Locally Advanced Breast Cancer: Treatment Patterns and Predictors of Survival in a Saudi Tertiary Center

Abstract

Background Breast cancer (BC) is the most common cancer in the Kingdom of Saudi Arabia (KSA) and the second leading cause of cancer-related mortality. About 40% of BC in KSA is locally advanced BC (LABC), which has been associated with poorer survival compared with early diagnosed BC. Objective To review the presentation and outcomes of LABC, including the characteristics of the disease, different treatment modalities, overall survival (OS), disease-free survival (DFS), and local recurrence in relation to different radiotherapy (RT) techniques. Methods We retrospectively reviewed the medical records of 153 female patients with pathologically proven LABC diagnosed at King Abdulaziz University Hospital, Jeddah, KSA, between 2009 and 2017. We obtained data on patient demographics, stage of cancer at diagnosis, tumor characteristics (subtype and receptor status), type of surgery, systemic treatments received (hormonal, targeted therapy, and chemotherapy), RT variables, and recurrence and death dates. Data were analyzed to assess OS and DFS by using Kaplan-Meier analyses and the log-rank test. Univariate and multivariate Cox proportional hazard regression analyses were used to explore and identify factors associated with survival. Results The median survival time in the study population was 9.16 years. Older age (65+ years) was associated with worse OS and DFS than was younger age (<65 years) (hazard ratio (HR) 3.20, 95% CI 1.48-6.90, P = 0.003 and HR 2.21, 95% CI 1.12-4.36, P = 0.022, respectively). Regarding the type of surgery, having a mastectomy was associated with worse OS and DFS than was having a lumpectomy (HR 2.44, 95% CI 0.97-6.12, P = 0.05 and HR 2.41, 95% CI 1.13-5.14, P = 0.023, respectively). Positive estrogen and progesterone receptor status was associated with better OS and DFS than was a negative estrogen or progesterone receptor status (HR 0.13, 95% CI 0.05-0.30, P < 0.001 and HR 0.21, 95% CI 0.11-0.41, P < 0.001, respectively). Patients who received RT had a lower risk of recurrence than did those who did not receive RT (P = 0.011). Moreover, three-dimensional conformal RT was associated with lower local recurrence than intensity-modulated RT or volumetric-modulated arc therapy (P = 0.003). Conclusion Multiple factors can affect the OS and DFS in LABC. Younger patients, having hormone-positive disease, and undergoing lumpectomy were associated with better outcomes. Adjuvant RT may improve local control and the use of three-dimensional conformal RT was superior for local control. Prospective studies with larger sample sizes are needed to further highlight these findings and to assess the role of chemotherapy and targeted therapy in patients with LABC.

Keywords: breast cancer; disease-free survival; locally advanced; outcome; overall survival; relapse; saudi arabia; survival.

Figure 1. Kaplan-Meier estimator for age groups, log-rank test (P = 0.044).

Figure 2. Kaplan-Meier estimator for estrogen (ER)/progesterone (PR) status, log-rank test (P < 0.0001).

ER and PR status were combined as both negative (NN), both positive (PP), or only one positive (NP).

Figure 3. Kaplan-Meier estimator for surgery, log-rank test (P = 0.02).

Figure 4. Validated nomogram to predict five-year survival of patients with locally advanced breast cancer.

Estrogen receptor (ER) and progesterone receptor (PR) status were combined as both negative (NN), both positive (PP), or only one positive (NP).

Figure 5. Kaplan-Meier estimator for the type of breast cancer, log-rank test (P = 0.026).

Figure 6. Kaplan-Meier estimator for N stage, log-rank test (P = 0.027).

Figure 7. Kaplan-Meier estimator for estrogen receptor (ER)/progesterone receptor (PR) status, log-rank test (P < 0.001).

ER and PR status were combined as both negative (NN), both positive (PP), or only one positive (NP).

Figure 8. Kaplan-Meier estimator for the type of breast surgery, log-rank test (P = 0.01).

Figure 9. Validated nomogram to predict the probability of five-year disease-free survival for patients with locally advanced breast cancer.

Estrogen receptor (ER) and progesterone receptor (PR) status were combined as both negative (NN), both positive (PP), or only one positive (NP).