Age-related differences in presentation and outcomes of breast cancer: A prospective, comparative study of Colombian patients younger and older than 40 Years

Clinicopathological features and prognoses of very young patients (≤35 years) with breast cancer: a retrospective population-based study in China.

Breast cancer is the most commonly diagnosed invasive cancer among women both globally and within the United States and the number one cause of cancer-related deaths among women globally ([1, 2][1]). Less than 1% of diagnosed breast cancers occur in men ([2][2]) and, therefore, male breast cancer is

Background Breast cancer is relatively rare in women younger than 35 years of age, accounting for 2–4% of the total number of breast cancer cases diagnosed each year in western countries and the USA 1–3. However, the proportion of young age-onset breast cancer was much higher in the Asian population 3–6. Breast cancer at a young age has been reported to have a more aggressive biological behavior and to be associated with worse prognosis compared with the disease in older patients 5,7–17. Higher incidence of recurrence and risk of death were detected in younger patients, even when more aggressive therapies were administered 10–14. Neoadjuvant chemotherapy (NCT) has been considered the standard treatment for locally advanced breast cancer patients. In human epidermal growth factor receptor 2 (HER2)-positive and triple-negative tumors, achievement of a pathological complete response (pCR) after NCT was associated with better survival outcomes 18. In recent studies, young breast cancer patients were reported to obtain higher pCR rates compared with older counterparts 19,20. However, it remains unclear whether pCR is a predictor for better prognosis in young breast cancer patients. In this study, we aimed to investigate chemotherapy response and its relation with prognosis in young breast cancer patients (<35 years old) who were treated with NCT. Patients and methods Patients From January 2003 to December 2013, patients with operable or locally advanced breast cancer who were treated with NCT at the Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College were reviewed systemically. The inclusion criteria for the study were as follows: (i) 35 years or younger or 60 years or older; (ii) diagnosis of invasive carcinoma confirmed by core needle biopsy before NCT and the lymph node status was evaluated by fine needle aspiration of palpable lymph node if applicable; (iii) immunohistochemical examination for estrogen receptor (ER), progesterone receptor (PgR), and HER2 status using tumor specimens from core needle biopsy; (iv) newly diagnosed breast cancer patients; (v) combination of paclitaxel and carboplatin (PC) in patients with triple-negative breast cancer as NCT; for other patients, a combination of cyclophosphamide and epirubincin (CE) as NCT with postoperative paclitaxel, or epirubincin in combination with paclitaxel (ET) as NCT 21; (vi) adequate hematologic, hepatic, and renal functions. The exclusion criteria for the study were as follows: (a) stage IV disease, bilateral breast cancer, male breast cancer, and patients complicated with other malignancies; (b) patients who did not have complete clinical information or immunohistochemistry; (c) patients who were lost to follow-up immediately after treatment. This study was a retrospective observational research and patients' information was collected in the hospital database. There was no direct intervention in patients' treatment or care. Therefore, a patient's consent was not required. This study was approved by the Ethics Committee of Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College. Treatment Before the initiation of NCT, bilateral breast MRI or ultrasound, chest radiography, abdominal ultrasound, or computed tomography scans were performed to determine clinical stage. All patients were staged according to the 7th TNM (tumor–node–metastasis) staging system maintained by the American Joint Committee on Cancer (AJCC). All patients received NCT with CE, or ET, or PC regimens. CE-T regimen: cyclophosphamide 600 mg/m2 intravenously, day 1, and epirubicin 80 mg/m2 intravenously, day 1, q14d×4 cycles in NCT, followed by postoperative sequential paclitaxel 175 mg/m2 intravenously, day 1, q14d×4 cycles; ET regimen: epirubincin 75 mg/m2 intravenously, day 1, and paclitaxel 175 mg/m2 intravenously, day 2, q21d×4 cycles as NCT; and two cycles of ET regimen were repeated after surgery; PC regimen: paclitaxel 175 mg/m2 intravenously, day 1, and carboplatin area under the curve=5 intravenously, day 1, q21d×6 cycles as NCT. Mastectomy or breast-conserving surgery was performed within 1 month after the completion of NCT. Adjuvant radiotherapy was prescribed at the discretion of physicians mainly on the basis of the TNM stage before NCT, followed by endocrine therapy in cases with ER-positive or PgR-positive tumors. Trastuzumab was recommended in HER2-positive patients, but not compulsory. Efficacy evaluation Clinical efficacy was estimated every two cycles by clinical, mammographic, B-ultrasound examinations, and MRI according to Response Evaluation Criteria in Solid Tumors 1.1 criteria. Pathological efficacy was assessed by pathologic report after surgery and imaging data. Efficacy evaluation indicators included pCR, clinical complete response (CR), clinical partial response (PR), overall objective response rate (ORR=CR+PR), clinical progressive disease (PD), and clinical stable disease (SD). pCR was defined as no histological evidence of malignancies or only in-situ residuals in breast tissue after surgery, and complete disappearance of lymph node metastasis. CR was defined as disappearance of all known lesions. PR was defined as at least a 30% decrease in the sum of the largest diameters of target lesions. PD was defined as at least a 20% increase in the sum of the largest diameters of target lesions or new lesions detected. SD was defined as a reduction in the largest sum diameters of tumors by no more than 30% or an increase of no more than 20%. Patients with overall objective response rate received planned treatment and sequential surgery. Patients who fulfilled the criteria for SD or PD at the initial efficacy evaluation received surgery as soon as possible and were then treated with alternative postoperative regimens. Statistical analysis All data were analyzed using SPSS medical statistical software (version 15.0; SPSS Inc., Chicago, Illinois, USA). Disease-free survival (DFS) was defined as the period from the date of receiving NCT to the date of recurrence or metastasis or last follow-up; overall survival (OS) was defined as the period from the date of receiving NCT to the date of death for any cause or last follow-up. Both OS and DFS were analyzed using the Kaplan–Meier method. Comparisons of OS or DFS between groups were performed using the log-rank test. A two-tailed P value less than 0.05 was considered statistically significant. The χ2 or Fisher's exact test was performed to compare the clinicopathological variables and pCR rates between the subgroup of younger than 35 years of age and the subgroup of older than 60 years of age. Results Patient characteristics and treatment From January 2003 to December 2013, a total of 141 breast cancer patients were enrolled in this study and 74 (52.5%) of these patients were younger than 35 years old. As shown in Table 1, younger patients presented a tendency to have a tumor size of more than 5 cm (P=0.085), to have axillary positive nodes (P=0.118), and to have lymphovascular invasion (P=0.007) compared with their older counterparts (≥60 years old). As for the treatment, younger patients were more likely to choose breast-conserving surgeries (P=0.024) and to receive adjuvant radiotherapy after surgeries (P<0.001). For the entire cohort, the median number of NCT cycles was 4 (range: 4–6 cycles). The chemotherapy regimens were changed for a total of 31 patients who had a poor response to preoperative chemotherapies (including 26 SD and five PD). Overall, 52% (16/31) of these patients were in the young group, and the other 15 patients were older than 60 years. All 96 patients with preoperative or postoperative pathological ER-positive or PgR-positive breast cancer received different postoperative adjuvant endocrine therapies. In all, 18.9% (14/74) of patients in the young group and 16.4% (11/67) of patients in the old cohort received 1 year of trastuzumab after surgery or adjuvant chemotherapy.Table 1: Patients' baseline characteristicsTreatment response All patients were evaluable for response to NCT. The rates of pCR, clinical PR (except clinical PR, but confirmed as pCR finally), clinical SD, and clinical PD were 12.8% (18/141), 65.2% (92/141), 18.4% (26/141), and 3.5% (5/141), respectively. pCR rates were similar between the young group and the old cohort (12.2 vs. 13.4%, P=0.821). The PC regimen tended to yield higher pCR rates in the young cohort, but this was not statistically significant. HER2-positive or inflammatory breast cancer patients in young group were also more likely to achieve pCR compared with their older counterparts. As shown in Table 2, there were no significant differences between the pCR rates of young and old patients across various subgroup analyses, including hormone receptor status, axillary lymph node metastasis from primary tumors, primary tumor size, HER2 expression status, and NCT regimens.Table 2: Clinical and pathological factors affecting pathological complete response ratesSurvival analysis By the last follow-up on 1 November 2015, with a median follow-up of 32 months, 38 relapse events and 11 deaths have occurred. Patients in the young group showed significantly lower 5-year DFS compared with their old counterparts (Fig. 1a, 62.2 vs. 77.8%, P=0.037). However, no significant difference in 5-year OS was observed between the young group and the old cohorts (Fig. 1b, 84.0 vs. 94.8%, P=0.212).Fig. 1: (a) Kaplan–Meier curves of disease-free survival (DFS) in the young group (N=74) and the elderly group (N=67); Kaplan–Meier curves of overall survival (OS) in the young group (N=74) and the elderly group (N=67).In the group of young patients, pCR was not a significant predictor for DFS (Fig. 2a, P=0.408), whereas significant differences were observed with respect to the ascending TNM stage at diagnosis (Fig. 2b, P=0.001). In the subset of old patients, neither pCR nor TNM stage was a prognostic factor against DFS (Fig. 2c, P=0.129 and Fig. 2d, P=0.174).Fig. 2: Disease-free survival (DFS) curves by chemotherapy response (a) and TNM stage at diagnosis (b) in young patients; DFS curves by chemotherapy response (c) and TNM stage at diagnosis (d) in old patients. pCR, pathological complete response.To further explore the difference in survival between young and old groups, we carried out a stratified analysis. As shown in Fig. 3, the 5-year DFS was lower in the young group than in the old group within the subgroup of patients who presented with inflammatory breast cancer [56.5 vs. 75.1%, hazard ratio (HR)=2.47, P=0.044], with a large primary tumor (46.7 vs. 81.4%, HR=2.93, P=0.053), with lymph node involvement (57.7 vs. 74.8%, HR=2.40, P=0.025), and with higher TNM stage at diagnosis (46.7 vs. 67.1%, HR=2.52, P=0.027). Subgroup analyses on OS were carried out across predefined subsets and no significant difference was observed (Fig. 4).Fig. 3: Forest plot of disease-free survival. Hazard ratio more than 1 indicated that old patients had better survival outcome. CI, confidence interval; ER, estrogen receptor; PgR, progesterone receptor; TNBC, triple-negative breast cancer.Fig. 4: Forest plot of overall survival. Hazard ratio more than 1 indicated that old patients had better survival outcome. CI, confidence interval; ER, estrogen receptor; NA, not available; PgR, progesterone receptor; TNBC, triple-negative breast cancer.Discussion Although there was no consensus definition for young breast cancer, it had been widely believed that breast cancer at a young age had a more aggressive biological behavior compared with the disease arising from older patients. Tumors in younger women present with a higher grade, a higher T stage, a higher N stage, and more dedifferentiation, and have a higher proliferating fraction and more vascular invasion 5,7–17. In our study, the clinicopathological characteristics of young patients were consistent with previous researches. Keegan et al.22 and Colleoni et al. 23 found that higher proportions of HER2-positive tumors occurred in young patients. It was reported that about 25% of all breast cancers are ER or PgR negative, but a large proportion of hormone receptor-negative tumors occur in young women 13,15,17,24. Azim et al. 11 reported that there was a significantly higher proportion of basal-like tumors (34.3%) in young patients compared with those aged 41–52 (27.7%). No significant differences in the breast cancer subtype pattern were observed in this study and this could be attributed to the limited sample size of our study. It has been shown that younger age was associated with a less favorable prognosis 5,7–17. Tang et al. 15 found that with a follow-up of 54 months, inferior 5-year DFS (72 vs. 83%, P<0.01) and 5-year OS (87 vs. 93%, P <0.01) were observed in patients aged younger than 40 years compared with those aged 40–50 years. In our study, worse 5-year DFS was observed in young patients (62.2 vs. 77.8%, P=0.037), which was consistent with the results in previous studies. Stratified analysis showed that the predictive value of age on DFS was proven in the subgroup of patients with high-risk factors, including inflammatory breast cancer, large primary tumor, positive axillary lymph node, or higher TNM tumor stage at diagnosis, whereas no difference in the 5-year DFS was observed in patients without the above-mentioned risk factors. Similarly, in the study of Han et al. 5, there was no significant difference in DFS between young and old groups in lymph node-negative patients (P=0.223), whereas the younger group showed worse prognosis among lymph node-positive patients (P<0.001). In a Korean study, patients in the very young group with lymph node metastasis had poorer 5-year OS (70 vs. 83%, P<0.001) and DFS (58 vs. 74%, P <0.001) than their older counterparts; in patients without lymph node metastasis, the survival outcomes did not differ significantly between the two groups 17. Therefore, it is a key point to identify high-risk young breast cancer patients, and implement a tailored and aggressive treatment to improve the outcomes of these patients. It had been reported that improved survival outcomes were observed in patients with pCR compared with those with residual tumor 18,25–29. Further analysis showed that pCR was associated with better DFS in ER or PgR-positive/HER2-negative with grades 1–2, HER2-positive, and triple-negative disease, but not for those with ER or PgR-positive/HER2-positive, and ER or PgR-positive/HER2-negative with grade 3 tumors 18. In addition, in a meta-regression analysis of 29 heterogeneous neoadjuvant trials, pCR was not suggested to be a surrogate end point for DFS and OS in patients with breast cancer 30. At the 2016 annual meeting of American Society of Clinical Oncology, Robidoux et al. 31 reported 5-year outcomes of the NSABP protocol B-41 and found that long-term outcomes correlated with pCR status. Additional analyses indicated that pCR was related to a significant improvement in survival rates in the ER-negative subset, but not in the ER-positive cohort. In our study, young patients achieving pCR showed similar 5-year DFS compared with those with non-pCR (P=0.408). Therefore, pCR may be not an appropriate surrogate for prognosis in young breast cancer patients treated with NCT. The TNM staging system maintained by the AJCC is considered the most clinically useful cancer staging system for cancers. Orucevic et al. 32 reported on 782 Caucasian women diagnosed with invasive ductal carcinoma who were grouped according to TNM stage and molecular phenotype. The results supported the traditional TNM staging as a continued relevant predictive tool for breast cancer outcomes even with the emerging prognostic impact of tumor biomarkers (ER/PgR/HER2). Carey et al.33 suggested that classification of residual tumor in the breast and axillary surgical specimens after NCT using the AJCC TNM staging system could predict distant relapse and survival. In our study, young patients with higher TNM stage at diagnosis showed worse survival outcomes. Therefore, TNM stage may be more predictive of prognosis than pCR in breast cancer patients treated with NCT. This study is limited by its retrospective nature, nonrandomized design, small sample size, and relatively short follow-up duration. Trastuzumab was not covered by medical insurance in China and was much more expensive than common chemotherapy drugs. Therefore, some of the HER2-positive patients could not afford the expense. The diversity of NCT regimens and difference in the proportions of patients receiving trastuzumab between young and old cohorts may also have influenced the results of this study. Further prospective studies are warranted to validate the results. In recent years, researches have confirmed that breast cancer arising in young women is a unique disease entity driven by complex biologic processes extending beyond hormone receptors and hereditary cancer syndromes. Anders et al. 34 found 367 significant gene sets among young women's tumors that specifically distinguished them from tumors arising in older women, including those related to immune function, the mammalian target of rapamycin/rapamycin pathway, hypoxia, BRCA1, stem cells, apoptosis, histone deacetylase, and multiple oncogenic signaling pathways. In the study of Azim et al. 11, breast cancer in the young was enriched with processes related to immature mammary epithelial cells and growth factor signaling. There was also downregulation of apoptosis-related genes. The identification of genomic pathways specific to breast cancer arising in young patients provided a better understanding of the interplay of age and contributing biologic processes and a unique opportunity to explore therapeutic targets. Conclusion Young breast cancer patients treated with NCT present more aggressive clinicopathological features and worse prognosis compared with their elderly counterparts. TNM stage at diagnosis may be more predictive of prognosis than pCR in young breast cancer patients with NCT. The underlying biology of young breast cancer needs to be elucidated and the development of tailored treatment is crucial. Acknowledgements The authors thank all doctors and nurses of the Department of Medical Oncology for their help with the realization of this study. Binghe Xu and Jiayu Wang designed the research, analyzed the data, and wrote the paper; Jingjing Wang analyzed the data and wrote the paper; Jiayu Wang, Qing Li, Pin Zhang, Peng Yuan, Fei Ma, Yang Luo, Ruigang Cai, Ying Fan, Shanshan Chen, Qiao Li, Binghe Xu selected the cases and analyzed the clinical data. Conflicts of interest There are no conflicts of interest.

Background: Pathologic complete response (pCR) after neoadjuvant therapy (NAT) is a validated surrogate for long-term outcomes in breast cancer. Real-world data from Latin America are limited. We aimed to evaluate the pCR rate across molecular subtypes and its association with survival outcomes. Methods: We conducted a retrospective study of 488 patients with stage I–III breast cancer who received NAT and surgery (2019-2024) at a tertiary center in Cali, Colombia. Data were extracted from electronic records. pCR was defined as ypT0/Tis ypN0. Molecular subtypes were assigned by immunohistochemistry and FISH; staging followed AJCC 8th edition. Most patients received standard NAT according to institutional protocols: AC–T in luminal and AC–TC more often in triple-negative cases. HER2-positive patients received chemotherapy with either single-agent trastuzumab or dual blockade. Non-standard regimens were used based on clinical judgment or comorbidities. Primary outcome was pCR; secondary outcomes included recurrence, disease-free survival (DFS), and overall survival (OS). Associations were assessed using chi-square, Wilcoxon rank-sum, and multivariable logistic regression. Kaplan–Meier and log-rank tests were used for survival analyses. Results: Median age was 52 years (IQR: 44-61). Most tumors were invasive ductal carcinoma (93%) and grade III. Molecular subtypes were: Luminal A (13%), Luminal B (30%), HER2-Luminal B (17%), HER2-enriched (14%), and triple-negative (26%). Clinical stage was II–III in 97%, 56% T1–T2 and 59% node-positive. The overall pCR rate was 34.6% (169/488). Rates varied significantly across molecular subtypes: 60.3% in HER2-enriched, 54.9% in HER2-Luminal B, 44.2% in triple-negative, 17% in Luminal B, and 1.6% in Luminal A (p &amp;lt; 0.001). pCR was significantly more frequent in ER-negative (50.0% vs. 24.5%; p &amp;lt; 0.001) and PR-negative tumors (49.1% vs. 21.0%; p &amp;lt; 0.001). Among receptor-positive case, those with low ER and PR expression (1–10%) had higher pCR compared to high expression (&amp;gt;10%) (60.0% vs. 22.7%, p = 0.001; and 37.1% vs. 18.8%, p = 0.016, respectively). HER2-positive tumors showed greater pCR than HER2-negative (57.3% vs. 24.6%; p &amp;lt; 0.001), as did those with high Ki-67 &amp;gt;20% (39.0% vs. 13.3%; p &amp;lt; 0.001) and grade III histology (p &amp;lt; 0.001). T1–T2 tumors had higher pCR than T3–T4 (39.5% vs. 28.5%; p = 0.012). No significant associations were found with nodal status (p = 0.690) or clinical stage (p = 0.484). pCR rates did not differ significantly by regimen within molecular subtypes. In triple-negative tumors, adding carboplatin showed no benefit (AC–TC vs. AC–T: 43.6% vs. 47.7%, p = 0.351). In HER2-positive disease, dual vs. single-agent anti-HER2 therapy yielded similar pCR (52.8% vs. 59.2%, p = 0.782). Recurrence was lower in the pCR group (4.7% vs. 12.9%, p = 0.005), particularly for distant metastases (2.96% vs. 9.1%, p = 0.011). Patients who achieved pCR had significantly improved DFS compared to those who did not (log-rank p = 0.047). OS showed a numerical but non-significant difference (1.2% vs. 3.1% mortality, log-rank p = 0.35). Conclusion: In this real-world Latin American cohort, pCR rates and their prognostic significance were consistent with international evidence. HER2-positive and triple-negative tumors showed the highest response, while Luminal subtypes had limited benefit from standard NAT. pCR was independently associated with more favorable DFS. These findings support its value as a surrogate endpoint and highlight the need for subtype-adapted strategies in the neoadjuvant setting, such as immunotherapy in triple-negative disease. Citation Format: M. A. Solis Velasco, V. S. Muñoz-Anacona, D. F. Penagos-Cabrera, L. A. Olave-Asprilla, A. D. Fernandez-Osorio, U. O. Cardona-Nuñez, M. Zuluaga-Zuluaga, V. L. Roman-Vasquez, A. J. Guerrero-Villota. Pathologic Complete Response by Breast Cancer Molecular Subtype in a Colombian Cohort: Real-World Evidence from Latin America [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-06-10.

Antecedentes: La incidencia de Cáncer de Mama (CaMa) en jóvenes latinoamericanas es 20 %, en Colombia fluctúa entre 10 y 24 %. Su gravedad se atribuye al diagnóstico en estadios avanzados, mayor frecuencia de tumores triple negativo y HER2+. Objetivo: Describir la supervivencia global (SG) de mujeres ≤40 años con CaMa infiltrante operadas en el Instituto de Cancerología Las Américas auna (Medellín-Colombia), entre 2007-2016. Materiales y métodos: Estudio de seguimiento de una cohorte retrospectiva con datos del registro institucional. La supervivencia se calculó desde el diagnóstico hasta la fecha del último control médico o muerte. Se elaboraron curvas de supervivencia de Kaplan Meier y se compararon con log rank test. Resultados. En el periodo se operaron 4.059 mujeres, de estas 390 (9.6 %) tenían ≤40 años, 365 pacientes cumplieron criterios de inclusión. Al diagnóstico 67 (18.3 %) estadio I, 152 (41.6%) estadio II, 140 (38.3%) estadio III y 6 (1.6%) estadio IV. Por subtipos moleculares hubo 87 (24.1 %) Luminal A, 152 (42.1 %) Luminal B HER2-, 72 (19.9 %) Luminal B HER2+, 17 (4.7 %) HER2- enriquecido y 33 (9.1 %) Triple Negativo. 24.4 % de pacientes fueron HER2-positivas. Tuvieron recaída loco-regional 34 (9.3 %) pacientes y 132 (36.2 %) desarrollaron metástasis a distancia. La mediana de seguimiento fue 60 meses (rango 8-142 meses) y la SG de 81.3% (IC95 %: 76.3-85.4). La SG de tumores triple negativo fue la más baja, 67.7% (IC95 %: 48-81.3). Conclusiones. Se encontró mayor porcentaje de pacientes con cáncer Luminal B y HER2 positivo a lo reportado en la literatura. La SG fue similar a las reportadas por otros estudios y menor en estadios avanzados y tumores triple negativo.

The use of neoadjuvant chemotherapy (NAC) has improved outcomes in breast cancer (BC). The residual cancer burden index (RCB) predicts prognosis. This study evaluated RCB as a prognosticator in BC subtypes treated with NAC. A retrospective cohort of BC patients was analyzed. Five-year distant recurrence-free survival (DRFS), disease-free survival (DFS), and overall survival (OS) were analyzed. Statistical analyses included descriptive statistics, ANOVA, chi-square test, Fisher's exact test, Kaplan-Meier curves, Log-Rank test, and Cox regression. Among 562 women, RCB correlated with BC subtypes and predicted worse DRFS, DFS, and OS. In stratified analyses by molecular subtype, the association was significant only for luminal B and triple-negative subtypes, with inconsistent findings for luminal A and human epidermal growth factor type 2-overexpressed subtypes. The RCB index was shown to be a prognostic marker in BC in a Brazilian population with BC. Significant associations were found only for the luminal B and triple negative subtypes. Further research is required to investigate the prognostic utility of RCB in other larger populations.

Breast cancer poses a serious public health concern throughout the world in both developed and developing nations. Recent data show a small decline in breast cancer mortality in the United States and Northern Europe where the disease has been a leading cause of death.' This reduction has been attributed in part to the early detection of breast cancer in addition to advances in clinical management. The decline in mortality has also been postulated to be due to a decreased risk in women developing breast cancer in the last 2 decades associated with increased fertility as part of the post-Second World War baby boom. 1 Despite these encouraging results, other European nations such as Spain, Portugal, Greece, Hungary, Poland and Italy have not reported a reduction in breast cancer mortality. The true reasons for these breast cancer trends, particularly across continents, remain perplexing to both epidemiologists and clinicians. Any observed variation of incidence and oncologic outcome between different populations and ethnic backgrounds may relate to the underlying biological behavior of breast cancer at the cellular and molecular level. Application of biomarker studies could therefore enhance the information obtained from classical study designs and further expand the areas of scientific inquiry to which epidemiology can contribute. This approach may yield important clues in breast cancer pathogenesis, develop potential preventive strategies, improve early detection and treatment of disease with distinctive protocols, tailored to the needs of individual target populations. Conclusions from the workshop on Multicultural Aspects of Breast Cancer Etiology in Washington DC by the Etiology working group of the National Action Plan on Breast Cancer (NAPBC) in March 1999 highlighted the importance of ethno-oncology that addresses the comparison of population groups with extreme differences in the rates of incidence, mortality and survival. 2 This article reviews the evidence for global multiethnic differences in breast cancer outcome and discusses the future clinical implications of ethno-oncology.

Background: The COVID pandemic created significant challenges in breast cancer (BC) care which were most pronounced during 2020 when screening and treatment access were reduced. The aims of this study were to evaluate and compare the incidence of BC, treatment patterns, and outcomes during the year 2020 versus the immediate pre-pandemic (2018 and 2019) period. Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) program, we calculated age-adjusted incidence rates of ductal carcinoma in situ (DCIS) and invasive BC during 2018, 2019 and 2020, with a 95% confidence interval (CI) for each. In the invasive BC cohort, we compared chemotherapy and radiation utilization by year. To account for potential misclassification of cause of death (COD) during the pandemic, we evaluated outcomes by overall survival (OS) in the invasive cohort, defined as time from BC diagnosis until death from any cause. To assess the impact of COVID, OS was truncated at 12 months from diagnosis for each year and we compared OS at 12 months for patients (pts) diagnosed with invasive BC in 2020 versus 2018 and 2019. OS was compared in a multivariable Cox model with diagnosis year 2020 as the reference. The Cox model was adjusted for age at diagnosis, race and ethnicity, sex, tumor grade, histology, stage, tumor subtype, surgery, radiation, chemotherapy, marital status, median household income, and rurality. Results: There were 37,834 DCIS diagnoses, and 199,594 invasive BC diagnoses between 2018-2020, with the distribution by year shown in the table. In 2020, the age-adjusted incidence of female DCIS decreased to 31.0 cases per 100,000, and the age-adjusted incidence of female invasive BC decreased to 166.6 cases per 100,000. As shown in the table, the incidence of male BC did not change. Among females, the relative reductions in incidence from 2019 to 2020 were: 15% for DCIS, 12% for stage I, 6% for stage II, 3% for stage III, and 2% for stage IV. Comparing 2020 to 2018-2019, we observed small absolute decreases in the proportions of pts who had surgery (2%) or radiation therapy (2.8%), and a small absolute increase in chemotherapy (1.4%) (p&amp;lt; 0.001 for each). These treatment changes were present across each individual stage. The table shows the 12-month OS rates for each year of diagnosis. COVID was the COD for 77 pts in 2020, 43 pts in 2019 and 0 pts in 2018. In the Cox model, there were no significant differences in the risk of death between pts diagnosed 2018 and 2020 (adjusted Hazard Ratio: 0.95; 95% CI, 0.90 – 1.01; p=0.13) or between pts diagnosed 2019 and 2020 (adjusted Hazard Ratio: 0.95; 95% CI, 0.89 – 1.01; p=0.08). Conclusions: During the first year of the pandemic, the incidence of BC decreased significantly, largely driven by a decrease in DCIS and early-stage diagnoses. Of interest, there was no stage shift observed with respect to the incidence of stage III or de novo stage IV disease, and no change in male BC incidence. We hypothesize that the observed trends are due to a reduction in screening, but this needs further study. It will be critical to evaluate future trends in cancer incidence beyond 2020, as it is possible that the reduction in early-stage diagnoses represent missed diagnoses that will be identified at a later stage in subsequent years. Finally, while there was no difference in 12-month OS by year of diagnosis, the true impact of the COVID pandemic on BC-specific outcomes will require further follow-up. Citation Format: Jose Leone, Julieta Leone, Michael Hassett, Rachel Freedman, Jorge Avila, Carlos Vallejo, Nabihah Tayob, Sara Tolaney, Nancy Lin. Incidence, treatment patterns and outcomes of breast cancer during the first year of the COVID pandemic: A population-based study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-11-02.

The Wnt/β-catenin signaling pathway is implicated in mammary oncogenesis. Reports of β-catenin expression and its association with outcome in breast cancer are controversial. This study was performed to address the distribution of β-catenin expression in invasive breast cancer and the correlation between β-catenin expression and survival of breast cancer patients, and to determine whether β-catenin was specifically activated in any molecular subtypes. Immunohistochemistry was performed on a tissue microarray containing 169 invasive breast cancers to detect expression of β-catenin. One hundred thirty one of the 169 patients were followed up. Correlation between β-catenin expression and different molecular subtypes was determined using chi-square analysis. Overall survival (OS) was analyzed by Kaplan-Meier method with log-rank test. The invasive breast cancer displayed the different patterns of β-catenin expression from normal tissues with significantly increased cytoplasmic and nuclear staining of β-catenin. Aberrant β-catenin expression was observed in 109 in the 169 cases (64.50 %), and there was no difference in β-catenin expression in the four molecular subtypes. Furthermore, aberrant β-catenin expression was significantly associated with adverse outcome not only in the entire cohort but also in each of the different molecular subtypes. β-catenin activation is preferentially found and is associated with a poor clinical outcome in invasive breast cancer independent of molecular subtype.

Purpose: Disparities in breast cancer outcomes have been a long-standing and persistent challenge. Earlier onset, advanced stage at diagnosis, aggressive tumor subtypes [triple negative breast cancer (TNBC)], and worse overall survival (OS) are some of the characteristic features of breast cancer in non-Hispanic Black (NHB) women compared to their non-Hispanic White (NHW) counterparts, denoting one of the most significant examples of racial/ethnic differences in oncology. Given our location in South Florida, gateway to Latin America and the Caribbean, we discovered that these disparities in tumor characteristics and outcomes among NHB and NHW also extend to Hispanic Blacks (HB) compared to Hispanic Whites (HW). Since Hispanics are the second largest ethnic group in the US and have a rich genetic architecture with contributions from European (EU), West African (WA), and Native American (NA) populations, we sought to investigate genomic associations between observed inter and intra-racial/ethnic differences and breast cancer characteristics and outcomes. Methods: Patients with stage I-IV breast cancer were included. Patient socioeconomnic status (SES), tumor and treatment characteristics, and follow-up data were collected for each patient. Genomic analysis was performed on the peripheral blood from a cohort of 309 patients with breast cancer. This breast cancer cohort was comprised of 192 self-reported HW, 12 HB, 46 NHW, 47 NHB, and 12 unknown (declined to report) patients. Leukocyte DNA from each patient was genotyped, generating whole genome single nucleotide polymorphism (SNP) profiles. Global ancestral estimates, using &amp;gt;100,000 SNPs, were calculated against reference samples from EU, WA, NA, and East Asian (EA) ancestral populations. A genomic diversity space was generated via principal component analysis and ADMIXTURE was used to estimate the ancestral proportions among the patients. Results: The genetic structure of individual patient sample revealed a diverse ancestral admixture where average EU, WA, NA, and EA ancestries were 64.5%, 21.8%, 11.2%, and 2.5%, respectively. Multinomial logistic regression revealed a significant association between increasing WA ancestry and aggressive tumor subtypes (ER-/HER2+ and TNBC), p=0.009 and p=0.031, respectively. These findings remained significant when correcting for patient age and tumor stage; however, when adjusting for income, the association between WA ancestry and ER-/HER2+ and TNBC was no longer significant. Kaplan Meier survival curves showed a significant difference in 5-year OS for patients with &amp;gt;70% WA ancestry compared to those with &amp;lt;70% WA ancestry, p=0.023. Conclusions: In this first integrative approach studying genetic ancestry and SES on breast cancer characteristics and outcomes, we found a significant association between increasing WA ancestry and aggressive breast cancer subtypes, even after adjusting for known covariates. More striking, this association was negated when adjusting for income, suggesting potential gene-environment interactions not accounted for by genetic race. We also discovered that Hispanics have a more complex genetic architecture than non-Hispanic patients, which may in-turn drive genetically-associated survival patterns of resiliency with improved survival in HW compared to NHB patients. Furthermore, the OS differences based on quantitative genetic ancestry cut-offs may serve as a future tool in patient prognosis. Collectively, our results show that genetic ancestry and SES influence breast cancer subtypes and survival. This lays a foundation for future studies to investigate complex genomic relationships between race/ethnicity, SES, and breast cancer characteristics and outcomes through the lens of gene-environment interactions. Citation Format: Daniel A Rodriguez, Sina Yadegarynia, J. William Harbour, Nipun B. Merchant, Erin N. Kobetz, Neha Goel. Comprehensive analysis of global genetic ancestry and socioeconomic status on breast cancer outcomes [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 P3-13-05.

520 Background: BC diagnosed in women 35 years of age or younger is associated with aggressive clinical-pathological characteristics and poorer disease free survival. Our understanding of the biological processes associated with early onset BC is limited. Methods: We compiled clinical and gene expression profiling data from 4,831 early-stage BC patients across 31 datasets with a median follow-up of 6.6 years. Tumors were assigned to a molecular subtype and expression scores were computed for several published oncogenic pathway signatures. The chi-square and Mann-Whitney tests were used for between group comparisons. Distant metastasis free survival (DMFS) was estimated using the Kaplan-Meier method and compared by the log-rank test. Hazard ratios (HRs) were calculated using a Cox-proportional hazards model. Results: The pattern of molecular subtypes differed according to age at diagnosis (age ≤ 35: triple negative [TN] 39%, HER2 20%, LumA 16%, LumB 25%; age > 35: TN 19%, HER2 16%, LumA 30%, LumB 35%; p < 0.001). Young age was associated with an increased risk of distant metastasis (10-year DMFS 52.8% age ≤ 35 versus 69.1% age > 35, p = 0.002) that remained statistically significant after adjustment for known prognostic factors (HR 1.54, 95%CI 1.04-2.28, p = 0.031). This increased risk was most apparent in the TN (HR 2.05, 95%CI 1.10-3.90, p = 0.025) and LumB (HR 2.52, 95%CI 1.15-5.51, p = 0.021) subtypes. Compared with older patients (age>65), there was higher expression of proliferation, PTEN loss, and immune response and lower expression of stromal gene expression signatures (all p < 0.001) in young TN patients. In the LumB subset, young patients had increased expression of PI3K activated genes (p < 0.001). Histopathological validation of these genomic findings is ongoing. Conclusions: TN BC is more common in women ≤ 35 years of age. Young age is associated with a poor outcome from breast cancer, particularly for the TN and LumB subtypes. Increased expression of proliferation, immune response, and PTEN loss gene signatures in TN and PI3K activation in LumB suggests possible targets for biological investigation and future clinical trials in this high-risk population. No significant financial relationships to disclose.

Introduction: Previous studies have shown that breast cancer incidence rates are higher among female Veterans than the general population due to factors such as increased lifetime exposure to breast cancer risk factors or more accurate detection and surveillance. The present study explored relationships between nationally representative county-level breast cancer outcomes, mammography screening rates, female Veteran population density, and social vulnerability. Methods: Data for the present ecological study were obtained at the county level from the United States Census Bureau, the University of South Carolina's Hazards and Vulnerability Research Institute (HVRI), and the National Cancer Institute. We conducted ordinary least squares (OLS) multiple regression analyses to determine the relative influence of female Veteran population density, social vulnerability, and mammography screening rates on breast cancer incidence and mortality rates between 2010 and 2014. County-level covariates such as liquor store density, cigarette smoking prevalence, air pollution, and access to healthy foods, were entered into each model to determine the unique influence of each of the main study variables on breast cancer outcomes. Results: County-level breast cancer incidence rates were higher in counties with greater female Veteran population density, lower social vulnerability, and higher mammography screening rates ( n=2,698, F=33.669, p&lt;0.001). County-level breast cancer mortality rates were higher in counties with lower female Veteran population density, higher social vulnerability, and lower mammography screening rates ( n=1,803, F=18.180, p&lt;0.001). Discussion: The results of the present exploratory study were preliminary, and thus further research on relationships examined in this study are needed. However, because female Veterans were shown to live in counties with relatively high mammography screening rates and lower social vulnerability, their risk for mortality from breast cancer may be lower than for the general population – in particular due to early detection and treatment.

Introduction: Breast cancer (BC) represents 30.1 % of all cancers reported in Saudi females with median age at diagnosis 50 years. BC in young women (≤ 40 years ) accounts for 20% of all female BCs, and is histologically more aggressive as compared to the one seen in wome above 50 years of age. Differences with regard to tumor biology, presentation, genetics and molecular subtypes may contribute to poor prognosis among younger age group. BC in young Saudi women is a crucial problem and limited information exists regarding its pathologic characteristics and long term outcome. Purpose: This study investigated the long-term disease outcomes among young (≤ 40 years) Saudi BC patients as compared to older ones (&amp;gt;40 years), as well as assessed the clinicopathological parameters differeneces among the two groups. Methods: This was a retrospective longitudinal cohort study of 694 female BC patients over a 10-year period (January 2007 to December 2017). Demographic and clinicopathological data was collected. Disease presentation, disease characteristics. Cox regression analysis was performed and Kaplan-Meier curves were generated to assess overall survival. Cross tabulation was used to assess the difference in clinicopatholgical parameeters among the two age groups. Results: Among the included BC cases, 17.1% (N=119) were ≤ 40 years old . The mean survival time was 5.0 ± 2.6 years. ER, PR expression, molecular subtype, tumor grade, and N stage were variables significantly among the two age groups (p= &amp;lt;0.001, 0.002, 0.002, 0.003 and 0.038, respectively). More ER positive cases in older age group compared to the younger (76.2% vs 61.3%). PR was mainly positive in older age group (64.2% vs 49.6%), in contrast, Comparatively greater number of cases were Luminal A in older age group (33% vs 21%) while triple negative cases were more prevalent among the younger age group (23.5% vs 13.5%). Majority of the patients in younger age group had grade 3 tumors (56.3% vs 38.5%). The Nodal stage N2 was significantly more prevalent. among the younger age group (26.9% vs 16.3%). Although not statistically significant, stage 3 &amp; stage 4 were more common among younger age group (22.7% vs 15.6% and 18.5% vs 15.6% respectively), while stage 1 was more common among the older age group (16.7% vs 10.9%). Age did not influence the local therapy in the study cohort. The younger age group was more likely to develop metastasis in comparison to the older group (37.8% vs 24.3%; p=0.002). Recurrence and disease progression were more likely to occur in younger patients, compared to the older ones (12.6% vs 6.3% and 29.4% vs 18.2% respectively), while complete clinical remission was achieved more in older patients compared to the younger ones (76.7% vs 66.4%). The overall survival was not statistically different among two age groups, however, when stratified using molecular subgroup, Luminal A subtype was statistically significant (p=0.02) indicating a poor over all survival among younger patients. Conclusion: The long term overall survival of BC in younger patients (≤ 40 years) was not significantly worse than older patients. But, younger BC patients with luminal A subtype have a poor overall survival in comparison to older ones. ER and PR expression, molecular subtype, tumor grade, and N stage are significantly different among the two groups which may contribute to significanly more local recurrence and distance metastasis among younger patients. Citation Format: Omalkhair Abdullah Aboualkhair, Ahmad Omair, Emad Masuadi, Ghaida Alamri, Alaa Aljehani, Abdulmohsen Alkushi, Ann Partridge. Long-term outcomes among young Saudi women with breast cancer [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 P3-12-32.

Background: Breast cancer outcomes are influenced by tumor biology, stage at diagnosis, and access to timely care. Refugee populations may experience disparities in cancer outcomes despite formal access to healthcare services. Türkiye hosts the largest population of Syrian refugees globally and provides universal access to oncology care, offering a unique context to examine equity in breast cancer outcomes. Methods: We performed a retrospective cohort study of female patients diagnosed with invasive breast cancer between 2013 and 2022 at two tertiary oncology centers in Gaziantep, Türkiye. Patients were grouped as Syrian refugees or Turkish citizens based on recorded nationality. Baseline clinicopathologic features and stage at diagnosis were compared between groups. Overall survival (OS) was estimated by the Kaplan-Meier method and compared using log-rank tests. Survival analyses were performed overall and stratified by stage category (I-III vs. IV). Cox proportional hazards regression was used to evaluate the association between ethnicity and OS with adjustment for stage and molecular subtype (and other prespecified covariates as appropriate). Treatment delivery patterns (systemic therapy and radiotherapy) were descriptively compared to evaluate access after entry into care. Results: Among 499 patients (150 Syrian refugees; 349 Turkish citizens), Syrian patients were younger at diagnosis and more frequently presented with de novo metastatic disease. In the overall cohort with survival data (n = 430), unadjusted OS differed by ethnicity; however, survival differences were attenuated after stratification by stage. In stage I-III disease, OS did not significantly differ between groups, and in stage IV disease, median OS was comparable between ethnicities. In multivariable analysis adjusting for stage and molecular subtype, ethnicity was not independently associated with OS, whereas stage and molecular subtype remained prognostic. Treatment delivery patterns in both the non-metastatic and metastatic settings were broadly similar between groups. Conclusions: Within a universal healthcare system, the dominant disparity between Syrian refugees and Turkish citizens was more advanced stage at presentation. After accounting for stage and tumor biology, ethnicity itself was not independently associated with overall survival, suggesting that efforts to reduce outcome gaps should prioritize earlier diagnosis and linkage to care.

Background: Comorbidities may influence health outcomes from breast cancer and can significantly contribute to health disparities. Studies examining the association of specific comorbidities with breast cancer outcomes in underrepresented African-American and Hispanic women have been few. Notably, underrepresented women are more likely to have comorbidity. Presence of comorbidity may impact not only breast cancer risk and progression, but also likelihood to complete treatment and therapy. Therefore, the aims of the present study are to evaluate comorbidity and breast cancer among African-American and Hispanic women. In addition, the study will assess the consequence of comorbidity on therapy completion and breast cancer survival. Methods: The study included a cross-sectional cohort of 426 African-American and Hispanic women from South Los Angeles. Personal and medical history was obtained during the informed consent process and from post-hoc medical chart. The results were evaluated using the chi-square test and logistic regression with multivariate analysis. Five year disease free survival analysis (DFS) was performed using Kaplan-Meier survival curves with log rank test. The two-sided P-value less than 0.05 was considered significant. Results: Our study identified a high frequency of comorbidity among women with breast cancer compared with women without breast cancer (55% vs.45%, respectively: P = 0.032). Diabetes was also more frequent among breast cancer patients than non-cancer participants (62% vs. 38%; P = 0.005). African-American women were more likely than Hispanic women to have comorbidity (P = 0.003), particularly hypertension and hypertension with diabetes. Hispanic women were more likely to have diabetes only. In univariate analysis, the presence of any comorbidity was significantly associated with breast cancer (OR = 1.536; 95% CI = 1.045-2.255; P-value = 0.029). In the adjusted multivariate model, this association was borderline significant (P-Value = 0.057). The association of compound comorbidity (diabetes with hypertension) was significant in both the univariate and multivariate models (OR = 3.333; 95% CI = 1.290-8.611; P-Value = 0.013). Women with an increasing number of comorbidities were increasingly less likely to complete treatment with chemotherapy (P = 0.022). African-American women with compound comorbidity were least frequently able to complete treatment with chemotherapy (P = 0.002). Lastly, women who completed treatment with chemotherapy had a significantly higher survival vs. women who did not complete (Log rank = 5.09; P = 0.024). Conclusions: The presence of comorbidity can affect risk of breast cancer, likelihood of completion of therapy, and subsequent survival. African-American and Hispanic women have higher frequency of comorbidities and this may place women, especially with compound comorbidity, at a greater risk for breast cancer and lower survival outcomes. Citation Format: Marianna Sarkissyan, Yanyuan Wu, Jaydutt V. Vadgama. Comorbidities contribute to breast cancer disparities among African-American and Hispanic women. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1765.