With Molecular Subtypes

Saba Qaisar, Salahuddin Qaisar, Farah Shah, Aasia Yousuf, Danyal Zahoor, Aliza Abidi

Abstract

Objective

To evaluate the changes in the clinicopathological features after neoadjuvant chemotherapy (NACT) in patients with locally advanced breast cancer (LABC) and its relation to molecular subtype characteristics.

Study design

Retrospective cross-sectional study.

Place & Duration of study

Department of General Surgery, Jinnah Postgraduate Medical Centre (JPMC) Karachi, from November 2024 to April 2025.

Methods

The study included 54 female patients between the ages of 18 and 70 years who had stage IIB to IIIC invasive ductal carcinoma based on histological examination. All patients received NACT treatment before undergoing surgical resection. The classification of tumors was done by immunohistochemical analysis of estrogen receptor (ER) and progesterone receptor (PR) combined with HER2/neu expression and Ki-67 measurement. The Miller-Payne grading and Residual Cancer Burden (RCB) was used for measuring pathological results. Statistical data analysis was done through SPSS version 26. Quantitative variables such as tumor size before and after neoadjuvant chemotherapy were compared using the paired t-test. Chi square test was used to find out the association of molecular subtype with the response to NACT. A p<0.05 was taken as significant.

Results

Majority of the tumors (n=18 - 33.3%) were of a Luminal B subtype. There were 14 (25.9%) HER2-enriched cases. The triple-negative and Luminal A tumors comprised 12 (22.2%) and 10 (18.5%) respectively. Nineteen (35.2%) patients achieved a pathological complete response (pCR) in general with HER2-enriched tumors showing the highest response rate at 50% along-with triple-negative tumors at 41.6%. Molecular subtype noted to have a statistically relevant connection to pCR results (p=0.041). The tumors decreased in size from 6.2 cm during pre-NACT to 2.4 cm after NACT treatments (p<0.001). Nodal down-staging was noted in 22 (40.7%) patients.

Conclusion

All LABC patients showed remarkable clinicopathological outcomes after NACT therapy based on their molecular subtype analysis. HER2-enriched and triple negative breast cancer subtypes achieved better treatment outcomes. Immunochemical tissue analysis improved the treatment outcome.

Key words

Breast cancer, Neoadjuvant chemotherapy, Molecular subtypes, Pathological complete response, HER2-enriched, Triple-negative breast cancer.