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Breast neoplasm, COVID-19, Delayed diagnosis, Pandemics, What&,rsquo s Known The COVID-19 pandemic led to delays in breast cancer diagnosis and treatment, resulting in patients presenting with larger tumors, increased axillary involvement, and more advanced disease stages. Previous studies reported decreased cancer screenings and delayed diagnoses caused by COVID-19 restrictions, leading to more advanced disease at presentation. What&,rsquo s New This study provided unique regional data from Shiraz, Iran, quantifying the rise in tumor size, axillary lymph node involvement, and advanced staging among breast cancer patients during the pandemic. The findings highlighted a significant post-pandemic decline in the utilization of adjuvant chemotherapy and intraoperative radiotherapy, underscoring critical gaps in subsequent patient management. IntroductionEarly diagnosis is the most critical factor in improving survival and longer-term quality of life for cancer patients. 1, Unfortunately, standard protocols for the early detection of cancer were disrupted by the coronavirus disease 2019 (COVID-19) pandemic, a global health concern that emerged in December 2019. 2, The management of various cancers, including breast cancer, was significantly affected, creating critical challenges for patients. 3, Furthermore, cancer has been established as a significant risk factor and comorbidity for COVID-19, with infection potentially leading to more severe and even fatal events in these patients. 4, - 6, Regarding the enormity of this pandemic, numerous complications emerged. The outbreak impacted not only the diagnosis and treatment of several severe diseases but also their follow-up protocols. Recent studies have demonstrated a clear correlation between the COVID-19 pandemic and the efficiency of healthcare systems. 7, - 10, In Iran, this disruption was associated with a decrease in life expectancy of one year. 11, Breast cancer is the most common malignancy among women and, after lung cancer, the most life-threatening. It affected 7.8 million people by the end of 2020. 12, Research by Minami and colleagues indicated that the treatment delay was an important factor in disease progression among patients with breast cancer. 13, Results from a meta-analytic study by Marty and colleagues demonstrated a higher rate of metastatic tumors, particularly breast cancer, following the COVID-19 pandemic. 14, The pandemic has significantly influenced breast cancer management, leading to alterations in various factors, such as tumor size, grade, stage, lymph node involvement, and care delays. 15, Given the importance of timely diagnosis and treatment, a survey in Guangzhou, China, demonstrated that poor follow-up resulted in more advanced clinical stages and a poorer prognosis of breast cancer. 16, Moreover, Alaidy and colleagues showed that postponed diagnosis could lead to increased tumor size. 17, However, some researchers argued that the local recurrence of some types of breast cancers was more closely associated with the tumor size than with delays in late radiotherapy. 18, The COVID-19 pandemic is a likely contributor to these outcomes. As a notable example, a study noted that unprecedented pressures on the health system led to a decline in patient referrals to oncologists, depriving many of effective anticancer treatments and resulting in increased morbidity and mortality during the pandemic. 19, Due to the critical importance of early diagnosis and treatment in breast cancer, and given the limited investigation into the specific effects of the COVID-19 pandemic on these processes, this study was conducted to determine the correlation between the pandemic and key breast cancer parameters. These parameters, assessed at diagnosis and after primary treatment, included tumor size, stage, and referral for adjuvant therapy. Elucidating this relationship would further help us to make better decisions about cancer patients, particularly those with breast cancer, during future pandemics or other major global health crises. Patients and Methods Study Design and Variables This retrospective study utilized data from patients with breast cancer, including 811 patients diagnosed in the year before the COVID-19 pandemic (from September 2018 to September 2019) and 624 patients diagnosed in the year after its onset (from March 2020 to March 2021). Patient information was obtained from Shiraz Breast Cancer Registry (SBCR) and cancer centers affiliated with Shiraz University of Medical Sciences (Shiraz, Iran). The registry included data on baseline characteristics, clinical history, physical examination, imaging, disease course, prognosis, and surgical and pathological parameters. 20, Patients were divided into two groups based on whether they were diagnosed before or after the start of the pandemic. The compared variables included age, tumor size, stage, subtype (luminal A, luminal B, triple-negative, and HER2-enriched), multifocality, in situ component, tumor necrosis, type of involvement (perineural, vascular, or both), receptor status, type of surgery (breast-conserving surgery [BCS] or mastectomy), type of axillary management (axillary lymph node dissection [ALND], sentinel lymph node biopsy [SLNB], or both), and the use of adjuvant chemotherapy, radiotherapy, intra-operative radiotherapy (IORT), and hormonal therapy. Due to the well-established importance of neoadjuvant chemotherapy in selected cases, a subgroup analysis comparing these variables was also performed for patients who received neoadjuvant chemotherapy and for those who did not. Inclusion and Exclusion Criteria The inclusion criteria were female sex of any age, a diagnosis of breast cancer within one year before or after the start of the COVID-19 pandemic (December 2019), and having relatively complete medical records regarding tumor size, stage, subtype, type of surgery, axillary management, lymph node involvement, and chemotherapy. Patients with metastatic disease at diagnosis were excluded. Ethical Considerations This study protocol was approved by the Ethics Committee of Shiraz University of Medical Sciences (approval ID, IR.SUMS.MED.REC.1399.628). All patients were informed about the use of their data for research. Due to the retrospective nature of the study, the requirement for written informed consent was waived by the Ethics Committee. Patient information was obtained from hospital records, de-identified before analysis, and confidentiality was guaranteed and protected. Permission to conduct the study and access records was granted by the university administrators. Additionally, the study was conducted in accordance with the relevant guidelines and regulations and the Declaration of Helsinki. Statistical Analysis Statistical analysis was performed using IBM SPSS software (version 26, IBM, Chicago, USA). Continuous variables were described as mean&,plusmn SD, and categorical variables were presented as frequency and percentage. Independent sample t tests were used to compare normally distributed continuous variables (e.g., tumor size) between the pre- and post-pandemic groups. Paired sample t tests were applied where necessary to compare pre- and post-pandemic values within the same patient group. The Wilcoxon signed-rank test was used for non-normally distributed repeated measures. For categorical data comparisons (e.g., stage, receptor status), Pearson&,rsquo s Chi square test was applied, and the Kruskal-Wallis test was used for non-normally distributed categorical data. Effect sizes were recalculated as Cohen&,rsquo s d for continuous variables and Cram&,eacute r&,rsquo s V or the Phi coefficient for categorical variables. Statistical significance was defined as P&,lt 0.05. Results Demographic The study included 1,435 patients 811 patients were diagnosed with breast cancer before the pandemic, and 624 patients were diagnosed after. The mean age of the participants was 49.1&,plusmn 11.4 in the pre-pandemic group and 49.3&,plusmn 11.7 in the post-pandemic group. Tumor Size The mean tumor size was significantly larger in the post-pandemic group (2.29&,plusmn 1.44 cm) than in the pre-pandemic group (2.11&,plusmn 1.39 cm). This difference was statistically significant (P=0.001, Cohen d, -0.127, indicating a small effect size). Among patients who did not receive neoadjuvant chemotherapy, the tumor size was also significantly larger in the post-pandemic group (2.55&,plusmn 1.3 cm vs. 2.28&,plusmn 1.3 cm P=0.002). In contrast, no significant differences in tumor size were observed before and after the pandemic in the subgroup that received neoadjuvant chemotherapy (P=0.428, table 1,).VariableSubgroupYear GroupP valuePre-pandemic (2018-2019)Post-Pandemic (2020-2021)Tumor size (cm, mean&,plusmn SD)Neoadjuvant CT1.58&,plusmn 0.471.57&,plusmn 0.680.428No neoadjuvant CT2.28&,plusmn 1.32.55&,plusmn 1.30.002Total2.11&,plusmn 1.39 2.29&,plusmn 1.440.001Stage (n, %)Neoadjuvant CTIII19 (8.6)17 (10.8)0.042II30 (13.6)33 (20.9)I71 (32.1)47 (29.7)Not defined101 (45.7)61 (38.6)Non-neoadjuvant CTIII38 (6.7)46 (10.2)0.001II39 (6.8)59 (13.1)I173 (30.3)133 (29.4)Not defined321 (56.2)214(47.3)TotalIII57 (7)63 (10.1)0.001II69 (8.5)92 (14.8)I244 (30.1)180 (28.9)Not defined441 (54.4)289 (46.2)SubtypeNeoadjuvant CTEnriched-HER226 (11.6)17 (10.2)0.211Triple-negative36 (16.1)19 (11.3)Luminal B44 (19.6)29 (17.2)Luminal A86 (38.4)65 (38.7)Not defined32 (14.3)38(22.6)Non-neoadjuvant CTEnriched-HER262 (10.6)54 (11.8)0.417Triple-negative47 (8.0)21 (4.6)Luminal B91 (15.5)67 (14.7)Luminal A286 (48.7)217 (47.6)Not defined101 (17.2)97 (21.3)TotalEnriched-HER288 (10.9)71 (11.4)0.02Triple-negative83 (10.2)40 (6.4)Luminal B135 (16.6)96 (15.4)Luminal A372 (45.9)282 (45.2)Not defined133 (16.4)135 (21.6)Chi square test was used P&,lt 0.05 was considered statistically significant. COVID, Coronavirus disease CT, Chemotherapy |
| نویسندگان مقاله |
Alireza Rezvani |
Department of Internal Medicine, Division of Hematology and Oncology, Shiraz University of Medical Sciences, Shiraz, Iran
Reza Heydarzadeh |
Department of Internal Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Reza Golchin Vafa |
Department of Internal Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Sina Sohrabizadeh |
Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Mohammad Hossein Rahmani |
Department of Internal Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Vahid Zangouri |
Department of General Surgery, Division of Surgical Oncology, Breast Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Hossein Molavi Vardanjani |
Department of Epidemiology and Biostatistics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Hourshad Zarifkar |
Department of Internal Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Houman Zarifkar |
Department of Internal Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Houyar Zarifkar |
Department of Internal Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Reza Shahriarirad |
Department of Surgery, Thoracic and Vascular Surgery Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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