ABSTRACT
Introduction: Breast cancer (BC) is one of the commonest cancers among women worldwide. Differences regarding tumor biology, presentation, genetics, and molecular subtypes may contribute to the relatively poorer prognosis among younger women. Limited information exists regarding pathologic characteristics and long-term outcomes among this group. Methods: This retrospective cohort study included 695 BC patients diagnosed over a 10-year period and investigated the clinicopathological characteristics and long-term disease outcomes among patients diagnosed at age less than or equal to 40 years compared with older ones. Cox regression analysis was performed, and Kaplan-Meier curves were generated to assess overall survival (OS). Results: Compared with the younger patients (⩽40 years) estrogen receptor (ER) and progesterone receptor (PR) expression was mainly positive in older patients (>40 years) (76.2% vs 61.3% and 64.2% vs 49.6%, respectively). The most common molecular subtype in both age groups was luminal B (44.1% in older and 40.3% in younger). A clinical complete remission after neoadjuvant therapy was observed more frequently in older patients (76.7%; N = 442) in comparison with the younger patients (66.4%; N = 79) (P = .018). Recurrence and disease progression were significantly more likely to occur among younger patients accounting for 12.6% and 29.4% of the cases, compared with 6.3% and 18.2% in older patients (P = .016 and P = .006, respectively). The overall mortality was 132 (19%) of 695, with 88% cancer-related deaths. Estrogen receptor and PR expression (P ⩽ .001 and P = .003, respectively), molecular subtype (P = .002), tumor grade (P = .002), and N stage (P = .038) were the variables that were found to be significantly influenced by age. The OS was not statistically different among 2 age groups, but younger patients with luminal A molecular subtype showed significantly poor outcome (P = .019). Conclusion: Overall survival in women diagnosed with BC at age less than or equal to 40 years is not significantly worse than older patients. However, among patients with luminal A subtype, younger women had relatively poor survival. Further research is needed to understand this age-based disparity in outcomes.
ABSTRACT
Background Neoadjuvant chemotherapy (NAC) is being widely used in treating breast cancer (BC). This study aimed to analyze the correlation between clinicopathological features, immunohistochemistry (IHC)-based molecular subtypes, and the pathological response to NAC and its relationship with disease-free survival (DFS) and overall survival (OS). Materials and methods A retrospective analysis of 211 breast cancer patients who received NAC between 2008 and 2018 was performed. Tumors were classified by IHC into luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple-negative subtypes. The chi-square test was used to assess the association between pathological response and clinicopathological parameters. Cox regression analysis was used to assess factors related to DFS and OS. Results Post NAC, 19.4% of patients achieved a pathologic complete response (pCR). Estrogen receptor (ER), progesterone receptor (PR), HER2 (p<0.001, 0.005, and 0.02), Ki67 (p=0.03), molecular subtypes (p<0.001), T stage (p=0.04), and N stage (p=0.01) were significantly associated with pathological response. The rate of pCR was highest among HER2-enriched and triple-negative tumors (45.2% and 28%, respectively) with OR=0.13 and p<0.001 for the HER2-enriched subtype. Patients with pCR were 61% less likely to develop metastasis (adjusted hazard ratio [aHR]=0.39, p=0.06, 95% CI=0.14-1.06) and were significantly associated with better OS (aHR=0.07, p=0.02, 95% CI=0.01-0.61). Patients who were ≤40 years old (aHR=2.1, p=0.01), with T4 (aHR=3.4, p=0.02), grade 3 (aHR=2.5, p=0.01), and node-positive disease (HR=2.24, p=0.02) were at an increased risk of developing metastasis. High Ki67 was found to be significantly associated with better DFS (p=0.006). Conclusion HER2-enriched and triple-negative BC were associated with a higher rate of pCR. Patients with pCR had significantly better DFS and OS. Younger age, advanced stage, higher grade, and lymph node involvement were risk factors for metastasis.
ABSTRACT
INTRODUCTION: The Oncotype DX assay plays an important role in the identification of the specific subset of hormone receptor (HR)-positive and node-negative breast cancer (BC) patients, who would benefit the most from adjuvant chemotherapy. The current study aimed at assessing the level of agreement among medical oncologists on adjuvant chemotherapy decisions before and after Oncotype DX, as well as the intra-observer agreement of each medical oncologist's decision of prescribing adjuvant chemotherapy based on clinicopathological and immunohistochemical parameters only and followed by Oncotype DX recurrence score (RS) results. METHODS: A retrospective analysis of data related to clinicopathological and immunohistochemical parameters, and Oncotype DX RS result for 145 female, estrogen receptor (ER)-positive, HER2 negative, and both node-negative and positive BC patients was performed. Initially, the data without Oncotype DX RS was sent to 16 oncologists in multiple centers in the Middle East. After one week, the same data with the shuffling of cases were sent to the oncologists with the addition of the Oncotype DX RS result for each patient. The inter and intra-observer agreement (kappa and Fleiss multi-rater kappa) among oncologists' decision of prescribing adjuvant chemotherapy pre and post-Oncotype DX RS results were assessed. Oncotype DX risk scores were used as continuous variables as well as based on old RS grouping, categorized into low (0-17), intermediate (18-30), and high risk (≥ 31) groups. A test with a p-value of < 0 .05 will be considered statistically significant. RESULTS: The mean age ± SD of the cohort was 51.9 ± 9.4 years. Sixty-nine patients (47.6%) were premenopausal whereas 76 patients (52.4%) were postmenopausal. The mean Oncotype DX RS was 17.8 ± 8.6 and 54.5% had low recurrence risk (RR), 37.9% had intermediate RR and only 7.6% had high RR. The majority of our cases were grade two (53.1%) and T stage one (49%), whereas 29.7% had positive one to three lymph nodes. The addition of Oncotype DX results improved the agreement among oncologists' decision from fair to moderate (kappa = 0.52; p <0.001). On average, an oncologist's decision of prescribing adjuvant chemotherapy pre and post-Oncotype DX had an agreement in 70.6% of the cases, with agreement observed mostly for cases where the initial decision of adjuvant chemotherapy was (no) and it was retained with post-Oncotype DX assay (46.1%), compared to 24.5% cases where the initial decision was (yes) and it was retained with post-Oncotype DX assay (kappa = 0.39; p <0.001). The addition of the Oncotype DX RS result avoided chemotherapy in 20.4% of cases and identified 9% of cases as candidates for adjuvant chemotherapy (kappa = 0.38; p <0.001). The disagreement was highest among cases with intermediate RR (33.6%) followed by high and low RR (31.3% and 21.6%) with a statistical significance of <0.001. CONCLUSION: We conclude that the Oncotype DX RS significantly influenced the decision to prescribe adjuvant chemotherapy among HR-positive, HER2 negative, and both node-negative and positive patients, as it increased the level of agreement among oncologists and led to a decrease in the use of adjuvant chemotherapy compared to the pre-Oncotype recommendations.
